Human Milk Oligosaccharides Reduce Murine Group B Streptococcus Vaginal Colonization with Minimal Impact on the Vaginal Microbiota.

Human Milk Oligosaccharides Reduce Murine Group B Streptococcus Vaginal Colonization with Minimal Impact on the Vaginal Microbiota.
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人乳寡聚肽减少小鼠B族链球菌阴道定植,对阴道微生物群的影响最小。

DOI:
10.1128/msphere.00885-21
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发表时间:
2022-02-23
期刊:
影响因子:
4.8
通讯作者:
Patras KA
Patras KA
中科院分区:
生物学2区
文献类型:
--
作者:
Mejia ME;Ottinger S;Vrbanac A;Babu P;Zulk JJ;Moorshead D;Bode L;Nizet V;Patras KA

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B族链球菌(GBS)在相当大比例的健康女性的阴道粘膜中定植,并且是新生儿细菌感染的主要原因。目前,孕妇在怀孕的最后一个月接受筛查,GBS阳性的妇女在分娩期间接受抗生素治疗,以防止细菌传播给新生儿。最近,从母乳中分离的人乳低聚糖(HMO)被发现在体外抑制GBS生长和生物膜形成,并且生产某些HMO的女性不太可能被GBS阴道定殖。使用体外人阴道上皮细胞和小鼠阴道定植模型,我们通过16S rRNA扩增子测序测试了HMO治疗对GBS负荷和内源性微生物群组成的影响。HMO治疗降低了体内GBS阴道负荷,对阴道微生物群的改变最小。HMO在体外显示出对GBS的有效抑制活性,但HMO预处理并没有改变GBS或益生菌鼠李糖乳杆菌对人阴道上皮细胞的粘附。此外,假定的GBS糖基转移酶(Δsan_0913)的破坏使细菌在体外和体内对HMO抑制具有很大的抗性,但在不存在HMO的情况下不会损害其粘附、定殖或生物膜形成。我们得出结论,HMO是一种有前途的治疗生物活性,以限制GBS阴道定植,对阴道微环境的影响最小。怀孕期间,GBS Ascension进入子宫可导致胎儿感染或早产。此外,分娩期间暴露于GBS会给脆弱的新生儿和产后母亲带来严重疾病的风险。目前推荐的预防措施包括在分娩过程中对GBS阳性的母亲使用广谱抗生素。虽然抗生素显著减少了GBS新生儿疾病,但也有一些意想不到的后果,包括改变新生儿肠道细菌和增加其他类型感染的风险。因此,显示出更有针对性的抗微生物活性,同时保持母体微生物群完整的创新预防措施很有吸引力。使用小鼠模型,我们发现人乳低聚糖(HMO)可以降低GBS负担,而不会干扰阴道微生物群。我们的结论是,HMO是一个有前途的替代抗生素,以减少GBS新生儿疾病。
Group B Streptococcus (GBS) colonizes the vaginal mucosa of a significant percentage of healthy women and is a leading cause of neonatal bacterial infections. Currently, pregnant women are screened in the last month of pregnancy, and GBS-positive women are given antibiotics during parturition to prevent bacterial transmission to the neonate. Recently, human milk oligosaccharides (HMOs) isolated from breastmilk were found to inhibit GBS growth and biofilm formation in vitro, and women that make certain HMOs are less likely to be vaginally colonized with GBS. Using in vitro human vaginal epithelial cells and a murine vaginal colonization model, we tested the impact of HMO treatment on GBS burdens and the composition of the endogenous microbiota by 16S rRNA amplicon sequencing. HMO treatment reduced GBS vaginal burdens in vivo with minimal alterations to the vaginal microbiota. HMOs displayed potent inhibitory activity against GBS in vitro, but HMO pretreatment did not alter adherence of GBS or the probiotic Lactobacillus rhamnosus to human vaginal epithelial cells. In addition, disruption of a putative GBS glycosyltransferase (Δsan_0913) rendered the bacterium largely resistant to HMO inhibition in vitro and in vivo but did not compromise its adherence, colonization, or biofilm formation in the absence of HMOs. We conclude that HMOs are a promising therapeutic bioactive to limit GBS vaginal colonization with minimal impacts on the vaginal microenvironment. IMPORTANCE During pregnancy, GBS ascension into the uterus can cause fetal infection or preterm birth. In addition, GBS exposure during labor creates a risk of serious disease in the vulnerable newborn and mother postpartum. Current recommended prophylaxis consists of administering broad-spectrum antibiotics to GBS-positive mothers during labor. Although antibiotics have significantly reduced GBS neonatal disease, there are several unintended consequences, including altered neonatal gut bacteria and increased risk for other types of infection. Innovative preventions displaying more targeted antimicrobial activity, while leaving the maternal microbiota intact, are thus appealing. Using a mouse model, we found that human milk oligosaccharides (HMOs) reduce GBS burdens without perturbing the vaginal microbiota. We conclude that HMOs are a promising alternative to antibiotics to reduce GBS neonatal disease.
DOI: 10.3389/fnut.2021.640100
发表时间: 2021
影响因子: 5
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