Microbiome Shifts and Their Impact on Gut Physiology in Irritable Bowel Syndrome

Abstract

Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders characterized by recurrent abdominal pain and altered bowel habits. The exact pathophysiological mechanisms for IBS development are not completely understood. Several factors, including genetic predisposition, environmental and psychological influences, low-grade inflammation, alterations in gastrointestinal motility, and dietary habits, have been implicated in the pathophysiology of the disorder. Additionally, emerging evidence highlights the role of gut microbiota in the pathophysiology of IBS. This review aims to thoroughly investigate how alterations in the gut microbiota impact physiological functions such as the brain-gut axis, immune system activation, mucosal inflammation, gut permeability, and intestinal motility. Our research focuses on the dynamic "microbiome shifts", emphasizing the enrichment or depletion of specific bacterial taxa in IBS and their profound impact on disease progression and pathology. The data indicated that specific bacterial populations are implicated in IBS, including reductions in beneficial species such as Lactobacillus and Bifidobacterium, along with increases in potentially harmful bacteria like Firmicutes and Proteobacteria. Emphasis is placed on the imperative need for further research to delineate the role of specific microbiome alterations and their potential as therapeutic targets, providing new insights into personalized treatments for IBS.

Keywords: IBS; brain–gut axis; gut microbiota; irritable bowel syndrome; microbiome; pathophysiology; visceral hypersensitivity.

Figure 1

Microbiome shifts in irritable bowel syndrome. Created with BioRender.com (accessed on 14 November 2024).

Figure 2

Microbiome–Gut–Brain axis interactions and their role in irritable bowel syndrome pathophysiology. Figure 2 illustrates the complex interplay between microbiome alterations, gut physiology, immune system activation, and neuroendocrine pathways in the context of irritable bowel syndrome (IBS). At the intestinal lumen, food particles are broken down, releasing various metabolites such as short-chain fatty acids (SCFAs), bile acids, and indoles. These metabolites, alongside lipopolysaccharides (LPS) from disrupted gut bacteria, modulate intestinal permeability by affecting tight junctions and enterocyte integrity. The immune system of the intestinal tissue is activated by this microbial translocation, leading to the secretion of proinflammatory cytokines by macrophages, dendritic cells (DCs), and T cells. These cytokines further perpetuate immune activation, mast cell degranulation (releasing histamine and proteases), and enteric glial cell stimulation. The activation of the immune cells and the release of neurotransmitters result in sensitization of enteric neurons, contributing to visceral hypersensitivity, a hallmark of IBS symptoms. Serotonin (5-HT), primarily released by enteroendocrine cells, alongside glucagon-like peptide-1 (GLP-1), influences gut motility and sensory signaling through enteric neurons. Impaired tight junctions allow further interactions between gut metabolites like indoles and the immune system, exacerbating gut–brain axis dysregulation. The hypothalamic–pituitary–adrenal (HPA) axis is shown to be impaired, with stress playing a critical role in increasing cortisol levels, which regulates both immune responses and the central nervous system. This feedback loop involving stress and immune mediators contributes to increased visceral hypersensitivity and IBS symptoms through vagus nerve signaling and neurotransmitter alterations. Created with BioRender.com (accessed on 1 November 2024). Abbreviations: SCFAs, short-chain fatty acids; LPS, lipopolysaccharides; 5-HT, serotonin; DC, dendritic cell; TLR, toll-like receptor; GLP-1, glucagon-like peptide-1; HPA, hypothalamic–pituitary–adrenal.