Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review

Abstract

Irritable bowel syndrome (IBS) is a chronic functional disorder which alters gastrointestinal (GI) functions, thus leading to compromised health status. Pathophysiology of IBS is not fully understood, whereas abnormal gut brain axis (GBA) has been identified as a major etiological factor. Recent studies are suggestive for visceral hyper-sensitivity, altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients. Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors, such as microbiota population and diversity, microbial metabolites, dietary uptake, and psychological abnormalities. Strategic efforts focused to study these interactions including probiotics, antibiotics and fecal transplantations in normal and germ-free animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology. Additionally, neurotransmitters act as communication tools between enteric microbiota and brain functions, where serotonin (5-hydroxytryptamine) plays a key role in pathophysiology of IBS. It regulates GI motility, pain sense and inflammatory responses particular to mucosal and brain activity. In the absence of a better understanding of various interconnected crosstalks in GBA, more scientific efforts are required in the search of novel and targeted therapies for the management of IBS. In this review, we have summarized the gut microbial composition, interconnected signalling pathways and their regulators, available therapeutics, and the gaps needed to fill for a better management of IBS.

Keywords: Irritable bowel syndrome; Microbiota; Gut brain axis; Stress; Serotonin

Core Tip: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder with a dysregulated gut brain communication. Gut microbiota functional characterization is still underappreciated but their roles have been found to be pivotal. Various microbial species and their metabolites with altered composition and diversity have been found to be specific to IBS. Clinical manipulation of these microbial species improved the symptom profile in IBS patients while the associated mechanisms have been identified for a bidirectional communication between gut microbiota and brain. This in turn seems promising for future treatments specific to microbiota manipulation and targeting various cross-talks for the management of IBS and associated symptoms.