Gut microbiome and cardiometabolic comorbidities in people living with HIV

Abstract

Background: Despite modern antiretroviral therapy (ART), people living with HIV (PLWH) have increased relative risk of inflammatory-driven comorbidities, including cardiovascular disease (CVD). The gut microbiome could be one of several driving factors, along with traditional risk factors and HIV-related risk factors such as coinfections, ART toxicity, and past immunodeficiency.

Results: PLWH have an altered gut microbiome, even after adjustment for known confounding factors including sexual preference. The HIV-related microbiome has been associated with cardiometabolic comorbidities, and shares features with CVD-related microbiota profiles, in particular reduced capacity for short-chain fatty acid (SCFA) generation. Substantial inter-individual variation has so far been an obstacle for applying microbiota profiles for risk stratification. This review covers updated knowledge and recent advances in our understanding of the gut microbiome and comorbidities in PLWH, with specific focus on cardiometabolic comorbidities and inflammation. It covers a comprehensive overview of HIV-related and comorbidity-related dysbiosis, microbial translocation, and microbiota-derived metabolites. It also contains recent data from studies in PLWH on circulating metabolites related to comorbidities and underlying gut microbiota alterations, including circulating levels of the SCFA propionate, the histidine-analogue imidazole propionate, and the protective metabolite indole-3-propionic acid.

Conclusions: Despite recent advances, the gut microbiome and related metabolites are not yet established as biomarkers or therapeutic targets. The review gives directions for future research needed to advance the field into clinical practice, including promises and pitfalls for precision medicine. Video Abstract.

Fig. 1

Gut microbiota differences in cases versus unaffected controls across 20 common human diseases. A For diseases assessed using the American Gut Project, differences between cases and controls in distribution of confounding variables were assessed as previously described by comparing cases to randomly selected controls [48]. For PLWH, previously reported differences between PLWH and the HIV-uninfected population are represented for alcohol [54], diet [50, 51], sex, and anal receptive intercourse [55]. B Sequencing data were collated from the American Gut Project and prior analyses of the AGEhIV cohort and were processed in identical fashion [46, 48, 52] using dada2 [56]. For both datasets, Canberra beta-diversity matrices were calculated, and PERMANOVA tests were performed to quantify significance and effect sizes of ecological distances between cases and controls for each disease. Sample sizes are shown in parentheses encompassing balanced cohorts of cases and controls matched for confounding variables displayed at top left. For HIV cohorts, PERMANOVA statistics were calculated on five total sample groups from two studies [46, 52] including the following: men who have sex with men (n = 76) [46], females (n = 38) [46], men who have sex with women (n = 34) [46], combined females and males (irrespective of sexual behavior (148) [46], and a separate cohort of men who have sex with men (n = 102) [52]