Abstract 7391: Longitudinal changes in the gut microbiome among newly diagnosed colorectal cancer patients
Authors: Maria F. Gomez, Stephanie R. Hogue, Jessica R. Burns, Seth I. Felder, Esther Jean-Baptiste, Adetunji T. Toriola, Jane C. Figueiredo, Christopher I. Li, David Shibata, Victoria Damerell, Christoph Kahlert, Erin M. Siegel, Rashmi Sinha, Emily Vogtmann, Sheetal Hardikar, Mary Playdon, Leigh Greathouse, Biljana Gigic, Cornelia M. Ulrich, Doratha A. Byrd
Journal: Cancer Research (2025)

Abstract Background: The gut microbiome may be linked to colorectal cancer (CRC) prognosis. Few studies characterized the gut microbiome longitudinally across CRC treatment. Herein, we investigated the gut microbiome dynamics before and up to two years after surgery among newly diagnosed CRC patients. Methods: We extracted DNA from stool collected longitudinally at baseline (pre-surgery) and at 6, 12, and 24-months after in the ColoCare Study. We characterized fecal bacteria using 16S rRNA gene sequencing (16S; N=133; baseline and 6 months only) and whole-genome shotgun sequencing (WGS; N=41; all timepoints). We estimated rarefied alpha diversity (richness and Shannon index) and beta diversity (Bray Curtis). We calculated centered-log ratio transformed relative abundances of a priori-selected taxa and functional genes (WGS only). We used permutational multivariate analysis of variance to estimate the percentage explained in variability of the Bray Curtis distance matrix. We estimated average differences in the microbiome metrics across time using linear mixed effects models adjusted for study center and treatment. Results: In total, 43% of the cohort received adjuvant therapy and 24% received neoadjuvant therapy. On average, from baseline to 6 months, alpha diversity decreased, with statistically significant declines in the Shannon index for 16S (β = -0.32, 95% CI = -0.47, -0.17; P &amp;lt;0.001) and WGS (β = -0.38, 95% CI = -0.56, -0.20; P &amp;lt;0.001). WGS alpha diversity tended to somewhat recover at 12 and 24 months. Bray Curtis distance variation was primarily explained by subject (e.g., for 16S: 75%, P=0.03); whereas timepoint explained about 3% of variation in 16S and WGS Bray Curtis distance (all P &amp;lt; 0.05). Among 16S genera (presented per 1-unit increase in log ratio), there was an average 0.33-unit increase in Fusobacterium (95% CI = 0.05, 0.62; P= 0.02) and a -0.98-unit decrease in Prevotella (95% CI = -1.41, -0.56; P &amp;lt;0.001) abundance over 6 months. At the species-level (WGS), there were progressively stronger decreases from baseline up to 24 months in multiple potentially pathogenic a priori bacteria. For example, the changes β’s (95% CIs) in Porphyromonas asaccharolytica were -1.33 (-2.11, -0.57; P&amp;lt;0.001) at 6 months, -1.53 (-2.33, -0.74; P&amp;lt;0.001) at 12 months, and -1.18 (-2.05, -0.31; P=0.01) at 24 months. Acetolactate synthase gene abundance, involved in branch chain amino acid synthesis, increased on average from baseline to 6 and 12 months. Conclusion: We found that microbial diversity tended to decrease over time, recovering somewhat around a year. We found that the abundance of multiple oral-originating species previously associated with CRC presence and prognosis tended to decrease over time (except Fusobacterium in the less detailed 16S data). Overall, our intriguing findings highlight that the microbiome may shift after tumor removal. Next steps will interrogate these shifts as they relate to clinical outcomes. Citation Format: Maria F. Gomez, Stephanie R. Hogue, Jessica R. Burns, Seth I. Felder, Esther Jean-Baptiste, Adetunji T. Toriola, Jane C. Figueiredo, Christopher I. Li, David Shibata, Victoria Damerell, Christoph Kahlert, Erin M. Siegel, Rashmi Sinha, Emily Vogtmann, Sheetal Hardikar, Mary Playdon, Leigh Greathouse, Biljana Gigic, Cornelia M. Ulrich, Doratha A. Byrd. Longitudinal changes in the gut microbiome among newly diagnosed colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7391.