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

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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.

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Acknowledgments

This study was partially supported by Mendes s.r.l. to Bini Luca.

Data availability statement

In accord to Italian law and regulations on patients’ privacy, data are not publicly available but can eventually be made available upon request.

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Authors and Affiliations

  1. Laboratory Functional Proteomics, Department Life Sciences, University of Siena, Siena, Italy

    Claudia Landi, Laura Bianchi, Enxhi Shaba & Luca Bini

  2. Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Rome, Italy

    Letizia Santinelli & Carolina Scagnolari

  3. Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy

    Giancarlo Ceccarelli, Eugenio Nelson Cavallari, Cristian Borrazzo, Claudia Pinacchio, Vincenzo Vullo & Gabriella d’Ettorre

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  1. Claudia Landi
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Contributions

C.L.: Design and conceptualized the study, analyzed the data, and drafted the manuscript for intellectual content. L.S., L.B., and S.E.: Acquired, analyzed, and interpreted the data. G.C.: Enrolled patients, analyzed and interpreted the data, and drafted and revised the manuscript for intellectual content. ENC Enrolled patients, critically revised data and manuscript. CB: critically revised data and performed and revised statistical analysis. C.P.: Acquired, analyzed, and interpreted the data. C.S.: Acquired, analyzed, and interpreted the data, drafted the manuscript for intellectual content. V.V., L.B, and G.d’E.: design and conceptualized study, analyzed the data, drafted the manuscript for intellectual content.

Corresponding author

Correspondence to Giancarlo Ceccarelli.

Ethics declarations

The study was approved by the internal committee of the Infectious Diseases Department and by the Ethics Committee of “Sapienza” University of Rome. A written informed consent was obtained from all patients prior to enrollment.

Conflict of interest

Dr. Landi, Dr. Santinelli, Dr. Bianchi, Dr. Shaba, Dr. Ceccarelli, Dr. Pinacchio, Prof. Scagnolari, Prof. Vullo, and Prof. d’Ettorre report no disclosures. Prof. Bini was partially supported by Mendes s.r.l. (Ardea, Roma).

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Landi, C., Santinelli, L., Bianchi, L. et al. Cognitive impairment and CSF proteome modification after oral bacteriotherapy in HIV patients. J. Neurovirol. 26, 95–106 (2020). https://doi.org/10.1007/s13365-019-00801-7

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