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Gut Microbiota & Gut-Brain Axis GUT MICROBIOTA RESEARCH & PRACTICE edited by ESNM GUT MICROBIOTA & GUT-BRAIN AXIS A selection of content from the Gut Microbiota for Health 2016 January 2017 www.gutmicrobiotaforhealth.com SUMMARY The digestive tract and the brain and brain development, and ques- are intimately linked - this, scientists tions that emerged at a recent have known for many years. What's event discussing developmental newer is the idea that the microbial influences of microbiota and other communities living in the gut have hot topics related to the gut-brain a major role to play in how the gut axis. and the brain communicate. Emer- ging scientific insights about the When it comes to brain-related gut-brain axis are of particular disorders, researchers are working interest in neurogastroenterology, to discover more about the role of the subspecialty of gastroentero- the gut microbiota in pathophysio- Prof. Dr. Paul Enck, Director of logy focusing on connections logy. Below we feature an article Research, Dept. of Psychosomatic between the central nervous providing clues about the influence Medicine and Psychotherapy, system and the enteric nervous of gut bacteria on depressive University Hospital Tübingen, system. As an organization dedi- behaviours; and turning to mecha- Germany. He is board cated to sharing new research in nisms, we provide a review of the member/treasurer of the this particular field, the ESNM is nascent study of gut bacterial European Society of pleased to support the GMFH metabolites as neuromediators. Neurogastroenterology and publishing team in bringing you this Motility and of the German document on gut microbiota and With new therapeutics, insights on Society of Neurogastroenterology the gut-brain axis. the gut-brain axis could really make and Motility, and has served as a difference for patients. Here we reviewer for many international We open with a summary editorial highlight a systematic review on journals and grant agencies. by Premysl Bercik - gastroenterolo- probiotics for improving human gist and Associate Professor in the mental health; an article on how Division of Gastroenterology at probiotics can influence social McMaster University (Canada) - behaviours in mice; and an article who, along with his colleagues, is speculating on how a high-fibre carrying out leading-edge gut-brain diet could positively affect the research that investigates links brain. between the brain, gut microbiota, and immune system. The editorial is Finally, in our editors' wrap-up followed by a selection of recent interview with Premysl Bercik, they articles on the microbiota-gut-brain discuss an important question: "Can axis from the Gut Microbiota for the science of the microbiota-gut- Science writer Kristina Campbell Health website. brain axis be made relevant to (M.Sc.), from British Columbia clinical practice?" We hope you (Canada), specializes in First, Emeran Mayer, author of a enjoy reading on this topic - and be communica-ting about the gut popular book called The Mind-Gut sure to check the GMFH website for microbiota, digestive health, and Connection, offers his perspective more scientific content about the nutrition. Author of the best on microbes in gut-brain communi- microbiota-gut-brain axis in the selling Well-Fed Microbiome cation. Then we feature brief cove- months ahead. Cookbook, her freelance work rage of several studies showing that has appeared in publications gut-brain communication is a two- around the world. Kristina joined Paul Enck way street, a review of a provoca- the Gut Microbiota for Health publishing team in 2014. tive hypothesis on sex hormones Kristina Campbell GUT MICROBIOTA RESEARCH & PRACTICE edited by ESNM 2 TABLE OF CONTENT EDITORIAL 4 SELECTED CONTENT FROM GUTMICROBIOTAFORHEALTH.COM • Pinpointing the role of microbes in human gut-brain communication 8 • Do development and maturation of the gut-brain axis differ between the sexes? 10 • Gut microbiota changes may be responsible for depressive-like behaviours in mice through alterations in host metabolism 12 • Neuromediators in the Gut-Brain Axis 14 • Could probiotics be used to improve human mental health? 15 • The potential of probiotics and diets to reverse asocial behaviours in mice that are seen in autism spectrum disorders 17 • Can a high-fibre diet prevent and/or treat neurological disorders? 