Association of gut microbiota and inflammation with carotid atherosclerosis in HIV infection with poor immune reconstitution.

BACKGROUND

People living with HIV (PLWH) have an excess risk of cardiovascular disease (CVD), but little is known regarding intrinsic links between gut microbiota profiles, inflammatory factors, and the risk of carotid atherosclerosis in HIV infection with poor immune reconstitution (INR).

METHODS

Well-controlled HIV patients were enrolled to analyze risk factors for carotid intima-media thickness (cIMT). Participants were stratified based on CD4+T cell count; fecal samples were collected for 16S rRNA sequencing, and plasma inflammatory markers were assessed.

RESULTS

Of 518 participants with a mean age of 45.1 years (SD, 12.0), 212 (40.9%) had carotid atherosclerosis. The prevalence of carotid atherosclerosis was significantly elevated (50/212, 23.6% vs 48/306, 15.7%; P < 0.05) in poor immune reconstitution subgroup (CD4+T cell count <350 cells/µL). CD4+ T-cell count and IL-6 levels were significantly associated with carotid atherosclerosis in multivariable analysis. Compared with IRs, INRs exhibited significantly elevated IL-6 levels. In terms of gut microbiota, INRs showed reduced α-diversity, an increased abundance of the f_Enterobacteriaceae, and multi-omics analysis revealed upregulated LPS levels. Furthermore, Network analysis revealed strong connections between gut microbes and carotid phenotypes. Gammaproteobacteria correlated positively with IMT and IL-6, while Christensenellaceae and Oscillospiraceae correlated negatively.

CONCLUSIONS

In PLWH with poor immune reconstitution, gut microbiota dysbiosis and increased inflammation were associated with an elevated risk of carotid atherosclerosis. Alterations in gut microbiota might be intertwined with systemic inflammation and poor immune reconstitution.