“The Microbiota–Gut–Brain axis in gastrointestinal disorders: Stressed bugs, stressed brain or both?” Giada De Palma, Stephen M. Collins, Premysl Bercik and Elena F. Verdu. Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada
This article reviews the current literature connecting the central nervous system and the gastrointestinal (GI) tract including the microbiota of the gut. There is bidirectional communication between these systems through neural pathways, including the vagus nerve, in addition to humoral and cellular mediators such as the immune system and the hypothalamic–pituitary–adrenal (HPA) axis. There is sufficient evidence that all major disorders of the gut such as inflammatory bowel disease, irritable bowel syndrome, and coeliac disease are associated with dysbiosis (alterations in the composition of the normal gut microbiota). Research has yet to find a common pattern of dysbiosis which may be due to differences in sampling at different sections of the gut (small intestine, colon, fecal) that may host different microbiota colonies. There is a bidirectional relationship between the microbiota and brain. Dysbiosis influences peripheral and central nervous system function affecting brain function and behavior. In turn, stress and depression can influence gut microbiota.
The article describes how our gut is inhabited mostly by bacteria but also archaea, viruses, and protozoa. The total number of cells outnumbers human cells by a factor of 10. At birth the human intestinal tract is sterile and becomes colonized after birth. In early life the microbiota make-up has increased flexibility to change but as we age, it becomes more stable. It has been proposed that there may be different patterns of colonization (bacteroides, prevotella, or ruminococcus) among humans.
The authors depict that the function of the microbiome is symbiotic with the human host and is important in proper development, carbohydrate processing, digestion of dietary fiber, bile acid metabolism, providing a barrier against pathogenic bacteria, and modulating the immune system. Meanwhile, the human host provides a nutrient rich environment at a constant temperature.
The article demonstrates how causes of dysbiosis may be related to disease, long term dietary habits, antibiotics, and medications. Shifts in microbiota content may be short term or long term. Psychological stress in early life may cause long term changes in the microbiome population thus creating susceptibility to future disease processes. There is a correlation between expression of anxiety behavior and microbiota.
As stated previously, the microbiota-gut-brain axis comprises bidirectional communication through multiple pathways. Stress at the level of the CNS can influence gut function and microbiota composition. Likewise, dysbiosis can cause increased cathecolamine and GABA production, increased pain perception, and altered behavior. A trigger on either side of the axis can perpetuate dysfunction in the other.
The article discusses correlations between antiobiotic use, altered microbiota, and impaired brain function including depression and autism. Bacteroides fragilis, a Gram-negative anaerobic bacterium that inhabits the lower GI tract, has been shown to improve anxiety, sensorimotor, communicative, and repetitive behavior. Gut inflammation can induce anxiety-like behavior and alter CNS biochemistry.
The authors describe stress as a risk factor for the development of GI dysfunction and may present itself in the form of psychological or physical. It has been shown that stress can affect the composition of the microbiota likely favoring pathogenic composition. Social stress has been shown to increase the production of cytokines and risk of inflammatory diseases by gene expression of pro-inflammatory processes. Stress influences intestinal secretion of IgA also facilitating inflammatory processes and further dysbiosis. Psychological and physical stress activate the HPA axis and thus the release of corticotrophin-releasing hormone and subsequently adrenocorticotrophic hormone which stimulates glucocorticoid synthesis in the adrenal cortex. The catecholamines noradrenaline and adrenaline are also released. These chemicals can influence the function and make-up of the microbiota. Increased activity of the HPA axis affects autonomic control of gut motility as well as the microbiota.
The review describes how early exposure to stress such as maternal separation can result in long-lasting hyperactivity of the HPA axis, anxiety like behavior, and altered cholinergic activity in the gut with increased intestinal permeability. Probiotics have shown to improve some of these effects. Pro-biotic bacteria have been shown to modulate anxiety behavior and neurotransmitter metabolism via the vagus nerve.
This article clearly defines a bi-directional relationship between the gut’s microbiota composition and nervous system function. Stress is a major player in creating dysfunction of this descending pathway in addition to dysbiosis creating stress in an ascending format towards the nervous system. A stressed nervous system will include activation of the HPA axis. Furthermore, the HPA axis is intimately connected to the sympathetic nervous system via the hypothalamus to the locus ceruleus in the brainstem. Likewise, stress in of itself will mobilize the sympathetic nervous system which in turn affects nearly every tissue in the body including the somatic muscle system. We may see this clinically as unilateral or bilateral postural extension patterns in the body (L AIC, R/B BC, PEC, R/B TMCC).
By neutralizing the overly dominant postural extension patterns in the body we are inherently talking back to the autonomic nervous system and attempting to inhibit sympathetic activity and facilitate parasympathetic activity. This in turn can also influence the state of the gut. Likewise, by maintaining a properly balanced microbiota the nervous system will maintain a calmer, parasympathetically dominant system. The bidirectional relationship between the gut and nervous system must be respected.
As a general concept, stress (whether it be physical or psychological) is the common denominator in generating a sympathetic response. This article identifies our microbiota as a player that can create stress in our bodies. Therefore, it would seem reasonable to consider our patient’s microbiota in our impressions of the overall state of their system’s allostasis. We may be able to influence the health of one’s microbiota with dietary education. Examples include introduction of fermented foods, probiotics, and elimination of processed foods and excess sugar. Clinically, I find that including this integrative piece within the intervention plan, yields better results and at times is a missing link to success in achieving a reciprocal alternating nature of function in the body.