Novel Microbial Signatures in the Faecal Microbiome Associated with Severe Alcoholic Hepatitis: Bacteroides Finegoldii and Veillonella Dispar

Abstract

Background: Alcoholic hepatitis is associated with dysbiosis, resulting in compositional changes in the gut microbiome, endotoxin transfer to the portal vein, and activation of inflammatory signalling pathways in the liver. However, the microbiome signature of severe alcoholic hepatitis (AH) patients of Indian origin is unknown. Aim: To investigate the microbiome diversity of Indian AH patients in comparison to non-alcoholic healthy controls (HC). Methods: 16S rRNA amplicon-based metagenomics analysis of faecal samples at the time of AH diagnosis (n=12) was compared with HC (n=6), and correlation with survival status, co-occurrence networking, Linear Discriminant Analysis Effect Size (LEfSe), and the relationship between diet – microbiome were performed. Results: 16S rDNA data showed a significant abundance of the Enterobacteriaceae family belonging to the phylum Proteobacteria and a depletion of the phylum Firmicutes in AH. A species-level classification identified Klebsiella pneumonia, Klebsiella variicola, and Parabacteroides distasonis as having the highest predictive performance value with reference to mortality at 60 days. Apart from this, a unique finding was the abundance of Bacteroides finegoldii and Veillonella dispar in AH patients. Moreover, the co-occurrence networking analysis revealed a higher level of connectivity and complexity within the microbial community of AH patients compared to HC. Thus, indicating the significant positive association (Spearman r > 0.7, p < 0.01) among members of the Firmicutes, Bacteroidetes, and Proteobacteria phyla in AH. Wilcoxon-Rank Sum test (p < 0.01) identified Firmicutes phyla occurrence associated with high carbohydrate intake and Actinobacteria phyla with low protein intake. Conclusion: The findings provide the baseline occurrence profile of the gut microbiome signature of liver damage and the diet-microbiome relationship in patients with severe AH. The study demonstrated an abundance of Proteobacteria phyla, indicating their role in inflammatory conditions, and further identified Bacteroides finegoldii and Veillonella dispar in severe AH patients. Additionally, Klebsiella pneumonia, Klebsiella variicola, and Parabacteroides distasonis were identified as mortality-predictive risk biomarkers.