By Kim E. Barrett, Division of Gastroenterology, Department of Medicine, University of California, San Diego, USA, @Jphysiol_eic.
This article originally appeared in our magazine, Physiology News.
The numerous microbes living inside of us help break down nutrients and “educate” our immune system to fight infection, but how do they help us respond to stress?
The microbiota as a mediator of responses to stress
Gut microbes change when people have intestinal diseases, such as inflammatory bowel diseases and irritable bowel syndrome. Indeed, some of the characteristics of these diseases can be transferred to animals in the lab that lack microbes, using microbes from diseased mice or humans. It is also becoming increasingly clear that gut microbes and their products may have effects well beyond the confines of the intestine itself.
Perhaps the most intriguing aspects of this area of research is that which ties the composition of the gut microbiome to brain function and the brain’s response to stress. Further, the adverse effects of stressful situations on gut function depend on the presence of intestinal microbes. To date, research supports bi-directional communication between the gut and brain (pictured below) that influences the normal function of both bowel and brain alike. This may explain, for example, why some digestive and psychiatric disorders go hand-in-hand (Gareau, 2016).
Evidence in human patients largely shows correlation not causation so far. Still, it is intriguing to observe that derangements in the microbiome have been associated with many conditions, including depression, autism, schizophrenia and perhaps even Parkinson’s disease (Dinan & Cryan, 2017).
Therapeutic manipulation of the microbiota – from probiotics to transplants
So if both intestinal and neuropsychiatric conditions are potentially caused by changes in the gut microbes (at least in part), and if such alterations also mediate the impact of stress on the relevant organ systems, can we mitigate these outcomes by targeting the microbiota?
Several approaches have been posited to have either positive or negative effects on the make-up of the gut microbiota and its intestinal and extra-intestinal influences. Perhaps the most obvious of these is the diet. While the gut microbiota was at one time felt to be relatively immutable in adulthood, improved techniques indicate that its make-up, in fact, is profoundly influenced by the composition of the diet and even by the timing of meals. For example, Western diets, high in meat and fat, decrease the diversity of the microbiota (and may even promote the emergence of pathogenic properties in commensals), whereas diets rich in plant-based fibre increase it.
Another approach to targeting the microbiota is the use of antibiotics, although for the reasons discussed in Part 1, these are likely to be mainly deleterious, particularly early in life. The composition of the microbiota can also be altered directly by the administration of probiotics, which are commensal microorganisms (the host benefits, while the microbes are unaffected) selected for their apparent health benefits that can be taken orally. Studies in animal models demonstrate that probiotics can improve both gut and cognitive function in animals exposed to a variety of stressors, or can negate the cognitive dysfunction accompanying intestinal inflammation or infection. However, not all probiotics are created equal, and much work remains to be done both to validate animal studies in human clinical trials, and to define characteristics of probiotic strains that predict efficacy in a given clinical setting.
Perhaps the approach to targeting the microbiota that has attracted the most recent public attention is the practice known as faecal microbial transplant (FMT), where faecal material is transferred from a healthy donor (often a relative) to someone suffering from a specific intestinal or extraintestinal disease. Enthusiasm for FMT derived initially from its dramatic efficacy in some patients suffering from disabling and persistent diarrheal disease as well as other symptoms associated with treatment-resistant infections by C. diff (a harmful bacteria). More recently, there have been encouraging data suggesting that FMT may be effective in producing remission in inflammatory bowel disease, although the long-term consequences are unknown, and larger, well-controlled studies are needed. Exploratory reports even suggest beneficial effects of FMT on gastrointestinal and behavioural symptoms of autism, or in obesity and metabolic syndrome (a cluster of conditions that occur together and increase your risk of heart disease, stroke and other conditions), but much further work is needed to validate these preliminary data. Ideally, FMT procedures should be conducted under carefully-controlled and physician-supervised conditions to screen for the potential presence of pathogens or toxins. Nevertheless, despite the obvious “yuck” factor, “do-it-yourself” instructions can readily be found online (there are even Facebook groups), and some individuals are sufficiently distressed by their condition to give it a try.
Mitigating negative effects of stress
In conclusion, it is clear that our response to stress, whether manifested in our thought patterns or in our gut, is dramatically shaped by the microbiota that resides in the intestines. Particularly in humans, studies conducted to date have largely been confined to cataloguing the key players in a given setting, but animal data are provocative, and studies focusing on microbes’ roles and functions in humans will doubtless follow. No matter what, in the coming years, the explosive growth of studies aiming to target the microbiota for health benefits should give us a much better understanding of which approach, if any, is likely to be most beneficial for a given condition and even a given individual, since host factors clearly can also impact our microbial composition. This work holds the promise of ameliorating negative effects of stress, and perhaps may offer new avenues for the therapy or even prevention of the myriad of stress-related disease states that are increasing in incidence in developed countries.
Dinan TG & Cryan JF. (2017). Gut instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration. The Journal of physiology 595, 489-503.
Gareau MG. (2016). Cognitive function and the microbiome. International Review of Neurobiology 131, 227-246.