Gut-adipose tissue axis in hepatic fat accumulation in humans

Background & Aims: Recent evidence suggests that in animals gut microbiota composition (GMC) affects the onset and progression of hepatic fat accumulation. The aim of this study was to investigate in humans whether subjects with high hepatic fat content (HHFC) differ in their GMC from those with low hepatic fat content (LHFC), and whether these differences are associated with body composition, biomarkers and abdominal adipose tissue inflammation. Methods: Hepatic fat content (HFC) was measured using proton magnetic resonance spectroscopy (H-1 MRS). Fecal GMC was profiled by 16S rRNA fluorescence in situ hybridization and flow cytometry. Adipose tissue gene expression was analyzed using Affymetrix microarrays and quantitative PCR. Results: The HHFC group had unfavorable GMC described by lower amount of Faecalibacterium prausnitzii (FPrau) (p <0.05) and relatively higher Enterobacteria than the LHFC group. Metabolically dysbiotic GMC associated with HOMA-IR and triglycerides (p <0.05 for both). Several inflammation-related adipose tissue genes were differentially expressed and correlated with HFC (p <0.05). In addition, the expression of certain genes correlated with GMC dysbiosis, i.e., low FPrau-to-Bacteroides ratio. Conclusions: HHFC subjects differ unfavorably in their GMC from LHFC subjects. Adipose tissue inflammation may be an important link between GMC, metabolic disturbances, and hepatic fat accumulation. (C)2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.