Pilot Sub-Study of the Effect of Hepatitis C Cure by Glecaprevir/Pibrentasvir on the Gut Microbiome of Patients with Chronic Hepatitis C Genotypes 1 to 6 in the Mythen Study.

Melanie Harrer Kuster,Nasser Semmo,Olivier Clerc,Lorenzo Magenta,Lisa Ruckstuhl,Beat Müllhaupt,Bahtiyar Yilmaz,Ralph Torgler

doi:10.3390/ph14090931

Abstract

In this small pilot sub-study, longitudinal gut microbiota composition changes, after successful treatment of hepatitis C virus (HCV) with the co-formulated glecaprevir/pibrentasvir (GLE/PIB), were analyzed before treatment (baseline) and 12 weeks post-treatment. Participating patients provided a fresh stool sample the week before their study visit, from which microbial DNA was extracted and sequenced for the 16S rRNA region in an Illumina MiSeq2 platform. Microbial and statistical analyses were conducted to determine the alpha-diversity (number of different taxa within a sample) and beta-diversity (number of overlapping taxa between samples). Stool samples from 58 patients were eligible for analysis. There were 27 patients with HCV genotype 1, 10 with genotype 2, 16 with genotype 3, and 5 with genotype 4. No statistically significant differences in gut microbiota diversity, species richness, or microbial community pattern were found at baseline and at post-treatment Week 12. Lack of statistically significant differences remained consistent in further analysis by demographic and baseline disease characteristics. Surprisingly, no statistically significant changes in alpha- and beta-diversity were seen in the microbiota after GLE/PIB treatment, though there was a trend toward less richness over time. Further investigation is needed into this unexpected outcome to better understand the role of HCV treatment and the gut microbiota.

Highlights

Taxonomic and functional changes to the composition of the gut microbiota have been implicated in multiple human diseases, ranging from gastroenterological disorders to neurological, respiratory, metabolic, hepatic, and cardiovascular illnesses
Significant changes in the gut microbiota have been observed in patients positive for hepatitis
Samples from 58 patients who consented to the gut microbiota analyses were eligible for analysis

Summary

Introduction

Taxonomic and functional changes to the composition of the gut microbiota have been implicated in multiple human diseases, ranging from gastroenterological disorders to neurological, respiratory, metabolic, hepatic, and cardiovascular illnesses. The extended metabolic potential of biochemical pathways in microbes crucially contributes to human physiology, including digestive [2,3] and protective [4,5,6,7] functions (by out-competing the pathogens or via maturation of the host mucosal immune system) [8,9,10,11,12], catabolism of otherwise indigestible foodstuffs [13], provision of essential amino acids, synthesis of vitamins, completion of the bile salt cycle, and pre-systemic metabolism of drugs and Pharmaceuticals 2021, 14, 931.

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Discussion

Conclusion