IMS Magazine Fall 2021 by IMS Magazine

THINK. LEARN. DISCOVER.

FALL 2021

GI Tract and Gut Microbiome

Inflammatory Bowel Disease Causes and Treatments

Pros of Probiotics

Never Give Up!

How the Microbiome Impacts Health

Dr. Peter Giacobbe on Achieving the Impossible

Student-led initiative

Co-presidents, Kayvan Aflaki and Serena Peck, would like to thank the outgoing executive team for their excellent leadership and support with transitioning roles to the new executive team

Meet the IMSSA Executives Kayvan Aflaki Co-President, MSc. Student Kayvan studies maternal mortality with the Ontario Coroner. His favourite snack is bananas with peanut butter and if he could have any superpower, it would be the ability to steal other people's superpowers.

Serena Peck Co-President, MSc. Student Serena studies the cardiovascular health of women with breast cancer during and after treatment. Her favourite snack is chocolate covered pretzels and if she could have any superpower it would be to read minds.

Alex Boshart VP External Affairs, MSc. Student Alex studies kidney transplant rejection, focusing on antibody-mediated rejection. His favourite snack is flat pretzels from Costco with hummus. If he could have any superpower, it would be telekinesis so he could get food from the fridge while sitting on the couch.

Upcoming Events

December December 16th IMSSA Winter Party

January New Student Orientation (Date TBD) 3 Minute Thesis Competition (3MT) (Date TBD) Skating @ Nathan Phillips Square (Date TBD)

Isis So VP Internal Affairs, MSc. Student Isis studies brain recovery after traumatic brain injury. Her favourite snack is sour cream and onion chips. If she could have any superpower, it would be flying so she could beat traffic while commuting and because it would be so cool.

IN THIS ISSUE Letter from the Editors................................... 4 Director’s Message........................................ 5 Contributors................................................... 6 Infographic..................................................... 8 Features....................................................... 10 BMC Showcase............................................ 18 Viewpoints................................................... 20 Faculty Highlights........................................ 28 Faculty Spotlight.......................................... 30 Student Spotlight......................................... 32 Diversity in Science..................................... 34 Past IMS Event............................................. 36 Book Review................................................ 37 Raw Talk 100th Episode............................... 38

MAGAZINE STAFF EDITORS-IN-CHIEF: Jason Lo Hog Tian Mikaeel Valli EXECUTIVE DIRECTORS: Stacey J. Butler Dorsa Derakhshan Elizabeth Karvasarski PHOTOGRAPHERS: Dorsa Derakhshan (Director) Mikaeel Valli SOCIAL MEDIA TEAM: Sandy Lee Cindy Ha DESIGN EDITORS: Amy Zhang (Director) Sherry An Amy Assabgui Yuejun (Mimi) Guo Abeeshan Selvabaskaran Michie (Xingyu) Wu

JOURNALISTS & EDITORS: S. Hussain Ather Vritika Batura Stacey J. Butler Daniel Diatlov Sonja Elsaid Rehnuma Islam Paras Kapoor Zahra Khan Kate Maksyutynska Anisa Nazir Serena Peck Nayaab Punjani Madhumitha Rabindranath Iciar Iturmendi Sabater Shu’ayb Simmons Archita Srinath Kyla Trkulja Chelsia Watson Sally Wu

FEATURE INFOGRAPHIC By Abeeshan Selvabaskaran, MScBMC Candidate (2T2)

Copyright © 2021 by Institute of Medical Science, University of Toronto. All rights reserved. Reproduction without permission is prohibited. The IMS Magazine is a student-run initiative. Any opinions expressed by the author(s) are in no way affiliated with the Institute of Medical Science or the University of Toronto.

COVER ART By Yuejun (Mimi) Guo, MScBMC Candidate (2T2) FOLLOW US ON SOCIAL MEDIA! www.imsmagazine.com @IMSMagazine @IMSMagazine IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME |

LETTER FROM THE EDITORS

Letter from the

EDITORS I

t was amazing to see the hard work and dedication of the IMS Magazine team in making this issue on Gut Health and the Microbiome possible! The gut is an important contributor to our health and has been getting more research and media attention in recent years, so it seemed like an appropriate time to highlight the excellent work being done in this area by the IMS community.

This issue features Drs. Margaret Hahn, Mark Silverberg, Tony Lam, and Nicola Jones, and their important work aiming to understand factors affecting gut health and how it impacts other aspects of an individual’s health. We also put the spotlight on Dr. Peter Giacobbe as he explains his work on treatment-resistant depression and shares his recipe for becoming a great researcher. For our student spotlight, we feature Natalie Osborne, former Editor-in-Chief of the IMS Magazine, as she walks us through her quest to study chronic pain. We have many talented journalists, and their writing skills are showcased in our Viewpoint articles. Read starting on page 20 about the pros and cons of early autism diagnosis, the role of AI in the future of medicine, the recent controversy surrounding the implementation of vaccine passports, and whether probiotics are effective at improving your health. There is also a thought-provoking Diversity in Science article on page 34 exploring mental health stigma among racial and ethnic communities. It has been a great learning experience working on our first issue as Editors-in-Chief and we are grateful to our team for their invaluable contributions. We hope you enjoy reading this issue as much as we did in producing it. We look forward to creating more content for you in the 2021-2022 academic year!

Jason Lo Hog Tian

Mikaeel Valli

Jason is a fourth year PhD student examining the mechanisms linking HIV stigma and health under the supervision of Dr. Sean Rourke.

Mikaeel is a fifth year PhD student. He works with Dr. Antonio Strafella’s lab that uses neuroimaging techniques to understand the underlying mechanisms in Parkinson’s disease with nonmotor complications.

@JasonLoTweets

4 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

linkedin.com/in/mikaeel-valli/

DIRECTOR’S MESSAGE Photo Credit: Mikaeel Valli

DIRECTOR’S MESSAGE

s the new Acting Director of IMS, it is a pleasure to see the hard work and commitment from our graduate students towards science communication through the production of IMS Magazine. It is wonderful to see many of our students and faculty return to the campus and the Fall 2021 issue is a great opportunity to acknowledge all the fantastic work that has been going on at IMS.

DR. LUCY OSBORNE Acting Director, Institute of Medical Science Professor, Departments of Medicine and Molecular Genetics

There’s no doubt that our gastrointestinal tract and its related microbiome plays an important role in influencing our overall health and wellbeing. This issue of IMS Magazine takes the opportunity to shine light on researchers involved in this intriguing field with the goal to better understand the gut and find ways to improve lives of patients in the process. Read the work by Dr. Margaret Hahn and her group that looks at the interplay between the gut and brain and how it influences mental health. In another feature, you will learn about inflammatory bowel disease, and how Dr. Mark Silverberg and his team is trying to understand the influence of genetics on this condition. Dr. Tony Lam and his colleagues explore how the nutrient sensing molecules within the gut is implicated in diabetes and obesity. Turn the pages to learn about the work of Dr. Nicola Jones and her team in trying to understand the cause and effect of Helicobacter pylori infection on the gastrointestinal health. Every year we host the Ori Rotstein Lecture in Translational Research with the goal to celebrate exceptional scientific contributions of our scientific community. This 11th year, we were privileged to have Dr. Mary Gospodarowicz as our keynote speaker. You can read more about this event on page 36. My heartfelt congratulations to the organizing committee for making this event a smashing success. I also would like to congratulate the new faculty joining IMS. Check out pages 28-29 about their inspiring research! Welcome to the IMS and I am looking forward to your continued success in your research endeavors. The IMS aims to foster a sense of community and the IMS Magazine truly expresses that. I am honoured to be a member of such a community. I hope you enjoy reading the articles within this issue as much as I did! Sincerely, Dr. Lucy Osborne Acting Director, Institute of Medical Science

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME |

CONTRIBUTOR PAGE

Contributors For the Fall 2021 Issue

peck_s_s

Serena Peck is a second year MSc student studying under the supervision of Dr. Paaladinesh Thavendiranathan. Her research looks at physical activity levels during cancer treatment and posttreatment cardiac function, cardiorespiratory fitness, and quality of life in women with breast cancer. Serena loves being in nature and tending to her plants!

Vri_9

S. Hussain Ather is a firstyear PhD student working under John Griffiths at the Centre for Addiction and Mental Health (CAMH). He uses and develops computational modelling techniques to investigate the brain connectivity structures underlying neuropsychiatric disorders. He also likes cosplaying.

Vritika Batura is a third year PhD student with Dr. Aleixo Muise at Sickkids Hospital. She is investigating the role of genetic aetiologies and targeting the associated signaling pathways in the pathogenesis of pediatric inflammatory bowel disease (IBD). She is using patient samples, including patient derived organoids, to understand the mechanism involved in the onset of patient IBD. Apart from research, she loves traveling with the incentive to explore new places, culture and food! Iciar Iturmendi Sabater is a first year PhD student working with Dr. Meng-Chuan Lai at the Center for Addiction and Mental Health. Her research focuses on understanding how people with autism spectrum disorder cover-up or mask their social and communication differences, a process known as ‘camouflaging’. Iciar enjoys traveling, meeting new people and spending time with family and friends.

iciar_itur Kyla Trkulja is a first-year MSc student at IMS studying under the supervision of Dr. Armand Keating, Dr. John Kuruvilla, and Dr. Robert Laister at Princess Margaret Hospital. Her work focuses on novel cancer therapies for lymphoma. Outside of academia, Kyla enjoys reading, writing, road trips, and going for walks in nature. 6 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

Nayaab Punjani is a second year MSc student at IMS working with Dr. Michael G. Fehlings. Her research is examining a preclinical drug treatment that aims to provide a multifaceted approach targeting neural regeneration and inflammation following cervical spinal cord injury. She enjoys watching action and mystery genre movies and TV shows, as well loves sketching in her free time. Layout by Amy Zhang

CONTRIBUTOR PAGE Sally Wu is a secondyear IMS MSc student investigating antipsychoticinduced cerebral insulin resistance in a preclinical model under the supervision of Drs. Mahavir Agarwal and Margaret Hahn. Outside the lab, she enjoys weightlifting, running, and exploring new restaurants in the city.

Madhumitha (Madhu) Rabindranath is a first year MSc student at IMS who is supervised by Dr. Mamatha Bhat. Her research focuses on leveraging AI to non-invasively diagnose liver graft fibrosis in posttransplant patients. Outside the lab, Madhu likes reading a good book and exploring the city.

Stacey J. Butler is a third year PhD student at IMS, specializing in respiratory medicine and epidemiology, under the supervision of Dr. Andrea Gershon. Outside of academia, Stacey enjoys creative activities, board games and cooking hearty vegetarian meals.

StaceyBeePhD Archita Srinath is a first year PhD student in Dr. Nigil Haroon’s lab. Her research focuses on investigating novel therapeutic markers in a chronic inflammatory form of arthritis called Ankylosing Spondylitis. Outside the lab, Archita enjoys cooking, baking and true crime podcasts!

Sonja (Kasapinovic) Elsaid is a third-year PhD student investigating brain function and cannabis use in individuals with social anxiety. Prior to going back to school, Sonja was a clinical research and medical communications professional with nearly 20 years of experience.

2T2 IMS Design Team is a group of second year MSc students in the Biomedical Communications (BMC) program. Turning scientific research into compelling visualizations is their shared passion, and they are thrilled to contribute to the IMS Magazine.

