Gut microbiome–driven colorectal cancer via immune, metabolic, neural, and endocrine axes reprogramming

Jan 22, 2026NPJ biofilms and microbiomes

How Gut Bacteria May Promote Colorectal Cancer by Changing the Immune, Metabolism, Nervous, and Hormone Systems

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Abstract

Colorectal cancer (CRC) is increasingly recognized as influenced by gut microbial communities.

The gut microbiome is associated with CRC initiation, progression, and response to therapy.
in CRC is marked by an increase in harmful bacteria and a decrease in beneficial ones that produce short-chain fatty acids.
Certain microbes contribute to cancer development through mechanisms such as DNA damage and inflammation.
Distinct bacterial metabolites are linked to specific mutations in human cancer genomes.
CRC is conceptualized as a disease driven by complex interactions within microbial communities that affect immune and metabolic functions.
Emerging strategies targeting the microbiome, including dietary changes and probiotics, may influence CRC prevention and treatment.

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Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide and is increasingly recognized as the outcome of complex host-microbe interactions. Beyond established genetic and environmental drivers, the gut microbiome has emerged as a causal and mechanistic contributor to CRC initiation, progression, and therapy response. This review synthesizes current molecular, ecological, and translational evidence to explain how gut microbial communities reprogram immune, metabolic, neural, and endocrine networks within the tumor microenvironment. CRC-associated is characterized by enrichment of pathobionts such as Fusobacterium nucleatum, pks⁺ Escherichia coli, and enterotoxigenic Bacteroides fragilis, and by loss of protective, short-chain-fatty-acid-producing commensals. These microbes promote carcinogenesis through -induced DNA damage, epithelial barrier disruption, metabolic rewiring, and chronic inflammation that collectively sustain immune suppression and tumor growth. Defined mutational signatures from bacterial metabolites, including colibactin, cytolethal distending toxin, and indolimines, now directly link microbial exposures to human cancer genomes. By integrating these findings, this review conceptualizes CRC as a biofilm-structured, microbiome-driven ecosystem disease, where polymicrobial consortia coordinate barrier breakdown, immune evasion, and metabolic cooperation. Finally, we highlight emerging microbiota-targeted strategies, including dietary modulation, pre- and probiotics, postbiotics, bacteriophage therapy, engineered live biotherapeutics, and fecal microbiota transplantation, that translate these insights into precision prevention and therapy. Through this integrative framework, the review aims to reposition the microbiome from a correlative feature to a tractable determinant of CRC pathogenesis and treatment response.

Key numbers

85%

85% mucosal colonization

Prevalence of Bacteroides fragilis in colorectal cancer patients

3.8×10¹³

3.8×10¹³ microorganisms

Estimated number of microorganisms in the human gastrointestinal tract

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Gut microbiome–driven colorectal cancer via immune, metabolic, neural, and endocrine axes reprogramming

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