Cognitive impairment and CSF proteome modification after oral bacteriotherapy in HIV patients

J Neurovirol. 2020 Feb;26(1):95-106. doi: 10.1007/s13365-019-00801-7. Epub 2019 Nov 1.

Abstract

Objective: To investigate whether a probiotic supplementation to cART patients modifies the cerebrospinal fluid (CSF) proteome and improves neurocognitive impairment.

Methods: 26 CSF samples from 13 HIV-positive patients [six patients living with HIV (PLHIV) and seven patients with a history of AIDS (PHAIDS)] were analyzed. All patients underwent to neurocognitive evaluation and blood sampling at baseline and after 6 months of oral bacteriotherapy. Immune phenotyping and activation markers (CD38 and HLA-DR) were evaluated on peripheral blood mononuclear cells (PBMC). Plasma levels of IL-6, sCD14, and MIP-1β were detected, by enzyme-linked immunosorbent assay (ELISA). Functional proteomic analysis of CSF sample was conducted by two-dimensional electrophoresis; a multivariate analysis was performed by principal component analysis (PCA) and data were enriched by STRING software.

Results: Oral bacteriotherapy leads to an improvement on several cognitive test and neurocognitive performance in both groups of HIV-positive subjects. A reduction in the percentage of CD4+CD38+HLA-DR+ T cells was also observed at peripheral level after the probiotic intake (p = 0.008). In addition, the probiotic supplementation to cART significantly modifies protein species composition and abundance at the CSF level, especially those related to inflammation (β2-microglobulin p = 0.03; haptoglobin p = 0.06; albumin p = 0.003; hemoglobin p = 0.003; immunoglobulin heavy chains constant region p = 0.02, transthyretin p = 0.02) in PLHIV and PHAIDS.

Conclusions: Our results suggest that oral bacteriotherapy as a supplement to cART could exert a role in the amelioration of inflammation state at peripheral and CNS level.

Keywords: Bacteriotherapy; Functional proteomics; HIV; Immunoactivation; Probiotic.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / immunology
  • AIDS Dementia Complex / microbiology*
  • Acquired Immunodeficiency Syndrome / complications
  • Acquired Immunodeficiency Syndrome / immunology
  • Acquired Immunodeficiency Syndrome / microbiology
  • Adult
  • Anti-HIV Agents / therapeutic use
  • Cerebrospinal Fluid / drug effects
  • Cerebrospinal Fluid / immunology
  • Cognitive Dysfunction / etiology
  • Female
  • HIV Infections / complications*
  • HIV Infections / immunology
  • HIV Infections / microbiology*
  • Humans
  • Male
  • Microbiota / drug effects
  • Middle Aged
  • Mouth / microbiology
  • Probiotics / pharmacology*
  • Proteome

Substances

  • Anti-HIV Agents
  • Proteome