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

Background/Objectives: Nutritional status and the gut microbiome play key roles in supporting treatment tolerance and recovery among patients with colon cancer receiving chemotherapy. This pilot study examined (1) changes in diet quality and fecal microbiome profiles during 6-month chemotherapy and (2) associations between diet quality and microbiome diversity and composition over time. Methods: A longitudinal study of 48 adults with stage II–III colon cancer receiving 5-Fluouracil (FU)–based chemotherapy assessed diet quality and the gut microbiome at baseline and 6 months post-chemotherapy initiation. Diet quality was measured using 3-day dietary recalls to compute Healthy Eating Index (HEI) scores. Stool samples collected at both timepoints underwent 16S rRNA sequencing to quantify Shannon diversity and taxonomic composition. Pre–post differences were examined using paired tests, and associations between HEI and microbiome indicators were evaluated with multivariable linear regressions adjusting for demographic and clinical covariates. Results: Diet quality declined during chemotherapy (HEI 62.4→54.2, p=0.015). Shannon diversity also decreased (1.20→1.05, p=0.011). Microbiome composition shifted, with declines in Short-Chain Fatty Acids (the result of fiber fermentation)-producing taxa (Agathobacter, Bifidobacterium, and Prevotella), and increases in Bacteroides and Proteobacteria. Higher baseline HEI was linked to greater microbial diversity, higher levels of beneficial Firmicutes, and lower Proteobacteria. Changes in HEI were significantly aligned with changes in fecal microbiome profiles. Conclusions: Chemotherapy worsens diet quality and gut microbial health. Higher baseline diet quality appeared protective against microbial disruption, supporting a bidirectional diet–microbiome relationship. Early nutritional and microbiome-supportive strategies may help preserve gut resilience during chemotherapy.