Longitudinal integrated analysis of gut microbiota and metabolites in rectal cancer patients undergoing chemoradiotherapy
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background Longitudinal changes in the fecal microbiome and metabolome during concurrent chemoradiotherapy (CCRT) for rectal cancer remain incompletely characterized. Methods In this prospective single-center cohort, 19 patients with rectal cancer were enrolled and 17 were included in the longitudinal analysis after two prespecified sampling-window exclusions. Fecal specimens were scheduled at nine time points: R0, collected before the first dose of capecitabine and before radiotherapy, and R3 through R24 at three-fraction intervals during treatment. Twenty unmatched healthy volunteers provided one fecal specimen for a descriptive pretreatment comparison. Full-length 16S rRNA gene sequencing and untargeted metabolomics were performed. Longitudinal microbial counts were analyzed using negative-binomial generalized linear mixed models, and metabolite features were analyzed using linear mixed-effects models; participant was included as a random intercept, and P values were adjusted using the Benjamini–Hochberg false discovery rate (FDR). Results Nineteen genera and 27 of 176 analyzed species showed significant linear time trends during CCRT (FDR < 0.05). Parvimonas micra, Peptostreptococcus stomatis , and Gemella morbillorum decreased, whereas Lachnoclostridium pacaense, Blautia hydrogenotrophica, [Eubacterium] sulci , and Coprococcus eutactus increased. Of 2,873 analyzed metabolic features, 393 changed significantly over time. In a secondary same-cohort analysis, 17 of 50 correlation-selected taxon-metabolite pairs remained significant in time-adjusted mixed-effects models, including a positive association between C. eutactus and a feature annotated as stercobilin. Among 103 significant features with KEGG identifiers, three pathways met a nominal raw-P threshold, but none remained significant after FDR correction. Pretreatment patient samples had lower Shannon diversity and differed from healthy-control samples by ANOSIM; these comparisons were descriptive because the groups were not matched for age or sex. Five species shared the same case-control direction in this cohort and GMrepo reports, but only P. stomatis and G. morbillorum also showed significant longitudinal declines during CCRT. Conclusion This small, intensively sampled cohort identifies exploratory fecal microbial and metabolic trajectories during capecitabine-based CCRT. The findings do not establish causal mechanisms, microbial functions, disease specificity, or biomarker performance and require independent confirmation in larger cohorts.
Source: Frontiers in Microbiology
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221821341