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

<b>Background/Objectives</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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, <i>Actinobacteriota</i> decreased, while <i>Bacteroidota</i> and <i>Proteobacteria</i> increased. At the genus level, only <i>Streptococcus</i> (decreased) and <i>Escherichia</i> (increased) remained significantly altered after multiple testing correction. Higher baseline diet quality and improvements over time were associated with greater microbial diversity and lower <i>Proteobacteria</i> abundance. Diet quality was inversely associated with <i>Streptococcus</i> and <i>Escherichia</i> and positively associated with short-chain fatty acid-producing, fiber-responsive genera (<i>Faecalibacterium</i>, <i>Mediterraneibacter</i>, <i>Ruminococcus_E</i>, <i>Fusicatenibacter</i>). Baseline gut microbiota did not significantly associate with changes in diet quality. <b>Conclusions</b>: 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.