Abstract 2215: Effects of a high-fiber, high-fruit and -vegetable, low-fat dietary intervention on rectal tissue bacteria

Abstract Introduction. Emerging evidence suggests that the bacteria residing in colon and rectal tissue are plausibly associated with colorectal cancer (CRC). Prior studies investigated the effects of dietary interventions on the fecal microbiome but few assessed colorectal tissue microbiome endpoints. We investigated the effects of a high-fiber, high-fruit and -vegetable, low-fat dietary intervention on the rectal tissue microbiome in the Polyp Prevention Trial (PPT). Methods. PPT is a 4-year randomized clinical trial, with specific goals including consuming: 1) ≥ 18g of fiber per 1,000 kcal/day; 2) ≥ 3.5 servings of fruits and vegetables per 1,000 kcal/day; and 3) <20% of kcal/day from fat. We extracted DNA from rectal biopsies using the AutoGen Animal Tissue DNA Extraction Kit and sequenced the V4 region of the 16S rRNA gene to characterize the bacteria in biopsies collected at baseline and the end of years 1 and 4 (N=233 in intervention arm and N=222 in control arm). We estimated effects of the intervention on rarefied alpha diversity and a priori-selected presence and relative abundance (presented as percentages summing to 100) of 10 bacteria most strongly historically associated with CRC presence using repeated-measures linear mixed-effects models. We also explored intervention effects on presence/abundance of all bacteria (with Bonferroni correction for multiple testing) and stratified the analysis among intervention arm participants who adhered to 75% of the dietary goals (super compliers) over the 4 years (N=48) and comparable participants in the control arm (N=64). Results. The intervention did not statistically significantly modify rectal tissue alpha diversity. Compared to the control arm, relative abundance of a priori-selected Porphyromonas (absolute difference-in-difference (DiD) at T1 vs. T0 = -0.24 and T4 vs. T0 = -0.12; P=0.004) and Prevotella (absolute DiD at T1 vs. T0 = -0.40 and at T4 vs. T0 = -0.32; P=0.01) were more strongly decreased in the intervention arm. Other bacteria selected for exploratory analyses were not statistically significantly modified by the intervention after accounting for multiple testing. Among super compliers and comparable control arm participants, the findings were similarly weak. Conclusion. Overall, our findings did not strongly support that a high-fiber, -fruit, and -vegetable, and low-fat diet intervention influences rectal tissue microbiome diversity nor the abundance of most bacteria, except for two oral-originating bacteria that were previously associated with CRC presence. It is possible that dietary exposures over longer periods of time (than 4 years) may more strongly influence the tissue microbiome. Future intervention studies, including tissue samples collected throughout the colon and rectum among larger, diverse study populations for longer periods of time are warranted to inform potential primary prevention strategies for CRC. Citation Format: Doratha Armenthus Byrd, Maria Gomez, Stephanie Hogue, Ana Ortega-Villa, Yunhu Wan, Andrew Warner, Bin Zhu, Casey Dagnall, Kristine Jones, Belynda Hicks, Paul Albert, Gwen Murphy, Rashmi Sinha, Emily Vogtmann. Effects of a high-fiber, high-fruit and -vegetable, low-fat dietary intervention on rectal tissue bacteria [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2215.