不同种类益生菌对高胆红素血症新生儿肠道菌群、短链脂肪酸及Treg/Th17平衡的不同影响

Differential effects of different probiotics on intestinal flora, short-chain fatty acids and Treg/Th17 balance in neonates with hyperbilirubinemia

摘要:

目的 比较布拉氏酵母菌与双歧杆菌四联活菌对高胆红素血症新生儿肠道菌群结构、粪便短链脂肪酸水平及外周血Treg/Th17平衡的影响，并评估其对黄疸相关临床结局与安全性的影响。方法 选取2023年3月—2025年11月宁波大学附属第一医院收治的120例高胆红素血症新生儿为研究对象。将患儿随机分为两组，每组60例，均接受以蓝光为主的双面强光照射治疗。观察组给予布拉氏酵母菌，对照组给予双歧杆菌四联活菌，疗程3 d。记录每日经皮胆红素值、光疗总时长、住院时间、光疗达标至停药的时间间隔及不良事件。于干预前与干预第7天检测新生儿总胆红素（TBIL）、间接胆红素（IBIL）；评估肠道菌群α多样性香农指数（Shannon）、基于丰度的覆盖估计指数（ACE）及β多样性；检测粪便短链脂肪酸（乙酸、丙酸、丁酸）；采用流式细胞术检测外周血调节性T细胞（Treg）和辅助性T细胞17（Th17），并计算Treg/Th17比值。结果 观察组光疗总时长及光疗达标至停药的时间间隔均较对照组更短（P 0.05）；两组住院时间比较，差异无统计学意义（P 0.05）。观察组干预后TBIL、IBIL水平均低于对照组（P 0.05）；观察组干预前后TBIL、IBIL水平的差值均大于对照组（P 0.05）。对照组干预后Shannon指数、ACE指数均高于观察组（P 0.05）；对照组干预前后Shannon指数、ACE指数的差值均大于对照组（P 0.05）。对照组干预后乙酸、丙酸、丁酸水平均大于观察组（P 0.05）；对照组干预前后乙酸、丙酸、丁酸水平的差值均大于对照组（P 0.05）。对照组干预后Treg、Th17、Treg/Th17水平均高于观察组（P 0.05）；对照组干预前后外周血Treg、Th17、Treg/Th17的差值均大于观察组（P 0.05）。观察组不良事件总发生率高于对照组（P 0.05）。结论 在光疗基础上，布拉氏酵母菌可进一步缩短光疗总时长及达到光疗标准至结束光疗的时间，并降低总胆红素与间接胆红素水平，但不良事件在特定高风险状态下较高。双歧杆菌四联活菌更有利于改善肠道菌群α多样性、提高粪便短链脂肪酸水平，并表现为Treg升高、Th17降低及Treg/Th17比值升高等免疫调节优势。不同益生菌在降胆红素效率、微生态代谢及免疫调节方面的效应存在差异。

Abstract:

Objective To compare the differential effects of Saccharomyces boulardii VS Bifidobacterium tetravaccine on intestinal flora structure, fecal short-chain fatty acid levels and peripheral blood Treg/Th17 balance in neonates with hyperbilirubinemia, and to evaluate their impacts on jaundice-related clinical outcomes and safety.Methods A total of 120 neonates with hyperbilirubinemia admitted between March 2023 and November 2025 were enrolled and randomly divided into two groups. Both groups received double-sided intensive phototherapy as the main treatment. The observation group (60 cases) received Saccharomyces boulardii, and the control group (60 cases) received Bifidobacterium quadruple viable bacteria for 3 days. Daily transcutaneous bilirubin, total phototherapy duration, total length of hospital stay, time from meeting phototherapy criteria to discontinuation, and adverse events were recorded. Total bilirubin (TBIL) and indirect bilirubin (IBIL) were measured before intervention and on day 7. The Shannon index, ACE index and β-diversity of intestinal flora were evaluated. Fecal short-chain fatty acids (acetic acid, propionic acid, butyric acid) were detected. Peripheral blood regulatory T cells (Treg) and T helper 17 cells (Th17) were measured by flow cytometry, and the Treg/Th17 ratio was calculated.Results The observation group had shorter total phototherapy duration and shorter interval from meeting phototherapy criteria to phototherapy termination (P 0.05). There was no significant difference in total hospital stay between the two groups (P 0.05). After intervention, the levels of TBIL and IBIL in the observation group were lower than those in the control group (P 0.05), and the pre-post intervention differences of bilirubin indicators were greater in the observation group (P 0.05). After treatment, the Shannon index and ACE index of the control group were higher than those of the observation group, with greater changes in the above indicators and beta diversity (P 0.05). The post-intervention levels of acetic acid, propionic acid and butyric acid in the observation group were lower, and the pre-post differences in these short-chain fatty acids in the control group were greater than those in the observation group (P 0.05). The control group had higher Treg level and Treg/Th17 ratio but lower Th17 level, and presented more obvious changes in Treg, Th17 and Treg/Th17 ratio before and after intervention (P 0.05). The overall incidence of adverse events in the observation group was higher than that in the control group (P 0.05).Conclusion On the basis of phototherapy, Saccharomyces boulardii further shortens phototherapy duration and the time to discontinuation, and reduces TBIL and IBIL levels, but with a higher adverse event rate. Bifidobacterium tetravaccine is more beneficial for improving the Shannon index, ACE index of intestinal flora and fecal SCFA levels, and exhibits better immunological improvement including increased Treg, decreased Th17 and elevated Treg/Th17 ratio.