BACKGROUND: Emerging evidence suggests that bacteria residing in colorectal 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 intervention goals of consuming: 1) ≥ 18 g 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. Using 16S rRNA gene sequencing, we characterized bacteria in rectal 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 alpha/beta diversity and relative abundance of a priori-selected bacteria using repeated-measures linear mixed-effects models. 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 intervention effects [standard errors] at T1 vs T0=-0.24 [0.07] and T4 vs T0=-0.12 [0.07]
P = .004) and Prevotella (absolute intervention effects at T1 vs T0=-0.40 [0.14] and at T4 vs T0=-0.32 [0.15]
P = .01) were more strongly decreased in the intervention arm. CONCLUSION: The PPT intervention did not influence rectal tissue microbiome diversity nor the relative abundance of most bacteria, except for two oral-originating bacteria that were previously associated with CRC presence. ORIGINAL CLINICAL TRIAL REGISTRY NUMBER: NCT00339625.