口服鼠李糖乳杆菌对早产儿肠道菌群及免疫的影响

Effects of Lactobacillus rhamnosus GG on intestinal flora and immunity in premature infants

目的探讨口服鼠李糖乳杆菌对早产儿肠道菌群、免疫及胃肠道功能的影响。方法选取2018年4~10月生后24 h内收住华中科技大学同济医学院附属同济医院新生儿科、胎龄<34周且出生体重<2500 g的早产儿进行前瞻性研究。根据入选顺序单双号分为对照组和观察组。生后第1天起观察组给予鼠李糖乳杆菌溶液(4×10^(9) CFU/ml,0.25 ml/d)、对照组给予等量玉米油口服,疗程30 d。收集第21天和第42天新鲜粪便进行16S rDNA测序分析;同时检测生后第1天和第42天血免疫球蛋白、淋巴细胞亚群、干扰素γ(interferon-γ,IFN-γ)和白细胞介素4(interleukin-4,IL-4)水平。结果最终完成29例,其中对照组15例、观察组14例。生后第21天观察组肠道乳杆菌属比例高于对照组(P<0.05),第42天观察组肠道链球菌属比例低于对照组(P<0.05)。第21天观察组检测物种数指数大于对照组(P<0.05),第42天两组各指数差异无统计学意义(P>0.05)。两组出生第1天、第42天血免疫球蛋白水平差异均无统计学意义(P>0.05);与第1天相比,两组第42天IgM均上升、IgG均下降(P<0.05)。与第1天相比,观察组第42天NK细胞、B细胞、CD3^(+)T细胞和CD4^(+)T细胞计数明显升高(P<0.05),对照组第42天B细胞、CD3^(+)T细胞和CD8^(+)T细胞计数明显升高(P<0.05);生后第1天及第42天两组NK细胞及各淋巴细胞计数差异均无统计学意义(P>0.05)。与第1天相比,第42天对照组IFN-γ水平下降(P<0.05),观察组上升(P<0.05);IL-4水平差异无统计学意义(P>0.05)。观察组发生喂养不耐受4例,对照组9例,差异无统计学意义(P>0.05)。结论生后早期补充鼠李糖乳杆菌能够调节早产儿肠道菌群组成,增加乳杆菌属,减少链球菌属,可能减少喂养不耐受的发生、促进NK细胞和CD4^(+)T细胞增殖,激活淋巴细胞表达IFN-γ。

Objective To study the effects of oral Lactobacillus rhamnosus GG on intestinal flora,immunity and gastrointestinal function in premature infants.Method Premature infants with gestation age 28~34 weeks and birth weight<2500 g admitted to our hospital were enrolled in the prospective study,which were randomly assigned into observation group and control group.From the first day after birth,Lactobacillus rhamnosus GG for the observation group and the same amount of corn oil for the control group were orally given for 30 days.Fresh feces were collected on the 21st and 42nd day for 16S rDNA sequence analysis.Meanwhile,peripheral blood was collected on the 1st and 42nd day after birth for the detection of immune globulins,lymphocyte subsets,and cytokines IFN-γand IL-4 in serum.Result A total of 29 premature infants were completed,including 15 cases in the control group and 14 cases in the observation group.On the 21st day after birth,the proportion of Lactobacillus in the observation group was higher than that in the control group(P<0.05),and the proportion of Streptococcus in the observation group was lower than that in the control group on the 42nd day(P<0.05).The observed species index of the observation group was higher than the control group on the 21st day(P<0.05),and there was no difference in each index on the 42nd day.There was no difference in the level of immune globulins between the two groups on the 1st and 42nd day(P>0.05).Compared with the 1st day,two groups showed significant increase in IgM and decrease in IgG on the 42nd day(P<0.05).Compared with the 1st day,the counts of NK cells,B cells,CD3^(+)T cells and CD4^(+)T cells in the observation group significantly increased on the 42nd day.And the counts of B cells,CD3^(+)T cells and CD8^(+)T cells in the control group significantly increased on the 42nd day.There was no significant difference in NK cells and lymphocytes between the two groups on the 1st and 42nd day.The level of IFN-γin the control group significantly decreased on the 42nd day(P<0.05),while it significantly increased in the observation group(P<0.05).There was no significant difference in the level of IL-4(P>0.05).The occurrence of feeding intolerance was found in the observation group(n=4)and control group(n=9),and there was no statistical difference between the two groups(P>0.05).Conclusion Oral administration of Lactobacillus rhamnosus GG in the early postnatal period can regulate the content of intestinal flora in premature infants,increase the lactobacillus and reduce the streptococcus.LGG may reduce the occurrence of feeding intolerance,promote the proliferation of NK cells and CD4^(+)T cells,and activate the expression of IFN-γin lymphocytes.