Abstract Body: Introduction: The relationships among gut microbial alterations, host inflammation, and cardiac dysfunction remain understudied, particularly in the context of HIV.

Hypothesis: We hypothesized that higher abundance of pro-inflammatory gut bacteria is associated with higher levels of host circulating inflammatory makers and cardiac dysfunction.

Methods: We examined associations of gut microbial features (16S rRNA sequencing) with cardiac dysfunction (Echocardiography) in 973 women from the MACS/WIHS Combined Cohort Study. Cardiac dysfunction was defined as the presence of left ventricular systolic (LV ejection fraction<54%) or diastolic (ASE 2016 criteria) dysfunction. In a subset (n=397), we further integrated cardiac dysfunction-associated microbial features (Shotgun metagenomics sequencing) with serum proteomic inflammatory markers (Olink platform inflammation panel) in relation to cardiac dysfunction.

Results: The potentially pathogenic bacteria Streptococcus, Eggerthella and Anaeroglobus, were positively associated with cardiac dysfunction, while the beneficial genera Roseburia and Alistipes were linked to lower odds of cardiac dysfunction (Fig. 1A). Results were consistent in women with and without HIV. These cardiac dysfunction-associated bacteria were associated with a number of circulating proteomic inflammatory markers (Fig. 1B). For example, the pathogenic Streptococcus was positively associated with the pro-inflammatory cytokines IL-8 and IL-6, the chemokine MCP-3 (linked to immune response and atherosclerosis), and the inflammatory mediator OSM (associated with vascular inflammation and heart failure). Proteomic inflammatory scores were generated for each genus based on their specific inflammatory marker profiles. The inflammatory score for Streptococcus was significantly associated with cardiac dysfunction (Fig. 1C). Associations between bacterial genera and cardiac dysfunction were attenuated after further adjustment for specific microbial associated inflammatory markers (Fig. 1D).

Conclusion: Among women living with or at risk of HIV, we identified gut microbial features associated with cardiac dysfunction, with certain microbiota-related inflammatory markers partially explaining these associations.