Mediation effect of intestinal microbiota on the relationship between fiber intake and colorectal cancer

Higher fiber intake has been associated with a lower risk of colorectal cancer (CRC) and has been shown to protect against CRC based on probable evidence. Recent studies revealed a possible mechanism whereby the interaction between intestinal microbiota and fiber intake mediates CRC risk. However, the specific intestinal bacteria and the amount of these bacteria involved in this mechanism are not fully known. Therefore, this single‐center study aimed to determine whether specific intestinal bacteria mediated the relationship between fiber intake and CRC risk. We enrolled patients who received colonoscopy at National Cancer Center Hospital. This cross‐sectional study included 180 patients with clinically diagnosed CRC and 242 controls. We conducted a causal mediation analysis to assess the natural indirect effect and natural direct effect of specific intestinal bacteria on association between fiber intake and CRC risk. The median age was 64 (interquartile range, 54‐70) years, and 58% of the participants were males. We used metagenomics for profiling gut microbiomes. The relative abundance of each species in each sample was calculated. Among the candidate, Fusobacterium nucleatum and Gemella morbillorum had a significant natural indirect effect based on their highest fiber intake compared to the lowest fiber intake, with a risk difference (95% confidence interval, proportion of mediation effect) of −0.06 [−0.09 to −0.03, 23%] and −0.03 [−0.06 to −0.01, 10.5%], respectively. Other bacteria did not display natural indirect effects. In conclusion, Fusobacterium nucleatum and Gemella morbillorum were found to mediate the relationship between fiber intake and CRC risk. What's new? A high‐fiber diet provides accessible carbohydrates for intestinal bacteria and is linked to reduced colorectal cancer (CRC) risk. Moreover, alterations in microbial populations are associated with CRC progression. Whether specific microbial populations mediate effects between fiber intake and CRC risk, however, remains unclear. The present investigation, involving patients who received endoscopy for CRC treatment or who had a positive fecal occult blood test, shows that Fusobacterium nucleatum and Gemella morbillorum bacteria indirectly effect CRC risk in relation to high fiber intake. No effects were detected for other bacterial species. The findings provide new insight into potential mechanisms of CRC development.