Altered gut microbial profile accompanied by abnormal short chain fatty acid metabolism exacerbates nonalcoholic fatty liver disease progression

Abstract

Dysregulation of the gut microbiome has associated with the occurrence and progression of non-alcoholic fatty liver disease (NAFLD). To determine the diagnostic capacity of this association, we compared fecal microbiomes across 104 participants including non-NAFLD controls and NAFLD subtypes patients that were distinguished by magnetic resonance imaging. We measured their blood biochemical parameters, 16 S rRNA-based gut microbiota and fecal short-chain fatty acids (SCFAs). Multi-omic analyses revealed that NAFLD patients exhibited specific changes in gut microbiota and fecal SCFAs as compared to non-NAFLD subjects. Four bacterial genera (Faecalibacterium, Subdoligranulum, Haemophilus, and Roseburia) and two fecal SCFAs profiles (acetic acid, and butyric acid) were closely related to NAFLD phenotypes and could accurately distinguish NAFLD patients from healthy non-NAFLD subjects. Twelve genera belonging to Faecalibacterium, Subdoligranulum, Haemophilus, Intestinibacter, Agathobacter, Lachnospiraceae_UCG-004, Roseburia, Butyricicoccus, Actinomycetales_unclassified, [Eubacterium]_ventriosum_group, Rothia, and Rhodococcus were effective to distinguish NAFLD subtypes. Of them, combination of five genera can distinguish effectively mild NAFLD from non-NAFLD with an area under curve (AUC) of 0.84. Seven genera distinguish moderate NAFLD with an AUC of 0.83. Eight genera distinguish severe NAFLD with an AUC of 0.90. In our study, butyric acid distinguished mild-NAFLD from non-NAFLD with AUC value of 0.83. And acetic acid distinguished moderate-NAFLD and severe-NAFLD from non-NAFLD with AUC value of 0.84 and 0.70. In summary, our study and further analysis showed that gut microbiota and fecal SCFAs maybe a method with convenient detection advantages and invasive manner that are not only a good prediction model for early warning of NAFLD occurrence, but also have a strong ability to distinguish NAFLD subtypes.