Variety of Fruit and Vegetables and Alcohol Intake are Associated with Gut Microbial Species and Gene Abundance in Colorectal Cancer Survivors.

BACKGROUND: Adherence to the American Cancer Society (ACS) guidelines of avoiding obesity, maintaining physical activity, and consuming a diet rich in fruits, vegetables, and whole grains is associated with longer survival in colorectal cancer (CRC) survivors. Dietary components of the ACS guidelines may act in part by changing the microbiome, which is implicated in CRC outcomes. OBJECTIVES: We conducted a pilot cross-sectional study to explore associations between ACS guidelines and the gut microbiome. METHODS: Stool samples and questionnaires were collected from 28 CRC survivors at the University of California, San Francisco from 2019 to 2020. ACS scores were calculated based on validated questionnaires. Gut microbial community structure from 16S amplicons and gene/pathway abundances from metagenomics were tested for associations with the ACS score and its components using ANOVA and general linear models. RESULTS: The overall ACS score was not significantly associated with variations in the fecal microbiota. However, fruit and vegetable intake and alcohol intake accounted for 19% (P = 0.005) and 13% (P = 0.01) of variation in the microbiota, respectively. Fruit/vegetable consumption was associated with increased microbial diversity, increased Firmicutes, decreased Bacteroidota, and changes to multiple genes and metabolic pathways, including enriched pathways for amino acid and short-chain fatty acid biosynthesis and plant-associated sugar degradation. In contrast, alcohol consumption was positively associated with overall microbial diversity, negatively associated with Bacteroidota abundance, and associated with changes to multiple genes and metabolic pathways. The other components of the ACS score were not statistically significantly associated with the fecal microbiota in our sample. CONCLUSIONS: These results guide future studies examining the impact of changes in the intake of fruits, vegetables, and alcoholic drinks on the gut microbiome of CRC survivors.

Host and gut bacteria share metabolic pathways for anti-cancer drug metabolism.

Pharmaceuticals have extensive reciprocal interactions with the microbiome, but whether bacterial drug sensitivity and metabolism is driven by pathways conserved in host cells remains unclear. Here we show that anti-cancer fluoropyrimidine drugs inhibit the growth of gut bacterial strains from 6 phyla. In both Escherichia coli and mammalian cells, fluoropyrimidines disrupt pyrimidine metabolism. Proteobacteria and Firmicutes metabolized 5-fluorouracil to its inactive metabolite dihydrofluorouracil, mimicking the major host mechanism for drug clearance. The preTA operon was necessary and sufficient for 5-fluorouracil inactivation by E. coli, exhibited high catalytic efficiency for the reductive reaction, decreased the bioavailability and efficacy of oral fluoropyrimidine treatment in mice and was prevalent in the gut microbiomes of colorectal cancer patients. The conservation of both the targets and enzymes for metabolism of therapeutics across domains highlights the need to distinguish the relative contributions of human and microbial cells to drug efficacy and side-effect profiles.