Amy Zhang

Sherry An

Amy Assabgui

Mimi Guo

(Director) amykzhang.com

sher.i.an

amya_visuals amyassabgui.weebly.com

mimi.guo.art mimiguoart.com

Abeeshan Selvabaskaran

Michie Wu

abeeshan.art

michiewu michiewu.com

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME |

INFOGRAPHIC

8 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

Compiled by Stacey J. Butler

INFOGRAPHIC

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME |

FEATURE

Exploring the brain-gut connection in mental health An interview with Dr. Margaret Hahn

By Sally Wu

rillions of living microorganisms reside in pockets of bustling communities in the human body. An array of bacteria, viruses, fungi, and other microbes collectively form microbiomes—the microbial inhabitants that contribute to human health and well-being. Ongoing efforts by scientists to characterize the functions of microbes, specifically the gut microbiome, have discovered its tremendous impact on metabolism, the immune system, the heart, and other important physiological functions.1 We are only now beginning to understand and acknowledge the importance of having a healthy gut microbiome and its role in health and disease. More recently, studies have suggested that the gut microbiome may also affect mental health.2 Dr. Margaret Hahn (along with Dr. Daniel Mueller), their team at the Centre for Addiction and Mental Health (CAMH), and their collaborators at the Farncombe Institute at McMaster University are leading translational studies to investigate the complex interplay between the gut and the brain. Their research aims to better understand the underlying mechanisms of the metabolic burden observed in patients with schizophrenia. Dr. Hahn completed her undergraduate studies in biochemistry and immunology at McGill University. She has always 10 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

had an interest in metabolic pathways and how these may interact with the immune system. As she completed her MD at the University of Calgary, Dr. Hahn reminisced that “while I enjoyed medical school and seeing patients, I’ve always had the interest to discover novel things and to improve the care of patients. I always felt like the way to do that was through research.” As the “brain was a more undiscovered frontier…that has more potential for discovery and to further the care of patients”, she decided to complete her residency in psychiatry. She later completed her Doctoral degree at the Institute of Medical Science at the University of Toronto. “Thanks to Dr. Gary Remington who managed to convince me that on top of all these years of studies that a PhD was a good idea.” Dr. Hahn laughed and continued, “In the long run, it was a good idea because it gave me the background in not only psychiatry but [also] allowed me to focus on the metabolic comorbidity in schizophrenia.” As the Director of the Mental Health and Metabolism Clinic at CAMH, Dr. Hahn expressed that “working as a clinician in this field has highlighted the lack of ability to improve patient outcomes in so many domains. This includes the huge gaps in physical care and addressing the high cardiovascular mortality rates that represent the leading cause of death in

schizophrenia patients and other severe mental illnesses, [surpassing] suicide.” Even before patients with schizophrenia are prescribed antipsychotics, they present with premorbid metabolic dysregulation, particularly insulin resistance and dysglycemia.3 To make matters worse, antipsychotics additionally induce adverse metabolic side effects, such as insulin resistance, weight gain, and contribute to the very high prevalence of type 2 diabetes in patients.4 A potential culprit of this observed metabolic dysregulation is the gut microbiome. “There is a really complex interplay between the brain and body. We tend to treat each system separately. One of the systems that is linked to mental illness and most certainly a key aspect of metabolism is the gut microbiome,” Dr. Hahn explains. A few years ago, Dr. Hahn and Dr. Daniel Mueller along with other scientists in different areas of research at CAMH had the good fortune to receive a donation from the Farncombe family to ignite a collaboration between CAMH and the Farncombe Family Digestive Health Research Institute at McMaster University (Drs. Elena Verdu and Premysl Bercik) to conduct one of the first pilot projects examining the gut microbiome and mental health in Canada. Their interest and passion in the metabolic health of Graphic design by Amy Assabgui

FEATURE

DR. MARGARET HAHN MD, PhD, FRCPC Director of the Mental Health and Metabolism Clinic | Clinician-Scientist in the Schizophrenia Division at the Centre for Addiction and Mental Health | Associate Professor at the University of Toronto | Kelly and Michael Meighen Chair in Psychosis Prevention Photo Credit: CAMH

patients led them to create a proposal suggesting that the gut microbiome may contribute to the increased risk of pre-morbid metabolic dysfunction, as well as antipsychotic-induced metabolic dysregulation in patients with psychosis spectrum illnesses. This proposal has grown into a project that first started in humans but has now (through a successful Pilot and Feasibility funding competition

from the Banting and Best Diabetes Centre) taken a backward translational approach into rodent models. In humans, antipsychotic-naïve patients are followed over twelve weeks to investigate the effects of pre-and post-antipsychotic treatment on metabolic functions. Basic metabolic panels are completed, and stool samples are collected. Weight and body mass index are also recorded to monitor for antipsychotic-induced weight gain, which occurs in a subset of individuals. The pre-antipsychotic treatment stool samples from the individuals who go on to gain weight are then transplanted to germ-free mice to examine the causality of these metabolic side effects. “The hope is that in the future we can find which gut microbiome signatures predispose patients to these metabolic side effects. Then we can intervene with probiotics in a subset of patients—a type of personalized medicine.” “Taking a step back, our research focuses on schizophrenia, but all mental illnesses have a very large metabolic burden. The gut microbiome may explain some but not all of the interactions between the body and brain,” says Dr. Hahn.

and the gut microbiome could represent a link between the two. Going forward, we can’t work in silos. Our field needs multidisciplinary collaborations from different specialties to address different aspects of a complex multisystemic illness in order to move to novel interventions. You can’t have a good quality of life or functional outcomes if you don’t have good mental and physical health.” At the end of it all, Dr. Hahn exuded gratitude and appreciation for her team, collaborators, mentors, study participants and the generosity of her funding sources and the Farncombe family, all of whom make this work possible and rewarding. References 1. Shreiner AB, Kao JY, Young VB. The gut microbiome in health and in disease. Curr Opin Gastroenterol. 2015; 31(1):69-75. 2. Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016: 21(6):739-748. 3. Papanastaiou E. The prevalence and mechanisms of metabolic syndrome in schizophrenia: a review. Ther Adv Psychopharmacol. 2013: 3(1):33-51. 4. Rajkumar AP, Horsdal HT, Wimberley T, et al. Endogenous and antipsychotic-related risks for diabetes mellitus in young people with schizophrenia: a danish population-based cohort study. Am J Psychiatry. 2017: 174(4):686-694.

When asked to share the most important thing that the public should understand about the gut microbiome and mental health, Dr. Hahn emphasized that “you can’t separate physical and mental health, IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 11

FEATURE

Unravelling the Complexity of

Inflammatory Bowel Disease

By Kyla Trkulja

nflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal (GI) tract that affects millions of people worldwide.1 IBD includes conditions such as Crohn’s disease and ulcerative colitis, and is one of the most prevalent GI diseases with accelerating incidence in newly industrialized countries.1 In this condition, chronic inflammation of the GI tract causes an influx of immune cells that produce cytokines and free radicals that damage the intestinal epithelium, causing painful ulcers and symptoms such as abdominal pain, diarrhea, bloody stools, and weight loss.1 The exact cause of IBD remains largely unknown, but is thought to be a complex combination of genetic susceptibility, composition of the intestinal microbiome, environmental factors, and abnormalities in the immune system.1 The lack of a clear etiology makes this disease very difficult to treat; in fact, for decades, treatment focused only on controlling the symptoms instead of the underlying disease.2 Thankfully, recent advances in the past 20 years have generated treatments aimed at helping patients achieve remission, allowing patients to achieve a better quality of life.2 However, the complexity of the disease results in patients presenting 12 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

clinically different from each other, known as heterogeneity; this makes it difficult to find an optimal therapy that works for all patients.2 One researcher working to help overcome this issue is Dr. Mark Silverberg, a clinician-scientist at Mount Sinai Hospital. He has been involved in many of the treatment advances made in IBD, and continues to research new treatments and ways to tailor them appropriately to patients. He was a student at the University of Toronto for many years, where he completed his medical education, gastroenterology residency, and PhD studying the genetics of IBD. Dr. Silverberg has been taking care of patients with IBD for over 20 years and has led many clinical trials and research studies to improve disease management. His research looks for causes of IBD, treatments, and ways to develop tools that allow clinicians to predict a patient’s clinical course with the disease based on their genetic and bacterial signatures. Dr. Silverberg was inspired to study IBD by his mentors during his training. He worked under a clinician-scientist who he said, “was probably the first person that got me excited about the area that I ended up pursuing.” During his PhD, genetics

of complex diseases was just starting to become a “hot topic” as a result of the ongoing Human Genome Project, and researchers thought that finding genes for chronic diseases was going to be the key to curing them. “That was why I started in the research field and in looking for genetic variants that lead to inflammatory bowel disease,” Dr. Silverberg explained. However, as research unveiled that chronic diseases involve both genetic susceptibility and environmental contributions, Dr. Silverberg realized that focusing on genetics alone was not going to be the answer to the problem. “So, I started to shift into more of the environmental side. In particular, I was always interested in diet and food and its effect on disease and in particular, on the microbiome,” he described. Over the next several years, he pivoted his work to combine his knowledge of genetics with the environmental aspect of IBD, inspiring his research in biomarkers related to disease severity, clinical markers related to treatment outcomes, and the microbiome and its effect on prognosis. An example of this can be seen in one of his recent projects, where his team examined gene expression and microbiome profiles in patients with Graphic design by Michie (Xingyu) Wu

FEATURE

IBD patients who only healed in one of these two ways were compared to that of IBD-free individuals. Their results showed patients with histological healing had gene expression and microbial patterns that were similar to healthy individuals without the disease. The project “proved from a biomarker standpoint, from a biologic standpoint… that histologic healing is a better target,” Dr. Silverberg explained. With a clearer idea of the optimal treatment goal for IBD patients, doctors will be able to better monitor and care for their patients.

DR. MARK SILVERBERG MD, PhD, FRCPC Clinician-Scientist & Gastroenterologist, Mount Sinai Hospital | Professor, Department of Medicine, University of Toronto | Founder & Director, Toronto Immune and Digestive Health Institute Photo Credit: Dr. Silverberg

IBD. This knowledge was used to better understand whether the treatment target for IBD should be bowel healing, as seen during a colonoscopy, or histological healing, as seen by looking at the patient’s tissue sample under a microscope. Gene expression and microbiome patterns in

Despite the challenges of precision medicine in IBD, Dr. Silverberg still has hope that progress will be made on this front. “It’s a very heterogeneous disease… personalized medicine and precision medicine is probably going to be critical in making better progress in treatment and understanding etiology,” he said. To get there, Dr. Silverberg says, “the next few years will focus on gut bacteria and how its composition will define precision medicine. By finding relationships between the microbiome and the type of IBD a patient has, how aggressive it is, what parts of the bowel are affected, and whether they respond to different therapies, better precision medicine targets will hopefully be achieved.”

Part of Dr. Silverberg’s success in this field has been due to his role as a clinicianscientist. He describes the role as challenging, as “you need to stay up to date and be progressive when you have clinical responsibilities, and to try to compete for grants and write papers at the same time as making sure you answer your patients’ questions and help them when they’re not doing well. So, it’s a tricky balance.” However, the challenges of the role are what allow his work to be so groundbreaking; as Dr. Silverberg describes, “a lot of our research questions and approaches all derive from clinical problems that we face. It’s the questions that we see in the office and with patients that drive our excitement to do the research to solve it.” Through his dual role and hard-working, innovative team, knowledge on underlying causes and optimal treatments for IBD will continue to advance. References 1. Guan Q. A Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel Disease. J Immunol Res. 2019 Dec 1;2019:7247238. doi: 10.1155/2019/7247238. 2. Jeong DY, Kim S, Son MJ, et al. Induction and maintenance treatment of inflammatory bowel disease: A comprehensive review. Autoimmun Rev. 2019 May;18(5):439-454. doi: 10.1016/j. autrev.2019.03.002.

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 13

FEATURE

From Obesity to Diabetes Role of Gut Microbiome Nutrient Sensing Molecules in Modulating Weight Gain and Glucose Metabolism

By Nayaab Punjani

y the year 2040, it is estimated that 600 million people will develop diabetes.1 Even more will have pre-diabetes, which is marked by blood glucose levels that exceed the normal range and is influenced by various lifestyle factors. For example, obesity puts individuals at risk for this condition, and if left untreated, may progress to type 2 diabetes (T2D).1 With the obesity and diabetes epidemics exacerbated by increasingly sedentary lifestyles, a greater understanding of the underlying factors controlling glucose metabolism and weight gain is key. This is what Dr. Tony Lam’s lab aims to examine, through their study of the role of nutrient sensing molecules and the gut microbiome. Beginning with his Ph.D. at the University of Toronto, Dr. Lam investigated how “nutrients such as fatty acids could affect insulin action in the liver, and eventually affect glucose homeostasis.” He continued in this field during his post-doctoral appointment in New York City by examining the role of the hypothalamus in modulating glucose levels. He explains, “the end result for me is always the same: how glucose and energy homeostasis is achieved and how [it] is disrupted in the context of diabetes type 2, as well as obesity.” Following this work, Dr. Lam began investigating independently and concluded that one of the initial points 14 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

of nutrient processing and absorption following a meal occurs at the site of the upper small intestine. This led him to study nutrient processing in the gastrointestinal (GI) tract and the complex interactions with diet, glucose homeostasis, obesity, diabetes, and the gut microbiome. Dr. Lam explains, “nutrients such as glucose and fatty acids, once ingested from the meal, will trigger various signaling pathways within the upper small intestine. It will tell the body to lower glucose levels and food intake. In the context of diabetes and obesity, this control is disrupted. We want to find out how this control is disrupted and how it can be restored.” His research highlights the role of the gut microbiome in altering gut nutrient sensing molecules. He studies the impact of sodium glucose cotransporter 1 (SGLT1), which is present in the upper small intestine and acts to lower glucose levels. High fat diets inhibit the activity of SGLT1 and disrupt the microbiome by decreasing levels of healthy bacteria, such as Lactobacillus, required in nutrient sensing.2 In order to mediate these impacts, Dr. Lam’s lab has also examined the role of metformin, a medication used to treat T2D, to regulate glucose levels in the rodent gut microbiome. His research has demonstrated that metformin helps to restore Lactobacillus and SGLT1mediatiated glucose sensing in rodents.2

DR. TONY LAM Professor, Departments of Medicine and Physiology | Cross appointed with the Institute of Medical Science | Associate Director, Banting & Best Diabetes Centre, University of Toronto | Canada Research Chair, Tier 1, in Diabetes and Obesity Research, University of Toronto | Jon Kitson McIvor Endowed Chair in Diabetes Research, TGHRI | Senior Scientist, Toronto General Hospital Research Institute (TGHRI) Photo Credit: Mikaeel Valli

