乳酸杆菌GR-1&RC-14对妊娠晚期生殖道B族链球菌定植及阴道菌群微生态的影响

Effect of oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on vaginal Group B Streptococcus colonization and vaginal microbiome in late pregnancy

目的探讨乳酸杆菌GR-1&RC-14对妊娠晚期生殖道B族链球菌(GBS)阳性患者GBS定植、妊娠结局及阴道菌群微生态的影响。方法选取2019年3月~2019年11月于南方医科大学珠江医院门诊行妊娠晚期GBS检测且结果阳性患者符合纳排标准155例,剔除乳酸杆菌干预<2周或产后复查32例,根据有无乳酸杆菌干预,分为干预组(60例)、无干预组(63例);干预组60例根据再次检测GBS结果分为转阴组(18例)、持续阳性组(42例);计算GBS转阴率,比较各分组妊娠结局;从干预组60例患者中随机选取配对乳酸杆菌干预前后阴道分泌物5对行扩增子测序及生物信息分析。结果干预组GBS转阴率为30%(18/60),无干预组GBS转阴率为23%(3/13);乳酸杆菌干预降低胎膜早破发生率(P<0.05),并降低抗生素应用(P<0.05)。阴道分泌物OTU分析提示乳酸杆菌干预后总序列数、GBS序列数减少及物种组成增加。乳酸杆菌干预后链球菌属物种丰度降低,差异有统计学意义(P<0.05)。MetaStat提示乳酸杆菌干预后肠球菌、葡萄球菌属、链球菌属物种丰度均减少且差异有统计学意义(P<0.05)。结论乳酸杆菌对妊娠晚期生殖道GBS定植、妊娠结局有一定的改善作用,乳酸杆菌降低链球菌属物种相对丰度及致病菌物种丰度,对阴道菌群微生态有一定改善作用。

Objective To explore the effects of intervention with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on vaginal Group B Streptococcus(GBS)colonization,pregnancy outcome and vaginal microbiome in GBS-positive women in the third trimester of pregnancy.Methods This study were conducted among 155 women in the third trimester of pregnancy with positive results of GBS culture in the Outpatient Department of Zhujiang Hospital from March to November,2019.After excluding 32 patients who received lactobacillus intervention for less than 2 weeks or underwent postpartum GBS retesting,the women were divided into oral probiotics intervention group(60 cases)and non-intervention group(63 cases).According to the results of GBS retesting,the 60 women in the intervention group were divided into GBS-negative group(18 cases)and persistent GBS-positive group(42 cases).At the end of the intervention,the rates of negative GBS culture result were calculated and the pregnancy outcomes were compared.From 5 women randomly selected from the intervention group,samples of vaginal secretions were collected before and after the intervention for amplicon sequencing and bioinformatics analysis.Results At the end of the intervention,the GBS-negative rate in the intervention group was 30%(18/60),as compared with 23%(3/13)in the non-intervention group.Probiotic intervention significantly reduced the incidence of premature rupture of membranes(P<0.05)and reduced the use of antibiotics during pregnancy(P<0.05).OTU analysis of the vaginal secretions suggested probiotic intervention decreased the total sequence number and GBS sequence number,increased the species composition,and significantly decreased GBS abundance(P<0.05).Probiotics intervention also significantly decreased the species abundance of Enterococcus,Staphylococcus and Streptococcus in the vaginal flora(P<0.05).Conclusion Intervention with oral probiotics can reduce vaginal GBS colonization in late pregnancy and improve the pregnancy outcome.Lactobacillus is capable of reducing the abundance of GBS and other pathogenic bacteria to improve the microbiome of vaginal flora.