Probiotics Differently Affect Gut-Associated Lymphoid Tissue Indolamine-2,3-Dioxygenase mRNA and Cerebrospinal Fluid Neopterin Levels in Antiretroviral-Treated HIV-1 Infected Patients: A Pilot Study.

Carolina Scagnolari,Carla Selvaggi,Giuseppe Corano Scheri,Vincenzo Vullo,Sara Serafino,Andrea Mastrangelo,Gabriella D’Ettorre,Noemi Giustini,Gianfranco Fanello,Giancarlo Ceccarelli,Ivan Schietroma,Paolo Pavone,Claudia Pinacchio,Saeid Najafi Fard

doi:10.3390/ijms17101639

Abstract

Recently the tryptophan pathway has been considered an important determinant of HIV-1 infected patients’ quality of life, due to the toxic effects of its metabolites on the central nervous system (CNS). Since the dysbiosis described in HIV-1 patients might be responsible for the microbial translocation, the chronic immune activation, and the altered utilization of tryptophan observed in these individuals, we speculated a correlation between high levels of immune activation markers in the cerebrospinal fluid (CSF) of HIV-1 infected patients and the over-expression of indolamine-2,3-dioxygenase (IDO) at the gut mucosal surface. In order to evaluate this issue, we measured the levels of neopterin in CSF, and the expression of IDO mRNA in gut-associated lymphoid tissue (GALT), in HIV-1-infected patients on effective combined antiretroviral therapy (cART), at baseline and after six months of probiotic dietary management. We found a significant reduction of neopterin and IDO mRNA levels after the supplementation with probiotic. Since the results for the use of adjunctive therapies to reduce the levels of immune activation markers in CSF have been disappointing so far, our pilot study showing the efficacy of this specific probiotic product should be followed by a larger confirmatory trial.

Highlights

A key role of tryptophan metabolism in causing the chronic immune activation status in patients with HIV-1 infection has been proposed [1,2]
Since the dysbiosis described in HIV-1 patients might be responsible for the microbial translocation, the chronic immune activation, and the altered utilization of tryptophan observed in these individuals, we speculated a correlation between high levels of immune activation markers in the cerebrospinal fluid (CSF) of HIV-1 infected patients and the over-expression of indolamine-2,3-dioxygenase (IDO) at the gut mucosal surface
Since the results for the use of adjunctive therapies to reduce the levels of immune activation markers in CSF have been disappointing so far, our pilot study showing the efficacy of this specific probiotic product should be followed by a larger confirmatory trial

Summary

Introduction

A key role of tryptophan metabolism in causing the chronic immune activation status in patients with HIV-1 infection has been proposed [1,2]. These aspects are relevant in the context of the contribution of the microbiota composition in modulating the gut–brain axis (GBA) [3]. This enzyme can induce an increase in kinurenine and other metabolites, such as quinolinic acid Those molecules have been reported to be associated with the neuronal toxicity and neurocognitive disorders in HIV-1 infected patients [9,10,11,12,13]. In light of the above considerations, we performed the first longitudinal pilot study evaluating the effects of a high concentration multistrain probiotic product on neopterin levels in cerebrospinal fluid (CSF) and on the expression of IDO mRNA measured in lymphocytes of lamina propria (LPLs) of the gut in cART-treated HIV-1-positive patients with long-term virologic suppression

Methods

Results

Conclusion