Kleefstra Syndrome (KS) is a rare monogenetic syndrome, caused by haploinsufficiency of the euchromatic histone methyl transferase 1 (EHMT1) gene, an important regulator of neurodevelopment. The clinical features of KS include intellectual disability, autistic behavior and gastrointestinal problems. The gut microbiota, an important modifier of the gut-brain-axis, may constitute an unexplored mechanism underlying clinical KS variation. We investigated the gut microbiota composition of 23 individuals with KS (patients) and 40 of their family members, to test whether (1) variation in the gut microbiota associates with KS diagnosis and (2) variation within the gut microbiota relates with KS syndrome symptoms. Both alpha and beta diversity of patients were different from their family members. Genus Coprococcus 3 was lower in abundance in patients compared to family members. Moreover, abundance of genus Merdibacter was lower in patients versus family members, but only in participants reporting intestinal complaints. Within the patient group, behavioral problems explained 7% of beta diversity variance. Also, within this group, we detected higher levels of Atopobiaceae – uncultured and Ruminococcaceae Subdoligranulum associated with higher symptom severity. These significant signatures in the gut microbiota composition in patients with KS suggest that microbiota differences are part of the KS phenotype.

中文翻译：

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肠道微生物群在克利夫斯特拉综合征患者中的作用

Kleefstra 综合征 (KS) 是一种罕见的单基因综合征，由常染色质组蛋白甲基转移酶 1 (EHMT1) 基因（神经发育的重要调节因子）单倍体不足引起。KS 的临床特征包括智力障碍、自闭症行为和胃肠道问题。肠道微生物群是肠-脑轴的重要调节因子，可能构成临床 KS 变异的潜在机制。我们调查了 23 名 KS 患者（患者）及其 40 名家庭成员的肠道微生物群组成，以测试 (1) 肠道微生物群的变化是否与 KS 诊断相关，以及 (2) 肠道微生物群的变化与 KS 综合征症状相关。患者的α和β多样性与其家庭成员不同。与家庭成员相比，患者体内粪球菌属3 的丰度较低。此外，患者中Merdibacter属的丰度低于家庭成员，但仅限于报告肠道不适的参与者。在患者组中，行为问题解释了 7% 的 β 多样性差异。此外，在该组中，我们检测到较高水平的Atopobiaceae（未培养的）和Ruminococcaceae Subdolicapsulum 与较高的症状严重程度相关。KS 患者肠道微生物群组成的这些显着特征表明微生物群差异是 KS 表型的一部分。