Human Milk Oligosaccharides Mediate the Host-Microbe Interface in a Model Vaginal Community.

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL
ACS Infectious Diseases Pub Date : 2025-06-13 Epub Date: 2025-06-03 DOI:10.1021/acsinfecdis.5c00295
Julie A Talbert, Sabrina K Spicer, Shannon D Manning, Jennifer A Gaddy, Steven D Townsend
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引用次数: 0

Abstract

Group B Streptococcus (GBS) is an opportunistic bacterium that can cause severe infection during gestation, leading to adverse pregnancy outcomes and neonatal disease. As current treatments only decrease chances of early onset neonatal disease without impacting the risk of chorioamnionitis, preterm birth, or late-onset disease, novel therapeutics are needed. Here, we demonstrate that human milk oligosaccharides (HMOs) positively modulate cocultures of GBS and Lactobacillus spp., common inhabitants of a healthy vaginal microbiome, across in vitro, ex vivo, and in vivo experiments. HMOs shift the total cell population in vitro to favor Lactobacillus, which was qualitatively visualized via scanning electron microscopy. Lactobacillus adherence to EpiVaginal tissues was also increased with HMOs during coinoculation with GBS. Using an in vivo mouse model of reproductive GBS infection, Lactobacillus crispatus and HMOs prevented ascending infection, reducing bacterial burden in both the placenta and fetus. L. crispatus alone reduced the burden in all reproductive tissues tested except the vagina. Together, these results highlight the benefit of pre- and probiotic treatment to potentially reduce GBS colonization during gestation.

人乳寡糖介导阴道模型群落中宿主-微生物界面。
B群链球菌(GBS)是一种机会性细菌,可在妊娠期间引起严重感染,导致不良妊娠结局和新生儿疾病。由于目前的治疗方法只能降低早发新生儿疾病的机会,而不会影响绒毛膜羊膜炎、早产或迟发性疾病的风险,因此需要新的治疗方法。在这里,我们通过体外、离体和体内实验证明,人乳寡糖(HMOs)正调节GBS和乳酸菌(健康阴道微生物群的常见居民)的共培养。HMOs将体外总细胞群转移到有利于乳酸菌的位置,通过扫描电子显微镜对其进行定性观察。在与GBS共接种期间,HMOs也增加了乳酸菌对外阴组织的粘附。在体内小鼠生殖性GBS感染模型中,criscrisbacillus和HMOs可预防上行感染,减少胎盘和胎儿的细菌负担。在除阴道外的所有生殖组织中,单独使用crispatus可减轻负担。总之,这些结果强调了益生菌预处理和益生菌治疗在妊娠期间可能减少GBS定植的益处。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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