布拉氏酵母菌联合双歧杆菌四联活菌预防婴幼儿抗生素相关性腹泻的前瞻性随机对照研究OA

Objective To investigate the synergistic preventive effect of Saccharomyces boulardii combined with Bifidobacterium quadruple viable preparation(BQP)on antibiotic-associated diarrhea(AAD)in infants and young children,aiming to provide evidence for optimizing probiotic intervention strategies in clinical practice.Methods A prospective,randomized,parallel controlled trial enrolled hospitalized children aged 1-36 months requiring antibiotic treatment from October 2023 to June 2025.Participants were randomly assigned to four groups:control(no probiotic;n=59),Saccharomyces boulardii(Saccharomyces boulardii powder;n=59),BQP(BQP tablets;n=58),and combined group(Saccharomyces boulardii powder plus BQP tablets;n=60).Probiotic interventions were administered from antibiotic initiation until 7 days after discontinuation.The primary outcome was the incidence of AAD during treatment.Secondary outcomes included diarrhea duration,fecal microbiota composition(16S rRNA sequencing),inflammatory markers(fecal calprotectin,serum interleukin-6),and safety.Follow-up continued until 30 days after probiotic cessation.Results The combined group showed a significantly lower AAD incidence(7%)compared to the Saccharomyces boulardii group(15%),BQP group(17%),and control group(31%)(P<0.0083).On the 30th day after probiotic cessation,the combined group demonstrated a significantly higher Shannon diversity index than the other three groups(P<0.05);relative abundances of Bifidobacterium and Lactobacillus in feces were significantly higher in the combined group than the other three groups(P<0.05),while the relative abundances of Enterococcus were significantly lower than in the other three groups(P<0.05).On the 7th day after antibiotic cessation,the combined group showed significantly lower levels of inflammatory markers compared to the other three groups(P<0.05).Adverse event rates did not differ significantly among groups(P>0.05).Conclusions The combination of Saccharomyces boulardii and BQP prevents AAD in infants and young children more effectively than a single probiotic regimen,potentially through synergistic enhancement of beneficial bacterial colonization and accelerated gut microbiota restoration.This combined probiotic regimen warrants clinical promotion.