HIV-associated gut microbiome regulates intestinal intra-epithelial lymphocytes and opportunistic infection. HIV-associated gut microbiome regulates intestinal intra-epithelial lymphocytes and opportunistic infection

Despite suggested correlations, causative gut microbiome impacts on HIV manifestations remain elusive. We characterized microbiomes from two geographically-distinct cohorts of people living with HIV (PLWH) and uncovered disease-specific, geographically divergent HIV-related microbial signatures that associated with peripheral CD4+ T cell counts. Intriguingly, fecal microbiome transplantation (FMT) into germ-free or antibiotics-treated mice, from PLWH featuring high, but not from PLWH featuring low peripheral CD4+ T cells, induced colonic intraepithelial (IEL) CD4+ T cells in recipient mice. Importantly, impaired colonic IELs induction in FMT recipients of PLWH donors featuring low peripheral CD4+ T cells was associated with an altered protection from opportunistic Cryptosporidium parvum infection. In all, our results suggest a causal link between systemic immune dysfunction in PLWH, an altered gut microbiome, and a resultant impairment in gut mucosal immunity, that may predispose to opportunistic gut infection. As such, restorative microbiome interventions may prevent or ameliorate intestinal infectious complications in PLWH.