# S-Equol: a novel therapeutic for HIV-1-associated gastrointestinal dysbiosis

**Authors:** Mason T. Rodriguez, Sarah J. Olmstead, Kristen A. McLaurin, Charles F. Mactutus, Rosemarie M. Booze

PMC · DOI: 10.1515/nipt-2024-0024 · Neuroimmune Pharmacology and Therapeutics · 2025-12-25

## TL;DR

S-Equol may help treat gut and brain issues in HIV-1 patients by altering gut bacteria.

## Contribution

S-Equol is proposed as a novel therapeutic for HIV-1-associated gastrointestinal dysbiosis and neurocognitive dysfunction.

## Key findings

- SE treatment altered gut microbiome composition at phylum and genus levels.
- SE affected lever pressing behavior linked to cocaine motivation in HIV-1 Tg rats.
- Alloprevotella differentiated genotype by treatment effects, suggesting SE's impact varies by genetic background.

## Abstract

HIV-1 infection affects approximately 38.4 million people around the world. The advent of combination anti-retroviral therapy (cART) has greatly improved the quality of life of infected individuals; however, roughly 50 % of these individuals will still experience HIV-1-associated neurocognitive disorders (HAND). Additionally, the gastrointestinal microbiome has been reported to be dysbiotic in HIV-1 infected individuals, regardless of adherence to cART. Current research has pointed to the gut-brain-microbiota axis as a potential target to treat both cognitive deficits and microbial changes. The present study investigated S-Equol (SE) as a potential therapeutic for HAND by modulating the gastrointestinal microbiome.

The study included 21 HIV-1 Tg rats and 21 F344 control animals to test the effect 0.2 mg SE has on cocaine-maintained responding on a PR schedule of reinforcement.

Gastrointestinal microbiome alterations between genotypes were found at the phylum and genus level, regardless of treatment group, and SE treatment had both main effects and interactions with genotype. Prevotella_UCG_001 was significantly associated with lever presses for drug, suggesting an effect on motivation for cocaine. Alloprevotella was found to significantly differentiate between genotype by treatment effects, indicating that SE differently affects genotypes.

SE may provide a novel adjuvant treatment in addition to cART for HIV-1-associated dysbiosis and associated neurocognitive dysfunction.

## Linked entities

- **Chemicals:** S-Equol (PubChem CID 91469)
- **Species:** Homo sapiens (taxon 9606), Rattus norvegicus (taxon 10116)

## Full-text entities

- **Diseases:** dysbiosis (MESH:D064806), HAND (MESH:D020943), neurocognitive disorders (MESH:D019965), HIV-1 (MESH:D015658), cognitive deficits (MESH:D003072), infected (MESH:D007239)
- **Chemicals:** S-Equol (MESH:D060754), cocaine (MESH:D003042)
- **Species:** Prevotella (genus) [taxon 838], Alloprevotella (genus) [taxon 1283313], Rattus norvegicus (brown rat, species) [taxon 10116], Human immunodeficiency virus 1 (no rank) [taxon 11676]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12755389/full.md

## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC12755389/full.md

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Source: https://tomesphere.com/paper/PMC12755389