Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome

Abstract

Background:The gastrointestinal microbiota has emerged as a key regulator of gutbrain axis signalling with important implications for neurogastroenterology. There is continuous bidirectional communication between the gut and the brain facilitated by neuronal, endocrine, metabolic, and immune pathways. The microbiota influences these signalling pathways via several mechanisms. Studies have shown compositional and functional alterations in the gut microbiota in stress-related psychiatric disorders. Gut microbiota reconfigurations are also a feature of irritable bowel syndrome (IBS), a gut-brain axis disorder sharing high levels of psychiatric comorbidity including both anxiety and depression. It remains unclear how the gut microbiota alterations in IBS align with both core symptoms and these psychiatric comorbidities. Methods:In this review, we highlight common and disparate features of these microbial signatures as well as the associated gut-brain axis signalling pathways. Studies suggest that patients with either IBS, depression or anxiety, alone or comorbid, present with alterations in gut microbiota composition and harbor immune, endocrine, and serotonergic system alterations relevant to the common pathophysiology of these comorbid conditions. Keyresults:Research has illustrated the utility of fecal microbiota transplantation in animal models, expanding the evidence base for a potential causal role of disorderspecific gut microbiota compositions in symptom set expression. Moreover, an exciting study by Constante and colleagues in this issue highlights the possibility of counteracting this microbiota-associated aberrant behavioral phenotype with a probiotic yeast, Saccharomyces boulardii CNCM I-745. Conclusions and inferences: Such data highlights the potential for therapeutic targeting of the gut microbiota as a valuable strategy for the management of comorbid psychiatric symptoms in IBS.

Studies on irritable bowel syndrome associated with anxiety or depression in the last 20 years: A bibliometric analysis

“…With further research on IBS and the development of the theory of microbiota–gut–brain axis, the intestinal microbiota has been suggested as the pathophysiological basis of functional gastrointestinal disorders and psychiatric disorders, and FMT has been considered as an acceptable treatment option for IBS associated with anxiety or depression ( 31 , 32 ). Studies had found that alterations in gut microbiota composition existed in patients with either IBS, depression, or anxiety, alone or comorbid ( 33 ), and FMT could not only improve gastrointestinal symptoms but also show meaningful benefits in relieving anxiety and depression. Most scholars believed that the multiple effects of FMT on IBS patients with anxiety or depression should be attributed to the changes in the diversity and composition of the gut microbiota ( 34 – 36 ).…”

Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer’s Disease

“…The human gut microbiota comprise an enormous number of microorganisms, nearly 100 times larger than our own cells, and play crucial roles in human development, physiology, immunity, and nutrition, sometimes called the "second brain" (Dinan and Cryan, 2017;Sochocka et al, 2019). Continuous dynamic cross-talk between the gut and the brain is facilitated by neuronal, endocrine, metabolic, and immune pathways (Morais et al, 2021;Wilmes et al, 2021), which have been considered as the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders such as AD. Gut microbiota and the brain communicate with each other via various routes which include: (i) regulating immune activity and the production of proinflammatory cytokines (e.g., IL-1β, IL-6, and IL-17A) or antiinflammatory cytokines (e.g., IL-4 and IL-10) that can either stimulate the hypothalamic-pituitary-adrenal axis to produce corticotropin-releasing hormone, adrenocorticotropin hormone and cortisol, or directly impact on central nervous system (CNS) immune activity; (ii) production of short-chain fatty acids (SCFAs), branched chain amino acids, and peptidoglycans; (iii) the production of neurotransmitters (e.g., acetylcholine, GABA, dopamine, and serotonin) that may enter circulation and cross the blood-brain barrier; (iv) modulating tryptophan metabolism and downstream metabolites, serotonin, kynurenic acid and quinolinic acid; (v) affecting vagus nerve and the enteric nervous system; (vi) impacting enterochromaffin cells by SCFAs and indole (Kennedy et al, 2017;Cryan et al, 2019;Morais et al, 2021).…”

Characterization of the gut microbiota among Veterans with unique military-related exposures and high prevalence of chronic health conditions: A United States-Veteran Microbiome Project (US-VMP) study

“…Increased permeability of the GI lumen, commonly referred to as “leaky gut”, which also has been shown to lead to exaggerated inflammation ( Camilleri, 2019 ), has been identified in those suffering from affective, GI (e.g., inflammatory bowel disorders [IBD]), and cardiovascular disorders ( Ait-Belgnaoui et al., 2012 ; Bischoff et al., 2014 ; Novakovic et al., 2020 ). Similarly, it is common for those GI and cardiovascular disorders to have comorbid affective disorders ( Wilmes et al., 2021 ; Cohen et al., 2015 ). Given the high rates of inflammatory disorders among Veterans ( Tanielian et al., 2008 ; Breland et al., 2017 ), this is an important population within which to study the microbiota-gut-brain axis and physical and mental health.…”