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母体炎症性肠病相关抗体与早期肠道炎症状态及微生物群组成有关:来自脐带血的见解

Maternal IBD-related antibodies are associated with early life gut inflammatory status and microbiota composition: insights from cord blood.

作者信息

Kim Taegyu, Nicoletti Paola, Estevinho Maria Manuela, Tarassishin Leonid, Picker Mellissa, Debebe Anketse, Nguyen Isabella, Dutra-Clarke Rhiannon, Young Courtney, Stone Joanne, Bar-Gil Shitrit Ariella, Agrawal Manasi, Colombel Jean-Frederic, Torres Joana, Ng Siew C, Zhang Lin, McGovern Dermot P B, Peter Inga

机构信息

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Department of Gastroenterology, Unidade Local de Saúde Gaia Espinho, Vila Nova de Gaia, Portugal.

出版信息

bioRxiv. 2025 Aug 6:2025.08.04.668517. doi: 10.1101/2025.08.04.668517.

Abstract

PURPOSE

Antibodies in peripheral blood are used to aid in the diagnosis of inflammatory bowel disease (IBD), but their presence in neonatal cord blood and potential effects on early life development remain unknown.

METHODS

We measured anti-CBir1, ANCA, anti-OmpC, ASCA IgA, and ASCA IgG levels in the cord blood of babies born to 78 mothers with or without IBD. Their association with fecal calprotectin (FC), and microbiota composition, characterized by 16S rRNA sequencing, was assessed throughout pregnancy and during the first 3 years of life using linear mixed-effects models.

RESULTS

Antibodies were detected in cord blood, with significantly higher levels of anti-CBir1 and ASCA IgG in babies born to mothers with Crohn's disease (p = 0.002) and higher abundance of ANCA and anti-OmpC in babies of mothers with ulcerative colitis (p = 0.002), compared to controls. ASCA IgG levels positively correlated with babies' FC (p = 0.006), while babies' microbiota Shannon diversity was negatively associated with ANCA, anti-OmpC, and ASCA IgA levels (p = 0.003, 0.04, and 0.008, respectively). spp., spp., spp., , , and spp. were positively correlated with either or both ANCA and anti-OmpC levels (all multiple testing adjusted q < 0.1).

CONCLUSION

Our findings suggest that maternal IBD-associated antibodies cross the placenta barrier and may be associated with intestinal inflammation and imbalanced microbiota colonization. Whether these serological profiles negatively influence the priming of the baby's immune system or IBD risk later in life remains to be determined.

摘要

目的

外周血中的抗体可辅助诊断炎症性肠病(IBD),但其在新生儿脐带血中的存在情况以及对早期生命发育的潜在影响尚不清楚。

方法

我们检测了78名患有或未患有IBD的母亲所生婴儿脐带血中的抗CBir1、抗中性粒细胞胞浆抗体(ANCA)、抗OmpC、抗酿酒酵母抗体(ASCA)IgA和ASCA IgG水平。在整个孕期以及生命的前3年,使用线性混合效应模型评估了它们与粪便钙卫蛋白(FC)以及通过16S rRNA测序表征的微生物群组成之间的关联。

结果

在脐带血中检测到了抗体,与对照组相比克罗恩病母亲所生婴儿的抗CBir1和ASCA IgG水平显著更高(p = 0.002),而溃疡性结肠炎母亲所生婴儿的ANCA和抗OmpC丰度更高(p = 0.002)。ASCA IgG水平与婴儿的FC呈正相关(p = 0.006),而婴儿微生物群的香农多样性与ANCA、抗OmpC和ASCA IgA水平呈负相关(分别为p = 0.003、0.04和0.008)。 属、 属、 属、 、 和 属与ANCA和抗OmpC水平中的一个或两个呈正相关(所有多重检验校正后的q < 0.1)。

结论

我们的研究结果表明,与母体IBD相关的抗体可穿过胎盘屏障,可能与肠道炎症和微生物群定植失衡有关。这些血清学特征是否会对婴儿免疫系统的启动或日后患IBD的风险产生负面影响仍有待确定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf8c/12340837/56e0262eb109/nihpp-2025.08.04.668517v1-f0001.jpg

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