Dietary inflammatory potential in relation to the gut microbiome among persons at varied risk of colorectal neoplasia

Purpose: Diet modulates gut microbiome composition and systemic inflammation—both intermediary factors in the development of colorectal neoplasia. We investigated the association of total dietary inflammatory potential, as assessed by the literature-derived dietary inflammatory index (DII®), with gut microbiota diversity and composition, microbial gene pathways, and circulating markers. Methods: This epidemiological study was comprised of 36 cancer-free colonoscopy patients (79% positive for precancerous polyps) and 65 healthy volunteers from the medical center community (N=101). Participants completed dietary assessments and provided stool samples for 16S rDNA sequencing >1 month after colonoscopy/polyp removal or antibiotic use. In a subset (n=47), we conducted whole genome shotgun (WGS) sequencing and collected a fasting blood sample. Energy-adjusted (E)-DII score was calculated for each subject and categorized into tertiles. The association between E-DII and fecal microbiota alpha- and beta-diversity was examined. Linear discriminant analysis Effect Size (LEfSe) was used to identify differentially abundant taxa by E-DII level. Multiple linear regression models were used to examine associations controlled for confounders. Results from the least absolute shrinkage and selection operator (LASSO) method and Spearman’s correlation were used to select and evaluate associations of bacterial species with E-DII, their functional pathways, and circulating markers. Results: We observed large between-person variation in Bacteroidaceae and Enterobacteriaceae, two dominant bacteria in the overall sample. Neither alpha- nor beta-diversity significantly differed across E-DII levels. Ruminococcus torques, Acidaminococcus intestine, and Clostridium leptum were most abundant in the most pro-inflammatory diet group, while Akkermansia muciniphila was enriched among subjects with the most anti-inflammatory diet. In the WGS subset, Luteimonas mephitis was inversely associated with E-DII, circulating Lipocalin-2 (r=-0.34; P=0.02), and plasminogen activator inhibitor-1 (r=-0.29; P=0.05). Akkermansia muciniphilaappeared to be inversely correlated with monocyte chemoattractant protein-1 (r=-0.26; P=0.09). Two microbial pathways inversely associated with E-DII, AMP-activated protein kinase (AMPK) and carbon metabolism, were also inversely correlated with C-peptide (AMPK: r=-0.35, P= 0.02; carbon: r=-0.30, P=0.04). Conclusions: Dietary inflammatory potential was associated with differential composition of specific microbes, but not overall diversity of the gut microbiome. Species associated with E-DII were similarly associated with circulating inflammatory biomarkers. Microbial AMPK signaling and carbon metabolism pathways may underlie diet-microbiota interactions that modulate systemic inflammation. Citation Format: Jiali Zheng, Kristi L. Hoffman, Nitin Shivappa, Jonathan Busquets, Jiun-Sheng Chen, Samir Hanash, Susan Schembre, James Hebert, Joseph Petrosino, Peng Wei, Carrie R. Daniel. Dietary inflammatory potential in relation to the gut microbiome among persons at varied risk of colorectal neoplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3320.