Dr. Lam also illustrates the role of the enzyme acyl-CoA synthetase 3 (ACSL3) in pre-absorptive fatty-acid sensing in the upper small intestine. Pre-absorptive ACSL3-mediated fatty acid sensing is involved in moderating glucose tolerance. Rodents fed high fat diets were observed Graphic design by Amy Assabgui

FEATURE

to have decreased Lactobacillus levels and disrupted ACSL3. However, healthy microbiome transplantation restored ACSL3 fatty acid sensing and thus glucose homeostasis, along with Lactobacillus levels.3 These studies demonstrate the regulatory role of these nutrient sensing molecules and the impact of high fat feeding on their activity. Dr. Lam has also explored other applications of these nutrient-sensing molecules beyond, and in relation to, the gut microbiome. His lab recently discovered that changes in the gut microbiome result in altered production of secondary bile acids. Once these secondary bile acids are absorbed into the blood through the small intestine, cross the blood-brain-barrier, and bind to bile acid receptors, this may induce insulin resistance and affect glucose homeostasis. Increased production of these bile acids occurs in T2D as well as during shortterm high fat feeding. Interestingly, healthy microbiome transplantation into the upper small intestine results in reduced production of these bile acids and improved glucose regulation.4 Based on his current findings, Dr. Lam has various next steps for his research. This includes further investigating the impact of the microbiome on bile acids, the receptors involved in this interaction,

and eventually how this alters the gene expression of nutrient sensing molecules. This would be followed by determining the cells impacted in maintaining glucose homeostasis, as well as the therapeutic potential of metformin in helping mediate altered nutrient sensing and restoring the gut microbiome. In addition to his research, Dr. Lam works closely with the Banting and Best Diabetes Centre (BBDC) as the Associate Director. The goal of the BBDC is to promote diabetes research in part through various funded summer and graduate studentships as well as post-doctoral fellowships. These applications are examined through a rigorous peer-review process involving ten faculty members and chaired by himself, providing fair grounds for selection. He mentions, “[these stipends are] not just going into one single lab or person, it is benefiting the whole Toronto community at all levels.” The BBDC also conducts a seminar series, inviting key researchers in the fields of diabetes and obesity, with plans of offering this in-person beginning in January 2022. For students planning to pursue research in the diabetes field, Dr. Lam offers various suggestions. The first is to apply for BBDC summer studentships. These paid positions provide students with the opportunity to get hands-on experience in a lab for 12

weeks, allowing you to determine whether you would like to continue pursuing this research field for graduate studies. There are also undergraduate courses taught by various faculty members, such as Dr. Lam’s PSL425 course, which focus on studying metabolism. Dr. Lam summarizes the application of his work to everyday life: “the general public should be aware of the fact that there are many molecules that could be activated or inhibited by nutrients that we take in each day—each meal. These signaling pathways could eventually affect glucose levels as well as weight in the body.” Furthermore, he reflects on how sedentary lifestyles result in excess calories that could greatly influence these nutrient-dependent molecules. From alterations to the gut microbiome composition, to nutrient metabolism, we must be cognizant of the types of foods that we consume and their effect on our body. References 1. Boles A, Kandimalla R, Reddy PH. Dynamics of diabetes and obesity: Epidemiological perspective. Biochim Biophys Acta BBA - Mol Basis Dis. 2017 May 1;1863(5):1026–36. 2. Bauer PV, Duca FA, Waise TMZ, et al. Metformin Alters Upper Small Intestinal Microbiota that Impact a Glucose-SGLT1-Sensing Glucoregulatory Pathway. Cell Metab. 2018 Jan 9;27(1):101-117.e5. 3. Bauer PV, Duca FA, Waise TMZ, et al. Lactobacillus gasseri in the Upper Small Intestine Impacts an ACSL3-Dependent Fatty Acid-Sensing Pathway Regulating Whole-Body Glucose Homeostasis. Cell Metab. 2018 Mar 6;27(3):572-587.e6. 4. Zhang S-Y, Li RJW, Lim Y-M, et al. FXR in the dorsal vagal complex is sufficient and necessary for upper small intestinal microbiome-mediated changes of TCDCA to alter insulin action in rats. Gut. 2021 Sep;70(9):1675–83.

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 15

FEATURE

Lets play hide and seek with the immune system:

Understanding the cause and effect of Helicobacter pylori infection on gastrointestinal health By Vritika Batura

ost-pathogen interactions are highly dynamic processes, that can include adhesion, invasion and resolution.1 The process begins with the pathogen infecting its host and ultimately ends with the host initiating an appropriate immune response to clear the infection and build immunity for future encounters.1 But what happens when the pathogen hides from the host? What mechanisms are at play? Is the host able to resolve the infection? That’s the tale of Helicobacter pylori, a gram negative spiral shaped bacterium, that infects 50% of the world population.2 Dr. Nicola Jones garnered interest in studying H. pylori during her fellowship in Paediatric Gastroenterology at The Hospital for Sick Children (Sickkids). She joined the lab of Dr. Philip Sherman to do research as part of the fellowship training with the goal of ultimately returning to the clinic as a full-time clinician. However, the intellectually stimulating environment in the Sherman lab allowed her to look at scientific problems in a new way, where she was able to combine patient care with microbiology and molecular genetics. This motivated her to pursue a PhD in this field and was the start of her journey towards becoming a well-established clinicianscientist in Gastroenterology and the Director of Integrated Physician Scientist Training Program at the University of Toronto. Her current appointments speak to her merit as a dedicated clinicianscientist and are reflective of her success and commitment to both research and patient care. 16 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

During her PhD, she started exploring host-pathogen interactions. The Nobel prize winning discovery of H. pylori by J Robin Warren and Barry Marshall had gained much attention at the time. It was evident that the bacteria was highly pathogenic and had an active role in chronic gastritis.3 Dr. Jones recalls, “I really wanted to understand how the infection evades the immune system or the host responses so that you get chronic infection for life with most people not developing any complications and only ten percent developing peptic ulcer disease and less than one percent developing gastric cancer. How does this happen?”

with strains that did not secrete vacA, did not have intracellular bacteria.⁶ This finding of intracellular bacteria during infection with VacA+ but not VacA- H. pylori was also seen in gastric biopsies obtained from patients. Subsequent studies showed that antibiotic treatment of mice infected with VacA- H. pylori resulted in complete eradication of the infection, whereas intracellular bacteria persisted in mice infected with VacA+ H. pylori.⁶ Dr. Jones explains, “Having this intracellular niche actually protects the bacteria from eradication therapy and potentially host responses. It’s a place for the bacteria to hide from clearance.”

H. pylori is a genetically diverse bacterial species and is considered the most significant risk factor for gastric cancer.2 Studies have shown that eradicating the bacteria through therapy can reduce the risk of gastric cancer.4 Current therapy to treat H. pylori infection involves the use of aggressive antibiotic treatment but antibiotic resistance is a major hurdle in H. pylori eradication.2 The real question then became, how does the bacteria acquire this resistance? Dr. Jones mentioned that during her PhD, she noticed the presence of vacuoles in gastric cells infected with H. pylori. It was later found that these vacuoles were induced by a bacterial toxin called the vacuolating cytotoxin (VacA), and these vacuoles formed a niche that permitted survival of H. pylori inside of the cells.⁵ Interestingly, with the use of an animal model her lab showed that mice infected with strains of H. pylori that secreted the toxin had bacteria detected within gastric cells but mice infected

How does this bacterial strain form these vacuoles and hide inside the cells? Dr. Jones research delineated that it inhibits a specific calcium channel, TRPML1, that is involved in endosomal trafficking.⁷ Her recent paper highlighted the mechanism that is at play by H. pylori (vacA+) strain. VacA inhibits the channel and disrupts endolysosomal trafficking resulting in the formation of these large vacuoles (dysfunctional lysosomes) that ultimately provide safe haven for the bacteria to hide from host immune responses.⁶ She is now looking into a potential drug that would activate this channel. Treatment with a small molecule TRPML1 agonist (ML-SA1), causes resolution of the large vacuoles in VacA+ infected gastric epithelial cells and human gastric organoids, resulting in formation of normal functional lysosomes and ultimately bacterial killing.⁶ Targeting TRPML1 could be a novel treatment to get rid of the niche that allows the bacteria to Graphic design by Sherry An

FEATURE escape antibiotics and the host immune response. This could be a potential treatment to be used as part of eradication therapy and would hopefully decrease antibiotic resistance. When asked how H. pylori infection leads to increased risk of gastric cancer, she explained that H. pylori forms these vacuoles only in certain cell types, specifically parietal cells. Parietal cells are the acid secreting cells of the stomach and are long-lived gastric cells. “Smart for the bacteria to hide in these cells where they can live happily for a long time and every so often get out in the lumen and infect other cells.” She mentions that if during H. pylori infection, gastric acid secretion is inhibited, it can increase the risk of gastric cancer development. Other risk factors include chronic inflammation, gastric atrophy (loss of parietal cells) and intestinal metaplasia. She hopes that studying the effects of the intracellular bacteria can shed light on mechanisms involved in gastric cancer development. But is H. pylori all bad? She explained that studies have shown an inverse relationship between H. pylori infection and inflammatory bowel disease (IBD) and asthma. In fact, some animal studies have shown that exposure to H. pylori in young animals can provide protection against IBD and asthma. Hence, there

DR. NICOLA JONES MD, PhD | Professor, Department of Pediatrics, University of Toronto | Professor, Department of Physiology, University of Toronto | Professor, Institute of Medical Science, University of Toronto | Director, Integrated Physician Scientist Training Program, Faculty of Medicine, University of Toronto | Staff Gastroenterologist, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children | Senior Scientist, Cell Biology, Sickkids Research Institute Photo Credit: Dorsa Derakhshan

are conflicting schools of thoughts: one believes that H. pylori must be eradicated as its pathogenic and the other believes that it might have some health benefits. Dr. Jones believes that being a clinicianscientist provides unique opportunities to contribute to her field of gastroenterology

by beginning to understand the pathophysiology of H. pylori infection. She says, “As a clinician-scientist you have a unique lens; you can identify what the clinical problems are, which allows you to ask relevant questions and then hopefully discover pathways or novel treatment options that ultimately have a positive impact on patients.” It was the opportunity, support and mentorship provided to her during her fellowship and PhD, which allowed her to pursue this direction. She considers this a privilege and has dedicated part of her career to the development of new clinician-scientists as an advocate and mentor. References

Gastric organoids stained with lysosome markers (LAMP1 and Cathepsin D) to show the effect of H. pylori infection with strain containing vacuolating cytotoxin A (vacA+, bottom panel) and missing vacA (vacA-, top panel). Use of ML-SA1 (a molecular compound) resolved the vacuoles in VacA+ H. pylori infected cells. Image adapted from Capurro et al. 2019. Nat Microbiol.

1. Jo, E-K. Interplay between host and pathogen: immune defense and beyond. Exp. Mol. Med. 2019;51(12), 1–3. 2. Miller, AK, Williams, SM. Helicobacter pylori infection causes both protective and deleterious effects in human health and disease. Genes & Immunity. 2021;22(4):218-26 3. Robin Warren, J., Marshall, B. Unidentifed curved bacilli on gastric epithelium in active chronic gastritis. The Lancet. 1983;321(8336), 1273–1275. 4. Mégraud, F, Bessède, E,Varon, C. Helicobacter pylori infection and gastric carcinoma. Clin. Microbiol. Infect. 2015;21(11), 984–990. 5. Cover TL, Blanke SR. Helicobacter pylori VacA, a paradigm for toxin multifunctionality. Nat. Rev. Microbiol. 2005;3(4), 320–332. 6. Capurro, MI, Greenfield LK, Prashar A, et al. VacA generates a protective intracellular reservoir for Helicobacter pylori that is eliminated by activation of the lysosomal calcium channel TRPML1. Nat Microbiol. 2019;4(8), 1411–1423

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 17

BMC SHOWCASE Master of Science in

Biomedical Communications Tal Bavli

Adult Skull (top) and Neck and Brachial Plexus (bottom) by Tal Bavli

“Why can’t you just draw something from your imagination?” I was once asked. The simple truth is that I’ve always found the world around me much more compelling than digging inwards into my imagination; I found that I draw the things around me to study them. It was genuine curiosity and a love for learning that led me to medical illustration. I first learned about this field while getting my undergrad in illustration. Years later, after travelling the world, with my husband and two little boys, I am finally here.

18 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

Layout by Amy Zhang

BMC SHOWCASE

Amy Assabgui

Amy Zhang I was always happy having art as a hobby because it allowed me to take interesting “detours” during my undergraduate years. I was volunteering on an art project on one occasion and learned of the BMC program from a teammate. Medical illustration left an overwhelming impression on me, and I found a purpose I could fulfill as a scientifically-minded illustrator and designer.

The Pathology of Alcoholic Liver Disease by Amy Zhang

Weaving the Perfect Biosensor by Amy Assabgui

While studying Medical Cell Biology during my undergraduate degree, I developed a love for creating visuals that simplified science for others. I went on to study art at Sheridan College and began to take part in interactive design sprints, opening my eyes to the large number of problems within the fields of medicine, healthcare, and science that could be solved using both static and interactive visual media. At BMC, I’ve continued to develop this passion, finding creative ways to communicate science to others in many different formats.

