Gut Microbiota Interactions in Colorectal Cancer

Colorectal cancer arises from complex interactions between the gut microbiota and host. Commensal and pathogenic microbes modulate tumour initiation and progression via chronic inflammation, production of genotoxins and alteration of epithelial barrier integrity. Microbial metabolites such as short-chain fatty acids, bile acids and indoles act on host receptors to influence cell proliferation, immune responses and DNA damage. Dysbiosis, or imbalance in microbial communities, is characterised by enrichment of taxa such as Fusobacterium nucleatum, Parvimonas micra and Peptostreptococcus anaerobius, which can adhere to colonic epithelium, activate pro-tumorigenic pathways and impair barrier function. Conversely, beneficial species including Lactobacillus and Bifidobacterium can produce anti-inflammatory metabolites and strengthen barrier integrity. Advances in sequencing and quantitative profiling have refined microbial biomarkers for early detection, prognosis and prediction of therapeutic response. Preclinical models and clinical cohorts highlight the potential for microbiota-targeted interventions, such as dietary modulation, probiotics or faecal microbiota transplantation, to complement existing therapies and improve patient outcomes.

Research from Nature Portfolio

Quantitative microbiome profiling combined with stringent covariate control has revealed that factors such as bowel transit time, inflammation and body mass index account for a substantial proportion of variation in faecal microbial composition, superseding differences between healthy, adenoma and carcinoma groups. When these confounders are accounted for, associations with classic CRC-linked species such as Fusobacterium nucleatum may weaken, whereas other taxa (Anaerococcus vaginalis, Parvimonas micra, Peptostreptococcus anaerobius and Porphyromonas asaccharolytica) remain robust, refining the selection of microbial biomarkers. In parallel, interrogation of the arachidonic acid synthesis axis mediated by delta-5 desaturase has demonstrated that elevated arachidonic acid in the colonic milieu drives expansion of gram-negative bacteria and enhances tumour growth via TLR4/MYD88-dependent induction of prostaglandin E2, providing mechanistic insight into lipid-microbiota crosstalk in colorectal carcinogenesis.

Gut Microbiota Interactions in Colorectal Cancer publication trend

The graph below shows the total number of articles in gut microbiota interactions in colorectal cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Dysbiosis: An imbalance in the composition or function of the gut microbial community linked to disease.

Quantitative microbiome profiling: Measurement of absolute microbial abundances rather than relative proportions, often via spike-in controls.

Aryl hydrocarbon receptor (AHR) pathway: A host signalling pathway activated by microbial metabolites that regulates immune responses and epithelial homeostasis.

Delta-5 desaturase (FADS1): An enzyme catalysing the synthesis of arachidonic acid, a precursor of pro-inflammatory lipids.

Horizontal gene transfer (HGT): The movement of genetic material between organisms, which can alter microbial functions in the gut.

References

1. Microbiome confounders and quantitative profiling challenge predicted microbial targets in colorectal cancer development. Nature Medicine (2024).
2. FADS1-arachidonic acid axis enhances arachidonic acid metabolism by altering intestinal microecology in colorectal cancer. Nature Communications (2023).
3. Black rice diet alleviates colorectal cancer development through modulating tryptophan metabolism and activating AHR pathway. iMeta (2024).
4. Traditional Medicine Pien Tze Huang Suppresses Colorectal Tumorigenesis Through Restoring Gut Microbiota and Metabolites. Gastroenterology (2023).
5. Enhancing insights into diseases through horizontal gene transfer event detection from gut microbiome. Nucleic Acids Research (2024).