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

NeuroImmune pharmacology and therapeutics Pub Date : 2025-12-25 eCollection Date: 2025-12-01 DOI:10.1515/nipt-2024-0024
Mason T Rodriguez, Sarah J Olmstead, Kristen A McLaurin, Charles F Mactutus, Rosemarie M Booze
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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-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.

Methods: 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.

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.

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

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s -雌马酚:一种治疗hiv -1相关胃肠道失调的新药物。
目的:全世界约有3840万人感染HIV-1。联合抗逆转录病毒疗法(cART)的出现大大改善了感染者的生活质量;然而,大约50% %的这些人仍然会经历hiv -1相关的神经认知障碍(HAND)。此外,据报道,无论是否坚持cART, HIV-1感染者的胃肠道微生物群都存在生态失调。目前的研究指出,肠道-大脑-微生物群轴是治疗认知缺陷和微生物变化的潜在目标。本研究探讨了s -雌马酚(SE)通过调节胃肠道微生物群作为HAND的潜在治疗药物。方法:采用21只HIV-1 Tg大鼠和21只F344对照动物,研究0.2 mg SE 对PR强化计划下可卡因维持反应的影响。结果:无论治疗组如何,胃肠道微生物组在门和属水平上均存在差异,SE 治疗既有主要作用,也与基因型有相互作用。普雷沃氏菌a_ucg_001与杠杆按压毒品显著相关,提示对可卡因的动机有影响。同种异体沃氏菌在治疗效果上存在显著的基因型差异,说明SE 对基因型的影响存在差异。结论:除了cART之外,SE可能为hiv -1相关生态失调和相关神经认知功能障碍提供一种新的辅助治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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