Changes in the fecal bacterial microbiota associated with disease severity in alcoholic hepatitis patients

Abstract

Background and Aims: Alcoholic hepatitis is the most severe form of alcohol-related liver disease. While the gut microbiome is known to play a role in disease development and progression, less is known about specific compositional changes of the gut bacterial microbiome associated with disease severity. Therefore, the aim of our study was to correlate gut microbiota features with disease severity in alcoholic hepatitis patients. Methods: We used 16S rRNA gene sequencing on fecal samples from 74 alcoholic hepatitis patients, which were enrolled at 9 centers in Europe, the United States, and Mexico in a multicenter observational study. The relative abundance of gut bacterial taxa on genus level, as well as the microbiome diversity, was correlated to various clinical, laboratory, and histologic parameters. Results: We observed a negative correlation between the model for end-stage liver disease score and Shannon diversity, independent of potentially confounding factors (P adjust = 0.046). Alcoholic hepatitis patients with more severe disease had significantly decreased relative abundances of Akkermansia while the relative abundance of Veillonella was increased. We observed a reduction in the Bacteroides abundance (P adjust = 0.048) and Shannon diversity (P adjust = 0.018) in antibiotictreated patients and patients receiving steroids had an increase in Veillonella abundance (P adjust = 0.005), which was both independent of potentially confounding factors. Conclusion: We observed distinct changes in the gut bacterial microbiome of alcoholic hepatitis patients with more severe disease. The gut bacterial microbiome might be an attractive target to prevent and treat this deadly disease.

Gut dysbiosis as a driver in alcohol-induced liver injury

“…Morganella [21]. There was a significant reduction in alpha diversity in the high MELD group, and furthermore, increasing MELD score correlated with reduction in diversity as a continuous variable [21].…”

“…There was a significant reduction in alpha diversity in the high MELD group, and furthermore, increasing MELD score correlated with reduction in diversity as a continuous variable [21]. Patients with coexisting cirrhosis on liver biopsy had a significant increase in Clostridium sensu stricto and unclassified Gammaproteobacteria compared to non-cirrhotic patients with AH [21]. There was an increase in Enterococcus, Bifidobacterium, Lactococcus, Oribacterium, Desulfovibrio, and Veillonella in patients with high grade steatosis [21].…”

“…We recently completed an analysis of fecal samples of 74 AH patients J o u r n a l P r e -p r o o f from 9 centers internationally, with particular attention paid to dysbiosis associated with severity of disease. As a surrogate for disease severity, severe hyperbilirubinemia was associated with a significant reduction in unclassified Enterobacteriaceae and Akkermansia [21]. The most significant expansions were among taxa of very low abundance, however, there was a prominent expansion of Veillonella in the high bilirubin group (the relative abundance of which also positively correlated with degree of hyperbilirubinemia on a continuum) [21].…”

“…As a surrogate for disease severity, severe hyperbilirubinemia was associated with a significant reduction in unclassified Enterobacteriaceae and Akkermansia [21]. The most significant expansions were among taxa of very low abundance, however, there was a prominent expansion of Veillonella in the high bilirubin group (the relative abundance of which also positively correlated with degree of hyperbilirubinemia on a continuum) [21]. MELD score exceeding 21 in AH patients was associated with higher amounts of unclassified Neisseriaceae and reduction in unclassified Clostridiales, unclassified Prevotellaceae, Anaerostipes, and…”

“…Akkermansia is largely considered to be a beneficial inhabitant of the microbiome, and its role in fatty acid metabolism contributes to the barrier function of the human intestine [22]. Depletion of Akkermansia is implicated in cirrhosis secondary to non-alcoholic steatohepatitis, however, there is increasing evidence of its involvement in the dysbiosis of ALD [17,21,22]. In 2018,…”