PAEDIATRIC
PROBIOTICS AND PAEDIATRIC GUT HEALTH
Farihah Choudhury Health and Wellbeing Co-ordinator, University of Southampton Farihah is a Prospective Master’s student of Nutrition for Global Health. She is interested in public health nutrition, particularly in changing population health patterns as a result of dynamic food environments, food security and food waste, food poverty, food marketing and literacy.
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Gut health is a big contemporary talking point. We know that gut microflora is largely influenced by our diets and that a human’s entire life diet can be determined by analysing gut microbiota. The average person is becoming more aware of the fact that we host helpful bacteria, which populates our digestive systems and can influence our physical and mental wellness. A human adult carries around 0.2kg of bacteria1 with the gastrointestinal system carrying a cocktail of bacteria, including Lactobacillus, Streptococcus, Bacteroides and Candida. The ultrahealth conscious amongst us now brew their own kefir and eat a myriad of bacteria-promoting foods, and faecal transplants have been popularised in the media. The impact of the overall microbiome on health is thought to be so vast that, similarly to the Human Genome Project, the Human Microbiome Project2 has been pioneered in order to understand the microbiome’s role in conjunction with the rest of the human body, and the gut microbiota is merely one component of this complex system. In the last five years or so, increasing evidence is suggesting that not only can probiotics help maintain a healthy gut and immune function in children, but can also contribute to reducing the risk and prevalence of disease. FUNCTIONAL FOODS – PROBIOTICS AND PREBIOTICS
Some foods confer additional health benefits beyond the basic nutrition provided by the food itself. Some foods may contain live cultures of beneficial bacteria (probiotics), such as Lactobacilli and Bifidobacteria. The WHO define a probiotic as a ‘live organism, which provides a benefit to the host when provided in adequate quantities’.3 32
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Other foods are indigestible to humans, but are selectively digestible by mutualistic microflora in the large intestine, the by-products of which in turn promote a healthy gut – these are prebiotics. Prebiotics are most commonly non-digestible oligosaccharides, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS). Both probiotic and prebiotic-containing foods, then, are examples of functional foods. Mutualistic gut microflora not only produce useful compounds, but have a protective effect against nefarious bacteria, such as sulphate-reducing bacteria and Pseudomonas aeruginosa. AEROBIC VS ANAEROBIC DIGESTION
Unlike in aerobic human systems, where carbohydrates are converted into energy, carbon dioxide and water, the anaerobic processes within gut bacteria convert carbohydrates into energy, organic acids and hydrogen. Varying short-chain fatty acid (SCFA) patterns are produced by different gut bacteria: bacteriodetes produce mainly acetate and propionate, whilst firmicutes produce butyrate, which is the SCFA with the biggest role in human health. Propionate has a role in metabolism and satiety and acetate is the most abundant. SCFAs can be detected in biological samples. It has been proposed that SCFAs may have wider metabolic effects, specifically in regards to appetite and obesity. This suggestion comes in
PAEDIATRIC
Now evidence is emerging that suggests probiotics can tangibly aid in the direct treatment or prevention of some diseases in infants and children.
response to the observation that a high-fibre diet provides protection against obesity. Moreover, a recent study supplementing overweight adults with an inulin-propionate ester for six months showed weight gain prevention.4 In the absence of carbohydrates, bacteria can still ferment alternative molecules, ie, protein and fats. Products of protein fermentation include ammonia, tryptophan metabolites and phenolic compounds, which are potential carcinogens; protein fermentation has been implicated in colorectal cancer and ulcerative colitis.5,6 Another positive role of gut microbiota is in the synthesis of a handful of water-soluble (B group vitamins, vitamin C) and fat-soluble vitamins (vitamin K); the vitamins produced depend on the specific bacteria genera. In turn, some of these vitamin products may be available for human nutrition if colonic absorption is possible, as the colon does have specific carriers for vitamin absorption. Bile salts aid in the absorption of fat-soluble vitamins, as well as the absorption of fat and cholesterol, by acting as a detergent. There are over 30 bile salts and the diversity of these is driven by gut microflora. Non-pathogenic commensal gut bacteria interact with the host-associated immune system through either direct interaction and/ or chemical mediators, thereby improving host immune function. Constant and impactful
antigenic stimulation from invasive pathogens gives the host immune system strong protective immunity.7,8 DIET AND GUT MICROBIOTA
