Abstract 308: Personal determinants of the human gut microbiome

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Previous studies have examined the relationship between various factors, most notably adiposity and short-term diet, and gut microbiome. As the relationships between the gut microbiome and usual long-term dietary intake and other demographic and lifestyle factors remain unclear, we conducted a comprehensive study. Methods: We used freeze-dried fecal samples from 82 controls from a hospital-based case-control study of colorectal cancer conducted between 1985 and 1987. The participants provided information on age, sex, race, smoking status, body mass index (BMI), and usual diet intake. 16S rRNA genes in fecal bacterial DNA were amplified by universal primers, sequenced by 454 FLX technology and aligned to fully-sequenced microbial genomes using the QIIME pipeline. Microbiome overall diversity was assessed by Principal Coordinate Analysis (PCoA). By regression analyses, we also assessed the relationship of these diet and demographic factors to microbiome diversity and relative taxon abundances. Results: We found that sex and smoking were associated with overall gut microbial diversity (PCoA: p=0.001 and p=0.02, respectively). Multivariate regression analyses further substantiated these findings (p=0.03 and p<0.006, respectively). Sex and smoking were also associated with specific taxa, including Bacteroidetes (p=0.02 and p=0.03) and Actinobacteria (p=0.07 and p=0.001). Fruit and vegetable fiber intake was associated with overall diversity (PCoA: p=0.04; multivariate regression: p=0.03) and with increased relative abundance of Clostridia (OR for high vs. low Clostridia abundance=1.24, p=0.009) and decreased Bacteroidetes (OR=0.87, p=0.06). Bean fiber intake was related to increased Actinobacteria (OR=2.24, p=0.006 and FDR controlled P=0.05). BMI was not associated with and overall diversity or specific taxa. Conclusion: Results from this first comprehensive study indicate that sex, smoking status and dietary fiber from certain food sources are determinants of gut microbiome. Gut microbiome structural differences by sex has been observed in some studies possibly through sex hormones or sex-specific effects on gut transit time. Gut microbiota ferment dietary fiber to short-chain fatty acids, which decreases the pH in the gut, possibly suppressing gram-negative Bacteroidetes phylum while promoting gram-positive Clostridia. Actinobacteria has been consistently shown to be positively associated with a variety of fiber forms in both in vitro studies and in human studies. Given the potential relationship of the gut microbiome with diseases of the gut, our findings may have implications for prevention of diseases related to dysbiosis through long-term dietary manipulation of the gut microbiome. Citation Format: Christine Dominianni, Rashmi Sinha, James J. Goedert, Zhiheng Pei, Liying Yang, Richard B. Hayes, Jiyoung Ahn. Personal determinants of the human gut microbiome. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 308. doi:10.1158/1538-7445.AM2014-308