Gut microbiota modulation using prebiotics, probiotics, and synbiotics for CD4+ T-cell recovery in HIV: A systematic review and meta-analysis

Abstract

Introduction

Human immunodeficiency virus (HIV) compromises the immune system by targeting key regulatory lymphocytes essential for coordinating immune responses. It continues to pose a significant global health burden, with approximately 40 million cases recorded by the end of 2023. Currently, highly active antiretroviral therapy (HAART) is the key therapeutic strategy, but it has several limitations, prompting the importance of new therapeutic approaches. This paper evaluates the effectiveness of gut microbiota basesd immunomodulatory therapies, consisting of prebiotics, probiotics, and synbiotics in HIV treatment while considering clinical, socioeconomic, and therapeutic influencing factors.

Methods

This study was conducted based on PRISMA guidelines using multiple databases. Studies were employed based on established inclusion parameters, focusing on the efficacy of gut microbiota interventions in CD4⁺ T-cell counts.Subgroup analyses were performed based on intervention type, dosage, duration, HAART status, and clinical setting. Moreover, sensitivity analysis, meta-regression, and publication bias assessment were also performed to ensure findings robustness and explore source of heterogeneity.

Results

A total of 21 studies were assessed in this meta-analysis. Risk of bias assessment indicated that most studies had a low risk of bias, though some concerns were noted. Prebiotics showed the greatest improvement by a mean difference (MD) of 52.15 cells/mm³ (95 % CI: −5.64 to 109.93), though not statistically significant (p = 0.08). Synbiotics showed a more consistent and statistically significant effect (MD = 39.48 cells/mm³; 95 % CI: 34.39 to 44.58; p < 0.00001). Notably, greatest immunological benefits were observed among HAART-naive individuals, with low-dose prebiotics (4–10 g/day), moderate intervention durations (4–6 months), and in low- and middle-income countries (LMICs). Sensitivity analysis using leave-one-out method confirmed findings robustness, while meta-regression identified key variables contributing to heterogeneity. Moreover, publication bias using Egger's and Begg's test was not evident in most outcomes, except for LMIC-based studies, which showed potential small-study effects.

Conclusion

Gut microbiota based immunomodulators show promising potential in supporting immune function among people living with HIV. However, due to study variability, high heterogeneity and wide confidence intervals (CI) in some subgroups, these findings are hypothesis-generating. Further high-quality studies should focused in homogeneous populations to validate efficacy and guide clinical implementation.