Background
People living with HIV (PLWH) suffer from increased incidence of metabolic disease and chronic systemic inflammation, even with effective Antiretroviral therapy (ART). Prevotella-rich, Bacteroides-poor (PRBP) microbiomes are commonly found in men who have sex with men (MSM), which make up a large portion of PLWH in the United States. A high-fiber agrarian diet (AD) has been found to be metabolically beneficial in PRBP microbiomes and is also seen in agrarian populations. Furthermore, a high-fat western diet (WD) can exacerbate disease in HIV animal models. There is thus potential for high-fiber/low-diets diets to have health benefits in HIV positive MSM (HIV(+)MSM).
Methods
We conducted a 4-week diet intervention in HIV(+)MSM and HIV(-) control groups, with subjects randomized to an AD or WD arm. Blood samples were collected for measurement of plasma inflammatory markers, as well as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Fecal and colonic biopsy samples were collected for 16S rRNA sequencing and cytometry by time-of-flight mass spectrometry (CyTOF). Additional host and microbial RNA sequencing was performed on biopsy samples.
Results
Individuals randomized to the AD had reductions in levels of both HDL-C and LDL-C, with the sustained reductions in LDL-C being strongest in HIV(+)MSM. The AD was also associated with reduced PD1+ and CD40+ T cells and reduced monocytes in the blood, independent of HIV or MSM status. While the fecal microbiome did not significantly change on the AD, a baseline microbiome with higher Prevotella and lower Bacteroides abundance (lower Weighted Unifrac Axis 2) was observed in MSM groups (Figure 1A and B). Prevotella richness and Bacteroides poorness predicted greater decreases in LDL-C with the AD (Figure 1B). Analysis of host transcriptional changes in biopsy samples of individuals highly compliant to the AD-intervention showed an increase in immune activation and changes in small RNA signaling molecules with the AD.
Conclusions
Our findings suggest that matching PRBP microbiomes to an AD has the power to reduce dyslipidemia and immune activation and exhaustion in PLWH, providing clinical utility in HIV-associated metabolic disease.