Gut microbiome composition and metabolic activity in metabolic associated fatty liver disease

Metabolic Associated Fatty Liver Disease (MAFLD) impacts approximately 25% of the global population. The objective of our study was to elucidate the characteristics of the gut microbiome and alterations in plasma metabolites among MAFLD patients. Between April 2023 and July 2023, 60 patients with MAFLD, along with 60 age, ethnicity, and sex-matched healthy controls (HCs), were enrolled from Inner Mongolia Autonomous Region, China. Analysis of gut microbiota composition and plasma metabolic profiles was conducted using metagenome sequencing and LC-MS. LEfSe analysis identified five pivotal species: Eubacterium rectale, Dialister invisus, Pseudoruminococcus massiliensis, GGB3278 SGB4328, and Ruminococcaceae bacteria. In subgroup analysis, Eubacterium rectale tended to be increased by more than 2 times and more than double in the non-obese MAFLD group, and MAFLD with moderate hepatic steatosis（HS）respectively. Combinations of phenomics and metabolomics yielded the highest accuracy (AUC = 0.97) in the MAFLD diagnosis. Combinations of phenomics and metagenomics yielded the highest accuracy (AUC = 0.94) in the prediction of the MAFLD HS progress. Plasma samples identified 172 metabolites mainly composed of fatty acid metabolites such as propionic acid and butyric acid analogues. Ruminococcaceae bacteria have a strong positive correlation with β-Alanine, Uric acid and L-Valine. Pseudoruminococcus massiliensis have a strong positive correlation with β-Alanine. Increases in Eubacterium rectale and decreases in Dialister invisus seem to be indicative of MAFLD patients. Eubacterium rectale may predicts HS degree of MAFLD and play an important role in the development of non-obese MAFLD. Eubacterium rectale can generate more propionic acid and butyric acid analogues to absorb energy and increase lipid synthesis, and ultimately cause MAFLD. The observed association between Ruminococcaceae bacteria and β-Alanine or Uric acid in these patients could offer fresh insights into the disease mechanism.