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 19

VIEWPOINT

Should autism diagnoses be prevented early in development? By Iciar Iturmendi Sabater

utism is characterised by social and communication differences relative to the normative standards of the general population. It is considered a neurodevelopmental disorder since its neurobiological determinants are present very early in development, with the mean age of diagnosis being three and a half years for children who start showing early signs of autism before ten years of age.¹ As autistic* people usually claim their diagnosis as a critical part of their identity since childhood² the question arises: should research efforts aim at preventing or curing this neurodevelopmental condition? This question has sparked debate after the recent publication of a randomised controlled trial in JAMA Pediatrics.³

A positive parenting intervention to decrease autism symptomatology The JAMA Pediatrics study, carried out in Australia, tested the efficacy of a social skills training for caregivers of infants at risk of autism called the iBASIS Video Interaction for Positive Parenting (iBASISVIPP). The researchers hypothesized that the training would decrease autism diagnoses and symptom severity in children by the age of three. A team of specialised therapists (psychologists or speech pathologists) implemented the iBASIS-VIPP training 20 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

among 45 caregivers of infants at risk, while 44 caregivers received the traditional training (a two-hour information workshop on autism which is considered the current best practice on caregiver training). Both interventions had been piloted in previous studies and showed to produce no harm. Throughout the ten home-sessions over five months of iBASISVIPP intervention, specialised therapists guided caregivers in understanding the potential of their infants’ interaction styles while going over previously filmed caregiver-infant interactions. Its main objective was to achieve optimal interaction between infants and caregivers. Dr. Andrew Whitehouse’s research team found that, by three years of age, autism was diagnosed in 21% of infants whose parents did not receive the iBASISVIPP training, compared to only 7% of infants whose caregivers participated in the training. The iBASIS-VIPP positive parenting intervention lowered the odds of infants at risk of autism being diagnosed with the condition at three years of age. The severity of future autistic symptomatology was also significantly smaller among the children whose parents participated in the iBASIS-VIPP training. An important question that this study left unanswered was: might the effectiveness of the iBASIS-VIPP intervention in reducing the odds of autism diagnoses extend beyond childrens’ three years of age? Future research might aim to answer this question by performing a longitudinal study.

Controversy arises: should autism be prevented or ‘cured’? Soon after publication, these findings became a controversial topic among researchers and autistic individuals on Twitter, as different newspapers (e.g.: The Guardian5, The Telegraph6) cited the results of the study as potential evidence that the iBASIS-VIPP can ‘cure’ autism. In fact, The Guardian rectified its wording and now states at the bottom of the publication: “This article was amended on 1 October 2021 to remove a reference to the therapy not being “a cure” for autism, as this term is not appropriate within the context of reporting on autism”. But why is the term ‘cure’ problematic to describe the findings of this investigation and in the context of autism research in general? The aim of the iBASIS-VIPP intervention is not to change the interaction style of the infant at risk of autism to accommodate the ‘normative’ expectations of their caregivers and societal norms. Instead, the intervention seeks to help caregivers adapt to their infant’s communication styles and change their attitudes towards their autistic child. To that extent, the intervention does not aim to prevent or cure autism, but rather to construct a more understanding social environment that welcomes neurodiversity. It is thus problematic to state that the results of this study evidence the possibility of a Graphic design by Amy Assabgui

VIEWPOINT

‘cure’ or prevention of autism when the iBASIS-VIPP intervention actually changes expectations and behaviours in the social context of the child, but not in the child at risk of autism.

Moving beyond medical accounts of autism This iBASIS-VIPP approach attempts to battle medical accounts of autism by considering the ‘double empathy problem’ of autism. Medical explanations characterise autism by individual’s deficits in the capacity to understand the mental states and intentions of others. This psychological ability is known as theory of mind. However, more sociologicallyoriented researchers and autistic individuals themselves have emphasized that it is not only autistic individuals who struggle to understand their nonautistic counterparts, but also non-autistic persons who have trouble interpreting the intentions of autistic individuals. This is known as the double empathy problem, which proposes that the social and communication difficulties that define autism in medical diagnostic manuals like the International Classification of Diseases (ICD) or Diagnostic and Statistical Manual of Mental Disorders (DSM) are not within the autistic individual, but rather the result of interactions between two or more people who struggle to understand each other’s states of mind.⁴

Dr. Whitehouse released a Twitter statement7 addressing the debate his paper had given rise to, insisting: “Autism can’t be prevented, this is not an aim the study authors believe in. The babies remain neurodivergent, but they are not showing the same degree of developmental barriers that lead them to meet ‘deficit-focused’ DSM-5 diagnostic criteria of autism”. What Dr. Whitehouse means is that the findings of his research seem to show that infants whose caregivers are helped to better understand their interactional needs, grow in such a way that they are less likely to meet the deficit-focused medical definition of autism, which locates the social and communication problems within the autistic individual. Interventions such as the iBASIS-VIPP may in fact importantly shift the focus of autistic social and communication difficulties from the individual onto the social context, and thus make communities, not individuals, responsible for their remediation. Autistic individuals will remain autistic, but their autism may not result to be an impairment in their daily lives if their environment is understanding of the way they socially interact differently from others. Under this paradigm, autistic individuals may thrive as their differences become valuable sources of diversity in our communities. As Durkheim (1895) put it, deviance in society challenges standard norms and promotes social change.

*Identity-first language has been used throughout this article to fit the evidence available on the language preferences of the autism community8

References 1. Hof MV, Tisseur C, Berckelear-Onnes IV, et al. Age at autism spectrum disorder diagnosis: A systematic review and meta-analysis from 2012 to 2019 National Autistic Society [Internet]2020 [cited 2021 Oct 7];25(4):862–73. Available from: https://journals.sagepub. com/doi/full/10.1177/1362361320971107 2. Milton D, Sims T. How is a sense of well-being and belonging constructed in the accounts of autistic adults? Disability & Society [Internet]. 2016 [cited 2021 Oct 4];31(4):520–34. Available from: https://www.tandfonline.com/doi/abs/10.1080/09687599.2016.1 186529 3. Whitehouse AJO, Varcin KJ, Pillar S, et al. Effect of Preemptive Intervention on Developmental Outcomes Among Infants Showing Early Signs of Autism: A Randomized Clinical Trial of Outcomes to Diagnosis. JAMA Pediatr [Internet]. 2021 [cited 2021 Oct 5];e213298–e213298. Available from: https://jamanetwork.com/ journals/jamapediatrics/fullarticle/2784066 4. Milton D. On the ontological status of autism: the ‘double empathy problem.’ Disability & Society [Internet]. 2012 [cited 2021 Oct 4];27(6):883–7. Available from: https://www.tandfonline.com/doi/ abs/10.1080/09687599.2012.710008 5. Sample I. Autism therapy aimed at infants may reduce likelihood of later diagnosis [Internet]. The Guardian. Guardian News and Media; 2021 Sept 20 [cited 2021 Oct 17]. Available from: https:// www.theguardian.com/society/2021/sep/20/autism-therapy-infants-study-social-development 6. Knapton S. ‘Coaching’ parents found to reduce autism diagnosis by two-thirds [Internet]. The Telegraph. Telegraph Media Group; 2021 Sept 20 [cited 2021 Oct 17]. Available from: https://www.telegraph. co.uk/news/2021/09/20/two-thirds-autism-cases-could-prevented-baby-video-intervention/ 7. Whitehouse, A. Comment on JAMA Pediatrics paper: https:// twitter.com/AJOWhitehouse/status/1441709985763713031 2021 September 25th [cited 2021 Oct 18[Tweet]. Available from: @ AJOWhitehouse 8. Kenny L, Hattersley C, Molins B, Buckley C, Povey C, Pellicano E. Which terms should be used to describe autism? Perspectives from the UK autism community [Internet]. 2015 Jul 1 [cited 2021 Oct 17];20(4):442–62. Available from: https://journals.sagepub.com/ doi/full/10.1177/1362361315588200?casa_token=3HaB8RzSKmcAAAAA%3A2x7-glkC3anF3vr4z6gK8--gpbFFg2Ke8_OmivjZ_MKhxFatf3H8zoaTmPwg-VsrqeYoRz62nt9z

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 21

VIEWPOINT

FROM PAST TO FUTURE:

AI AND ITS APPLICATIONS IN MEDICINE

By Madhumitha Rabindranath

rtificial intelligence (AI), machine learning, and big data are predominantly associated with tech industries; however, these tools are becoming increasingly applicable to other disciplines, especially medicine. Institutions are offering workshops and courses about AI and the University of Toronto recently founded the Temerty Center for AI Research and Education in Medicine (T-CAIREM) to drive AI innovation in healthcare.1 For individuals who are removed from the world of computer science, AI concepts can be overwhelming.

Within AI exists different subclasses that are implemented for specific functions. Machine learning (ML) is a set of algorithms that are trained to analyze large datasets and create predictive models. Deep learning (DL) has a similar function to ML but is useful for unstructured data such as imaging and requires less human input for training. Other types include natural language processing and robotics. With diverse functionalities, AI is a promising tool that has the potential to revolutionize our world.

What is AI?

Although the buzz around AI is recent, its concept was first envisioned in the 1950s. John McCarthy and Alan Turing, two of the founding fathers of AI, coined the term at a Dartmouth summer conference, spearheading AI research.3,4 While many scientists tried to build complex machines, there were limitations to their implementation such as cost and low computational power.5,6 As technology improved, the gains in computational power and data storage were matched with lower costs, making AI models more attainable.

According to IBM, AI “leverages computers and machines to mimic the problem-solving and decision-making capabilities of the human mind”.2 To put it simply, companies continually mine for large datasets that AI can use to parse and make meaningful decisions, solving more complex and interesting problems. There are two forms of AI – narrow and general AI.2 Most applications use narrow AI where models perform specific tasks with high accuracy. For example, virtual chatbots are algorithms used to resolve routine issues. Conversely, general AI works to mimic the human mind such as achieving self-awareness. Examples of these are found in science-fiction such as in the film, I, Robot but have not been achieved in the real world. 22 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

Why is it a big deal now?

What are some clinical applications of AI? AI applications in medicine are endless, ranging from diagnostic and predictive models to assistive therapies. The general principle of building AI models requires training algorithms with large, labeled

datasets and testing the model on a novel cohort, validating its performance against gold standards. The process is long as models require continuous fine-tuning; thus, most medical applications are still in development. The following are some clinical applications of AI. Electronic Patient Records Electronic patient records (EPRs) have large amounts of clinical information which can be useful for research and clinical decision-making. However, EPRs are rarely structured and are difficult to parse through. One way to tackle this issue is to use natural language processing algorithms that flag keywords during patient-physician conversations and automatically fill in relevant EPR sections.7 This would facilitate standardized record-keeping and better patient-clinician interactions, reducing the burden of maintaining records on clinicians. Intelligent record-keeping systems can also assist clinicians in flagging patients for review and potentially interact with wearable technology to enable constant patient management. Histopathology and Medical Imaging To improve diagnostic workflows, DL can be used to learn specific features of medical imaging or pathology slides which can assist clinicians in providing diagnoses. Several studies have shown that using DL to diagnose various pathologies such as cancer type and fibrosis is comparable to clinicians.8–10 Some tools are also Graphic design by Michie (Xingyu) Wu

VIEWPOINT

undergoing approval for clinical use. For example, Medo.AI recently received FDA approval for their AI platform that detects hip dysplasia, common in infants, using ultrasound images.11

What are some issues with AI? Despite its advantages, there are some challenges to implementing AI in clinical settings. Many clinicians are enthusiastic about the implications of using AI, but its integration is stalled by the limitations of translating these models to the clinic. The following are some issues of AI in healthcare and how they can be overcome. The “Black Box” Problem The flexibility of using AI for diverse problems comes at a cost. Dubbed the “black box” problem, we are unable to explain AI decision-making as we can only make educated inferences, despite many AI models’ outputs matching clinical expertise. Without the means to understand AI decision-making, it is risky to use these tools in the clinic especially concerning patients’ lives. Fortunately, efforts to create more explainable AI models are underway but there are concerns about affecting AI performance.12 Another way to tackle this issue is to have domain-specific guidelines for interpretability.13 For example, in computer vision (a subclass of DL for image analysis), models can learn specific prototypes for parts of the image that are important for classification, and new images

testing the model are classified based on learned prototypes.13 These prototypes can provide more interpretability of its learning process, increasing our confidence in AI decision-making.

clinical problems and provide decisions that consider this complexity. AI, ML, and its variants will truly bring medicine to the digital era and provide opportunities to revolutionize healthcare.

