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

**Authors:** Bonan Chen, Guoming Chen, Xieyuan Leng, Qianfan Li, Wenhao Wu, Wenqiu Wu, Zixuan Liu, Zilan Zhong, Xiaohong Zheng, Wei Kang, Fazheng Ren, Yigan Zhang, Juan Chen

PMC · DOI: 10.1002/advs.202519949 · Advanced Science · 2026-02-06

## TL;DR

This review explores how gut microbes and non-coding RNA work together to influence immunity and disease, offering new diagnostic and therapeutic opportunities.

## Contribution

The paper provides a comprehensive overview of the gut microbiota-ncRNA axis as a modulator of immune responses and its clinical implications.

## Key findings

- Microbial metabolites can alter ncRNA expression to influence immune cell behavior.
- Dysregulation of the microbiota-ncRNA axis is linked to immune-related diseases like colorectal cancer and sepsis.
- Microbial and ncRNA profiles are being used as biomarkers and therapeutic targets for immune modulation.

## Abstract

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.

## Linked entities

- **Diseases:** colorectal cancer (MONDO:0005575), atherosclerosis (MONDO:0005311)

## Full-text entities

- **Diseases:** sepsis (MESH:D018805), colorectal cancer (MESH:D015179), atherosclerosis (MESH:D050197)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13042450/full.md

## References

543 references — full list in the complete paper: https://tomesphere.com/paper/PMC13042450/full.md

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Source: https://tomesphere.com/paper/PMC13042450