Abstract Details

Title Plasma Microbiome Composition among Brain Health Phenotypes in People with HIV (PWH)

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P10 - Poster Session 10 (5:00 PM-6:00 PM)

Poster/Presentation
Number 3-006

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.

Authors/Disclosures
Mohammadsobhan Sheikh Andalibi, MD (University of California San Diego) PRESENTER	Dr. Sheikh Andalibi has nothing to disclose.
Lora Khatib	Ms. Khatib has nothing to disclose.
BIN TANG (UCSD)	BIN TANG has nothing to disclose.
Donald Franklin, Jr., Research Administrator	Mr. Franklin has nothing to disclose.
Robert K Heaton	The institution of Robert K Heaton has received research support from NIH. Robert K Heaton has received intellectual property interests from a discovery or technology relating to health care. Robert K Heaton has received intellectual property interests from a discovery or technology relating to health care.
Rob Knight, PhD	Prof. Knight has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cybele Microniome, Inc. . Prof. Knight has received personal compensation in the range of $0-$499 for serving as a Consultant for DayTwo, Ltd.. Prof. Knight has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BiomeSense, Inc. . Prof. Knight has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for GenCirq, Inc. . Prof. Knight has stock in Biota, Inc.. Prof. Knight has stock in Micronoma.
Scott L. Letendre, MD (HNRC, UCSD)	The institution of Dr. Letendre has received research support from National Institutes of Health. The institution of Dr. Letendre has received research support from University at Buffalo. Dr. Letendre has received publishing royalties from a publication relating to health care.
Ronald J. Ellis, MD, PhD, FAAN (UC San Diego)	Dr. Ellis has nothing to disclose.

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