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

Abstract

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.

Keywords: colorectal cancer; early diagnosis; gut microbiota; inflammation; intestinal barrier.

Figure 1

The CRC Gut Axis: Barrier Disruption, Gut Dysbiosis & Inflammation Cascade. This diagram illustrates the vicious cycle wherein intestinal barrier compromise drives gut dysbiosis, which in turn fuels chronic inflammation, thereby generating a pro-carcinogenic microenvironment. Current intervention strategies focus on these interconnected processes; however, clinical translation remains challenging due to the issues of standardization, system bias, and the requisite for extensive cohort validation. Abbreviations: CRC, colorectal cancer; LPS, lipopolysaccharide; SCFAs, short-chain fatty acids; NF-κB, nuclear factor kappa B; STAT3, signal transducer and activator of transcription 3; TLR4, Toll-like receptor 4; MyD88, myeloid differentiation primary response 88.

Figure 2

Key mechanisms linking intestinal barrier disruption to colorectal cancer development. Disruption of the intestinal barrier leads to increased intestinal permeability, microbial translocation, and activation of inflammatory pathways. Microbial factors, such as LPS, drive inflammation through TLR4–NF-κB signaling, contributing to carcinogenic signaling via pathways like Wnt/β-catenin. This cascade ultimately increases the risk of CRC development.

Figure 3

Strategies for Early Diagnosis & Intervention in CRC. This figure outlines advanced strategies for CRC. Early diagnosis integrates serum biomarkers, microbial signatures, metabolomics, and AI models for high-accuracy detection. Early intervention focuses on barrier protection, microbiota modulation, and anti-inflammation. The integration of these elements aims to advance AI-driven precision medicine, pending resolution of challenges in standardization and clinical validation. Abbreviations: FMT, fecal microbiota transplantation; SCFAs, short-chain fatty acids; AI, artificial intelligence; CRC, colorectal cancer.