Limosilactobacillus fermentum, Lactococcus lactis and Thomasclavelia ramosa are enriched and Methanobrevibacter smithii is depleted in patients with non-alcoholic steatohepatitis

Abstract

Non-alcoholic fatty liver (NAFLD), and its complicated form, non-alcoholic steatohepatitis (NASH), have been associated with gut dysbiosis with specific signatures. Endogenous ethanol production by Klebsiella pneumoniae or yeasts has been identified as a potential physio-pathological mechanism. A species-specific association between Lactobacillus and obesity and metabolic diseases has been reported. In this study, the microbial composition of ten cases of NASH and ten controls was determined using v3v4 16S amplicon sequencing as well as quantitative PCR (qPCR). Using different statistical approaches, we found an association of Lactobacillus and Lactoccocus with NASH, and an association of Methanobrevibacter, Faecalibacterium and Romboutsia with controls. At the species level, Limosilactobacillus fermentum and Lactococcus lactis, two species producing ethanol, and Thomasclavelia ramosa, a species already associated with dysbiosis, were associated with NASH. Using qPCR, we observed a decreased frequency of Methanobrevibacter smithii and confirmed the high prevalence of L. fermentum in NASH samples (5/10), while all control samples were negative (p = 0.02). In contrast, Ligilactobacillus ruminis was associated with controls. This supports the critical importance of taxonomic resolution at the species level, notably with the recent taxonomic reclassification of the Lactobacillus genus. Our results point towards the potential instrumental role of ethanol-producing gut microbes in NASH patients, notably lactic acid bacteria, opening new avenues for prevention and treatment.

Keywords: Ethanol; Gut microbiota; Lactococcus lactis; Limosilactobacillus fermentum; Nonalcoholic steatohepatitis; Thomasclavelia ramosa.