澳大利亚自闭症生物库中孕产妇不良事件与长期肠道微生物组结果之间没有关联

IF 3.7 Q2 IMMUNOLOGY Brain, behavior, & immunity - health Pub Date : 2024-06-21 DOI:10.1016/j.bbih.2024.100814
Svetlina Vasileva , Chloe X. Yap , Andrew J.O. Whitehouse , Jacob Gratten , Darryl Eyles
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引用次数: 0

摘要

导言:母体免疫激活(MIA)和产前母体压力(MatS)是自闭症和精神分裂症等精神疾病的风险因素。动物研究提出肠道微生物组是这种关联的基础机制,并发现与风险因素相关的肠道微生物组改变会在成年后代中持续存在。在这项横断面研究中,我们使用散弹枪元基因组学方法评估了母体免疫激活和产前母体压力是否与儿童肠道微生物组的长期改变有关。这项横断面研究纳入了被诊断患有自闭症的儿童(92 人)、未被诊断患有自闭症的兄弟姐妹(42 人)以及未被诊断患有自闭症的无关儿童(40 人),他们都被纳入了澳大利亚自闭症生物库并提供了粪便样本。根据自我报告的数据推断出母体感染风险,包括哮喘/过敏、孕期引发免疫反应的并发症、自身免疫性疾病和急性炎症。孕产妇压力包括多达 9 种孕期生活压力事件中的任何一种,如离婚、失业和经济问题。共对 174 名儿童的数据进行了分析,其中 63 名(36%)儿童的母亲患有 MIA,84 名(48%)儿童的母亲在怀孕期间经历了母体压力(其中 33 名[19%]的母亲同时经历了这两种压力)。通过对儿童粪便样本进行散弹枪元基因组测序,对肠道微生物组数据进行了评估。方差分析显示,任何肠道微生物组数据集均与 MIA 或 MatS 无关。在对年龄、性别、饮食和自闭症诊断进行调整后,各组间的细菌丰富度、α-多样性或β-多样性均无显著差异。在主要分析中,我们发现物种丰度没有明显差异。然而,当按年龄对队列进行分层时,我们发现在 11-17 岁的 MIA 儿童中,Faecalibacterium prausnitzii E 明显减少。与动物研究不同的是,我们发现与 MIA 和母亲压力有关的微生物组差异微乎其微。鉴于目前人们对微生物组-肠-脑轴的关注,研究人员在将微生物组研究结果从动物模型转化到人类环境和临床环境时应谨慎行事。
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Absence of association between maternal adverse events and long-term gut microbiome outcomes in the Australian autism biobank

Introduction

Maternal immune activation (MIA) and prenatal maternal stress (MatS) are well-studied risk factors for psychiatric conditions such as autism and schizophrenia. Animal studies have proposed the gut microbiome as a mechanism underlying this association and have found that risk factor-related gut microbiome alterations persist in the adult offspring. In this cross-sectional study, we assessed whether maternal immune activation and prenatal maternal stress were associated with long-term gut microbiome alterations in children using shotgun metagenomics.

Methods

This cross-sectional study included children diagnosed with autism (N = 92), siblings without a diagnosis (N = 42), and unrelated children (N = 40) without a diagnosis who were recruited into the Australian Autism Biobank and provided a faecal sample. MIA exposure was inferred from self-reported data and included asthma/allergies, complications during pregnancy triggering an immune response, auto-immune conditions, and acute inflammation. Maternal stress included any of up to 9 stressful life events during pregnancy, such as divorce, job loss, and money problems. Data were analysed for a total of 174 children, of whom 63 (36%) were born to mothers with MIA and 84 (48%) were born to mothers who experienced maternal stress during pregnancy (where 33 [19%] experienced both). Gut microbiome data was assessed using shotgun metagenomic sequencing of the children's faecal samples.

Results

In our cohort, MIA, but not MatS, was associated with ASD. Variance component analysis revealed no associations between any of the gut microbiome datasets and neither MIA nor MatS. After adjusting for age, sex, diet and autism diagnosis, there was no significant difference between groups for bacterial richness, α-diversity or β-diversity. We found no significant differences in species abundance in the main analyses. However, when stratifying the cohort by age, we found that Faecalibacterium prausnitzii E was significantly decreased in MIA children aged 11–17.

Discussion

Consistent with previous findings, we found that children who were born to mothers with MIA were more likely to be diagnosed with autism. Unlike within animal studies, we found negligible microbiome differences associated with MIA and maternal stress. Given the current interest in the microbiome-gut-brain axis, researchers should exercise caution in translating microbiome findings from animal models to human contexts and the clinical setting.

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来源期刊
Brain, behavior, & immunity - health
Brain, behavior, & immunity - health Biological Psychiatry, Behavioral Neuroscience
CiteScore
8.50
自引率
0.00%
发文量
0
审稿时长
97 days
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