Differences of Biochemical Endotoxin-Related Markers and Faecal Microbiota in Patients with HIV and HCV Infections. Summary of the Doctoral Thesis

Abstract

Infections caused by the Human Immunodeficiency virus (HIV) and hepatitis C virus (HCV) have remained relevant since their discovery. Every year, 1.5 million new cases of both HIV and HCV are detected (UNAIDS, 2022; WHO, 2022). A hallmark of progressive HIV infection is chronic immune activation associated with microbial translocation from the gastrointestinal tract, allowing bacterial metabolic components to enter the general circulation without clinically and laboratory detectable bacteraemia. HCV-infected patients also show increased rates of microbial translocation and subsequent T cell activation. The potential causal relationship between the composition of the gut microbiota and its alterations is being investigated in the context of many diseases. HIV-infected patients have lower amount of total bacterial genes and lower bacterial diversity in the intestinal tract compared to healthy individuals, as well as changes in the composition of individual bacterial species, with an increase in pathogenic bacteria and a decrease in beneficial bacteria in the intestinal tract. In addition, about 60–80 % of CD4+ T lymphocytes in the human body are located in the gut-associated lymphoid tissues. In HIV infection, the population of these lymphoid cells and the composition of the gut microbiota are significantly altered, which may influence the further progression of HIV infection. The changes in the gut microbiota together with alterations in the barrier function of the intestinal mucosa, may facilitate the entry of bacterial metabolic intermediates or components into the bloodstream, thereby stimulating and sustaining immune activation that continues to perpetuate a chronic inflammatory condition. Changes in the diversity and composition of the gut microbiota are also observed in liver diseases, including chronic viral hepatitis C. Increased intestinal permeability and translocation of bacterial components from the intestinal tract may also be associated with immune activation and progressive liver damage. To understand the interplay between gut microbiota and microbial translocation, it is necessary to assess the differences between the faecal microbiota and endotoxin-related markers of microbial translocation and their potential impact on the course of HIV and HCV infections. The aim of this study was to identify and analyse differences in endotoxin-associated microbial translocation markers and faecal microbiota in HIV and HCV-monoinfected and HIV / HCV-coinfected patients, and to evaluate the correlations between these parameters in the study groups. The study included 81 patients, 28 HIV-monoinfected, 24 HCV-monoinfected and 29 HIV / HCV-coinfected. We measured microbial translocation markers such as soluble CD14 (sCD14), lipoprotein binding protein (LBP) and antibodies to endotoxin core antigen (EndoCAb), indirect markers of liver fibrosis, and analysed the composition and diversity of the faecal microbiota. We found lower microbial translocation parameters in HCV-monoinfected patients compared to HIV-monoinfected and HIV / HCVcoinfected patients, but no differences between HIV-monoinfected and HIV-coinfected patients. Faecal microbiota diversity was higher in the HCV-monoinfected group compared to the HIV-monoinfected and HIV / HCV-coinfected groups, between which no differences were observed. A total of 1651 taxonomic units were found in the fecal microbiota, of which more than 98 % belonged to 10 bacterial phyla. However, only four of them were predominant: Firmicutes, Bacteroidota and Proteobacteria in HIV-infected patients, and Firmicutes, Bacteroidota and Actinobacteriota in HCV-monoinfected patients. We found differences in different bacterial taxonomic levels between patient groups, but the largest differences were observed between HCV-monoinfected and HIV-monoinfected patients, but not between HIV-monoinfected and HIV / HCV-coinfected patient groups. At the level of bacterial families, a higher representation of Enterobacteriaceae, Enterococcaceae and Lactobacillaceae was observed in HIV-infected compared to HCV-monoinfected patients. In addition, bacterial families Lachnospiraceae, Oscillospiraceae, Peptostreptococcaceae and Ruminococcaceae, belonging to Clostridia class, as well as Bifidobacteriaceae family which belongs to Actinobacteriota class, were less abundant in the microbiota of HIV-infected patients. Certain bacterial classes (Gammaproteobacteria, Coriobacteria, Bacilli, Desulfovibrionia) were associated with markers of microbial translocation as well as HIV infection activity parameters (CD4+ T cells, HIV RNA). HIV-monoinfected and HIV / HCV-coinfected patients showed more pronounced microbial translocation than HCV-monoinfected patients, as well as significant changes in the diversity and composition of microbiota, and certain bacterial classes showed a significant association with the extent of microbial translocation in HIV-monoinfected and HIV / HCV-coinfected patients.