Background: Intestinal microbiota, and their metabolites are increasingly recognized as important players in the genesis of colorectal adenomas and cancer. Epidemiological studies have also shown that polyunsaturated fat intake is associated with decreased risk of colorectal adenomas. This study examined the association between adherent gut microbiota and mucosal bile acids, and total polyunsaturated fat intake in relation to colorectal adenomas in a case-control study.

Methods: Participants were 217 adenoma cases and 218 adenoma-free controls who underwent screening colonoscopies and completed food frequency questionnaires. The mucosal adherent microbiota was characterized by bacterial 16S rRNA sequencing. Global metabolomics of colonic mucosal tissue was conducted by gas chromatography and mass spectrometry on a subset of samples. Genus level microbiota and bile acids were compared between cases and controls using t-test with correction for multiple comparison. Logistic regression and Pearson correlations were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs), and correlation coefficients for the association among microbiota abundance, bile acids concentration, and total polyunsaturated fat intake.

Results: Adenoma subjects had a significantly higher bacterial abundance of Sphingomonas, Marinomonas and Ralstonia, but lower abundance of Adlercreutzia compared to controls. The concentration of eleven bile acids (Chenodeoxycholate, Cholate, Deoxycholate, Glycochenodeoxycholate, Glycocholenate sulfate, 7-ketodeoxycholate; 12-dehydrocholate, Taurochenodeoxycholate, Taurocholate, Taurodeoxycholate, Taurolithocholate 3-sulfate, and Tauroursodeoxycholate) were significantly elevated in cases compared to controls. Subjects with increased abundance of Sphingomonas and Ralstonia were significantly more likely to have adenomas (OR 2.17, 95% CI 1.31-3.57; OR 1.19, 95% CI 1.02-1.38) respectively. Subjects with increased abundance of Adlercreutzia were less likely to have adenomas (OR 0.44, 95% CI 0.21-0.93). The multivariable adjusted OR for those in the high relative to the low level of total polyunsaturated fat intake was 0.46 (95% CI 0.27-0.80). The correlations between bacterial diversity and eleven bile acids also significantly differed by case control status.

Conclusion: The interactions of the gut microbiota, bile acids and consumption of polyunsaturated fat are associated with colorectal adenoma risk.

Citation Format: Tengteng Wang, Nicole M. Brown, Amber N. McCoy, Robert S. Sandler, Temitope O. Keku. Associations of polyunsaturated fat, bile acids, and gut microbiota on colorectal adenoma risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 239. doi:10.1158/1538-7445.AM2017-239