Interdepartmental Program "Autism 0-90", "G. Martino" University Hospital of Messina, Messina, Italy.
IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy.
Autism Res. 2022 Jan;15(1):56-69. doi: 10.1002/aur.2639. Epub 2021 Nov 23.
Chronic constipation is common among children with ASD and is associated with more severe hyperactivity, anxiety, irritability, and repetitive behaviors. Young autistic children with chronic constipation display higher urinary, and foecal concentrations of p-cresol, an aromatic compound produced by gut bacteria, known to negatively affect brain function. Acute p-cresol administration to BTBR mice enhances anxiety, hyperactivity and stereotypic behaviors, while blunting social interaction. This study was undertaken to prospectively assess the behavioral effects of gut mobilization in young autistic children with chronic constipation, and to verify their possible correlation with urinary p-cresol. To this aim, 21 chronically constipated autistic children 2-8 years old were evaluated before (T0), 1 month (T1), and 6 months (T2) after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors, anxiety, and hyperactivity. Gut mobilization yielded a progressive and highly significant decrease in all behavioral symptoms over the 6-month study period. Urinary p-cresol levels displayed variable trends not significantly correlated with changes in behavioral parameters, mainly increasing at T1 and decreasing at T2. These results support gut mobilization as a simple strategy to ameliorate ASD symptoms, as well as comorbid anxiety and hyperactivity, in chronically constipated children. Variation in p-cresol absorption seemingly provides limited contributions, if any, to these behavioral changes. Further research will be needed to address the relative role of reduced abdominal discomfort following mobilization, as compared to specific modifications in microbiome composition and in gut bacteria-derived neuroactive compounds.
慢性便秘在自闭症谱系障碍（ASD）儿童中很常见，与更严重的多动、焦虑、易怒和重复行为有关。患有慢性便秘的年轻自闭症儿童尿液和粪便中 p-甲酚浓度较高，p-甲酚是一种肠道细菌产生的芳香化合物，已知会对大脑功能产生负面影响。急性 p-甲酚给药可增强 BTBR 小鼠的焦虑、多动和刻板行为，同时削弱社交互动。本研究旨在前瞻性评估肠道动员对慢性便秘自闭症儿童的行为影响，并验证其与尿 p-甲酚的可能相关性。为此，我们评估了 21 名 2-8 岁慢性便秘自闭症儿童在肠道动员前（T0）、1 个月（T1）和 6 个月（T2）时的行为评分、尿 p-甲酚浓度以及社会互动障碍、刻板行为、焦虑和多动等行为评分。肠道动员在 6 个月的研究期间，所有行为症状均呈渐进性和高度显著下降。尿 p-甲酚水平呈变化趋势，但与行为参数的变化无显著相关性，主要在 T1 时增加，在 T2 时减少。这些结果支持肠道动员作为一种简单的策略，可以改善慢性便秘儿童的 ASD 症状以及共患的焦虑和多动。p-甲酚吸收的变化似乎对这些行为变化的贡献有限，如果有的话。需要进一步的研究来确定动员后腹部不适减轻与微生物组组成和肠道细菌衍生的神经活性化合物的具体变化的相对作用。
