Gut-derived bacterial toxins impair memory CD4+ T cell mitochondrial function in HIV-1 infection

Alterations in circulating markers in HIV/AIDS patients with poor immune reconstitution: Novel insights from microbial translocation and innate immunity

“…Gut bacterial-derived solutes (GBDSs), such as p-cresol sulfate (PCS) and indoxyl sulfate (IS), could impair mitochondrial fitness and thus result in an INR-specific reduction in CD4 + T cells; and fecal samples of INRs were enriched with bacterial genera capable of producing PCS (23). Ghneim K et al found that senescent INRs were associated with higher HIV persistence and were driven by the plasma metabolome and microbes with a rich butyrate/bile acid (BA) (143).…”

“…One study found that fecal flora alpha diversity declined in PLWH and was independently associated with the patients’ immune status, and that patients with lower CD4 + T cell counts had decreased alpha diversity, suggesting that remodeling the intestinal flora may restore immune function in PLWH ( 22 ). Microbial diversity plays a crucial role in host immune homeostasis, and the introduction of ART could not fully restore the diversity of the gut microbiota ( 23 ). The metagenomic sequencing results of Yirui Xie’s team showed that the INRs and IRs could not be fully restored from the dysregulated gut microbiota in HIV infection.…”

“…Gut bacterial-derived solutes (GBDSs), such as p -cresol sulfate (PCS) and indoxyl sulfate (IS), could impair mitochondrial fitness and thus result in an INR-specific reduction in CD4 + T cells; and fecal samples of INRs were enriched with bacterial genera capable of producing PCS ( 23 ). Ghneim K et al.…”

Metabolism-dependent ferroptosis promotes mitochondrial dysfunction and inflammation in CD4+ T lymphocytes in HIV-infected immune non-responders

“… 50 Bacterial toxins from microbial gut translocation could hamper mitochondrial function, which is frequently linked to increased inflammation through the creation of ROS, a major source of oxidative stress and cell death. 4 The enteric microbiota’s enhanced inflammatory characteristics and damage to the gut mucosa with concomitant microbial translocation are the main causes of the chronic inflammation linked to HIV. 51 We then measured levels of ROS, MMP, and lipid peroxides of the total population included.…”

“…However, none of these independent factors can fully be explained. 3 , 4 , 5 , 6 , 7 Conversion or intense ART regimens in INRs have no effect on CD4 cell counts, and the latter are more vulnerable to AIDS-related and non-AIDS-related illness and death. 8 , 9 Thymic output is a pivotal process in immune reconstitution and can be inferred by assessing T cell receptor excision circles (TREC) and naive CD4 cells expressing CD31 + , which are termed recent thymic emigrants (RTE).…”