Associations of the gut microbiome with hepatic adiposity in the Multiethnic Cohort Adiposity Phenotype Study

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for liver cancer and prevalence varies by ethnicity. Along with genetic and lifestyle factors, the gut microbiome (GM) may contribute to NAFLD and its progression to advanced liver disease. Our cross-sectional analysis assessed the association of the GM with hepatic adiposity among African American, Japanese American, White, Latino, and Native Hawaiian participants in the Multiethnic Cohort. We used MRI to measure liver fat and determine nonalcoholic fatty liver disease (NAFLD) status (n = 511 cases) in 1,544 participants, aged 60–77 years, with 12–53% overall adiposity (BMI of 17.8–46.2 kg/m 2 ). 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.

The Mechanism Underlying the Influence of Indole-3-Propionic Acid: A Relevance to Metabolic Disorders

“…An imbalance of intestinal microbes affects the TLR9-and TLR4-related inflammatory pathways in the liver (71). In multi-ethnic cohort studies, intestinal microbial a diversity was generally low in patients with metabolic diseases (72). In a clinical cohort study of 1,018 middle-aged women from TwinsUK, the relationship between serum IPA levels and gut microbial genes was evaluated, and a positive correlation between microbiota alpha diversity and serum IPA content was found (Shannon diversity: b [Shannon diversity: beta (95% CI] = 0.19 [0.13; 0.25], p = 6.41 × 10 −10 ) (73).…”

Effect of ancient wheat pasta on gut microbiota composition and bacteria-derived metabolites: A randomized controlled trial

“…In this regard, Martin-Gallausiaux and colleagues have documented that members of genus Erysipelatoclostridium are bacteria producing butyrate, a crucial SCFA with renowned and potent anti-inflammatory properties ( 23 ). In addition, the [Bacteroides]_pectinophilus_group is well known as a genus constituted by complex carbohydrate degrading bacteria ( 24 ). As to Holdemanella spp., Pujo and collaborators showed its anti-inflammatory properties in ulcerative colitis patients ( 25 ).…”

Dietary Intake Mediates Ethnic Differences in Gut Microbial Composition

“…The protocols for laboratory analysis and bioinformatic data processing have been described in detail [ 10 , 26 ] and also included in the online Supplementary Materials Figures S1 and S2 ), along with information on data sharing. Briefly, DNA from stool samples was extracted and amplified for the V1–V3 region of the 16S rRNA gene at Fred Hutch and shipped to the Research and Testing Laboratory (RTL LLC, Lubbock, TX, USA) for sequencing.…”