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自闭症谱系障碍个体中肠道微生物群与表观基因组的相互作用。

Interactions between the intestinal microbiota and epigenome in individuals with autism spectrum disorder.

机构信息

Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

出版信息

Dev Med Child Neurol. 2022 Mar;64(3):296-304. doi: 10.1111/dmcn.15052. Epub 2021 Sep 15.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by variable impairment of cognitive function and interpersonal relationships. Furthermore, some individuals with ASD have gastrointestinal disorders that have been correlated with impairments in intestinal microbiota. Gut microbiota are important not only for intestinal health, but also for many other functions including food digestion, energy production, immune system regulation, and, according to current data, behavior. Disruption of the indigenous microbiota, microbial dysbiosis (imbalance between microorganisms present in the gut), overgrowth of potentially pathogenic microorganisms, a less diverse microbiome, or lower levels of beneficial bacteria in children with ASD can affect behavior. Metabolome analysis in children with ASD has identified perturbations in multiple metabolic pathways that might be associated with cognitive functions. Recent studies have shown that the intestinal microbiome provides environmental signals that can modify host response to stimuli by modifying the host epigenome, which affects DNA methylation, histone modification, and non-coding RNAs. The most studied microbiota-produced epigenetic modifiers are short-chain fatty acids, although other products of intestinal microbiota might also cause epigenetic modifications in the host's DNA. Here we review evidence suggesting that epigenetic alterations caused by modification of gene expression play an important role in understanding ASD.

摘要

自闭症谱系障碍(ASD)是一种神经发育障碍,其特征是认知功能和人际关系的不同程度受损。此外,一些 ASD 患者存在胃肠道疾病,这些疾病与肠道微生物群的损伤有关。肠道微生物群不仅对肠道健康很重要,而且对许多其他功能也很重要,包括食物消化、能量产生、免疫系统调节,根据目前的数据,还包括行为。肠道原籍微生物群的破坏、微生物失调(肠道中存在的微生物之间的失衡)、潜在致病性微生物的过度生长、微生物组多样性降低或 ASD 儿童体内有益细菌水平降低,都可能会影响行为。对 ASD 儿童的代谢组学分析已经确定了多个代谢途径的紊乱,这些紊乱可能与认知功能有关。最近的研究表明,肠道微生物群提供的环境信号可以通过修饰宿主的表观基因组来改变宿主对刺激的反应,从而影响 DNA 甲基化、组蛋白修饰和非编码 RNA。研究最多的微生物群产生的表观遗传修饰物是短链脂肪酸,尽管肠道微生物群的其他产物也可能导致宿主 DNA 的表观遗传修饰。在这里,我们综述了表明由基因表达修饰引起的表观遗传改变在理解 ASD 方面发挥重要作用的证据。

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