Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children With Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine.
Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children With Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine.
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DOI：
10.3389/fpsyt.2021.824933
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发表时间：
2021
影响因子：
4.7
通讯作者：
Hicks SD
中科院分区：
文献类型：
--
作者：
Beversdorf DQ;Sohl K;Levitskiy D;Tennant P;Goin-Kochel RP;Shaffer RC;Confair A;Middleton FA;Hicks SD
胃肠道（GI）疾病在患有神经发育障碍（如自闭症谱系障碍，ASD）的儿童中很常见。对使该人群易患胃肠道疾病的生物学因素了解有限，阻碍了针对这一重要医学问题的个体化治疗的发展。本研究的目的是确定唾液微转录组的成分是否能为自闭症相关胃肠道紊乱儿童特有的生物学扰动提供见解。这项队列研究包括898名儿童（年龄18 - 73个月），他们患有自闭症、非自闭症发育迟缓（DD）或典型发育（TD）。用RNA测序评估每个儿童的唾液微转录组。将结果与微生物和人类数据库进行比对。采用克鲁斯卡尔 - 沃利斯方差分析（ANOVA）来比较1821种微转录组特征在不同神经发育状态（自闭症、发育迟缓或典型发育）以及有无胃肠道疾病情况下的水平。还使用方差分析来比较胃肠道亚组（便秘、反流、食物不耐受、其他胃肠道疾病、无胃肠道疾病）之间的微转录组水平，并识别服用三种常见胃肠道药物（益生菌、反流药物或泻药）的儿童之间存在差异的RNA。对在方差分析测试中确定的特征之间的关系进行检查，以确定其与《自闭症诊断观察量表第二版》（ADOS - 2）和《文兰适应行为量表》得分的关联。自闭症儿童的胃肠道紊乱发生率高于典型发育的同龄人，但与发育迟缓儿童相似。五种piwi相互作用RNA和三种微生物RNA显示出发育状态和胃肠道紊乱之间的相互作用。57种唾液RNA在胃肠道亚组之间存在差异——食物不耐受组和反流组之间的微小RNA差异最为常见。12种微小RNA显示出胃肠道紊乱的影响，并与胃肠道药物使用和行为指标相关。这12种微小RNA在13种生理途径上表现出富集，包括代谢/消化、长时程抑制和成瘾的神经生物学。本研究确定了在自闭症相关胃肠道紊乱儿童中具有差异表达的唾液微转录组特征。一部分RNA显示出与治疗方式的关系，并与自闭症行为相关。微转录组标记物的病理生物学靶点可作为个体化治疗干预的靶点，旨在缓解自闭症相关胃肠道紊乱中出现的疼痛和行为困难。
Gastrointestinal (GI) disorders are common in children with neurodevelopmental disorders such as autism spectrum disorder (ASD). A limited understanding of the biologic factors that predispose this population to GI disorders has prevented development of individualized therapies to address this important medical issue. The goal of the current study was to determine if elements of the salivary micro-transcriptome could provide insight into the biologic perturbations unique to children with ASD-related GI disturbance. This cohort study included 898 children (ages 18–73 months) with ASD, non-ASD developmental delay (DD), or typical development (TD). The saliva micro-transcriptome of each child was assessed with RNA-seq. Outputs were aligned to microbial and human databases. A Kruskal Wallis analysis of variance (ANOVA) was used to compare levels of 1821 micro-transcriptome features across neurodevelopmental status (ASD, DD, or TD) and GI presence or absence. An ANOVA was also used to compare micro-transcriptome levels among GI sub-groups (constipation, reflux, food intolerance, other GI condition, no GI condition), and to identify RNAs that differed among children taking three common GI medications (probiotics, reflux medication, or laxatives). Relationships between features identified in ANOVA testing were examined for associations with scores on the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2) and the Vineland Adaptive Behavior Scales. GI disturbance rates were higher among children with ASD than peers with TD but were similar to those with DD. Five piwi-interacting RNAs and three microbial RNAs displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI sub-groups–with microRNA differences between food intolerance and reflux groups being most common. Twelve microRNAs displayed an effect of GI disturbance and showed association with GI medication uses and measures of behavior. These 12 microRNAs displayed enrichment for 13 physiologic pathways, including metabolism/digestion long-term depression, and neurobiology of addiction. This study identifies salivary micro-transcriptome features with differential expression among children with ASD-related GI disturbance. A subset of the RNAs displays relationships with treatment modality and are associated with autistic behaviors. The pathobiologic targets of the micro-transcriptome markers may serve as targets for individualized therapeutic interventions aimed at easing pain and behavioral difficulties seen in ASD-related GI disturbance.
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微生物群转移疗法改变肠道生态系统并改善胃肠道和自闭症症状：一项开放标签研究。
影响因子：
15.5
作者：
Kang DW;Adams JB;Gregory AC;Borody T;Chittick L;Fasano A;Khoruts A;Geis E;Maldonado J;McDonough-Means S;Pollard EL;Roux S;Sadowsky MJ;Lipson KS;Sullivan MB;Caporaso JG;Krajmalnik-Brown R
通讯作者：
Krajmalnik-Brown R
影响因子：
3.7
作者：
Hicks, Steven D.;Rajan, Alexander T.;Middleton, Frank A.
通讯作者：
Middleton, Frank A.
影响因子：
8
作者：
Campbell, Daniel B.;Buie, Timothy M.;Levitt, Pat
通讯作者：
Levitt, Pat
影响因子：
4.7
作者：
Ferguson, Bradley J.;Dovgan, Kristen;Beversdorf, David Q.
通讯作者：
Beversdorf, David Q.
影响因子：
2.7
作者：
Ji, Li -Li;Ye, Yao;Tong, Lei
通讯作者：
Tong, Lei