Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism.
Microbiota-related Changes in Bile Acid & Tryptophan Metabolism are Associated with Gastrointestinal Dysfunction in a Mouse Model of Autism.
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DOI：
10.1016/j.ebiom.2017.09.020
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发表时间：
2017-10
期刊：
影响因子：
11.1
通讯作者：
Cryan JF
中科院分区：
文献类型：
--
作者：
Golubeva AV;Joyce SA;Moloney G;Burokas A;Sherwin E;Arboleya S;Flynn I;Khochanskiy D;Moya-Pérez A;Peterson V;Rea K;Murphy K;Makarova O;Buravkov S;Hyland NP;Stanton C;Clarke G;Gahan CGM;Dinan TG;Cryan JF
自闭症谱系障碍（ASD）是世界上最普遍的神经发育疾病之一。越来越多的人意识到ASD与胃肠道不适和肠道微生物组改变高度共病，并且宿主-微生物组相互作用可能导致疾病症状。然而，对自闭症中肠-脑轴信号传导的知识的缺乏构成了ASD中基于微生物群的精确疗法的发展的障碍。为此，我们探索了BTBR T+ Itpr 3 tf/J ASD小鼠模型中肠道微生物群、肠道生理学和社会行为之间的相互作用。在这里，我们表明，在BTBR肠道中非常特殊的细菌类群的相对丰度的减少-即，胆汁代谢双歧杆菌和布劳特氏菌属物种，-与肠道中的胆汁酸和色氨酸代谢不足，显著的胃肠道功能障碍，以及BTBR小鼠的社会互动受损。这些数据共同支持了靶向操纵肠道微生物群以逆转ASD中的胃肠道和行为代谢的概念，并在这一奋进中提供了具体的合理目标。BTBR小鼠在肠道中显示出降低的胆汁代谢双歧杆菌和布劳特氏菌属细菌物种丰度。BTBR小鼠表现出肠道中胆汁部分的细菌代谢缺陷。肠道微生物群的变化与BTBR小鼠中显著的胃肠道不适和社交能力降低相关。越来越多的人意识到肠道微生物组可能有助于自闭症谱系障碍（ASD）的胃肠道和行为障碍学。然而，肠道细菌影响自闭症肠-脑轴信号传导的确切机制还知之甚少。在这里，我们探讨了ASD小鼠模型中肠道微生物群，肠道生理学和行为之间的相互作用。我们发现，在“自闭症”小鼠中，特定肠道细菌丰度的减少与胃肠道不适和社会行为缺陷有关。这项工作支持了靶向肠道微生物群以逆转ASD胃肠道症状的概念，并确定了基于微生物群的干预措施的具体可行目标。
Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental conditions worldwide. There is growing awareness that ASD is highly comorbid with gastrointestinal distress and altered intestinal microbiome, and that host-microbiome interactions may contribute to the disease symptoms. However, the paucity of knowledge on gut-brain axis signaling in autism constitutes an obstacle to the development of precision microbiota-based therapeutics in ASD. To this end, we explored the interactions between intestinal microbiota, gut physiology and social behavior in a BTBR T+Itpr3tf/J mouse model of ASD. Here we show that a reduction in the relative abundance of very particular bacterial taxa in the BTBR gut – namely, bile-metabolizing Bifidobacterium and Blautia species, - is associated with deficient bile acid and tryptophan metabolism in the intestine, marked gastrointestinal dysfunction, as well as impaired social interactions in BTBR mice. Together these data support the concept of targeted manipulation of the gut microbiota for reversing gastrointestinal and behavioral symptomatology in ASD, and offer specific plausible targets in this endeavor. BTBR mice display a reduced abundance of bile-metabolizing Bifidobacterium and Blautia bacterial species in the intestine. BTBR mice demonstrate deficient bacterial metabolism of bile moieties in the gut. Changes in the gut microbiota are associated with marked gastrointestinal distress and reduced sociability in BTBR mice. There is growing awareness that the gut microbiome may contribute to gastrointestinal and behavioral symptomatology of autism spectrum disorder (ASD). However, the exact mechanisms by which intestinal bacteria can affect gut-brain axis signaling in autism are as yet poorly understood. Here we explore interactions between intestinal microbiota, gut physiology and behavior in a mouse model of ASD. We show that a reduction in the abundance of particular intestinal bacteria in “autistic” mice is associated with gastrointestinal distress and social behavior deficits. This work supports the concept of targeting the gut microbiota for reversing gastrointestinal symptoms in ASD, and identifies specific plausible targets for microbiota-based interventions.
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影响因子：
6.2
作者：
Fiorentino M;Sapone A;Senger S;Camhi SS;Kadzielski SM;Buie TM;Kelly DL;Cascella N;Fasano A
通讯作者：
Fasano A
影响因子：
3.7
作者：
Heo Y;Zhang Y;Gao D;Miller VM;Lawrence DA
通讯作者：
Lawrence DA
影响因子：
29.4
作者：
Alemi F;Poole DP;Chiu J;Schoonjans K;Cattaruzza F;Grider JR;Bunnett NW;Corvera CU
通讯作者：
Corvera CU
影响因子：
5.8
作者：
GREEN, AR;CURZON, G
通讯作者：
CURZON, G
通过表达突变型紧密连接膜蛋白，细胞旁通透性和跨上皮电阻的功能性分离以及顶端-基底外侧膜内扩散屏障的破坏。
影响因子：
7.8
作者：
Balda, M S;Whitney, J A;Flores, C;Gonzalez, S;Cereijido, M;Matter, K
通讯作者：
Matter, K