Effects of gut microbiota on the brain: implications for psychiatry.

It may be surprising to learn that the human gastrointestinal tract is home to 1014 bacterial organisms. In fact, there are more bacteria in the gut than there are somatic cells in the body. These resident bacteria are referred to as commensal microbiota, and their arrival during the first few postnatal days sets up a symbiotic association that is necessary and crucial to normal physiology. This lifelong association is essential to host pathogen defence and plays an important role in nutrient uptake and metabolism. Immunologists have been aware of this system and its importance to the development of the muscosal and systemic immune systems for a long time. What is new and noteworthy is emerging evidence that gut microbiota influence behaviour and central nervous system (CNS) function. This commentary provides a brief overview of research related to gut–brain communication in a context that allows neuroscientists and psychiatrists to take note and consider the role of microbiota in their research related to CNS function and behaviour. Colonization of the gastrointestinal tract, predominantly the colon, begins at birth, continues in early development and remains throughout life. The early profile of microbiota is influenced by genetics and postnatal environmental exposure. Several bacterial phylotypes are distributed in the human gastrointestinal tract and, although each person’s microbial profile is distinct, relative abundance and distribution along the gastrointestinal tract of these bacterial phylotypes is similar among healthy individuals. Commensal flora serve several physiologic functions. Gut microbiota facilitate nutrient uptake and metabolism, providing us with otherwise inaccessible nutrients and vitamins. Colonization and the presence of microbiota is important to the development, function and maintenance of a healthy gastrointestinal tract. Interestingly, gut microbiota are also essential and necessary for the proper development of the mucosal and systemic immune systems, an association we believe to be central when considering the impact that microbiota may have on the development and function of the brain. Gastrointestinal research has for many years highlighted the importance of the “gut–brain axis,” especially in relation to functional bowel disorders like irritable bowel syndrome, but much of this work has been focused on “top-down” control, or the examination of the impact that the brain can have on general gut function. New work involving intestinal microbiota, the resident bacteria present in the healthy gastrointestinal tract, is indicating that events occurring in the gut also have an impact on the development and function of the CNS. Using the top-down approach, recent work has demonstrated that early life stress in a rodent, known to lead to altered stress reactivity later in life, in parallel leads to an altered profile of gut microbiota. Gut microbiota are also known to influence energy balance and in turn, emerging evidence demonstrates the importance of gut microbiota to the pathophysiology of obesity. Energy balance and food intake are centrally mediated processes; however, the direct link between gut microbiota and central feeding circuits has not yet been made. This is an example of the less-studied “bottomup” control, which we believe will have an important impact on both the study and treatment of diseases that have been traditionally considered to be housed solely within the CNS. Almost 50 years ago, Gustafsson developed germ-free animals as a scientific tool. These mice have no commensal intestinal microflora and, as such, exhibit an undeveloped immune system. Germ-free mice have proven to be a useful tool for investigations into differences between adaptive and innate immunity. We propose that a vital pathway of communication from the gut to the brain is through the immune system and therefore suggest that experimentation in germ-free mice related to stress reactivity and related behaviours will provide answers to how intestinal microbiota influence CNS function. A recent report found that compared with specificpathogen-free mice, adult germ-free mice show an exaggerated stress response. Germ-free mice showed no difference in basal stress hormones but showed increased plasma