**Background:** Colorectal cancer (CRC) is the third most diagnosed cancer worldwide and the second leading cause of cancer mortality. Exercise consistently reduces CRC incidence, recurrence, and mortality, but the biological mechanisms remain unclear. The gut microbiota is increasingly recognized as a potential mediator, given its established role in CRC pathogenesis through dysbiosis, inflammation, and metabolite production. This narrative review synthesizes evidence from two rapidly developing fields—exercise–gut microbiota research and cancer–gut microbiota research—to identify overlapping mechanisms that may explain exercise's protective effects against CRC.
**Methods:** The authors conducted a narrative review of the literature, integrating findings from human observational studies, controlled exercise trials, murine models, and mechanistic studies. Key methodological considerations discussed include the heterogeneity of microbiota analysis techniques (16S rRNA gene amplicon vs. shotgun metagenomic sequencing), the challenge of defining a 'healthy' microbiome, and the importance of functional rather than purely taxonomic descriptors.
**Key Results:** Foundational work by Clarke et al. (2014) demonstrated that professional rugby players have greater gut microbiome diversity, greater abundance of metabolic pathways, and more gene expression for carbohydrate biosynthesis, amino acid biosynthesis, and energy metabolism compared to healthy male controls. Microbial short-chain fatty acid (SCFA) production was also greater in athletes due to higher abundance of SCFA-producing bacteria. Regression modelling by Estaki et al. (2016) found that cardiorespiratory fitness explained 20% of the variation in gut diversity. In a controlled trial of sedentary participants, Allen, Mailing, Niemiro et al. (2018) reported that following 6 weeks of exercise training (1 h continuous exercise at 60–75% heart rate reserve, three times per week), the greatest positive change in microbial diversity, abundance, and SCFA production occurred in lean individuals (BMI <25 kg/m²) compared to those with a high BMI (≥30 kg/m²). Significant correlations between exercise and butyrate-producing taxa were observed only in lean individuals: lean mass was highly correlated with abundance of these bacteria (r = 0.70, P < 0.01), fecal butyrate concentrations (r = 0.87, P < 0.01), and gene expression of butyrate production enzymes (BCoAT; P < 0.05). Percentage body fat was negatively correlated with butyrate-producing bacteria (r = −0.57, P < 0.05) and butyrate concentrations (r = −0.5, P < 0.05). Exercise-associated microbial changes commonly involve increased relative abundances of Akkermansia, Ruminococcus, Veillonella, Lachnospira, Prevotella, Faecalibacterium, and Roseburia. Akkermansia muciniphila abundance is inversely related to C-reactive protein, a key inflammatory biomarker. In murine models, Allen, Mailing, Cohrs et al. (2018) found that fecal transplantation from exercising mice donors to sedentary germ-free mice improved body composition, metabolic profile, and reduced colonic inflammation compared to transplantation from sedentary donors. Following dextran-sodium-sulphate (DSS) exposure to induce colitis, mice receiving transplants from active donors had an attenuated response with better preservation of the mucus layer and improved expression of cytokines involved in tissue regeneration. The abundances of Akkermansia, Lachnospiraceae, and Ruminococcus were higher in the exercising group.
**Clinical Implications:** The review proposes three primary mechanisms by which exercise-mediated gut microbiota changes may reduce CRC risk: (1) maintenance of gut barrier integrity, reducing bacterial lipopolysaccharide (LPS) translocation and the feed-forward loop of inflammation; (2) increased SCFA production, particularly butyrate, which promotes mucosal barrier health, inhibits NF-kB activation, increases CRC cell death through HDAC inhibition, and initiates apoptosis via GPR109A binding; and (3) reduced systemic inflammation through increased abundance of anti-inflammatory bacteria such as Akkermansia muciniphila and Faecalibacterium. The authors note that exercise-mediated changes appear to be the inverse of pro-CRC microbiota characteristics. However, they emphasize that no human trials have yet examined the specific influence of exercise on the gut microbiome of people with CRC. Key limitations include high methodological heterogeneity across studies, insufficient evidence on whether exercise reduces abundance of specific CRC-associated pathogens (Enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, pks+ Escherichia coli), and the need for studies determining optimal exercise dose, type, and intensity. Future research directions include exploring the gut–muscle axis, combined diet and exercise interventions, and the role of non-bacterial members of the gut microbiota (fungi, archaea, viruses).