Gut microbial community differentially characterizes patients with nonalcoholic fatty liver disease

Abstract

Background and aim: Discordant reports of the signature gut microbes involved in nonalcoholic fatty liver disease (NAFLD) have hampered understanding of the pathogenesis of the disease, and thus its diagnosis. Thus, we investigated diagnostic factors and the potential mechanisms for heterogenous NAFLD based on the gut environment, including microbes and functional pathways.

Methods: Stools from 16 biopsy-proven NAFLD patients were analyzed for bacterial taxonomy and functional pathways based on 16s rRNA gene sequencing. Data from the physical examination, serum biochemistry, and the gut environment were subjected to a decision tree classifier to identify diagnostic markers.

Results: We identified two NAFLD subpopulations: those with and without a gut microbiota similar to health controls (HCs), defined as P_HC-like and P patients, respectively. Stools of P_HC-like patients were significantly populated with Enterobacteriaceae and were inferred to be rich in metabolites degraded from dicarboxylic acid sugars. Significant colonization of Prevotella was observed in the stools of P patients, in parallel with enrichment of metabolites from heme b biosynthesis and sulfate reduction. As a potential mechanism, we suggest that protoporphyrin IX and/or protoheme from Prevotella participates in hepatic injury, and that endogenous hydrogen sulfide increases serum IL-6 level in P patients. However, endotoxin-producing Enterobacteriaceae are thought to produce glycerate, triggering a peroxisome proliferator- activated receptor-alpha-mediated decrease in IL-6 level and fat accumulation in P_HC-like patients.

Conclusions: Heterogenous NAFLD subpopulations were identified, defined according to gut microbial composition and their potential underlying pathogenic mechanisms; our results raise the possibility of personalized treatment for NALFD patients.

Keywords: diagnosis; gastrointestinal microbiome; nonalcoholic fatty liver disease; precision medicine.