Plasma Microbiome Composition among Brain Health Phenotypes in People with HIV (PWH)
Mohammadsobhan Sheikh Andalibi1, Lora Khatib2, Bin Tang5, Donald Franklin3, Robert K Heaton6, Rob Knight4, Scott Letendre7, Ronald Ellis6
1University of California San Diego, 2Neurosciences Graduate Program, 3Department of Psychiatry, 4Department of Pediatrics, University of California San Diego, 5UCSD, 6UC San Diego, 7HNRC, UCSD
Objective:
This study aimed to investigate the association between plasma microbiome composition and brain health phenotypes (BHPs) in people with HIV (PWH).
Background:
Neurobehavioral disorders and gut dysbiosis continue to occur in treated PWH, but the relationship between the plasma microbiome and BHPs remains unexplored. Plasma microbiome analysis offers unique insights into systemic microbial translocation and immune responses.
Design/Methods:
410 PWH who were taking antiretroviral therapy and had plasma HIV RNA ≤ 200 copies/mL underwent comprehensive neuromedical and neurobehavioral assessments and provided plasma for 16S rRNA amplicon sequencing. As previously described, 17 brain health features, including cognitive domains, depression subscales, and daily functioning, defined 4 BHPs using dimension reduction with self-organizing maps (SOM) followed by k-means clustering methods: BHP1: healthy (n=187), BHP2: depression-dominant (n=94), BHP3: unhealthy in all features (n=55), and BHP4: cognitive impairment-dominant (n=74). Alpha and beta diversity were measured using diversity metrics. Differential species abundance was analyzed using Bayesian Inferential Regression for Differential Microbiome Analysis (BIRDMAn), adjusting for age and gender.
Results:
Cohort characteristics: mean age 42.7 ± 8.9 years, 16.3% female, 44.9% Black, 59.3% AIDS, mean CD4+ T-cells 467.5/µL. Alpha diversity was lower in BHP2 than in either BHP4 or BHP1 (each p < 0.05). Beta diversity also differed between BHP2 and BHP4 using weighted (p = 0.03) and unweighted UniFrac metrics (p = 0.01). Genus Actinomycetospora and Mycobacterium, Flavobacteriaceae family, and species Rothia mucilaginosa were more abundant in people with BHP4 than BHP2.
Conclusions:
These findings support a role for the plasma microbiome in modulating brain health in PWH. This may occur in part by modulating immune responses: Mycobacteria can induce proinflammatory immune responses and Flavobacteriaceae produce anti-inflammatory short-chain fatty acids. These results are provocative, but the cross-sectional design limits causal inference. Understanding these complex interactions could support the development of personalized, microbiome-based interventions to improve brain health in PWH.
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