Background: Rotavirus is a leading cause of severe gastroenteritis in infants, resulting in significant global morbidity and mortality. Oral
rotavirus vaccines have reduced hospitalizations and deaths, yet their efficacy varies, particularly in high-mortality regions. Immunogenicity, the ability of a
vaccine to elicit an immune response, is influenced by modulator factors like Probiotics, live microorganisms that confer health benefits. This study explores the interplay between
probiotics and
rotavirus vaccine immunogenicity to identify strategies to enhance
vaccine effectiveness in vulnerable populations. Method: This systematic review was conducted based on the PICO criteria and following PRISMA guidelines. A comprehensive search was performed in PubMed, Scopus, Web of Science, and Cochrane Library for studies published between ۲۰۱۵ and ۲۰۲۵. Keywords included "probiotics," "vaccine," "infants," "rotavirus," and related terms. The inclusion criteria were randomized or controlled clinical trials in
infants that assessed probiotic supplementation and
vaccine immune responses. Exclusion criteria included animal studies, narrative reviews, and insufficient data. Study quality was assessed using the Cochrane Risk of Bias ۲ (RoB ۲) tool. The found articles were screened by two researchers separately. Result: Following inclusion and exclusion criteria, ۱۳ relevant studies were selected from an initial pool of ۱۴۳ articles. The clinical outcomes indicate a variation in
vaccine efficacy, ranging from ۸۵% to ۹۷% in low-mortality regions, compared to just ۳۵% to ۵۸% in high-mortality areas. This discrepancy is attributed to factors such as malnutrition, pathogen exposure, and imbalances in microbiota. Probiotics, including Lactobacillus rhamnosus GG and Bifidobacterium lactis, have been shown to enrich infant microbiota, inhibiting pathogenic organisms, strengthening mucosal barriers, increasing their production, and modulating innate immunity to reduce inflammation. When administered alongside
rotavirus vaccines, these
probiotics function as adjuvants by shifting immune responses toward Thl and activating regulatory T-cells, reducing the duration of
rotavirus diarrhea by approximately ۱-۳ days and increasing IgA/IgG titers by ۱۸% to ۲۲%, as well as enhancing IFN-y+ cells by ۳۰% to ۴۰%. Additionally, they boost overall
vaccine uptake by ۱۵% to ۱۸%. However, some studies paradoxically report a transient decrease in IgA seroconversion ranging from ۲۰% to ۳۷%, indicating that further extensive research is required to draw definitive conclusions. Conclusion: Considering strains, dosages, and the duration of supplementation,
probiotics emerge as an effective adjunct in the treatment of
rotavirus diarrhea by modulating both the immune system and intestinal microbiota. However, the current evidence remains inconclusive, highlighting the need for more studies to establish their efficacy.