目的 探讨布拉氏酵母菌联合双歧杆菌四联活菌对婴幼儿抗生素相关性腹泻（antibiotic‑associated diarrhea, AAD）的协同预防作用，为临床优化益生菌干预方案提供依据。 方法 采用前瞻性、随机、平行对照试验设计，纳入2023年10月—2025年6月收治的需抗生素治疗的1~36月龄住院患儿，随机分为4组：对照组（不予益生菌治疗；n=59）、布拉氏酵母菌组（给予布拉氏酵母菌散；n=59）、双歧杆菌组（给予双歧杆菌四联活菌片；n=58）、联合组（联用布拉氏酵母菌散和双歧杆菌四联活菌片；n=60）。所有益生菌干预从抗生素启用持续至停药后7 d。主要结局为治疗期间AAD的发生率；次要结局包括腹泻持续时间、粪便菌群结构（16S rRNA测序）、炎症指标（粪便钙卫蛋白、血清白细胞介素‑6）及安全性。随访至益生菌停服后30 d。 结果 联合组AAD的发生率（7%）显著低于布拉氏酵母菌组（15%）、双歧杆菌组（17%）及对照组（31%）（P<0.0083）。益生菌停服后第30天，联合组Shannon指数显著高于其他3组（P<0.05）；联合组粪便中双歧杆菌属、乳杆菌属的相对丰度显著高于其他3组（P<0.05），而肠球菌属的相对丰度显著低于其他3组（P<0.05）。抗生素停药后第7天，联合组炎症指标水平显著低于其他3组（P<0.05）。各组不良反应发生率差异无统计学意义（P>0.05）。 结论 布拉氏酵母菌与双歧杆菌四联活菌联用较单一益生菌能更有效预防婴幼儿AAD，其机制可能与协同促进有益菌定植、加速菌群重建有关；该联合方案具有临床推广价值。

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 weresignificantly 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.