Rose Shannon, Bennuri Sirish C, Murray Katherine F, Buie Timothy, Winter Harland, Frye Richard Eugene
Autism Research Program, Arkansas Children's Research Institute, Little Rock, Arkansas, United States of America.
Department of Pediatric Gastroenterology and Nutrition, MassGeneral Hospital for Children, Boston, Massachusetts, United States of America.
PLoS One. 2017 Oct 13;12(10):e0186377. doi: 10.1371/journal.pone.0186377. eCollection 2017.
Gastrointestinal (GI) symptoms are prevalent in autism spectrum disorder (ASD) but the pathophysiology is poorly understood. Imbalances in the enteric microbiome have been associated with ASD and can cause GI dysfunction potentially through disruption of mitochondrial function as microbiome metabolites modulate mitochondrial function and mitochondrial dysfunction is highly associated with GI symptoms. In this study, we compared mitochondrial function in rectal and cecum biopsies under the assumption that certain microbiome metabolites, such as butyrate and propionic acid, are more abundant in the cecum as compared to the rectum. Rectal and cecum mucosal biopsies were collected during elective diagnostic colonoscopy. Using a single-blind case-control design, complex I and IV and citrate synthase activities and complex I-V protein quantity from 10 children with ASD, 10 children with Crohn's disease and 10 neurotypical children with nonspecific GI complaints were measured. The protein for all complexes, except complex II, in the cecum as compared to the rectum was significantly higher in ASD samples as compared to other groups. For both rectal and cecum biopsies, ASD samples demonstrated higher complex I activity, but not complex IV or citrate synthase activity, compared to other groups. Mitochondrial function in the gut mucosa from children with ASD was found to be significantly different than other groups who manifested similar GI symptomatology suggesting a unique pathophysiology for GI symptoms in children with ASD. Abnormalities localized to the cecum suggest a role for imbalances in the microbiome, potentially in the production of butyrate, in children with ASD.
胃肠道（GI）症状在自闭症谱系障碍（ASD）中很常见，但病理生理学尚不清楚。肠道微生物群的失衡与ASD有关，可能通过破坏线粒体功能导致胃肠功能障碍，因为微生物群代谢产物调节线粒体功能，而线粒体功能障碍与胃肠道症状高度相关。在本研究中，我们比较了直肠和盲肠活检组织中的线粒体功能，假设某些微生物群代谢产物，如丁酸盐和丙酸，在盲肠中比在直肠中更丰富。在选择性诊断性结肠镜检查期间收集直肠和盲肠黏膜活检组织。采用单盲病例对照设计，测量了10名ASD儿童、10名克罗恩病儿童和10名有非特异性胃肠道症状的神经典型儿童的复合体I和IV、柠檬酸合酶活性以及复合体I-V蛋白量。与其他组相比，ASD样本中盲肠中除复合体II外所有复合体的蛋白水平显著更高。对于直肠和盲肠活检组织，与其他组相比，ASD样本显示出更高的复合体I活性，但复合体IV或柠檬酸合酶活性没有升高。研究发现，ASD儿童肠道黏膜中的线粒体功能与表现出类似胃肠道症状的其他组有显著差异，这表明ASD儿童胃肠道症状有独特的病理生理学。盲肠的异常表明微生物群失衡可能在ASD儿童中发挥作用，可能与丁酸盐的产生有关。
