Gut Microbiota-Non-Coding RNA Axis in Immune Modulation and Disease: From Mechanisms to Clinical Translation

Immune homeostasis is indispensable for preserving organismal integrity, orchestrated through complex molecular networks encompassing immune cell dynamics, microbial cues, and epigenetic regulation. Among these, the gut microbiota-non-coding RNA (ncRNA) axis has recently garnered substantial attention as a multifaceted modulator of host immunity. Emerging evidence indicates that microbial-derived metabolites can reprogram ncRNA expression, thereby modulating immune cell differentiation, activation, and effector responses. Notably, dysregulation of this axis has been mechanistically implicated in the etiology of diverse immune-related pathologies, including colorectal cancer, sepsis, atherosclerosis, and neuroimmune conditions. Particularly intriguing is its translational potential: both microbial signatures and ncRNA profiles are being leveraged as diagnostic biomarkers and actionable targets for immune modulation. In this review, we delineate the molecular frameworks underpinning the gut microbiota-ncRNA-immune and explore how its perturbation contributes to pathogenesis. We further highlight emerging therapeutic strategies targeting this axis, underscoring its significance in precision immunology and host-microbiota co-regulation.