IntroductionHIV infection is characterized by a persistent immune activation associated to a compromised gut barrier immunity and alterations in the profile of the fecal flora linked with the progression of inflammatory symptoms. The effects of high concentration multistrain probiotic (Vivomixx®, Viale del Policlinico 155, Rome, Italy in EU; Visbiome®, Dupont, Madison, Wisconsin in USA) on several aspects of intestinal immunity in ART‐experienced HIV‐1 patients was evaluated.MethodsA sub‐study of a longitudinal pilot study was performed in HIV‐1 patients who received the probiotic supplement twice a day for 6 months (T6). T‐cell activation and CD4+ and CD8+ T‐cell subsets expressing IFNγ (Th1, Tc1) or IL‐17A (Th17, Tc17) were stained by cytoflorimetric analysis. Histological and immunohistochemical analyses were performed on intestinal biopsies while enterocytes apoptosis index was determined by TUNEL assay.ResultsA reduction in the frequencies of CD4+ and CD8+ T‐cell subsets, expressing CD38+, HLA‐DR+, or both, and an increase in the percentage of Th17 cell subsets, especially those with central or effector memory phenotype, was recorded in the peripheral blood and in gut‐associated lymphoid tissue (GALT) after probiotic intervention. Conversely, Tc1 and Tc17 levels remained substantially unchanged at T6, while Th1 cell subsets increase in the GALT. Probiotic supplementation was also associated to a recovery of the integrity of the gut epithelial barrier, a reduction of both intraepithelial lymphocytes density and enterocyte apoptosis and, an improvement of mitochondrial morphology sustained in part by a modulation of heat shock protein 60.ConclusionsThese findings highlight the potential beneficial effects of probiotic supplementation for the reconstitution of physical and immunological integrity of the mucosal intestinal barrier in ART‐treated HIV‐1‐positive patients.

Introduction: The gut microbiota is involved in the regulation of cognition, mood, anxi-

Background: Gut microbiota has metabolic activity which influences mucosal homeostasis, local and systemic immune responses, and other anatomical systems (i.e., brain). The effects of dysbiosis are still poorly studied in Human Immunodeficiency Virus-1 (HIV-1) positive subjects and insufficient data are available on the impairment of the gut-brain axis, despite neurocognitive disorders being commonly diagnosed in these patients. This study evaluated the impact of a probiotic supplementation strategy on intrathecal immune activation and cognitive performance in combined antiretroviral therapy (cART) treated HIV-1 infected subjects. Methods: Thirty-five HIV-1 infected individuals were included in this study. At baseline (T0) a battery of tests was administered, to evaluate neurocognitive function and a lumbar puncture was performed to determine neopterin concentration in cerebrospinal fluid (CSF), as a marker of Central Nervous System (CNS) immune activation. Subsequently, a subgroup of participants underwent a 6-month course of multi-strain probiotics supplementation; this intervention group was evaluated, after probiotic treatment, with a second lumbar puncture and with repeated neurocognitive tests. Results: At T0, all participants showed impaired results in at least one neurocognitive test and elevated neopterin concentrations in CSF. After supplementation with probiotics (T6), the interventional group presented a significant decrease in neopterin concentration and a significant improvement in several neurocognitive tests. In contrast, no significant modifications were observed in the neurocognitive performance of controls between T0 and T6. The CNS Penetration Effectiveness Score of antiretroviral therapy did not show an influence from any of the investigated variables. Conclusions: Multi-strain probiotic supplementation seems to exert a positive effect on neuroinflammation and neurocognitive impairment in HIV-1 infected subjects, but large trials are needed to support the concept that modulation of the gut microbiota can provide specific neurological benefits in these patients.

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