Gut Microbiota and Nutritional Profiles of Colon Cancer Patients Undergoing Chemotherapy: A Longitudinal Pilot Study

Background/Objectives: Nutrition and the gut microbiota influence treatment tolerance and recovery in patients with colon cancer receiving chemotherapy. This pilot study examined changes in diet quality and fecal microbiota over 6 months of chemotherapy and evaluated longitudinal associations between diet quality and gut microbiota diversity and taxa. Methods: 48 adults with stage II–III colon cancer receiving 5-fluorouracil-based chemotherapy were assessed at baseline and 6 months post-initiation. Diet quality was measured using 3-day dietary recalls to calculate Healthy Eating Index (HEI) scores. Stool samples underwent 16S rRNA sequencing to assess Shannon diversity, Beta and taxonomic composition. Pre–post changes were analyzed using paired tests, and associations between HEI and microbiota measures were evaluated using multivariable linear regression adjusting for demographic and clinical covariates. Results: Diet quality declined during chemotherapy, with reduced intake of fiber, fruits and vegetables, and whole grains. Gut microbial alpha diversity decreased over time. At the phylum level, Actinobacteriota decreased, while Bacteroidota and Proteobacteria increased. At the genus level, only Streptococcus (decreased) and Escherichia (increased) remained significantly altered after multiple testing correction. Higher baseline diet quality and improvements over time were associated with greater microbial diversity and lower Proteobacteria abundance. Diet quality was inversely associated with Streptococcus and Escherichia and positively associated with short-chain fatty acid-producing, fiber-responsive genera (Faecalibacterium, Mediterraneibacter, Ruminococcus_E, Fusicatenibacter). Baseline gut microbiota did not significantly associate with changes in diet quality. Conclusions: Chemotherapy was associated with declines in diet quality, gut microbial alpha diversity, along with shifts in beta diversity and microbial taxa. Higher diet quality appeared protective against microbial disruption, supporting a bidirectional relationship between diet and the gut microbiome during chemotherapy. Nutritional and microbiota-focused approaches warrant further investigation in the context of chemotherapy.