Abstract B04: Gender-based impact of chemo-radiotherapy in the gut microbial diversity and short-chain fatty acid levels of adults with rectal cancers

Abstract

Abstract Background: The gut microbiome is essential in maintaining the host immune system and may influence the host response to cancer therapeutics. Particularly, by the production of short-chain fatty acids (SCFA) through fermentation of dietary fibers, the gut microbiota helps regulate the immune system. SCFA levels can be affected by changes in gut microbiome composition either by chemo-radiotherapy treatment (CRT) or by gender disparities. We had previously observed that CRT significantly reduced Shannon diversity index and the observed operational taxonomic units (OTUs) during CRT in rectal cancers. Here, we examined the impact of CRT on the levels of SCFAs in adults with RC and investigated gender disparities in the gut microbiome associated with CRT. Methods: We evaluated the gut microbiome of 35 newly diagnosed RC patients scheduled to receive CRT. Demographics, health forms, and stool samples were collected before and after CRT (12-16 treatments). We sequenced the V3-V4 hypervariable region of the 16S rDNA and measured levels of SCFA (from Acetate [C2] to Octonoate [C8]) by LC-MS/MS and results were expressed in log2 (nmol/mg). Alpha diversity (Shannon index [community diversity] and Observed OTUs [community richness]) was calculated using the QIIME2 software and all statistical analyses were performed in R statistical software. Results: Study participants were 35 subjects (20 males vs. 15 females) with an average age of 61.1±9.8 years, even though females tended to be younger than males (57.9±9.8 vs. 63.8±9.3, p=0.08). While females had a trend for a higher Shannon index when compared to males before CRT (6.46±0.31 vs. 6.11±0.43, p=0.09), they had significantly lower Shannon index (5.26±0.31 vs. 5.94±0.60, p=0.02) and observed OTUs (117±7.6 vs. 170±61.0, p=0.03) after CRT, and females had a higher reduction than males (p=0.04). In regard to SCFA, there was an overall increase on the levels of propionate after CRT compared to before CRT (4.10±0.78 vs. 3.64±1.00, p=0.02). However, while there was no difference in the levels of SCFA based on biologic gender after CRT, females had significantly higher levels of propionate (4.32 ±0.68 vs. 3.60±0.90) and butyrate (2.73 ± 0.82 vs. 1.70 ±1.29) at the end of CRT, while men did not show any significant difference in SCFA during CRT. Conclusion: Chemo-radiotherapy resulted in dysbiosis of the gut microbiome and also changed the levels of SCFA. However, these changes in the microbiome associated with CRT were different in females versus males. Our findings suggest that biologic sex may play a key role in the development of personalized cancer treatment strategies. Citation Format: Carlos Sola-Morla, Velda Gonzalez-Mercado, Josue Perez-Santiago. Gender-based impact of chemo-radiotherapy in the gut microbial diversity and short-chain fatty acid levels of adults with rectal cancers [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B04.