AbstractBackgroundmaternal health during pregnancy can affect the intestinal microbial community of offspring, but currently the impact of intrauterine environmental changes resulting from gestational diabetes mellitus (GDM) on the microbiota of offspring as well as its interaction with the immune system remains unclear.Aimsto explore the impact of intrauterine microbial exposure during pregnancy of gestational diabetes mellitus on the development of neonate’s intestinal microbiota and activation of immune responses.MethodsLevels of lipopolysaccharides in cord blood from GDM and expression of microbial recognition-related proteins in the placenta were measured.

摘要背景怀孕期间的母亲健康会影响后代的肠道微生物群落，但目前尚不清楚妊娠期糖尿病（GDM）引起的宫内环境变化对后代微生物群的影响及其与免疫系统的相互作用。目的探讨妊娠期糖尿病孕妇宫内微生物暴露对新生儿肠道微生物群发育和免疫反应激活的影响。方法测定GDM脐血中脂多糖水平和胎盘中微生物识别相关蛋白的表达。

To evaluate embryonic intestinal colonization, pregnant mice with GDM were administered with labeled Escherichia coli or Lactobacillus. The intestinal colonization of pups was analyzed through 16S rRNA gene sequencing and labeled microbial culture. Additionally, memory T lymphocyte and dendritic cell co-culture experiments were conducted to elucidate the immune memory of intestinal microbes during the embryonic stages.ResultGestational diabetes mellitus led to elevated umbilical cord blood LPS level and increased GFP labeled Escherichia coli in the offspring’s intestine after gestational microbial exposure.

为了评估胚胎肠道定植，给患有GDM的怀孕小鼠施用标记的大肠杆菌或乳酸杆菌。通过16S rRNA基因测序和标记的微生物培养分析幼崽的肠道定植。。结果妊娠期糖尿病导致脐血LPS水平升高，妊娠期微生物暴露后后代肠道中GFP标记的大肠杆菌增加。

The mouse model of GDM exhibited increased immune markers including TLR4, TLR5, IL-22 and IL-23 in the placenta and a recall response from memory T cells in offspring’s intestines, with similar observations found in human experiments. Furthermore, reduced intestinal microbiome diversity and an increased ratio of Firmicutes/Bacteroidetes was found in GDM progeny, with the stability of bacterial colonization been interfered.ConclusionsOur investigation has revealed a noteworthy correlation between gestational di.

GDM的小鼠模型表现出增加的免疫标志物，包括胎盘中的TLR4，TLR5，IL-22和IL-23，以及后代肠道中记忆T细胞的回忆反应，在人类实验中发现了类似的观察结果。此外，在GDM后代中发现肠道微生物组多样性降低，厚壁菌门/拟杆菌门比例增加，细菌定植的稳定性受到干扰。结论SOUR调查显示妊娠di之间存在值得注意的相关性。

IntroductionThe human microbiota encompasses a rich ecosystem that form a stable symbiotic relationship with the host and substantially impacts host’s metabolism and physiology [1]. In recent years, extensive attention has been focused on the microbiota development during pregnancy and early life, as disruptions of the microbiome have been linked to chronic diseases and mental disorders in the next generation [2,3,4].

引言人类微生物群包括一个丰富的生态系统，与宿主形成稳定的共生关系，并对宿主的代谢和生理产生重大影响。近年来，由于微生物组的破坏与下一代的慢性疾病和精神障碍有关，因此人们广泛关注妊娠期和早期的微生物群发育[2，3，4]。

Contrary to the past belief that the fetus remains germ-free during gestation, some studies have reported traces of microbes in human placental and fetal samples [5,6,7], emphasizing the potential for maternal transmission of microbes. Fetal exposure to maternally derived microbial components was also found which associated with early-life immune system development.

与过去认为胎儿在妊娠期间保持无菌的观点相反，一些研究报道了人类胎盘和胎儿样本中的微生物痕迹，强调了微生物在母体传播的潜力。还发现胎儿暴露于母体来源的微生物成分，这与早期免疫系统发育有关。

Lipopolysaccharide(LPS), a typical proinflammatory molecule produced by gram-negative bacteria in the intestines, can translocate to the maternal bloodstream from a leaky gut and adversely affect pregnancy outcomes such as impairing spermatogenesis and developing ASD-like behavior in the next generation [8, 9].Gestational diabetes mellitus (GDM) is prevalent worldwide.

脂多糖（LPS）是肠道中革兰氏阴性细菌产生的典型促炎分子，可从肠道渗漏转移至母体血流，并对妊娠结局产生不利影响，如损害精子发生和下一代发生ASD样行为[8，9]。妊娠期糖尿病（GDM）在世界范围内普遍存在。

Its high prevalence, along with associated transgenerational consequences and serious complications, necessitates new approaches to understand its pathophysiology [10, 11]. It has been suggested that GDM significantly alters the composition of the intestinal microbiota in offspring, potentially leading to health risks such as obesity, insulin resistance, and even diabetes in the next generation [12,13,14].

