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

Sep 28, 2026

Uploaded by jay

The study evaluates S-Equol (SE) as a potential adjuvant therapeutic targeting the gut-brain-microbiota axis to address HAND in the context of HIV-1. HIV-1 affects about 38.4 million people worldwide, and even with combination antiretroviral therapy, roughly half develop neurocognitive disorders. Gastrointestinal dysbiosis persists regardless of cART adherence. Methods test SE effects on gastrointestinal microbiome alterations and behavioral reinforcement measures in HIV-1 Tg rats and control animals.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Introduction

HIV-1, cART, and persistent HAND

Gastrointestinal dysbiosis and mechanisms

Gut-brain-microbiota axis as a treatment target

Methods

Animal model and S-Equol dosing

Behavioral and reinforcement testing

Results

Microbiome alterations by genotype and treatment

Prevotella associations with cocaine lever pressing

Genotype-specific differentiation by Alloprevotella

Mason T. Rodriguez, Sarah J. Olmstead, Kristen A. McLaurin, Charles F. Mactutus and Rosemarie M. Booze* S-Equol: a novel therapeutic for HIV-1-associated gastrointestinal dysbiosis [https://doi.org/10.1515/nipt-2024-0024](https://doi.org/10.1515/nipt-2024-0024) Received December 11, 2024; accepted October 28, 2025; published online December 25, 2025 Abstract Objective: 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-brainmicrobiota 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. Methods: The study included 21 HIV-1 Tg rats and 21 F344 control animals to test the effect 0.2 mg SE has on cocainemaintained responding on a PR schedule of reinforcement. Results: 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. Current address: Sarah J. Olmstead, Transcend Therapeutics, New York, NY, USA; and Kristen A. McLaurin, College of Pharmacy, University of Kentucky, Lexington, KY, USA. *Corresponding author: Rosemarie M. Booze, PhD, Carolina Trustees Professor and Bicentennial Endowed Chair of Behavioral Neuroscience, Cognitive and Neural Science Program, Department of Psychology, Barnwell College, University of South Carolina, 1512 Pendleton Street, Columbia, SC 29208, USA, E-mail: [booze@mailbox.sc.edu](booze@mailbox.sc.edu) Mason T. Rodriguez, Sarah J. Olmstead, Kristen A. McLaurin and Charles F. Mactutus, Cognitive and Neural Science Program, Department of Psychology, Barnwell College, University of South Carolina, Columbia, SC, USA Conclusions: SE may provide a novel adjuvant treatment in addition to cART for HIV-1-associated dysbiosis and associated neurocognitive dysfunction. Keywords: S-Equol; gut-brain-microbiota axis; dysbiosis; HIV; HIV-1-associated neurocognitive disorders Introduction Human immunodeﬁciency virus 1 (HIV-1) has infected an estimated 38.4 million people around the world [1] . Combination antiretroviral therapy (cART) is the main treatment for HIV and works to control the replication of HIV, resulting in improved CD4 T cell counts and preventing transmission to others by those compliant with the cART regimen (WHO, 2022) . The use of cART has also greatly decreased the prevalence of HIV-1-associated dementia (HAD), but HIV- 1-associated neurocognitive disorders (HAND) continue to persist, affecting approximately 50 % of HIV-1 seropositive individuals regardless of cART treatment [2] . Treatment is usually started as soon as a diagnosis is made but by then the infection has already established latent, viral reservoirs, that prevent full eradication of the virus by antiretrovirals, due to an inability of cART to reach these latent reservoirs [3] . The infection enters the body through the exchange of bodily ﬂuids (blood, semen, and vaginal secretions) with an infected individual. Once inside the body, HIV-1 initially binds to CD4+ T cells via the C-C chemokine receptor type 5 (CCR5) co-receptor. The gastrointestinal (GI) tract contains the largest mucosal immune system, making it

FAQs

What was the main objective of the study on S-Equol?

To assess whether S-Equol can serve as a potential therapeutic for HIV-1-associated neurocognitive disorders by modulating the gastrointestinal microbiome.

How was S-Equol tested in the study?

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

What microbiome findings were reported after S-Equol treatment?

Genotype-related gastrointestinal microbiome alterations were observed at the phylum and genus levels, and S-Equol showed main effects and interactions with genotype; Prevotella_UCG_001 related to drug lever pressing and Alloprevotella differentiated genotype by treatment effects.

Sep 28, 2026

Uploaded by jay