19 BOOKS AND RESOURCES 21 INTERNATIONAL SUMMIT & ECOSYSTEM 23 GUT MICROBIOTA RESEARCH & PRACTICE edited by ESNM 3 EDITORIAL In humans, signals travel between the gut and the brain through networks of neurons in the central nervous system (CNS) and parts of the peripheral nervous system - namely, the division of the autonomic nervous system called the enteric nervous system (ENS). With approximately 100 billion neurons in the brain and 100 million in the spinal cord, the job of the CNS is to integrate sensory information and generate the behaviours needed to successfully interact with the environment. The 200-600 million neurons in the ENS - which extend, web-like, along the length of the digestive tract - react to chemical and mechanical stimuli from the gastrointestinal tract and contribute to the pool of information received by the brain. The vagus nerve (i.e. cranial nerve X) is an important channel by which information is transmitted between the digestive tract and the brain. Signals are bidirectional, but the vast majority (90%) travel upward, keeping the brain constantly informed about gut activity. This bidirectional communication between the brain’s emotional and cognitive centers and peripheral intestinal functions is known as the gut-brain axis. Clinical evidence linking the diges- brains: defective and immature tive tract and the brain is well microglia(3), hypermyelinated axons known. Not only are brain and in the prefrontal cortex and an gastrointestinal diseases often upregulation of genes linked to comorbid, but also treatments for myelination(4), and altered forma- infection sometimes induce psy- tion of synapses (higher expression chiatric side effects, as in cases of of synaptic-related proteins in the antibiotic-induced psychosis(1). In striatum)(5). In addition, our lab has recent years, however, knowledge shown that germ-free mice or those about the connection between the with a severely disrupted micro- gut and the brain has been biota have altered expression of the enhanced by increased data on neuromodulator BDNF (brain- how the gut microbiota influence derived neurotrophic factor) in the gut-brain communication. hippocampus and amygdala(6). The microbiota-gut-brain axis Human evidence for the influence of gut microbes on the brain Increasing data from mice and include placebo-controlled inter- humans show how gut microbiota vention studies suggesting that influence the gut-brain axis. Germ- modulation of the gut microbiota free mice have an abnormal may produce observable changes response to stress, differing in mood or behaviour. Several patterns of social interaction and studies(7)(8) have reported that exploratory behaviors, and altera- mixtures of different probiotic tions in cognition(2), in addition to species can positively affect brain observable differences in their function in healthy individuals. One GUT MICROBIOTA RESEARCH & PRACTICE edited by ESNM 4 EDITORIAL study to date(9) has used functional establishment of a robust, diverse magnetic resonance imaging to gut microbiota, nor how this affects observe the impact of a probiotic- long-term brain health.. However, it containing fermented milk on brain seems that avoiding major micro- function of healthy women; after biota perturbations in the first few the intervention, researchers found years of life might be required for changes in the activity of the brain the development of the brain to regions that control emotion and proceed uninterrupted. sensation. Studies like these are the first step; researchers are poised to Mechanisms learn much more about mecha- nisms that account for the apparent Microbiota can influence gut-brain effects of gut microbiota on the communication through neural, brain. immune, and hormonal routes. Different kinds of bacteria appear Early life influences to influence ENS neurons diffe- rently, with some exciting How important are gut microbiota responses(13) and some dampening in early life for shaping the adult them(14). Gut microorganisms can brain? Results from mice show that also influence ENS activity by exposing them to stress in early affecting production of molecules, pregnancy changes their vaginal like gamma-aminobutyric acid microbiome and, at birth, can (GABA)(15), which act as local induce changes in the offspring’s neurotransmitters. Immune signal- gut microbiota. Potentially these ling is another way the gut micro- changes can reprogram the biota seems to alter messages to offspring’s brain and affect later- the brain, since evidence shows the life behaviour(10). Studies using gut microbiota can affect immune mouse maternal separation as a cells located in the gut mucosa model of early-life stress have that modify activity of sensory found some of the well described neurons of the ENS(16). Further- reactions of mice to stress more, the gastrointestinal tract and (anxiety-like behavior and beha- its bacteria contribute to the vioral despair) in adulthood only body’s production of hormones occur if the mice have a gut and neurotransmitters(17), which microbiota(11). And several studies affect different processes through- have now shown that some of the out the body, including those that alterations observed in the brains affect the brain. and behaviours in germ-free mice can be prevented if the mice are In some cases, gut-brain signalling exposed to a complex gut micro- could be initiated by metabolites - biota in early life(12). biologically active small molecules that are the products of gut bacte- In humans it is not certain how rial metabolism. Many of the early-life events contribute to the known metabolites exert their GUT MICROBIOTA RESEARCH & PRACTICE edited by ESNM 5 EDITORIAL effects on multiple tissues and Promising therapeutics Researchers will need to increas- organs in the body, including the ingly look at humanized mice to brain.
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