Associations of the gut microbiome with hepatic adiposity in the Multiethnic Cohort Adiposity Phenotype Study
Meredith A.J. Hullar, Isaac Jenkins, Timothy W. Randolph, Keith R. Curtis, Kristine R. Monroe, Thomas Ernst, John Shepherd, Daniel O. Stram, Iona Cheng, Bruce S. Kristal, Lynne R. Wilkens, Adrian A. Franke, Loı̈c Le Marchand, Unhee Lim, Johanna W. Lampe
Abstract
). The GM was measured by 16S rRNA gene sequencing and, on a subset, by metagenomic sequencing. Alpha diversity was lower overall with NAFLD and in certain ethnicities (African Americans, Whites, and Latinos). In models regressing genus on NAFLD status, 62 of 149 genera (40%) exhibited a significant interaction between NAFLD and ethnicity stratified analysis found 69 genera significantly associated with NAFLD in at least one ethnic group. No single genus was significantly associated with NAFLD across all ethnicities. In contrast, the same bacterial metabolic pathways were over-represented in participants with NAFLD regardless of ethnicity. Imputed secondary bile acid and carbohydrate pathways were associated with NAFLD, the latter of which was corroborated by metagenomics, although different genera in different ethnicities were associated with these pathways. Overall, we found that NAFLD was associated with altered bacterial composition and metabolism, and that bacterial endotoxin, assessed by plasma lipopolysaccharide binding protein (LBP), may mediate liver fat-associated systemic inflammation in a manner that seems to vary by ethnicity.