The numbers and types of bacteria are determined by diet. A typically ‘Western’ diet, comprised of animal protein and high saturated fat, lends itself to a gut microbiota populated substantially by Bacteriodes species, whereas the gut microbiota of an individual following a vegan or vegetarian diet is more likely populated by Provotella species.9 Probiotics are marketed as beneficial to children’s immune systems and, so, are administered in average diets in the form of yoghurts and yoghurt drinks, in a bid to diversify the gut microflora and take advantage of the protective effects probiotics can impart. Now evidence is emerging that suggests probiotics can tangibly aid in the direct treatment or prevention of some diseases in infants and children.10 PROBIOTICS AND INFECTION IN HUMANS
Administration of probiotics in children has been shown to hasten recovery from rotavirus and non-bloody diarrhoea and decrease the incidence and severity of diarrhoea in day care centres, as well as decrease the duration of antibiotic-induced diarrhoea. www.NHDmag.com May 2019 - Issue 144
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PAEDIATRIC In as early as 1994, in a randomised trial with five to 24-month-old hospitalised infants with a variety of conditions, infants were assigned a formula containing Bifidobacterium bifidis and Streptococcus thermophiles. Over 80 days, 31% of the infants with the control formula had diarrhoeal disease episodes, compared with 6.9% of infants with probiotic-containing formula.11 In an even earlier study conducted in 1991, four to 41-month-old infants hospitalised with acute diarrhoea had a reduced diarrhoea and rotavirus diarrhoea duration when administered Lactobacillus casei.12 A Cochrane meta-analysis of 25 studies looking at probiotics and antibioticassociated diarrhoea uncovered a pattern of an overall 0.43 reduction in risk ratio.13 Furthermore, probiotics have been seen to have a positive effect in preventing acute upper respiratory tract infections (URTI): the results of a systematic review show that probiotics were more effective than placebos in reducing the number of participants experiencing at least one episode of acute URTI, three or more episodes of acute URTI, as well as reducing antibiotic use.14 In a small number of intestinal diseases, such as Crohn’s disease, probiotics have not been seen to have any tangible health benefits, though more research is needed to confirm whether probiotics are completely ineffective, or might still have some effect on Crohn’s prognosis.15 PROBIOTICS AND NEONATES
The colonisation of gut microbiota proceeds directly after birth. Neonates have an immature immune system, though immunoglobulins can cross from the mother to the foetus via the placenta. Breast milk factors, such as immunoglobulins, carbohydrates, cytokines and leukocytes, can provide passive immunity and promote appropriate maturation of the newborn’s gastrointestinal system. The numbers and types of bacteria are influenced by disease – one study on Estonian and Swedish children over the first year of life, showed that those who were allergic to one or more agents had lower levels of Bifidobacteria. Similarly, pregnant women with family histories of atopy were randomly assigned placebos or L. casei in capsules two to four weeks prior to delivery; this treatment was continued postnatally. At two years and in a 34
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follow-up at four years of age, the infants in the treatment group had a lower incidence of atopic eczema than those in the control group.16,17 PAEDIATRIC DISEASE
Antibiotic use during pregnancy and early pregnancy often correlates with increased body size and risk of being overweight in childhood and beyond. The same risk is in place for babies born prematurely or by Caesarean section. Obesity has been linked to changes in gut microbiota at the phylum level. Unsurprisingly then, longer duration of breastfeeding is protective of obesity.18 Repeatedly, decreased gut microbial diversity in infants is seen to contribute to chronic IBD, diarrhoea and necrotising enterocolitis, all diseases linked to dysbiosis of commensal gut microflora and the gastrointestinal tract.19,20 GUT-IMMUNE-BRAIN AXIS
There is increasing evidence to suggest strong links between the gut microbiota and the brain. Some studies have demonstrated a link between individuals suffering from stress, anxiety and depression and their gut microbiota.21,22 SUMMARY
There is unequivocal evidence that probiotics are effective in managing and preventing illnesses of and relating to mechanisms of the gut, such as diarrhoea, obesity, acute respiratory infection, chronic IBD and enterocolitis. Weaker evidence suggests some link between probiotic use and Crohn’s disease and atopic disease, amongst others. Additionally, there is now plentiful evidence to suggest that diversity of the diet contributes to a thriving gut microflora, which in turn provides immune defence and protective action against pathogenic bacteria. Neonates are greatly affected by their mother’s gut microflora and birth complications, such as preterm birth and C-sections, have been associated with altered neonate microbiota, which, in turn, increases the risk of a host of gut-mediated diseases. There is certainly scope for more research in this area – the Human Microbiome Project2 will be instrumental in demonstrating the diversity of gut microbiota and how this complex microflora varies in humans.