## 6 Microbiota Alterations in HCV Patients
Given the emerging evidence linking gut dysbiosis to HCV pathogenesis and liver disease progression, microbiota-targeted therapeutic strategies are increasingly being explored as adjunctive approaches in HCV management. Probiotics and prebiotics, which selectively modulate beneficial microbial populations, have been proposed as potential interventions to restore gut homeostasis, enhance intestinal barrier integrity, and mitigate inflammation. Additionally, dietary modifications aimed at promoting microbiota diversity may offer protective effects against liver disease progression. Fecal microbiota transplantation (FMT), an innovative therapeutic strategy designed to reconstitute gut microbial communities, has shown promise in correcting dysbiosis in various gastrointestinal and metabolic disorders. However, further research is required to establish its efficacy, safety, and potential application in the context of HCV infection [44]. Variability in individual responses to medications can be attributed to several factors, one of which is the metabolism of these drugs by the human gut microbiota. This suggests that the gut microbiota may significantly influence the metabolism of antiviral agents used to treat HCV infection. Although there exists a body of research detailing the metabolic processes of various drugs mediated by gut microbiota, there remains a notable lack of studies specifically addressing the metabolism of antiviral drugs in this context. A set of microbiome-derived esterase enzymes, including acetyl esterase, lysophospholipase L1, and sialate O-acetylesterase, that participate in the metabolism of antiviral compounds were identified. However, further investigation is necessary to elucidate the complete array of microbiota genes involved in antiviral drug metabolism, potentially utilizing meta-proteomic and meta-transcriptomic approaches. Evidence that delebuvir is converted into the metabolite CD 6168 primarily through the metabolic activity of gut microbiota was provided. This conclusion was supported by experiments involving the incubation of delebuvir with fecal homogenates from humans and rats, as well as in vivo studies conducted in a pseudo-germ-free rat model, where the gut microbiota was largely eradicated through antimicrobial treatment, compared to control rats. Overall, these findings underscore the importance of evaluating the metabolism of antiviral drugs by gut microbiota and the implications of their metabolites in the context of drug development [42]. Research investigating the impact of hepatitis C virus (HCV) on microbiota dysbiosis has demonstrated that patients infected with HCV exhibit reduced bacterial diversity compared to healthy individuals. This alteration in diversity correlates directly with the severity and progression of the disease. Such findings may be linked to the production of immunoglobulin A (IgA) by gastric B lymphocytes infected with HCV, which subsequently induces modifications in the composition of the gut microbiota. Notably, advanced stages of chronic liver disease are associated with more significant changes in gut microbiota compared to patients with less severe disease. Furthermore, the reduction in gut microbiota diversity associated with HCV infection was found to be alleviated following treatment with antiviral medications. Conversely, a recent investigation indicated that healthy adults exhibited lower microbial diversity compared to treatment-naive patients newly diagnosed with HCV, highlighting the potential confounding influence of treatment in microbiome research. Additionally, variations in HCV-related diversity may stem from differences in ethnic backgrounds, therapeutic interventions, and stages of the disease among cohorts. During HCV infection, a significant depletion of the Clostridiales order has been observed, while the genera Lactobacillus and Streptococcus show notable increases.