Data Security and Safety Another concern stems from data security issues and biases in AI models. For generalizable and successful modeling, AI tools require large amounts of data, requiring researchers to use open-source datasets. However, in clinical applications, hospitals will need to make EPRs widely available and share data across institutions, posing serious data security concerns. Many private companies are also interested in healthcare applications of AI and can receive access to EPRs, infringing on patients’ privacy rights.14 Hence, anonymized data may be useful in these situations; however, reidentification is possible using these algorithms.14 To ensure ethical compliance, regulatory bodies can provide oversight. For example, the FDA is recently providing a new framework to regulate clinical applications of AI models.12

Final verdict? Despite these challenges, AI is a promising tool that has the capacity to transform medicine, both in research and clinic. Extensive validation studies are required before these algorithms are deployed to the clinic. With increasing innovation in this field, AI will help tackle complex

References 1. U of T launches new Temerty Centre for AI Research and Education in Medicine [Internet]. [cited 2021 Sep 27]. Available from: https:// tcairem.utoronto.ca/news/u-t-launches-new-temerty-centre-ai-research-and-education-medicine 2. What is Artificial Intelligence (AI)? [Internet]. 2021 [cited 2021 Sep 28]. Available from: https://www.ibm.com/cloud/learn/what-is-artificial-intelligence 3. Amisha, Malik P, Pathania M, et al. Overview of artificial intelligence in medicine. J Fam Med Prim Care. 2019;8:2328–31. 4. Artificial Intelligence (AI) Coined at Dartmouth [Internet]. Celebrate Our 250th. 2018 [cited 2021 Sep 28]. Available from: https://250.dartmouth.edu/highlights/artificial-intelligence-ai-coined-dartmouth 5. The History of Artificial Intelligence [Internet]. Science in the News. 2017 [cited 2021 Sep 28]. Available from: https://sitn.hms.harvard. edu/flash/2017/history-artificial-intelligence/ 6. Early Popular Computers, 1950 - 1970 - Engineering and Technology History Wiki [Internet]. [cited 2021 Sep 28]. Available from: http://ethw.org/Early_Popular_Computers,_1950_-_1970 7. Willyard C. Can AI Fix Medical Records? Nature. 2019;576:S59–62. 8. Ghahremani P, Li Y, Kaufman A, et al. DeepLIIF: Deep Learning-Inferred Multiplex ImmunoFluorescence for IHC Quantification [Internet]. 2021 May [cited 2021 Sep 24] p. 2021.05.01.442219. Available from: https://www.biorxiv.org/content/10.1101/2021.05. 01.442219v1 9. Yu Y, Wang J, Ng CW, et al. Deep learning enables automated scoring of liver fibrosis stages. Sci Rep. 2018;8:16016. 10. Dermatologist-level classification of skin cancer with deep neural networks | Nature [Internet]. [cited 2021 Jan 23]. Available from: https://www.nature.com/articles/nature21056 11. MEDO.AI. MEDO.ai receives FDA approval to automatically detect hip dysplasia, preventing the leading cause of early hip osteoarthritis and hip replacement surgery. GlobeNewswire News Room. 2020. 12. Kelly CJ, Karthikesalingam A, Suleyman M, et al. Key challenges for delivering clinical impact with artificial intelligence. BMC Med. 2019;17:195. 13. Rudin C. Stop explaining black box machine learning models for high stakes decisions and use interpretable models instead. Nat Mach Intell. 2019;1:206–15. 14. Murdoch B. Privacy and artificial intelligence: challenges for protecting health information in a new era. BMC Med Ethics. 2021;22:122.

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 23

VIEWPOINT

Vaccine Passports: The Current Controversy

By Archita Srinath

t has been almost two years since the COVID-19 pandemic shook up the world in ways we never knew possible. Phrases like “social distancing” and “work from home” are now in our everyday vocabulary and checking to see if you have your mask before leaving the house is as normal as checking for your phone, wallet, and keys. Moreover, people are dealing with the unimaginable trauma of losing their loved ones and livelihoods whilst unable to engage with their social support systems. With the constant fear of contracting this virus anytime we step out of our homes, it has made the last two years one of the most challenging times in our lifetime. So, when the scientific community ran shouting “help is on the way dear” like a vaccine wielding Mrs. Doubtfire, most of us breathed a sigh of relief. However, when the Ontario government mandated “vaccine passports” for entry into public spaces, concerns over safety, privacy and equitable access to the vaccine were raised. So, let me pose these questions: are these fears valid? And if they are, how can we work to resolve them?

them into getting a vaccine that they feel is unsafe. Making vaccination mandatory to hold certain jobs or attend social events impedes people’s financial and mental state, therefore, making them more likely to get the shot even if they do not want to. Although it is true that these mandates are warranted given the risk that COVID-19 poses on human health, safety concerns are valid. We need to acknowledge the fact that many people fear long-term effects. Medical research has failed countless times in the past which has resulted in the harm and death of numerous people. Therefore, the lack of trust in the medical system is understandable, especially in marginalized populations that have historically been the victims of medical malpractice. Even though clinical trials and public health data support the safety and efficacy of the COVID-19 vaccines, it is vital that efforts to communicate this are inclusive and comprehensive.1 Therefore, combating misinformation on social media should be prioritized and the media should avoid sensationalizing rare side effects by carefully presenting them with context.

Many people view the implementation of vaccine passports as a way to coerce

Most vaccine passport opposers feel that the government is overstepping its

24 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

boundaries by limiting the free will we expect in a democratic society. However, this argument is trite since proof of immunization for free movement in public spaces is not a new concept in Canadian society. One major system that requires proof of immunization against infectious diseases for entry are schools.2 Hospitals and other health care settings require their staff to show proof of vaccination before working on the premises. These requirements have been around for ages but has never seen the pushback that the COVID-19 vaccines have received. According to Dr. Raywat Deonandan, an epidemiologist from the University of Ottawa, labeling proof of immunization as “vaccine passports” contributes in part to this resistance as it reminds people of restrictive border security.3 Therefore, changing the way in which vaccine passports are referred to can also be helpful to reduce this anxiety. Another commonly cited reason against vaccine passports is loss of privacy. However, privacy concerns can be dispelled if the government takes measures to protect the app against security breaches and ensures that they are only tracking Graphic design by Sherry An

VIEWPOINT

relevant personal information. According to the Ontario Government, the app never stores personal information and does not display your health card number to the person checking your passport.⁴ Additionally, Ontario allows for proof of vaccination to be shown through a printed copy. So, if you have privacy concerns with the app, printing out a certificate or asking the Provincial Vaccine Contact Centre to mail you a copy is an ideal solution.⁴ With these provisions, vaccine passports are no more intrusive on personal privacy than verifying your identification at a local bar. There are also concerns from the Ontario Human Rights Commission over barriers to equitable vaccine access for everyone.⁵ People who are not able to get vaccinated even if they wanted could therefore face discrimination based on their immunization status. However, there are resources available to help combat many barriers for marginalized communities. The National Newcomer Network offers support in many languages to undocumented and migrant workers to get their vaccines without the need for government identification.⁶ The Accessible Drive to Vaccines program will ensure

that anyone who needs help getting to a clinic will be able to get a ride.⁷ This is meant to help individuals with disability and older people with mobility issues to get their shots. However, a major gap in the aid available does exist for people experiencing homelessness. Although there are avenues to get a vaccine without the need for a health card, showing proof of vaccination still proves to be difficult as they may not have a cell phone or be able to keep a printed copy safe from theft. Finally, according to the Centre for Disease Control, vaccinated individuals are much less likely to become seriously ill and spread the disease than unvaccinated people.1 Therefore, ensuring that everyone in a poorly ventilated public space like a gym or restaurant is vaccinated is helpful to slow down the spread of COVID19. As long as we continue to work at making vaccines more accessible to every single Canadian, curb the spread of misinformation on the internet, and protect everyone’s reasonable right to privacy, vaccine passport is a great new method to get us back to normal life. And who does not miss that?

References 1. Coronavirus Disease 2019 (COVID-19) [homepage on the Internet]. Centers for Disease Control and Prevention. 2021 [cited 2021 Oct 18]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated-people.html 2. Vaccines for children at school [homepage on the Internet]. ontario. ca. 2021 [cited 2021 Oct 18]. Available from: https://www.ontario. ca/page/vaccines-children-school#exemptions 3. Bensadoun E. ‘Vaccine passport’ or ‘immunization record’? Why experts say there’s power in words - National | Globalnews.ca [homepage on the Internet]. Global News. 2021 [cited 2021 Oct 18]. Available from: https://globalnews.ca/news/8171936/vaccine-passport-language-concerns/ 4. Ontario Newsroom [homepage on the Internet]. News.ontario.ca. 2021 [cited cited 2021 Oct 18]. Available from: https://news.ontario. ca/en/backgrounder/1000980/using-your-enhanced-vaccine-certificate-frequently-asked-questions 5. OHRC policy statement on COVID-19 vaccine mandates and proof of vaccine certificates | Ontario Human Rights Commission [homepage on the Internet]. Ohrc.on.ca. 2021 [cited 2021 Oct 18]. Available from: http://www.ohrc.on.ca/en/news_centre/ohrcpolicy-statement-covid-19-vaccine-mandates-and-proof-vaccinecertificates 6. Covid-19: Vaccination for undocumented and migrant workers in Ontario [homepage on the Internet]. National Newcomer Navigation Network. 2021 [cited 2021 Oct 18]. Available from: https://www.newcomernavigation.ca/en/news/covid-19-vaccination-for-ontario-undocumented-and-migrant-workers.aspx 7. Ontario Newsroom [homepage on the Internet]. News.ontario. ca. 2021 [cited 2021 Oct 18]. Available from: https://news. ontario.ca/en/release/1000389/ontario-providing-accessible-rides-to-covid-19-vaccination-sites

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 25

VIEWPOINT

The Pros of Probiotics

By Kyla Trkulja

he human microbiome is estimated to contain about 100 trillion bacteria consisting of over 1000 species.1 Over the past few decades, the importance of this group of organisms has become abundantly clear, as these microbes act as their own organ system with many metabolic, immunological, and endocrine-like functions that influence human health.2 For example, microbes in the gut synthesize vitamins, amino acids, and important metabolic byproducts for the human host.3 These include vitamin K for blood clotting and short chain fatty acids (SCFAs) for energy.3 Other benefits include the breakdown of dietary toxins, nutrients, and carcinogens, conversion of cholesterol into other essential fats, assisting in the maturation of the immune system, and protecting humans from harmful bacteria that could otherwise invade the gut.2 This wide variety of health benefits is due to the gut microbiota consisting of organisms that have specialized enzymes and abilities that differ from us humans, allowing them to live in our bodies and thrive without causing us harm while actually promoting health and preventing disease. 26 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

How does the microbiome influence health?

Manipulating the microbiome with probiotics

An imbalance in the microbiome, known as dysbiosis, has been associated with immune disorders, susceptibility to infections, and pathologies such as cardiovascular disease, obesity, diabetes, liver and brain disease, autism, and mood disorders.2,3 Various studies have examined the composition of the gut microbiome and its associations with conditions including inflammatory bowel disease (IBD), inflammatory skin diseases such as psoriasis and dermatitis, arthritis, diabetes, obesity, and atherosclerosis.3 In addition, recent research has found that our lifestyle and diet choices influence the microbiome of the gut; for example, high intake of red meat increases the abundance of bacteria that produce trimethylamine-N-oxide (TMAO), a compound that increases the risk of cardiovascular disease.3 Findings such as these have demonstrated that we as humans have the ability to influence our own microbiomes, which can improve our health if done strategically.

