Gut microbiota in health and disease.

Abstract

The gut microbiota is integral to host physiology, contributing to metabolic homeostasis, epithelial barrier integrity, immune balance, and bidirectional communication along gut-organ axes. Disruption of this ecosystem, commonly referred to as dysbiosis, is increasingly implicated in a wide range of gastrointestinal and extra-intestinal diseases. Rather than reflecting isolated compositional changes, microbiota-related pathology often involves interconnected disturbances in barrier function, microbial metabolism, immune regulation, genotoxicity, inflammatory and oncogenic signaling, and long-range communication with distal organs. However, key challenges remain, particularly in resolving causality, accounting for interindividual heterogeneity, and translating complex microbiome data into robust clinical tools. In this review, we summarize the role of the gut microbiota in maintaining host homeostasis and outline the concept, drivers, and consequences of dysbiosis. We then discuss the major mechanisms through which the gut microbiota contributes to disease development and progression, using colorectal cancer as a representative gastrointestinal example and gut-organ axes as a framework for extra-intestinal disorders. We further highlight current translational advances in microbiota-based biomarkers, dietary modulation, biotic and postbiotic strategies, fecal microbiota transplantation, and emerging precision microbiota therapies. By integrating mechanistic insights with translational perspectives, this review offers an updated framework for interpreting the gut microbiota in health and disease and may help inform the future development of more precise, mechanism-informed diagnostic and therapeutic strategies.