Abstract

Neurocognitive impairment (NCI) and gut microbiota dysbiosis are prevalent in patients with HIV infection. Docosahexanoic acid (DHA) supplementation may alleviate multiple neurocognitive diseases symptoms and plays important role in regulating gut microbiota. However, it is not known whether DHA algae oil supplements can alleviate neurocognitive impairment (NCI) and regulate gut microbiota and fecal metabolites. A randomized, double-blind, placebo-controlled trial was performed on 68 HIV-infected patients with NCI. Participants were randomized to receive a 3.15 g daily DHA algae oil supplement or placebo for 6 months. We collected blood and fecal samples from these patients before and after the trial. Mini mental state examination (MMSE) and neuropsychological tests (NP tests) were administered to assess the cognitive status of participants. The influence of DHA algae oil on the gut microbiota, fecal metabolomics, plasma proinflammatory, and oxidative stress factors was also investigated. There were no significant changes in NCI according to global diagnosis score (GDS) and MMSE score within the two groups, while patients receiving DHA had improvement in several blood lipids, pro-inflammatory and oxidative stress factors. The DHA supplement increased α-diversity indexes, increased abundances of Blautia, Bifidobacterium, Dorea, Lactobacillus, Faecalibacterium, Fusobacterium, and Agathobacter, and decreased abundances of Bacteroides and Prevotella_9. Furthermore, DHA supplement was correlated with improved fecal lipid metabolites as indicated by ceramides, bile acids, glycerophospholipids. In addition, the DHA supplement was associated with altered cholesterol metabolism and purine metabolism pathways. A daily supplement of DHA algae oil for 6 months has been shown to promote favorable transformations in gut microbiota, profiles of fecal metabolomic, and factors responsible for proinflammatory and oxidative stress, which might be beneficial for the prognosis of HIV-infected patients with NCI in the long-term.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04242004, identifier: NCT04242004.

Highlights

  • Patients infected with HIV are prone to neurocognitive impairment (NCI) [1]

  • There were no significant changes in NCI according to global diagnosis score (GDS) and Mini mental state examination (MMSE) score within the two groups, while patients receiving Docosahexanoic acid (DHA) had improvement in several blood lipids, pro-inflammatory and oxidative stress factors

  • DHA group had a lower low-density lipoprotein (LDL) level compared with the placebo group, while other clinical parameters and the intakes of dietary components had no difference between the two groups from the beginning of this study

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Summary

Introduction

Patients infected with HIV are prone to neurocognitive impairment (NCI) [1]. The NCI symptoms in HIV-infected individuals may be derived from the HIV infection, side effects of specific antiretroviral drugs (ARVs), or the aging of the HIV population [2]. Growing evidence reveals that gut microbiota has a great influence on the pathogenesis of neurocognitive diseases [4, 5]. Given the influence of n-3 PUFAs on microbiota and its anti-inflammatory effects, supplementation with n-3 PUFAs can be a potential intervention or therapy for many neurocognitive diseases [8]. In the HIV setting, many clinical trials have focused on the effect of n-3 PUFAs on the CD4 cell count and the level of triglycerides (TGs) [9,10,11]. There is a lack of clinical trials that evaluate the effect of n-3 PUFAs on NCI among HIV-infected individuals, as well as the gut microbiota. We hypothesized that supplementation with n3 PUFAs might alleviate the NCI symptoms associated with HIV infection, acting through gut microbiota regulation

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