Various foods such as cultured milk products and yogurts contain lactic acid bacteria, a source of consumable microbes that can promote a healthy gut microbiome.3 Commonly referred to as “probiotics”, these foods enriched in beneficial bacteria can have a positive impact on our health. In fact, companies even sell probiotic supplements that can be taken as capsules, tablets, packets, or powders so the benefits can be obtained without necessarily consuming the appropriate foods.⁴ The most widely used probiotics are the beneficial Lactobacillus and Bifidobacterium groups, which may have health benefits such as reducing body fat mass, improving glucose and lipid balance, and regulating the immune system.2, ⁴-⁵ Some of the health benefits of probiotics have been validated through randomized controlled trials and extensive research, but others are only supported by inconsistent evidence.4 There is strong Graphic design by Sherry An

VIEWPOINT

Figure 1 (left). The composition of the human gut microbiome, estimated to contain over 1000 species. Figure 2 (right). The widespread benefits of regular probiotic consumption extend far beyond the microbiome.

evidence supporting the use of probiotics to improve stool consistency, regulate bowel movements, reduce abdominal bloating, prevent vaginal, E. coli, and H. pylori infections, and reduce the incidence and symptoms of the common cold.⁶ Other less supported benefits may include improvement of mood, reduction of depression and anxiety symptoms, weight loss, and balancing of metabolic markers of health such as cholesterol and proinflammatory cytokines.2-3, ⁵-⁶ Furthermore, probiotics have been found to potentially aid in weight loss and have maximum health benefits when combined with diet and exercise. This is due to the bacteria breaking down metabolic byproducts like fermented proteins that are produced when exercising.⁷ Future research will hopefully be able to decipher which benefits are reliable, but even with our limited knowledge, the potential pros of consuming probiotics outweigh the cons. Nonetheless, it is important to note a few other considerations before taking probiotics. Most importantly, everyone’s body is different, and their age, gender, co-morbidities, genetics, and body environment may result in a different outcome when taking probiotics; as

a result, probiotics might not benefit everyone, and may even be harmful for some.1,⁸ Similarly, since probiotics contain live microorganisms, there is the risk of infections, side effects, and complications in some individuals.1,⁴ Those who are most at risk are immunocompromised individuals or people with immunological disorders; however, everyone should talk to their doctor before taking probiotic supplements, just like they would with any medication.⁸ The gut microbiota also depends on other factors such as genetics and diet; therefore, taking probiotic supplements will not result in benefits without taking this into consideration.⁶ Finally, it’s important to remember that the gut microbiome can change quickly, returning back to baseline within 1-3 weeks after ceasing probiotics.⁶ This emphasizes the fact that probiotics should be combined with a healthy lifestyle for maximum benefits, and that they are not a permanent solution to wellness. However, despite the considerations, probiotics are generally considered a safe, accessible, and well-tolerated way to balance the gut microbiome and improve

health. Talk to your doctor to determine which type of probiotics you should take, since they aren’t all created equal, and combine them with healthy living to let you and your microbiome thrive. References 1. Lordan, C., Thapa, D., Ross, R. P., et al (2020) Potential for enriching next-generation health-promoting gut bacteria through prebiotics and other dietary components. Gut Microbes, 11:1, 1-20, DOI: 10.1080/19490976.2019.1613124 2. Gérard, P. (2016) Gut microbiota and obesity. Cellular and Molecular Life Sciences, 73, 147–162. https://doiorg/10.1007/s00018-015-2061-5 3. Singh, R.K., Chang, HW., Yan, D. et al. (2017) Influence of diet on the gut microbiome and implications for human health. Journal of Translational Medicine, 15, 73. https:// doi.org/10.1186/s12967-017-1175-y 4. Williams, N. T. (2010) Probiotics. American Journal of Health-System Pharmacy, 67(6), 449–458. https://doi. org/10.2146/ajhp090168 5. Mueller, M., Ganesh, R. & Bonnes, S. (2020) Gut Health = Mental Health? The Impact of Diet and Dietary Supplements on Mood Disorders. Current Nutrition Reports, 9, 361–368. https://doi.org/10.1007/s13668-020-00340-2 6. Khalesi, S., Bellissimo, N., Vandelanotte, C. et al. (2019) A review of probiotic supplementation in healthy adults: helpful or hype? European Journal of Clinical Nutrition, 73, 24–37. https://doi.org/10.1038/s41430-018-0135-9 7. Sergeev, I. N., Aljutaily, T., Walton, G., et al (2020) Effects of Synbiotic Supplement on Human Gut Microbiota, Body Composition and Weight Loss in Obesity. Nutrients, 12(1), 222. https://doi.org/10.3390/nu12010222 8. Kothari, D., Patel, S., Kim, S. K. (2019) Probiotic supplements might not be universally-effective and safe: A review. Biomedical Pharmacotherapy, 111, 537-547. doi: 10.1016/j.biopha.2018.12.104.

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 27

FACULTY SPOTLIGHT

New IMS Faculty Dr. Frank Rudzicz (PhD) is a Scientist at Unity Health Toronto, Director of AI at Surgical Safety Technologies, Associate Professor of Computer Science at the University of Toronto, faculty at the Vector Institute, and CIFAR Chair in AI. His work in machine learning, natural language processing, and surgical safety has appeared in Scientific American, Wired, the New York Times, and Nature.

Dr. Linda Hiraki (MD, FRCPC, SM, ScD) is a Clinician-Scientist in the Division of Rheumatology and Scientist in Genetics & Genome Biology at the Hospital for Sick Children. Hiraki holds a Canada Research Chair in Genetics of Rare Systemic Inflammatory Diseases. She coordinates multicentre studies of lupus and rare diseases.

Dr. Joshua D. Rosenblat (MD, MSc, FRCPC) is a psychiatrist and clinicianscientist at Toronto Western Hospital. He conducts multi-site clinical trials evaluating novel, rapid-acting interventions for depression and bipolar disorder (e.g., ketamine, psilocybin). He has published over 130 peer-reviewed journal articles and has received numerous local, provincial and federal grants for his research.

Dr. Sukhvinder Kalsi-Ryan (Reg. PT, BScPT, MSc., PhD) the lead of the KITE Clinics is a clinician scientist who studies quantification of neurological disease and aims to discover new techniques for neuro-restoration. She has published over 40 peer-reviewed articles and trained 8 masters and PhD students. Dr. Kalsi-Ryan is an extramurally funded midcareer scientist with a passion to contribute to the transformation of rehabilitation. resistant mental illnesses.

Dr. Julia Orkin is the Medical Director of the Complex Care program at SickKids and an Associate Professor, University of Toronto. She is the Medical Officer for Integrated Community Partnerships focused on system integration. Her research focuses on innovations in care delivery for children with medical complexity and their families.

Dr. Sindhu R Johnson (MD PhD) is a Rheumatologist, Clinical Epidemiologist and Director of the Toronto Scleroderma Program. She is an Associate Professor of Medicine at the University of Toronto, and Clinician-Scientist at the Toronto Western and Mount Sinai Hospitals. Her program of research includes observational cohort studies and randomized trials of novel therapeutics for the treatment of the Scleroderma spectrum of disorders.

Dr. Mrinalini Balki (MBBS, MD) is a staff anesthesiologist at Mount Sinai Hospital and is a professor in the Dept of Anesthesiology & Pain Medicine, Obstetrics & Gynaecology, and Physiology at the University of Toronto. She is also a Senior Clinician Scientist at the Lunenfeld-Tanenbaum Research Institute and is a director of Fellowship program in Clinical and Basic Science in Obstetric Anesthesia. She has published over 100 peerreviewed articles and has mentored over 60 postgraduate students and fellows in research projects. Prof. Balki has received numerous research grants, awards and lectureships throughout her career.

Dr. Sunita Singh (MD, MSc, FRCPC) is a transplant nephrologist and clinician-investigator in the Division of Nephrology at the Toronto General Hospital, and an Assistant Professor of Medicine at the University of Toronto. She is also the medical director of the living kidney donation program at the Ajmera Transplant Centre. Dr. Singh’s research interests are focused on cardiorenal protection in kidney transplant recipients, and the evaluation and follow-up of living kidney donors. autism diagnoses extend beyond childrens’ three years of age? Future research might aim to answer this question by performing a longitudinal study.

Dr. Eyal Cohen (MD, MSc, FRCPC) co-founded the Complex Care program at the Hospital for Sick Children where he is Program Head of Child Health Evaluative Sciences and Co-Director of the Edwin S.H. Leong Centre for Healthy Children in the Department of Pediatrics at the University of Toronto. Prof. Cohen has published over 165 peer-reviewed manuscripts and enjoys mentoring research trainees in graduate studies and research fellowships.

28 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

Graphic design by Amy Assabgui

FACULTY SPOTLIGHT

Dr. Jamie Feusner, MD (Professor of Psychiatry, UofT; Clinician Scientist, CAMH; Director, Brain, Body, and Perception Research Program) has published over 120 peerreviewed articles and book chapters and has supervised multiple MD/PhD, PhD, and Master’s students. Prof. Feusner conducted the first, pioneering functional brain imaging studies in body dysmorphic disorder. Dr. Atul Verma is a staff cardiac electrophysiologist and Director of Arrhythmia Services at Southlake Regional Health Care Centre in Newmarket, Ontario, Canada. He is an Associate Professor with the University of Toronto and Adjunct Professor with McGill University. Specific interests include ablation of atrial fibrillation and ventricular tachycardia especially new techniques and technologies. Dr. Verma has served as Chair or writing member of a number of national and international guideline committees including the Canadian Cardiovascular Society Atrial Fibrillation Guidelines Committee and the HRS Consensus Statement on Catheter Ablation of AF. He has also led many clinical trials in cardiac ablation. Dr. Verma completed his medical school and cardiology residency at the University of Toronto and then specialized in cardiac electrophysiology at the Cleveland Clinic. He has published over 250 peerreviewed articles in many journals including the New England Journal of Medicine, JAMA, Lancet, Circulation, JACC, European Heart Journal, and others.

Jeff Kwong (MD, MSc, CCFP, FRCPC) is an epidemiologist, a specialist in public health and preventive medicine, and a family physician. Based at ICES and Public Health Ontario, his research interests include infectious diseases and vaccine epidemiologic research using large linkable databases. Dr. Jenny Rabin is an academic neuropsychologist and scientist at Sunnybrook Research Institute. Her research focuses on two main areas: 1) improving outcome measures in neuromodulation trials for difficult-to-treat neurological and psychiatric disorders and 2) examining risk and protective factors for dementia. Dr. Amer M. Burhan (MBChB, MSc. FRCPC in General and Geriatric Psychiatry, Certified in Behavioral Neurology/ Neuropsychiatry) is a Geriatric Psychiatrist, Physician-in-Chief and Endowed Chair for Applied Mental Health Research at the Ontario Shores Centre of Mental Health Sciences in the Whitby Ontario, and Associate Professor in Psychiatry at the University of Toronto. Also, he is Adjunct Research Professor in Psychiatry and associate member in the Department of Neurosciences at Western University, associate scientist at the Lawson Health Research Institute in London Ontario. He leads several pragmatic clinical trials in the area of neuropsychiatry of dementia and in therapeutic brain stimulation for resistant mental illness across the life-span in addition to being active in several initiatives to develop guidelines to standardize definitions, assessment and management of treatment resistant mental illnesses.

Dr. Behdin Nowrouzi-Kia (OT Reg. (Ont.), FRSA) is an assistant professor in the Department of Occupational Science and Occupational Therapy at the University of Toronto and is an affiliate scientist at the Krembil Research Institute at the University Health Network. Dr. Nowrouzi-Kia’s holds the inaugural Emily Geldsaler Grant Early Career Professor in Workplace Mental Health. Dr. Fayez A. Quereshy (MD, MBA, FRCSC, FACS) is a Surgical Oncologist and Minimally Invasive Surgeon at the University Health Network and is an active member of the Princess Margaret Cancer Program. His specialty interest focuses on gastrointestinal malignancies and colorectal cancer. Dr. Quereshy completed his residency training in General Surgery, and his fellowship in Surgical Oncology, at the University of Toronto. He received his Master’s degree in Business Administration (MBA) at the Rotman School of Management. He subsequently pursued advanced Robotic Colorectal training at the Queen Mary Hospital, University of Hong Kong. His academic interests center on operations management and systems efficiency, with the aim of improving cost effectiveness and quality of care. Dr. Quereshy is an Associate Professor in the Department of Surgery at the University of Toronto and is a Clinical Vice-President at the University Health Network (UHN).

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 29

FACULTY SPOTLIGHT

The Recipe to Achieving Almost the Impossible with Dr. Peter Giacobbe

By Sonja Elsaid

“N

ever give up!" This is Dr. Peter Giacobbe's recipe for achieving almost the impossible. We interviewed Dr. Peter Giacobbe, an Associate Professor at the Institute of Medical Science (IMS) and Department of Psychiatry at the University of Toronto, and the Associate Scientist at Sunnybrook Research Institute, to learn about his motivation for researching and treating patients with treatment-resistant depression. Dr. Giacobbe is one of the very few psychiatrists in the world with expertise in delivering Electroconvulsive Therapy (ECT), Deep-brain Stimulation (DBS), MRI-guided Focused Ultrasound Treatment, and repetitive Transcranial Magnetic Stimulation (rTMS). As an Interventional Psychiatrist, he provides the entire care continuum to his patients, including psychotherapy, various pharmacological treatments, and more invasive device-based regimens. Some patients do not get better, even after being repeatedly treated for their symptoms of depression. For many mental health workers, treatment-resistant depression is one of the most challenging psychiatric conditions to remedy. Only a few are up to the challenge of coming face-to-face with the almost impossible. When asked about his motivation to accept the challenge of treating persistent 30 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

depression, Dr. Giacobbe responded: "I was always interested in the world around me and 'how people work.' To answer this question, I pursued a Bachelor's in Science (BSc) degree in Neuroscience at the University of Toronto—a topic that helped me understand brain development, human personality, and behavior. That curiosity led me to the next level—the decision to become a psychiatrist. So, I went to medical school at the Western University in London and subsequently entered the psychiatric residency program at U of T. During the clinical rotations, I worked with patients who were very depressed. They repeatedly failed to respond to pharmacological treatments, but then they, all of a sudden, significantly improved with the ECT. I was fascinated! How could a non-esthetically pleasing procedure, such as ECT, performed at the basement of a hospital, produce such great results?" Thus, Dr. Giacobbe began exploring the biological paradigm that explains the physiological causes of depression. "We know that the brain is an electrochemical organ. Pharmacological treatments are only half of the equation. The electrical properties of the brain could also be changed by delivering electricity or magnetic pulses. We now know, that the brain is very responsive to externally delivered energy, which explains why

patients with depression who show little respond to other treatments can respond to the ECT or rTMS." Nevertheless, Dr. Giacobbe's desire to help patients went beyond learning to use all the available tools in his treatment kit. He wanted to improve the quantity and quality of life of his patients and destigmatize depression. By demonstrating that psychiatric illnesses are products of the brain, Dr. Giacobbe hoped that psychiatric disorders, like depression, would get the same level of acceptability as Parkinson's disease and epilepsy." Device-based treatments have the unique capability to destigmatize these illnesses. They [psychiatric disorders] are not illnesses of willpower or personality; they are illnesses of the brain. If we can alter the brain functioning of psychiatric patients therapeutically, then we can make people see that psychiatric illnesses are similar to neurological disorders." Dr. Giacobbe also pointed out how obtaining his Master's degree at the IMS was crucial for his career. "I did not only want to use all the treatments available, but also play a role in finding new ones. In my quest for discovery, I needed to learn how to pursue a hypothesis and choose the best methodology to test the questions I am passionate about." Graphic design by Michie (Xingyu) Wu

FACULTY SPOTLIGHT

DR. PETER GIACOBBE MD, MSc, FRCP(C) Photo Credit: Dorsa Derakhshan

According to Dr. Giacobbe, given that psychiatric diagnoses are very heterogeneous, a way forward is to deconstruct the inherent heterogeneity through the application of innovative technologies. Blood tests and brain scans hold the promise of helping to stratify different depression subtypes. Thus, similar to how breast cancer gene identification leads to specific treatments, Dr. Giacobbe wants to do the same for depression. "Brain imaging and eyetracking tests could supplement the

clinical wisdom and help us make the essential decisions about treatments for our patients. This is the way forward! One-size-fits-all treatments may not work for everyone, therefore by adding these technologies to our diagnostic toolbox, we can personalize treatments for depression based on the subtypes."

