Midya Vishal, Agrawal Manasi, Lane Jamil M, Gennings Chris, Tarassishin Leonid, Torres-Olascoaga Libni A, Eggers Joseph, Gregory Jill K, Picker Mellissa, Peter Inga, Faith Jeremiah J, Arora Manish, Téllez-Rojo Martha M, Wright Robert O, Colombel Jean-Frederic, Eggers Shoshannah
Department of Environmental Medicine and Climate Science, Icahn School of Medicine at Mount Sinai, New York 10029-6574, New York, United States.
The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York 10029-6574, New York, United States.
Environ Health (Wash). 2024 Aug 8;2(10):739-749. doi: 10.1021/envhealth.4c00125. eCollection 2024 Oct 18.
Alterations to the gut microbiome and exposure to metals during pregnancy have been suggested to impact inflammatory bowel disease. Nonetheless, how prenatal exposure to metals eventually results in long-term effects on the gut microbiome, leading to subclinical intestinal inflammation, particularly during late childhood, has not been studied. It is also unknown whether such an interactive effect drives a specific subgroup of children toward elevated susceptibility to intestinal inflammation. We used an amalgamation of machine-learning techniques with a regression-based framework to explore if children with distinct sets of gut microbes and certain patterns of exposure to metals during pregnancy (metal-microbial clique signature) had a higher likelihood of intestinal inflammation, measured based on fecal calprotectin (FC) in late childhood. We obtained samples from a well-characterized longitudinal birth cohort from Mexico City ( = 108), Mexico. In the second and third trimesters of pregnancy, 11 metals were measured in whole blood. Gut microbial abundances and FC were measured in stool samples from children 9-11 years of age. Elevated FC was defined as having FC above 100 μg/g of stool. We identified subgroups of children in whom microbial and metal-microbial clique signatures were associated with elevated FC (false discovery rate (FDR) < 0.05). In particular, we found two metal-microbial clique signatures significantly associated with elevated FC: (1) low cesium (Cs) and copper (Cu) in the third trimester and low relative abundance of (OR [95%CI]: 10.27 [3.57,29.52], FDR < 0.001) and (2) low Cu in the third trimester and high relative abundances of and (OR [95%CI]: 7.21 [1.81,28.77], FDR < 0.05). This exploratory study demonstrates that children with specific gut microbes and specific exposure patterns to metals during pregnancy may have higher fecal calprotectin levels in late childhood, denoting an elevated risk of intestinal inflammation.
孕期肠道微生物群的改变以及接触金属被认为会影响炎症性肠病。然而，产前接触金属最终如何对肠道微生物群产生长期影响，导致亚临床肠道炎症，尤其是在儿童晚期，尚未得到研究。同样未知的是，这种相互作用效应是否会使特定亚组的儿童更容易患肠道炎症。我们将机器学习技术与基于回归的框架相结合，以探究具有不同肠道微生物群和孕期特定金属接触模式（金属-微生物团特征）的儿童在儿童晚期基于粪便钙卫蛋白（FC）测量时患肠道炎症的可能性是否更高。我们从墨西哥城一个特征明确的纵向出生队列（n = 108）中获取了样本。在孕期的第二和第三个月，测量了全血中的11种金属。在9至11岁儿童的粪便样本中测量了肠道微生物丰度和FC。FC升高定义为FC高于100μg/g粪便。我们确定了微生物和金属-微生物团特征与FC升高相关的儿童亚组（错误发现率（FDR）<0.05）。特别是，我们发现两个金属-微生物团特征与FC升高显著相关：（1）孕晚期低铯（Cs）和铜（Cu）以及低相对丰度的 （比值比[95%置信区间]：10.27[3.57,29.52]，FDR<0.001）和（2）孕晚期低Cu以及高相对丰度的 和 （比值比[95%置信区间]：7.21[1.81,28.77]，FDR<0.05）。这项探索性研究表明，孕期具有特定肠道微生物和特定金属接触模式的儿童在儿童晚期可能有更高的粪便钙卫蛋白水平，这表明肠道炎症风险升高。
