Throughout gestation, the female body undergoes a series of transformations, including profound alterations in intestinal microbial communities. Changes gradually increase toward the end of pregnancy and comprise reduced α-diversity of microbial communities and an increased propensity for energy harvest. Despite the importance of the intestinal microbiota for the pathophysiology of inflammatory bowel diseases, very little is known about the relationship between these microbiota shifts and pregnancy-associated complications of the disease. Here, we explored the longitudinal dynamics of gut microbiota composition and functional potential during pregnancy and after lactation in Atg16l1∆IEC mice carrying an intestinal epithelial deletion of the Crohn's disease risk gene Atg16l1. Using 16S rRNA amplicon and shotgun metagenomic sequencing, we demonstrated divergent temporal shifts in microbial composition between Atg16l1 wildtype and Atg16l1∆IEC pregnant mice in trimester 3, which was validated in an independent experiment. Observed differences included microbial genera implicated in IBD such as Lachnospiraceae, Roseburia, Ruminococcus, and Turicibacter. Changes partially recovered after lactation. Additionally, metagenomic and metabolomic analyses suggest an increased capacity for chitin degradation, resulting in higher levels of free N-acetyl-glucosamine products in feces, alongside reduced glucose and myo-inositol levels in serum around the time of delivery. On the host side, we found that the immunological response of Atg16l1∆IEC mice is characterized by higher colonic mRNA levels of TNFα and CXCL1 in trimester 3 and a lower weight of offspring at birth. Understanding pregnancy-dependent microbiome changes in the context of IBD may constitute the first step in the identification of fecal microbial biomarkers and microbiota-directed therapies that could help improve precision care for managing pregnancies in IBD patients.

中文翻译：

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肠上皮细胞中缺陷的 Atg16l1 与小鼠怀孕期间粪便微生物群的改变和代谢变化有关。


在整个妊娠过程中，女性身体经历了一系列转变，包括肠道微生物群落的深刻变化。在怀孕末期，变化逐渐增加，包括微生物群落α多样性减少和能量收集倾向增加。尽管肠道菌群对炎症性肠病的病理生理学很重要，但人们对这些菌群变化与疾病妊娠相关并发症之间的关系知之甚少。在这里，我们探讨了携带克罗恩病风险基因 Atg16l1 肠上皮缺失的 Atg16l1∆IEC 小鼠怀孕期间和哺乳期后肠道微生物群组成和功能潜力的纵向动力学。使用 16S rRNA 扩增子和鸟枪法宏基因组测序，我们证明了 Atg16l1 野生型和 Atg16l1∆IEC 妊娠小鼠在妊娠 3 期微生物组成的不同时间变化，这在独立实验中得到了验证。观察到的差异包括与 IBD 有关的微生物属，例如 Lachnospiraceae、Roseburia、Ruminococcus 和 Turicibacter。哺乳后变化部分恢复。此外，宏基因组学和代谢组学分析表明，甲壳素降解能力增加，导致粪便中游离 N-乙酰氨基葡萄糖产物水平升高，同时在分娩时血清中的葡萄糖和肌醇水平降低。在宿主侧，我们发现 Atg16l1∆IEC 小鼠的免疫反应特征是妊娠期 3 结肠 mRNA 中 TNFα 和 CXCL1 的水平较高，而后代出生时体重较低。 了解 IBD 背景下的妊娠依赖性微生物组变化可能构成识别粪便微生物生物标志物和微生物群定向疗法的第一步，这可能有助于改善 IBD 患者妊娠管理的精准护理。