Chronic hepatitis D infection is associated with distinguishing microbial and functional features in the gut microbiome.

BACKGROUND

The microbiome of patients with hepatitis D virus (HDV) has yet to be characterized. This study aims to (1) characterize gut microbial composition in HDV, (2) determine its functional profile, (3) identify microbial species that contribute to changes in pathway expression, and (4) correlate the changes in the gut microbiome with clinical markers of disease severity.

METHODS

Cross-sectional analyses of 35 HDV-infected patients and 32 healthy controls (HCs) were performed. DNA and RNA were isolated from stool and sequenced by shotgun-sequencing. Microbial and functional profiles were compared between the HDV-cohort and HCs to identify disease-specific alterations to the gut microbiome. Clinical metadata were used to identify correlations with disease severity.

RESULTS

There were significant changes in the composition of the gut microbiome in HDV-infected patients as compared with HCs, spanning multiple bacterial phyla. Expression of 194 pathways was significantly increased in the HDV group. Pathways that were upregulated in the HDV cohort were related to amino acid and carbohydrate biosynthesis or involved important metabolic cofactors and carriers. Several microbial species, including Bacteroides fragilis, Cateibacterium mitsuokai, and Faecalibacterium prausnitzii, were identified as contributing to the differentially expressed pathways. Four genera correlated with hepatic venous pressure gradient (HVPG).

CONCLUSION

There are significant differences in microbial composition between HDV and HCs, several of which are found to be altered in other liver diseases. Upregulated pathways suggest a broader dysregulation of energy metabolism, even in early disease. These findings provide insight into pathways that may lead to liver disease progression in HDV.