BACKGROUND Gastrointestinal problems affect the health and quality of life of individuals with Rett syndrome (RTT) and pose a medical hardship for their caregivers. We hypothesized that the variability in the RTT phenotype contributes to the dysbiosis of the gut microbiome and metabolome in RTT, predisposing these individuals to gastrointestinal dysfunction. OBJECTIVES We characterized the gut bacterial microbiome and metabolome in girls and young women with RTT (n = 44) and unaffected controls (n = 21), and examined the relation between the composition of the microbiome and variations in the RTT phenotype. METHODS Demographics and clinical information, including growth and anthropometric measurements, pubertal status, symptoms, clinical severity score, bowel movement, medication use, and dietary intakes were collected from the participants. Fecal samples were collected for analysis of the gut microbiome using Illumina MiSeq-based next-generation sequencing of the 16S rRNA gene followed by bioinformatics analysis of microbial composition, diversity, and community structure. Selected end-products of microbial protein metabolism were characterized by liquid chromatography-mass spectrometry. RESULTS The gut bacterial microbiome differed within the RTT cohort based on pubertal status (p<0.02) and clinical severity scores (p<0.02) of the individuals and the type of diet (p<0.01) consumed. Although the composition of the gut microbiome did not differ between RTT and unaffected individuals, concentrations of protein end-products of the gut bacterial metabolome, including γ-aminobutyric acid (GABA) (p<0.001), tyrosine (p<0.02), and glutamate (p<0.06), were lower in the RTT cohort. Differences in the microbiome within RTT groups, based on symptomatic anxiety, hyperventilation, abdominal distention, or changes in stool frequency and consistency, were not detected. CONCLUSIONS Although variability in the RTT phenotype contributes to the dysbiosis of the gut microbiome, we presently cannot infer causality between gut bacterial dysbiosis and gastrointestinal dysfunction. Nevertheless, alterations in the gut metabolome may provide clues to the pathophysiology of gastrointestinal problems in RTT.

中文翻译：

---

评估患有 Rett 综合征的女孩和女性的肠道细菌微生物组和代谢组。

背景胃肠道问题影响患有雷特综合征(RTT)的个体的健康和生活质量，并且给他们的看护者带来医疗困难。我们假设 RTT 表型的变异性导致 RTT 中肠道微生物组和代谢组的失调，使这些个体易患胃肠功能障碍。目标我们表征了 RTT 女孩和年轻女性（n = 44）和未受影响的对照（n = 21）的肠道细菌微生物组和代谢组，并检查了微生物组的组成与 RTT 表型变化之间的关系。方法 从参与者那里收集人口统计学和临床​​信息，包括生长和人体测量、青春期状态、症状、临床严重程度评分、排便、药物使用和饮食摄入量。收集粪便样本用于使用基于 Illumina MiSeq 的 16S rRNA 基因下一代测序分析肠道微生物组，然后对微生物组成、多样性和群落结构进行生物信息学分析。微生物蛋白质代谢的选定终产物通过液相色谱-质谱法进行表征。结果 根据个体的青春期状态 (p<0.02) 和临床严重程度评分 (p<0.02) 以及消耗的饮食类型 (p<0.01)，RTT 队列中的肠道细菌微生物组存在差异。虽然肠道微生物组的组成在 RTT 和未受影响的个体之间没有差异，但肠道细菌代谢组的蛋白质终产物的浓度，包括 γ-氨基丁酸 (GABA) (p<0.001)、酪氨酸 (p<0.02) 和谷氨酸 (p<0.06), 在 RTT 队列中较低。未检测到 RTT 组内微生物组的差异，这些差异基于症状性焦虑、换气过度、腹胀或大便频率和稠度的变化。结论虽然 RTT 表型的变异性导致肠道微生物群的生态失调，但我们目前无法推断肠道细菌生态失调与胃肠功能障碍之间的因果关系。然而，肠道代谢组的改变可能为 RTT 中胃肠道问题的病理生理学提供线索。我们目前无法推断肠道细菌生态失调和胃肠功能障碍之间的因果关系。然而，肠道代谢组的改变可能为 RTT 中胃肠道问题的病理生理学提供线索。我们目前无法推断肠道细菌生态失调和胃肠功能障碍之间的因果关系。然而，肠道代谢组的改变可能为 RTT 中胃肠道问题的病理生理学提供线索。