揭示人类产前肠道微生物组在后代神经发育中的重要性。
Revealing the importance of prenatal gut microbiome in offspring neurodevelopment in humans.
机构信息
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Division of Pediatric Pulmonary Medicine, Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, 14642, USA.
出版信息
EBioMedicine. 2023 Apr;90:104491. doi: 10.1016/j.ebiom.2023.104491. Epub 2023 Mar 1.
BACKGROUND
It has been widely recognized that a critical time window for neurodevelopment occurs in early life and the host's gut microbiome plays an important role in neurodevelopment. Following recent demonstrations that the maternal prenatal gut microbiome influences offspring brain development in murine models, we aim to explore whether the critical time window for the association between the gut microbiome and neurodevelopment is prenatal or postnatal for human.
METHODS
Here we leverage a large-scale human study and compare the associations between the gut microbiota and metabolites from mothers during pregnancy and their children with the children's neurodevelopment. Specifically, using multinomial regression integrated in Songbird, we assessed the discriminating power of the maternal prenatal and child gut microbiome for children's neurodevelopment at early life as measured by the Ages & Stages Questionnaires (ASQ).
FINDINGS
We show that the maternal prenatal gut microbiome is more relevant than the children's gut microbiome to the children's neurodevelopment in the first year of life (maximum Q = 0.212 and 0.096 separately using the taxa at the class level). Moreover, we found that Fusobacteriia is more associated with high fine motor skills in ASQ in the maternal prenatal gut microbiota but become more associated with low fine motor skills in the infant gut microbiota (rank = 0.084 and -0.047 separately), suggesting the roles of the same taxa with respect to neurodevelopment can be opposite at the two stages of fetal neurodevelopment.
INTERPRETATION
These findings shed light, especially in terms of timing, on potential therapeutic interventions to prevent neurodevelopmental disorders.
FUNDING
This work was supported by the National Institutes of Health (grant numbers: R01AI141529, R01HD093761, RF1AG067744, UH3OD023268, U19AI095219, U01HL089856, R01HL141826, K08HL148178, K01HL146980), and the Charles A. King Trust Postdoctoral Fellowship.
背景
人们普遍认识到，神经发育的关键时期发生在生命早期，宿主的肠道微生物群在神经发育中起着重要作用。最近的研究表明，母体产前肠道微生物群会影响鼠模型后代的大脑发育，因此我们旨在探索人类中肠道微生物群与神经发育之间关联的关键时期是产前还是产后。
方法
在这里，我们利用一项大规模的人类研究，比较了母亲在怀孕期间的肠道微生物群和代谢物与儿童神经发育之间的关联。具体来说，我们使用 Songbird 中的多项回归分析，评估了母体产前和儿童肠道微生物群对儿童早期神经发育（通过年龄与阶段问卷 (ASQ) 进行衡量）的区分能力。
发现
我们发现，母体产前肠道微生物群与儿童生命第一年的神经发育更为相关（使用分类水平的分类群，最大 Q 值分别为 0.212 和 0.096）。此外，我们发现厚壁菌门在母体产前肠道微生物群中与 ASQ 中的精细运动技能较高更为相关，但在婴儿肠道微生物群中与精细运动技能较低更为相关（秩分别为 0.084 和-0.047），这表明相同分类群在胎儿神经发育的两个阶段对神经发育的作用可能相反。
解释
这些发现特别在时间方面为预防神经发育障碍的潜在治疗干预措施提供了启示。
资助
这项工作得到了美国国立卫生研究院（拨款号：R01AI141529、R01HD093761、RF1AG067744、UH3OD023268、U19AI095219、U01HL089856、R01HL141826、K08HL148178、K01HL146980）和 Charles A. King 信托博士后奖学金的支持。
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