Human gut microbiome in Korean NAFLD cohort

Objective: Despite the association of nonalcoholic fatty liver disease (NAFLD) with obesity, NAFLD is also found in non-obese individuals. Few studies have focused on the role of the gut microbiome in non-obese NAFLD. We aimed to compare gut microbiome profiles between non-obese and obese NAFLD subjects.Design: The gut microbiome profiles of 171 Asian subjects with biopsy-proven NAFLD and 31 metabolically healthy controls were analyzed using 16S rRNA sequencing. Study subjects were divided into non-obese (n=64) and obese (n=138) groups. Each group was classified into three subgroups according to fibrosis severity (stage, 0 vs. 1 vs. 2–4). The microbiome profiles were compared with clinical metadata, including metabolic traits and genetic variants.Results: Significant alterations in gut microbiota according to fibrosis severity were observed only in non-obese subjects. Specifically, Enterobacteriaceae, Veilloneallaceae, and other gram-negative bacteria were gradually enriched with increasing fibrosis severity. Ruminococcaceae, however, was depleted with significant fibrosis (=F2). Significant associations between these bacteria and serum free fatty acid, adipose tissue insulin resistance, and glycosylated hemoglobin were found only in non-obese subjects. Apparent and strong co-occurring/co-excluding interactions were shown in non-obese subjects. Particularly, the addition of microbial abundance of Enterobacteriaceae, Veilloneallaceae, and Ruminococcaceae to body mass index and fibrosis 4 index showed 0.953 of area under the receiver-operating characteristic curvefor predicting significant fibrosis in non-obese NAFLD subjects.Conclusion: Our results demonstrated disparate compositions in gut microbiota between obese and non-obese Asian NAFLD subjects according to fibrosis severity, highlighting the pathogenic role of gut microbiota, especially in non-obese NAFLD.