Abstract
Gut dysbiosis is regarded as a pathogenetic factor of nonalcoholic fatty liver disease (NAFLD), but its role in NAFLD persistence is unknown. We investigated the influence of the gut microbiota on persistent NAFLD. This cohort study included 766 subjects with 16S ribosomal RNA (rRNA) gene sequencing data from fecal samples at baseline who underwent repeated health check-up examinations. Fatty liver was determined using ultrasound at baseline and follow-up. Participants were categorized into four groups: none (control), developed, regressed, or persistent NAFLD. The persistent NAFLD group had lower richness compared with the control group. Significant differences were also found in both non-phylogenic and phylogenic beta diversity measures according to NAFLD persistence. Pairwise comparisons indicated that taxa abundance mainly differed between the control and persistent NAFLD groups. A relative high abundance of Fusobacteria and low abundance of genera Oscillospira and Ruminococcus of the family Ruminococcaceae and genus Coprococcus of the family Lachnospiraceae were found in the persistent NAFLD group. Based on the functional predictions, pathways related to primary and secondary bile acid biosynthesis were highly detected in the persistent NAFLD group compared with the control group. These findings support that the composition of the gut microbiome associated with dysregulation of bile acid biosynthetic pathways may contribute to the persistence of NAFLD. This is the first cohort study to demonstrate the influence of microbiota on persistent NAFLD. Our findings may help identify potential targets for therapeutic intervention in NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) that can progress to fibrosis, cirrhosis, liver failure, or hepatocellular carcinoma in a subgroup of patients [1,2]
In a large cohort study, patients with persistent NAFLD had a higher risk of subclinical carotid atherosclerosis development compared with those without NAFLD that was mediated by metabolic risk factors; this highlights the importance of persistent NAFLD as a risk factor for metabolic diseases and atherosclerotic cardiovascular disease (CVD) [11]
To better understand how the microbial community composition changed with NAFLD persistence, we investigated which organisms were present at different taxonomic levels and their relative abundance levels
Summary
Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of liver diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) that can progress to fibrosis, cirrhosis, liver failure, or hepatocellular carcinoma in a subgroup of patients [1,2]. NAFLD is considered a multisystem disease that is closely associated with various extrahepatic diseases, including type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, and cardiovascular disease (CVD) [6,7,8]. NAFLD is a reversible condition and fatty liver status can change over time [9,10]. Several studies suggested that persistent NAFLD is associated with an increased risk of incident diabetes or subclinical atherosclerosis [11,12]. In a large cohort study, patients with persistent NAFLD had a higher risk of subclinical carotid atherosclerosis development compared with those without NAFLD that was mediated by metabolic risk factors; this highlights the importance of persistent NAFLD as a risk factor for metabolic diseases and atherosclerotic CVD [11]. Identifying the underlying mechanisms for persistent NAFLD could be useful for developing new therapeutic targets
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