Gestational diabetes exacerbates intrauterine microbial exposure induced intestinal microbiota change in offspring contributing to increased immune response.

IF 4.6 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Nutrition & Diabetes Pub Date : 2024-10-19 DOI:10.1038/s41387-024-00346-7
Juncheng Liu, Yan Chen, Irakoze Laurent, Ping Yang, Xiaoqiu Xiao, Xinyu Li
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Abstract

Background: maternal 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.

Aims: to 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.

Methods: Levels of lipopolysaccharides in cord blood from GDM and expression of microbial recognition-related proteins in the placenta were measured. 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.

Result: Gestational 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. 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.

Conclusions: Our investigation has revealed a noteworthy correlation between gestational diabetes and intrauterine microbial exposure, as well as alterations in the neonatal microbiota and activation of immune responses. These findings highlight the gestational diabetes's role on offspring's gut microbiota and immune system interactions with early-life pathogen exposure.

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妊娠糖尿病会加剧宫内微生物暴露引起的后代肠道微生物群变化,导致免疫反应增强。
背景:妊娠期间母体的健康会影响后代的肠道微生物群落,但目前妊娠期糖尿病(GDM)导致的宫内环境变化对后代微生物群落的影响及其与免疫系统的相互作用仍不清楚:方法:测量妊娠期糖尿病患者脐带血中脂多糖的水平和胎盘中微生物识别相关蛋白的表达。为了评估胚胎肠道定植情况,给妊娠 GDM 小鼠注射了标记的大肠杆菌或乳酸杆菌。通过 16S rRNA 基因测序和标记微生物培养分析幼鼠的肠道定植情况。此外,还进行了记忆T淋巴细胞和树突状细胞共培养实验,以阐明胚胎期肠道微生物的免疫记忆:结果:妊娠期糖尿病导致脐带血中 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。GDM 小鼠模型显示胎盘中的 TLR4、TLR5、IL-22 和 IL-23 等免疫标记物增加,后代肠道中的记忆 T 细胞也出现了召回反应,这与人类实验中的观察结果相似。此外,GDM 后代的肠道微生物群多样性降低,固着菌/类杆菌比例增加,细菌定植的稳定性受到干扰:我们的研究揭示了妊娠糖尿病与宫内微生物暴露、新生儿微生物群改变和免疫反应激活之间的显著相关性。这些发现凸显了妊娠糖尿病对后代肠道微生物群和免疫系统与早期病原体暴露的相互作用。
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来源期刊
Nutrition & Diabetes
Nutrition & Diabetes ENDOCRINOLOGY & METABOLISM-NUTRITION & DIETETICS
CiteScore
9.20
自引率
0.00%
发文量
50
审稿时长
>12 weeks
期刊介绍: Nutrition & Diabetes is a peer-reviewed, online, open access journal bringing to the fore outstanding research in the areas of nutrition and chronic disease, including diabetes, from the molecular to the population level.
期刊最新文献
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