When asked “how to become a good researcher?” Dr. Giacobbe encouraged students to be open to feedback, continue to perserve, and develop resilience to rejection. "Good feedback is supposed to make you better, not bitter. You have to develop good communication skills to be able to work with multidisciplinary teams."

For some working in clinical research and recruiting human subjects, Dr. Giacobbe reminded us that the study participants might have a tremendous fear of the unknown when enrolled in clinical studies. "We must partner with them and treat them as collaborators, whose medical situation we are trying to understand so that we could enhance their outcomes." As graduate students, Dr. Giacobbe suggested that we give back to the scientific enterprise by participating in clinical studies ourselves. Only by becoming research participants, we can begin to understand how it feels to be a subject in a research study. "To be successful in recruiting participants," Dr. Giacobbe added, "be personable, develop good communication skills, and be open to being wrong. Be honest in revealing to potential participants that the treatment offered in a clinical trial may not work. Instead of overpromising and under-delivering, openness and honesty go a long way."

Furthermore, Dr. Giacobbe advised about the essence of cultivating our questions and, most notably, being passionate about our research. "It is important to pursue your own intellectual freedom and be in the research environment that supports your curiosity and the development of your path. Thus, it is vital to find a supervisor who will challenge you, drive you, and guide you. The relationship should be a dialogue with the openness to feedback. The strength of being an IMS student is that it is a large department where students can always find a scientist who researches the topic that interests them."

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 31

STUDENT SPOTLIGHT

Your brain is more powerful than you think: An Interview with Natalie Osborne

By Stacey J Butler

ur brains are incredibly powerful. Even when we are not conscious and our bodies are at rest, the brain is still working hard. The brain allows us to feel joy, happiness, and pleasure. But it also is the reason that we feel pain. Pain researchers use neuroimaging to try and understand how pain is “created” in the brain, and how brain plasticity may contribute to conditions such as chronic pain. With these advanced neuroimaging techniques, Natalie Osborne, a PhD Candidate in the Institute of Medical Sciences (IMS), is furthering our understanding of sexdifferences in chronic pain. Natalie’s journey to the IMS, and her quest to study chronic pain, began with her Master’s research at the University of Western Ontario. Under the supervision of Dr. Adrian Owen, Natalie learned how to use functional magnetic resonance imaging (fMRI) to measure cognition in patients with disorders of consciousness (DOC). Patients with DOC vary in their level of consciousness, from being in a coma to being awake but unable to communicate. At the bedside, patients may show no signs of awareness. But under the fMRI scanner, some patients are able to mentally respond to commands. Even though they were not able to physically 32 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

move, their brains still responded to a command such as imagining themselves playing tennis. Natalie was amazed by the power of our brains, which she got to witness first-hand. Her fascination grew when she met a patient who recovered from a vegetative state and they “brought him back to the lab to see if he remembered anything from his first visit, and he did!” This led Natalie to wonder what else these patients are experiencing and are unable to tell us. One question was at the forefront of her mind: “Are you in pain?”. Natalie wrote about this topic in the Summer 2017 issue of IMS Magazine, with her compassionate article entitled, ‘I feel, therefore I am? Understanding pain in disorders of consciousness’. The search for the answer to this important question drove Natalie to pursue her PhD with Dr. Karen Davis, a renowned researcher in chronic pain, at the University of Toronto. Along with a common interest in neuroimaging, the two researchers also shared a commitment to gender equality in science. Historically, women are underrepresented in research.1 Many studies that do include women, fail to analyze results separately by sex.1 Women and men can differ in their symptoms and the way they respond to treatments.1,2 With regards to chronic pain,

women are more likely to be affected than men.1,2 Too often however, women with chronic pain are dismissed by healthcare providers.2 Natalie believes this happens due to lack of preclinical and clinical research on how sex and gender influence pain3, disparities in funding for research on female-specific conditions4, biases and gender stereotypes about pain expression5, and general misunderstanding about chronic pain. Patients with chronic pain are often told that “It is all in their head”. Although this statement is technically true–after all our brain does tell us we are in pain–it is also misleading. Worst of all, it leaves patients feeling helpless and stigmatized. Patients should be reassured that what they are experiencing is in fact real and valid. Better yet, they may even be able to use the power of their brain to control their pain and find relief. In her PhD research, Natalie strives to understand how the brain functions in patients with conditions that cause chronic pain. She studies conditions that are more common in males (ex. Ankylosing Spondylitis) as well as female-dominant conditions (ex. Carpal Tunnel Syndrome). This approach is a unique way to account for sex-differences and has led to interesting findings. Natalie found abnormalities in a region Graphic design by Michie (Xingyu) Wu

STUDENT SPOTLIGHT

may develop a predominantly male condition and vice versa. Most notably, it underlines the importance of considering sex and gender in research.

NATALIE OSBORNE PhD Candidate, Krembil Research Institute, Institute of Medical Sciences, University of Toronto @NatalieRaeOz Photo Credit: Alaina Media

called the subgenual anterior cingulate cortex. This region is a key node in the descending antinociceptive system, which is associated with the brain’s ability to modulate pain. Surprisingly, the abnormalities were only present in patients of the non-dominant sex.6,7 Chronic pain is complex, but these results provide valuable insights into how connections in the brain and pain processing can differ among sexes. It also helps to uncover reasons why females

Natalie is keen to ensure her research has an impact. She shares the results of her research on Twitter in a way that is easily accessible for everyone. During her time with our team at IMS Magazine, she held almost every role possible, most recently leading as the Editor-in-Chief. Her first issue was, unsurprisingly, Women’s Health (Summer 2019). For Natalie, working on the magazine enhanced her graduate school experience and was a source of motivation for her own thesis work. She felt energized discussing with her peers the current hot topics in science and the exceptional research being done in the IMS. Natalie emphasizes that communicating research in a way that is easily understood requires a lot of training and gets easier with practice. It is not something that comes naturally to most scientists. The devastating impact of misinformation, or poorly communicated science, became all too clear during the pandemic. Natalie felt inspired by other scientists on Twitter, who have taken it upon themselves to increase accessibility, stop the spread of misinformation, and share the real evidence.

Completing a PhD thesis is already an incredibly challenging task–some may even equate it to climbing Mount Everest. Therefore, completing a PhD thesis during a global pandemic would be like climbing Mount Everest in a blizzard, with hurricane level winds. Although it was difficult, this experience helped Natalie learn how to be more adaptable, a trait that she can surely carry with her beyond graduate school. Wherever the road leads Natalie next, she will continue to advocate for women’s health and patient-centered research. She will keep using her brain to help us understand the power of ours. References 1. Mazure CM, Jones DP. Twenty years and still counting: including women as participants and studying sex and gender in biomedical research. BMC Womens Health, 2015; 15:94. 2. Billock J. Pain bias: The health inequality rarely discussed. BBC Future, The Health Gap, 2018 May 22. [cited Oct 14 2021]. Available from: https://www.bbc.com/future/article/20180518-the-inequalityin-how-women-are-treated-for-pain 3. Mogil, J.S. Qualitative sex differences in pain processing: emerging evidence of a biased literature. Nat Rev Neurosci, 2020; 21:353–365. 4. Mirin AA. Gender Disparity in the Funding of Diseases by the U.S. National Institutes of Health. J Womens Health (Larchmt). 2021; 30(7):956-963. 5. Zhang L, Losin EA, Ashar YK, Koban L, Wager TD. Gender biases in estimation of others’ pain. J Pain, 2021; 22(9):1048 – 1059. 6. Osborne NR, Cheng JC, Rogachov A, Kim JA, Hemington KS, Bosma RL, Inman RD, Davis KD. Abnormal subgenual anterior cingulate circuitry is unique to women but not men with chronic pain. Pain, 2021; 162(1):97-108. 7. Osborne NR, Anastakis DJ, Kim JA, El-Sayed R, Cheng JC, Rogachov A, Hemington KS, Bosma RL, Fauchon C, Davis KD. Sex-Specific Abnormalities and Treatment-Related Plasticity of Subgenual Anterior Cingulate Cortex Functional Connectivity in Chronic Pain. Front Pain Res, 2021; 9.

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 33

DIVERSITY IN SCIENCE

Addressing the stigma surrounding mental health among racial & ethnic minorities By S. Hussain Ather

34 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

Graphic design by Amy Assabgui

e often think of mental illness as solely a disorder of our minds and free from the biases and prejudices that come into play when we interact with each other. But it’s been observed that people of lower socioeconomic status may be more prone to mental illness.1 For a country with a diverse population — around 30% of the population identifying as PoC (person of color)2 — differences in the distribution of mental illness across race or ethnicity can never be ignored. Among the factors causing these disparities, there lie common themes of stigma and shame, intertwined in identity formation, further preventing individuals from seeking help.

Disparities in mental illness incidence and symptomatology Health administrative databases in Ontario do not collect data on race or ethnicity as regularly as they could. However, efforts have been made to study how mental health disparities exist between individuals based on race. By identifying Chinese and South Asian surnames from various sources of data, Dr. Maria Chiu, Staff Scientist at Institute for Clinical Evaluative Sciences (ICES)3,4,5 observed a higher prevalence of mental illness among Chinese & South Asian ethnic groups. There are many reasons why members of these groups don’t seek treatment, including self-stigma, internalizing stigmatizing ideas widely endorsed by the public, feelings of shame, and views and/or beliefs of mental illness that could prevent individuals from seeking treatment such as the notion that mental illness can make one weak or “inferior” to others.6,7,8,9 There is also high levels of public stigma, or how an individual’s community perceives mental illness.10

Asian values & mental health The traditional values that govern Asian families create the common stigma and shame surrounding mental illness within Asian communities. The family is a unit: each member defined in specific roles with a hierarchy coexisting in harmony. Mental illness can reflect poorly on this harmony.

DIVERSITY IN SCIENCE Asian societies also tend to be collectivist and emphasize the individual’s relationship to society as a whole, instead of the personal needs or desires of the individual. Group harmony, interdependence, and conformity rule above all, including one person’s needs to seek help.

The Black community and mental health Higher rates of psychiatric disorders have been reported among black Canadians. As well 30% of black respondents in the 2020 Statistics Survey reported experiencing moderate to severe generalized anxiety disorder, whereas roughly 24% of white individuals did.11 Stigma and a fear of being judged within the black community – and consequently shamed and embarrassed – have also been cited as reasons individuals may not seek help.12,13 Shame has also been observed among other ethnic groups such as Latinos.13

The roots of stigma & shame from a philosophical view But what is it exactly about shame and stigma that keeps these individuals from reaching out for help? The answer may come down to how these illnesses change our perceived sense of identity. More than somatic/physiological changes in our body, they change the way we perceive ourselves and the ways others perceive us. Within those perceptions, shame and stigma lie. According to the cognitivist views of emotions, emotions are object-oriented.14 Emotions like shame serve as guiding forces towards objects or goals. Shame, through this lens, serves to diminish one’s status as a member of a group – or stigmatize that person within a group.

