Abstract
Human immunodeficiency virus (HIV) disease outcomes have improved greatly due to advances in anti-retroviral therapies (ART). In the absence of curative treatments, HIV is increasingly managed as a chronic illness, as patient lifespan extends to that of the general population. With these developments, focus has shifted to addressing long-term HIV co-morbidities. One consequence of HIV infection is sustained gastrointestinal (GI) tract inflammation despite ART. Interleukin-6 (IL-6) is an inflammation marker associated with altered microbial taxa composition in endometriosis and Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) patients. While both HIV and IL-6 elevation are understood to impact microbiome characteristics, work that analyzes the effects of IL-6 levels in persons living with HIV (PLWH) is limited. Given the increased importance of understanding long-term health impacts in PLWH, and the essential role of the microbiome in a broad axis of pathologies, we sought to evaluate differences in microbial diversity, composition, and functionality in the gut microbiomes of PLWH with high and low levels of IL-6. This investigation used 16S rRNA sequencing from stool samples and plasma IL-6 data from blood samples collected from a cohort of 148 individuals, 106 of whom were PLWH and 42 were healthy controls. This was achieved through alpha and beta diversity analysis, core microbiome and differential expression sequence analysis, as well as functional pathway analysis. The results of these analyses demonstrated that IL-6 levels may be the main drivers of differences in microbial beta diversity and composition, but not functional activity. This study emphasizes the need to include more diverse populations with a broader range of IL-6 levels to assess the generalizability of these findings, and suggests that IL-6 may be a potential therapeutic target worth further investigating to inform therapeutic selection in PLWH.