Brain-gut microbiome interactions and functional bowel disorders

Abstract

Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined role for dysbiosis in the development of IBS symptoms has been established through characterization of altered intestinal microbiota in IBS patients and reported improvement of subjective symptoms after its manipulation with prebiotics, probiotics, or antibiotics. It remains to be determined whether IBS symptoms are caused by alterations in brain signaling from the intestine to the microbiota or primary disruption of the microbiota, and whether they are involved in altered interactions between the brain and intestine during development. We review the potential mechanisms involved in the pathogenesis of IBS in different groups of patients. Studies are needed to better characterize alterations to the intestinal microbiome in large cohorts of well-phenotyped patients, and to correlate intestinal metabolites with specific abnormalities in gut-brain interactions.

Keywords: Dysbiosis; Irritable Bowel Syndrome; Probiotics.

Figure 1. Bidirectional brain gut microbial interactions

A. Key components of brain gut microbial axis. A network of specialized target/transducer cells in the gut wall functions as an interface between the organism and the gut lumen. In response to external and bodily demands, the brain modulates individual cells (ECC – enterochromaffin cells; SMC – smooth muscle cells; ICC – interstitial cells of Cajal) within this network via the branches of the autonomic nervous system (ANS) (sympathetic and parasympathetic/vagal efferents) and the hypothalamic pituitary adrenal (HPA) axis. Such modulation can be transient (e.g. in response to transient perturbations) or longlasting (in response to chronically altered brain output). The microbiota are in constant bidirectional communication with this interface via multiple signaling pathways, and this communication is modulated in response to perturbations of the microbiota, or the brain. The integrated output of the brain gut microbial interface is transmitted to the brain via multiple afferent signaling pathways, including endocrine and neurocrine (vagal, spinal afferents) pathways. While acute alterations in this interoceptive feedback result in transient functional brain changes, chronic alterations are associated with neuroplastic brain changes. B. Functional and symptom-related consequences of brain gut microbial interactions. Several intestinal processes with possible relevance for IBS symptoms can be modulated both the brain (via the ANS, including its enteric nervous system [ENS] branch) and by signals from the microbiota. Microbiota generated molecules can signal to the brain indicrectly via activation of vagal (and possibly spinal) afferent nerve pathways, by microbiota stimulated cytokine and neurotransmitter release from immune or enteroendocrine cells, or such signals may reach the brain via an endocrine route. Microbiota gut brain signaling may contribute to the generation of abdominal pain and discomfort, while microbiota mediated modulation of enteric reflexes is likely to play a role in the pathophysiology of altered bowel habits.