Next steps in combating social stigma surrounding mental Understanding how these psychological forces are rooted in group identity can lead to individuals making more informed decisions on their personal health and well-being. This can include joining support groups within the community or reducing self-stigma through selfcompassion and self-care. The ways one may relate to those groups and the identity and status that come from them are part of the puzzle in combating shame and stigma. References 1. Kim YM, Cho SI. Socioeconomic status, work‐life conflict, and mental health. American Journal of Industrial Medicine. 2020 Aug;63(8):703-12. 2. Statistics Canada. “Visible Minority (15), Generation Status (4), Age (12) and Sex (3) for the Population in Private Households of Canada, Provinces and Territories, Census Metropolitan Areas and Census Agglomerations, 2016 Census‐25% Sample Data.” (2019). 3. Shah BR, Chiu M, Amin S, Ramani M, Sadry S, Tu JV. Surname lists to identify South Asian and Chinese ethnicity from secondary data in Ontario, Canada: a validation study. BMC medical research methodology. 2010 Dec;10(1):1-8. 4. Chiu M. Ethnic Differences in Mental Health and Race-Based Data Collection. Healthcare quarterly (Toronto, Ont.). 2017 Jan 1;20(3):6-9. 5. Corrigan PW, Druss BG, Perlick DA. The impact of mental illness stigma on seeking and participating in mental health care. Psychological Science in the Public Interest. 2014 Oct;15(2):37-70. 6. Bradby H, Varyani M, Oglethorpe R, Raine W, White I, Helen M. British Asian families and the use of child and adolescent mental health services: a qualitative study of a hard to reach group. Social science & medicine. 2007 Dec 1;65(12):2413-24. 7. Leong FT, Lau AS. Barriers to providing effective mental health services to Asian Americans. Mental health services research. 2001 Dec;3(4):201-14. 8. Loya F, Reddy R, Hinshaw SP. Mental illness stigma as a mediator of differences in Caucasian and South Asian college students’ attitudes toward psychological counseling. Journal of Counseling Psychology. 2010 Oct;57(4):484. 9. Tiwari SK, Wang J. Ethnic differences in mental health service use among White, Chinese, South Asian and South East Asian populations living in Canada. Social psychiatry and psychiatric epidemiology. 2008 Nov;43(11):866-71. 10. Taylor RE, Kuo BC. A Theory-Driven Exploration of Black Canadians’ Psychological Help-Seeking Intentions. Canadian Journal of Counselling and Psychotherapy. 2020 Aug 27;54(3):464-85. 11. Jones, RP. Report on Black mental health a good first step, advocates say. CBC News: Ottawa. 2020 Aug. 12. Ward EC, Heidrich SM. African American women’s beliefs about mental illness, stigma, and preferred coping behaviors. Research in nursing & health. 2009 Oct;32(5):480-92. 13. Wong EC, Collins RL, Cerully J, Seelam R, Roth B. Racial and ethnic differences in mental illness stigma and discrimination among Californians experiencing mental health challenges. Rand health quarterly. 2017 Jan;6(2). 14. Hutchinson P. Emotion-philosophy-science. In Emotions and understanding 2009 (pp. 60-80). Palgrave Macmillan, London.

For racial and ethnic minorities, group status is important as it relates to identity and broader collectivist ideals or how others in our respected community might judge that person. Being dependent on health services or medication may be a signal to others that we aren’t autonomous or strong, leading to these feelings of shame and stigma. IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 35

PAST EVENTS

By Serena Peck

n November 2nd, 2021, the Institute of Medical Science held the 11th Annual Ori Rotstein Lecture in Translational Research. Traditionally, this event is held in-person, however, due to the COVID-19 pandemic, the event was held virtually once again. Before the event, students were asked via survey to choose the topic for the keynote speech, with the majority selecting global health and epidemiology. This year’s keynote speaker was Dr. Mary Gospodarowicz, Professor of Radiation Oncology at the University of Toronto, past Chair of Radiation Oncology, and past Medical Director of Princess Margaret Cancer Centre. Dr. Gospodarowicz gave an excellent lecture entitled “Global Cancer Control - Challenges and Opportunities”. The beginning of the keynote lecture discussed the global cancer burden, and the accompanying equity gap. Dr. Gospodarowicz spoke at length about greater survival outcomes in highly developed areas due to (1) availability of care, specifically in prevention, early detection, and diagnostic services; (2) affordability; and (3) awareness. Dr. Gospodarowicz also discussed the economic benefits behind investing in cancer therapy, noting that investment 36 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

in radiotherapy can improve financial solvency of nations and save money over time. She also discussed artificial intelligence and how its development will continue to play a key role in cancer therapy. Dr. Gospodarowicz ended her talk discussing advocacy, engagement, and leadership. She noted how we need more “T-shaped people”, meaning that we need young leaders who not only have a deep-disciplined expertise, but also have cross-disciplined expertise. Healthcare and cancer care are complex systems, and young leaders should bring cross-discipline expertise and technology experience as leaders and healthcare advocates. Following the keynote speaker, the event transitioned into a panel discussion on highlighting unique journeys through research. The panel discussion was moderated by Dr. Ori Rotstein himself, the Vice President of Research and Innovation at Unity Health Toronto and a Professor and Associate Chair of the Department of Surgery at the University of Toronto. The discussion began with panelists describing their paths and journeys to their current position. The panel consisted of Dr. Atul Verma, Electrophysiologist at Southlake Regional Health Care Centre; Dr. Frank

Rudzicz, computer scientist at Unity Health Toronto; Dr. Janet Smylie, scientist at Unity Health Toronto; Dr. Samantha Yammine, neuroscientist, and science communicator; and our keynote speaker, Dr. Gospodarowicz. Panelists were asked to describe a defining moment in their career that got them to where they were today, and many gave very inspirational feedback. Some key advice that the entire panel agreed on were to (1) follow your passion; (2) understand the importance of networking - let people know what you are interested in; (3) keep asking questions, and lastly; (4) strengthen your writing skills and public speaking skills, as they are invaluable - practice, practice, practice! Overall, the Annual Ori Rotstein Lecture in Translational Research was a huge success. The students were engaged and asked thought-provoking questions. Personally, I thought this year’s event was amazing. The keynote speaker and panelists were distinguished, diverse, and genuinely interested in engaging with the student body. I am looking forward to seeing what next year’s event holds!

Graphic design by Sherry An

BOOK REVIEW

The Power of Gut Microbes to Heal and Protect Your Brain – for Life

By DR DAVID PERLMUTTER, MD Serena’s Pick

By Serena Peck

In Brain Maker, Dr. Perlmutter takes the reader on a journey explaining how our gut microbiome is connected to our brain and how a healthy gut is necessary for neurological protection—a subject that has often been neglected. Some topics covered in this book include the effects of diet and environment on our gut, disorders such as attention deficit hyperactivity disorder (ADHD), allergies, obesity, autism, and depression in relation to the gut microbiome, as well as prebiotic and probiotic foods. Brain Maker may seem like a heavy read with complex topics, but Dr. Perlmutter integrates patient stories and anecdotes to ease the reader into the content. The book begins with Part I discussing what the gut microbiome is and how

“ Graphic design by Sherry An

the state of our microbiome is key for health. For me, this was something I was somewhat familiar with, but it was a very well written overview and did touch upon new evidence I had yet to explore. Chapter One caught my attention as it takes the reader through different scenarios regarding the importance of our microbiome—even from the moment we are born! For example, Dr. Perlmutter describes that in the U.S., a third of infants are born by c-section and are thus exposed to antibiotics received by the mother. This results in the infant having a five-fold increased risk of allergies, triple the risk of ADHD, twice the risk of autism, 70 percent increased risk of type-1 diabetes, and a predisposed risk to many more disorders as well. Later in Part I, the book describes dietary, lifestyle, and environmental effects on the microbiome. Dr. Perlmutter lists how ailments most often found in North America (obesity, ADHD, diabetes, chronic fatigue, allergies, etc.) are a byproduct of the Western diet which can predispose us to disease. This had me thinking about my own life and what may be contributing to my unhealthy gut. I grew up on the

Western diet, and as I mentioned, I have always suffered from gut issues. Could this be why? Thankfully, not all hope is lost. Part II and III cover diet, prebiotic, and probiotic foods. Dr. Perlmutter gives explanations on what makes a food prebiotic or probiotic and lists examples of how to introduce these into your diet for improved gut health. Personally, I found this quite helpful and thus began slowly introducing these types of food into my diet. Overall, I think this book is an interesting read and can be a steppingstone for people to do their own research in this area. Brain Maker is written not as a scholarly publication but as a very powerful introductory source. It is also written with such enthusiasm that it was hard to put down. After reading this book, I began further educating myself on gut health and the microbiome to make changes to my diet for the better. I open the invitation to you. Perhaps you will find something useful by reading this book, or like me, you may find some answers about your own health.

What do your belly’s bugs have to do with the brain and related diseases? More than you ever imagined.

“

Have you ever heard of the notion that our gut microbiome is considered its own organ? While this may still be debated, it is undeniable that a healthy gut microbiome is important for our health like any other organ. Personally, I never paid too much attention to this topic, and never learned much about it in school. However, I have always suffered from gut issues and recently they became particularly severe. So, I figured why not read this book?

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 37

RAW TALK PODCAST

Raw Talk Podcast Celebrates 100th Episode with Insulin 100 By Anisa Nazir

he Institute of Medical Science’s (IMS) Raw Talk Podcast marked its 100th episode milestone by celebrating another anniversary—one hundred years since the discovery of insulin by Banting and Best at the University of Toronto (U of T).1, 2 Over the past century, this lifesaving Nobel prize-winning discovery established U of T as a world leader in diabetes research and led to significant advancements in healthcare research. The episode “100 Years Later: Insulin and Beyond” explores the current landscape of diabetes research, treatment accessibility and the global impact of the discovery of insulin.3 It addresses challenges faced by patients and the ongoing need for community education. “One of the points we’re trying to emphasize is that insulin is still unaffordable for many patients around the world, considering how the patent was originally sold for $1,” says Jesse Knight, Raw Talk Co-Executive Producer since Season 5. IMS alumni Richie Jeremian and Jabir Mohamed created the graduate studentrun podcast in 2016 to capture and learn from the diverse stories and insights of the IMS community. Since its founding, the podcast has expanded its mission to promote the research culture within the Temerty Faculty of Medicine and broader life sciences community; and engage the public in medical science innovations and translational research. “We changed the format to a narrative, and instead of having one or two perspectives, we incorporated multiple. We highlight diverse voices and include not only named researchers, but also students, early-career scientists and patients,” says Grace Jacobs, former 38 | IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME

Co-Executive Producer and current Show Host and Advisor. Noor Al Kaabi, Co-Executive Producer, added, “It is putting the science we create into context and how it affects people, communities, society. We’re making a conscious effort to incorporate equityrelated topics and ensure representation.” The Black Lives Matter movement changed the narrative on equity, diversity, and inclusion. There is a shift in how organizations, institutions and groups incorporate these changes in their mandates. “It was a pivotal moment for Raw Talk Podcast and a moment of reflection to see where we lacked in ensuring representation. It led to a change in dynamics within the team and taking concrete actions,” says Knight. The team has created new processes to ensure equity, diversity and inclusion in selecting topics and speakers, mandated anti-racism training for its members and introduced an ombudsperson to help with sensitive topics. Raw Talk has come a long way since its first episode. Now in its 6th Season, the show has over 70,000 downloads globally and includes 40+ team members from across Temerty Medicine and beyond. Some exciting upcoming episode topics include burnout in healthcare providers, health in prisons, and underrepresented voices in STEM. References 1. Raw Talk Podcast [Internet]. Available from: https://www.rawtalkpodcast.com/index 2. Insulin 100 - Celebrating a Century of Health Innovation at the University of Toronto [Internet]. The University of Toronto. Available from: https://insulin100.utoronto.ca/ 3. #100 Years Later: Insulin and Beyond [Internet]. Raw Talk Podcast. Available from: https://www.rawtalkpodcast.com/episode/100

Jesse Knight and Noor Al-Kaabi are Season 6 co-Executive Producers and Grace Jacobs is a former co-Executive Producer and a current Show Host and Advisor.

Graphic design by Sherry An

RAW TALK PODCAST

Behind every discovery, there’s a story. New episodes available every other Wednesday.

Raw Talk is a graduate student-run podcast at the University of

Toronto about medical science, and the people who make it happen. We focus on the journeys, perspectives, and expertise of health researchers, professionals, students, patients, and community members at the University of Toronto and beyond.

Listen wherever you get your podcasts or at

www.rawtalkpodcast.com

Get started with some of our favourite episodes: Ep. 100

Ep. 97

Ep. 90

Ep. 89

Ep. 80

Ep. 75

100 Years Later: Insulin and Beyond

Vaccines: Making History

Anti-Black Racism in Healthcare

Let’s Talk Grad School

COVID Decoded: Science and Society in the New Normal

The Healing Power of Music

IMS MAGAZINE FALL 2021 GI & GUT MICROBIOME | 39

READ IT ONLINE issuu.com/imsmagazine imsmagazine.com @IMSMagazine

IMS Magazine Fall 2021

Articles inside

Raw Talk 100th Episode

Book Review

Past IMS Event

Diversity in Science

Student Spotlight

Faculty Spotlight

BMC Showcase

Letter from the Editors

Faculty Highlights

Viewpoints

Director’s Message

Contributors

Features