XII) Organ-Gut Axis: Innovation to Practice

Symposium (XII)

ORGAN-GUT AXIS: INNOVATION TO PRACTICE

MICROBIOTA AND CARDIOVASCULAR DISEASES

Wei-Kai Wu Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

The gut microbiota plays an essential role in the development of cardiovascular disease through both immune-mediated and metabolite-mediated pathways. Shared pathogenic features have been observed between cardiovascular disease and dysbiosis, including chronic inflammation, insulin resistance and an imbalanced energy expenditure. Studies have also demonstrated a significant association between gut microbiota and cardiovascular disease and some microbiotadependent molecules are identified as signals that protect or induce cardiovascular phenotypes. Butyrate-producing bacteria such as Akkermansia muciniphila, Faecalibacterium prausnitzii, and Roseburia intestinalis were found to be depleted in patients with cardiovascular disease and have exhibited protective effects for atherosclerosis in animal studies. At molecular level, structure components of bacteria such as lipopolysaccharide and gut microbiota-derived metabolites, including trimethylamine N-oxide, indoxyl sulphate, and phenylacetylglutamine, have shown causative effects on atherosclerotic plaque formation and enhanced thrombosis potential. Thus, the gut microbiota is becoming a potential target for the development of an intervention in preventing or treating cardiovascular disease. Further studies are required to elucidate key pathophysiological pathways from host-microbe interactions which can be manipulable to improve outcomes in patients with cardiovascular disease.

Symposium (XII)

ORGAN-GUT AXIS: INNOVATION TO PRACTICE

GUT MICROBIOTA IN PEDIATRIC HEALTH AND DISEASES

Yen-Hsuan Ni Department of Pediatrics, College of Medicine and Children’s Hospital, National Taiwan University, Taipei, Taiwan

Gut microbiota signatures acquired in infancy may predict the future development of diseases. Currently, this may apply to metabolic diseases, obesity, allergic diseases, and neuropsychologic disorders. They modulate the development of immune, metabolic, neurologic and psychiatric systems, and trigger diseases onset through the metabolites generated by the microbiota. The diseases involved, such as metabolic diseases (diabetes, obesity), cancer (colon cancer and other gastrointestional malignancies), liver diseases (fatty liver, cirrhosis), immunologic diseases (atopic diseases), brain-gut disorders (irritable bowel syndrome, autism), may be attributed to the dysbiosis formed in the early life. There are many factors influencing the constitutions of the gut microbiota, including maternal nutrition, delivery routes, diet, geography, genetic factors, age, and drugs, and antibiotics. Generally speaking, the diversity of the gut microbiota composition are the measures to implicate “dysbiosis” or not. The origin of the bacteria colonizing the neonatal gastrointestinal tract is supposed to be affected by mode of delivery, breastmilk feeding and maternal conditions. Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were the major bacterial phyla patterns in infancy. The infants’ gut microbiota pattern gradually transit into the adult pattern at about the age of three, when the food intake of the children is similar to that of the adults. A long-term prospective monitoring on the development of diseases and the evolution of gut microbiota will be very helpful to unravel their critical role in the pathogenesis of many diseases and the gut microbiota may become the therapeutic target. We have already proven an early colonization with R. gnavus in the gut promoted allergic disease in infants. The concept may be applied to many immune-related conditions. The current focus of microbiota studies is on the metabolites, which are produced by the host-microbiota interaction to affect many organs and diseases in our bodies.

Symposium (XII)

ORGAN-GUT AXIS: INNOVATION TO PRACTICE

MICROBIOTA AND MALIGNANCIES

Chun-Ying Wu College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan

Importance of the topic:

1. Microbiota interacts closely with host immunity and inflammation, which play important roles in digestive cancers’ carcinogenesis. 2. Microbiota can be used as biomarkers to diagnose digestive cancers and to predict treatment outcomes.

Innovations in recent years:

1. The more detailed mechanisms how microbiota interacts with host immunity and inflammation have been reported recently. 2. Lower microbiota diversity is found in several digestive cancers and specific microbes were

reported to increase or reduce digestive cancer risks. 3. Microbiota plays important roles in cancer immunotherapy and influences treatment outcomes.

Impact on clinical practice:

1. Microbiota may become important biomarkers for digestive cancer diagnosis and outcome prediction. 2. Microbiota may become important treatment measures or adjuvant therapies for digestive cancers.

Symposium (XII)

ORGAN-GUT AXIS: INNOVATION TO PRACTICE

MICROBIOTA AND DIGESTIVE DISEASES

Deng-Chyang Wu Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan School of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Division of Gastroenterology, Department of Internal Medical, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

The human gastrointestinal microbiota consists in a group of microorganisms that live in the digestive tract. The microbiota has established a dynamic association of mutual benefits with the human organism, which results in the maintenance of normal immunological, metabolic, and motor functions, as well as correct nutrient digestion and absorption. Although a person’s microbiome is relatively stable and resilient over time, environmental factors that can alter the composition include diet, probiotics, prebiotics, viruses, and drugs, particularly antibiotics. Increasing evidence has shown that a permanent alteration in the microbiota composition or function can alter visceral sensitivity, intestinal motility, and permeability, as well as alter the immune response, thus promoting a proinflammatory state. Recent studies have also demonstrated the participation of the microbiota in the etiopathogenesis of many gastroenterologi¬cal diseases, such as irritable bowel syndrome, inflammatory bowel disease, celiac disease, non-alcoholic steatohepatitis and digestive neoplasms. As the importance of the gut microbiota in health and disease is increasingly recognized interest in interventions that can modulate the microbiota and its interactions with its host has soared. Apart from diet, prebiotics and probiotics represent the most commonly used substances taken in an effort to sustain a healthy microbiome or restore balance when it is believed bacterial homeostasis has been disturbed in disease. Besides, fecal microbiota transplantation which can directly change the patient’s gut microbiota to normalize the composition has been demonstrated to be a promising therapy in Clostridium difficile infection and other digestive diseases. Furthermore, recent studies have proved that modulation of the gut microbiota could even enhance treatment efficacy and reduce adverse effects of colorectal cancer therapies. In the future, we will look forward to the advanced personalized microbiota-modulating interventions in varied hosts and diseases along with medical and technological development.

Symposium (XII)

ORGAN-GUT AXIS: INNOVATION TO PRACTICE

MICROBIOTA AND DERMATOLOGICAL DISEASES

Yi-Ju Chen Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan

The association between chronic inflammatory skin disease and comorbidities include cardiovascular disease, depression, chronic renal disease, and inflammatory bowel diseases have been explored. Alterations of skin and gut microbiome were proposed to be involved in the pathogenesis of these chronic skin diseases. I will first talk about the clinical relevance of skin and gut microbiota in diseases such as psoriasis, atopic dermatitis and rosacea. We previously have reported an altered fecal microbial composition in psoriasis, and which resembles that of spondyloarthritis, transient ischemic stroke, and metabolic syndrome. Our recent study further demonstrated that early life infection or antibiotic exposure is independently associated with pediatric psoriasis and atopic dermatitis. These findings highlighted the significance of early colonization of gut microbiome in shaping the future immune system of individuals. I will talk about new advances in research and clinical implications on gut microbiome and chronic inflammatory skin diseases.