# The Barrier–Microbiota–Inflammation Axis in Colorectal Cancer: Mechanisms and Emerging Diagnostic & Therapeutic Strategies

## TL;DR

This paper reviews how intestinal barrier dysfunction, gut microbiota imbalance, and chronic inflammation work together to drive colorectal cancer, offering new insights for early detection and treatment.

## Contribution

The paper introduces the barrier–microbiota–inflammation axis as a unified framework for understanding and targeting colorectal cancer.

## Key findings

- Early colorectal lesions show reduced microbial diversity and shifts in microbial composition.
- Impaired intestinal barriers allow microbial products to trigger inflammation and tumorigenesis.
- Targeting this axis may improve early detection and precision treatment of colorectal cancer.

## Abstract

Colorectal cancer is one of the most common malignancies worldwide, and its development is closely linked to intestinal barrier dysfunction, dysbiosis of the gut microbiota, and chronic inflammation. Increasing evidence suggests that these three factors do not act independently but instead form a tightly interconnected barrier–microbiota–inflammation axis that drives tumor initiation, progression, and therapeutic resistance. In this review, we summarize current advances in understanding how epithelial barrier disruption alters microbial composition, how microbiota-derived signals shape inflammatory and immune responses—particularly Th17 and regulatory T cells—and how these processes collectively influence the colorectal tumor microenvironment. We further discuss the clinical implications of targeting this axis for early diagnosis, prognosis, and the development of novel therapeutic strategies. A better understanding of this integrated axis may provide new opportunities for precision medicine in colorectal cancer.

Colorectal cancer (CRC) is a leading cause of global cancer incidence and mortality, with rising prevalence among younger individuals. Accumulating evidence reveals a critical pathological axis linking intestinal barrier disruption, gut microbial dysbiosis, and chronic inflammation, collectively driving CRC initiation. Early colorectal lesions exhibit microbial shifts—reduced α-diversity with clear β-diversity separation, enrichment of oral-origin/pathobiont taxa and depletion of butyrate producers—alongside impaired mucus and tight junction integrity. Concurrent chemical barrier drifts, with decreased short-chain fatty acids and increased secondary bile acids, enhance epithelial stress and vulnerability. The resultant permeability facilitates the translocation of microbial products, triggering inflammation and tumorigenesis. This paper focuses on a review of the relationship between gut microbiota, intestinal barrier, inflammatory signaling pathways, and tumor initiation, sorting out its potential role in developing, diagnosing, and treating CRC. Collectively, this cascade axis offers theoretical and empirical support for the early pathological detection and intervention of CRC, indicating promising directions for future precision screening and stratified management strategies.