它的高发病率，以及相关的跨代后果和严重并发症，需要新的方法来了解其病理生理学[10，11]。有人提出，GDM显着改变了后代肠道微生物群的组成，可能导致下一代的肥胖，胰岛素抵抗甚至糖尿病等健康风险[12，13，14]。

However, the association between GDM, microbial signaling in the embryonic stage, postpartum microbiota construction, and early-life immune responses remains unclear.In this study, using samples from GDM women and animal model,.

然而，GDM，胚胎期微生物信号传导，产后微生物群构建和早期免疫反应之间的关联仍不清楚。在这项研究中，使用来自GDM女性和动物模型的样本，。

Data availability

Some data used in this study were obtained from the publicly accessible websites, http://submit.ncbi.nlm.nih.gov/subs/bioproject/SUB12628577

本研究中使用的一些数据来自可公开访问的网站，http://submit.ncbi.nlm.nih.gov/subs/bioproject/SUB12628577

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Download referencesFundingThis work was supported by the National Natural Science Foundation of China (81871222 to X.X.).Author informationAuthor notesThese authors contributed equally: Juncheng Liu, Yan Chen, Xiaoqiu Xiao, Xinyu Li.Authors and AffiliationsDepartment of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaJuncheng Liu, Irakoze Laurent & Xiaoqiu XiaoThe Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaJuncheng Liu, Yan Chen, Irakoze Laurent, Xiaoqiu Xiao & Xinyu LiDepartment of Gastroenterology, Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, ChinaJuncheng LiuDepartment of Endocrinology and Nephrology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, ChinaYan ChenYongchuan Hospital of Traditional Chinese Medicine, Chongqing, ChinaPing YangDepartment of Pharmacy, the First Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaXinyu LiAuthorsJuncheng LiuView author publicationsYou can also search for this author in.

下载参考文献资助这项工作得到了国家自然科学基金（81871222至X.X.）的支持。作者信息作者注意到这些作者做出了同样的贡献：刘俊成，陈燕，肖晓秋，李新宇。作者和附属机构重庆医科大学第一附属医院内分泌科，重庆，中国刘俊成，Irakoze-Laurent＆Xiaoqiu Xiao重庆医科大学第一附属医院重庆市主要代谢疾病转化医学重点实验室，重庆，中国刘俊成，陈燕，Irakoze-Laurent，肖晓秋，肖新宇LiDepartment of Gastroenterology，重庆大学肿瘤医院，重庆大学医学院，中国刘俊成重庆大学中心医院内分泌与肾脏科中国重庆市陈永川中医院重庆市杨平平重庆医科大学第一附属医院药剂科，ChinaXinyu LiAuthorsJuncheng Liu查看作者出版物您也可以在中搜索此作者。

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PubMed Google ScholarPing YangView author publicationsYou can also search for this author in

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PubMed Google ScholarContributionsJuncheng Liu: Methodology, Conceptualization, Investigation, Formal analysis, Visualization, Writing original draft. Yan Chen: Resources, Formal analysis. Irakoze Laurent: Investigation, Writing - review & editing. Xiaojing Lin: Investigation, Validation.

PubMed谷歌学术贡献刘俊成：方法论，概念化，调查，形式分析，可视化，撰写原稿。严晨：资源，形式分析。Irakoze Laurent：调查，写作-评论和编辑。林晓静：调查，验证。

Ping Yang: Investigation, Validation. Yuehua You: Methodology. Hongbin Ni: Validation. Jiayu Li: Writing - review & editing. Li Ma: Data curation, Methodology, Writing - review & editing. Xiaoqiu Xiao: Conceptualization, Project administration, Supervision. Xinyu Li: Conceptualization, Methodology, Supervision, Writing - review & editing.Corresponding authorsCorrespondence to.

杨平：调查，验证。尤月华：方法论。倪洪斌：验证。李嘉玉：写作-评论和编辑。李马：数据管理，方法论，写作-评论和编辑。肖秋晓：概念化，项目管理，监督。李新宇：概念化，方法论，监督，写作-评论和编辑。通讯作者通讯。

Xiaoqiu Xiao or Xinyu Li.Ethics declarations

肖秋晓或李新宇。道德宣言

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Reprints and permissionsAbout this articleCite this articleLiu, J., Chen, Y., Laurent, I. et al. Gestational diabetes exacerbates intrauterine microbial exposure induced intestinal microbiota change in offspring contributing to increased immune response.

转载和许可本文引用本文Liu，J.，Chen，Y.，Laurent，I。等人。妊娠糖尿病加剧了宫内微生物暴露引起的后代肠道微生物群变化，从而增加了免疫反应。

Nutr. Diabetes 14, 87 (2024). https://doi.org/10.1038/s41387-024-00346-7Download citationReceived: 10 September 2023Revised: 20 September 2024Accepted: 09 October 2024Published: 19 October 2024DOI: https://doi.org/10.1038/s41387-024-00346-7Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

营养。糖尿病14,87（2024）。https://doi.org/10.1038/s41387-024-00346-7Download引文接收日期：2023年9月10日修订日期：2024年9月20日接受日期：2024年10月9日发布日期：2024年10月19日OI：https://doi.org/10.1038/s41387-024-00346-7Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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