Activity-dependent neuroprotective protein (ADNP) and its protein snippet NAP (drug candidate CP201) regulate synapse formation and cognitive as well as behavioral functions, in part, through microtubule interaction. Given potential interactions between the microbiome and brain function, we now investigated the potential effects of the ADNP-deficient genotype, mimicking the ADNP syndrome on microbiota composition in the Adnp+/- mouse model. We have discovered a surprising robust sexually dichotomized Adnp genotype effect and correction by NAP (CP201) as follows. Most of the commensal bacterial microbiota tested were affected by the Adnp genotype and corrected by NAP treatment in a male sex-dependent manner. The following list includes all the bacterial groups tested-labeled in bold are male Adnp-genotype increased and corrected (decreased) by NAP. (1) Eubacteriaceae (EubV3), (2) Enterobacteriaceae (Entero), (3) Enterococcus genus (gEncocc), (4) Lactobacillus group (Lacto), (5) Bifidobacterium genus (BIF), (6) Bacteroides/Prevotella species (Bac), (7) Clostridium coccoides group (Coer), (8) Clostridium leptum group (Cluster IV, sgClep), and (9) Mouse intestinal Bacteroides (MIB). No similarities were found between males and females regarding sex- and genotype-dependent microbiota distributions. Furthermore, a female Adnp+/- genotype associated decrease (contrasting male increase) was observed in the Lactobacillus group (Lacto). Significant correlations were discovered between specific bacterial group loads and open-field behavior as well as social recognition behaviors. In summary, we discovered ADNP deficiency associated changes in commensal gut microbiota compositions, a sex-dependent biomarker for the ADNP syndrome and beyond. Strikingly, we discovered rapidly detected NAP (CP201) treatment-dependent biomarkers within the gut microbiota.

中文翻译：

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与ADNP缺乏症有关的微生物群变化：NAP（CP201）治疗ADNP综合征及以后的快速指标。

依赖于活性的神经保护蛋白（ADNP）及其蛋白片段NAP（候选药物CP201）部分地通过微管相互作用来调节突触的形成和认知以及行为功能。给定微生物组和大脑功能之间的潜在相互作用，我们现在研究ADNP缺陷型基因型的潜在影响，模拟ADNP综合征对Adnp +/-小鼠模型中微生物群组成的影响。我们发现了令人惊讶的强大的两性分型的Adnp基因型效应和NAP（CP201）校正，如下所示。测试的大多数共生细菌菌群均受Adnp基因型的影响，并通过NAP治疗以男性性别依赖性方式得到纠正。以下列表包括所有测试的细菌组，粗体标记为NAP可以增加和纠正（减少）的男性Adnp基因型。（1）真细菌科（EubV3），（2）肠杆菌科（Entero），（3）肠球菌属（gEncocc），（4）乳杆菌属（Lacto），（5）双歧杆菌属（BIF），（6）拟杆菌/小肠杆菌属（Bac），（7）梭状芽胞杆菌组（Coer），（8）轻梭状芽孢杆菌组（IV组，sgClep）和（9）小鼠肠道细菌（MIB）。在性别和基因型依赖性微生物群分布方面，男性和女性之间没有发现相似性。此外，在乳酸杆菌组（乳酸菌）中观察到女性Adnp +/-基因型相关的减少（男性相反）。发现特定细菌群负荷与开放视野行为以及社会认可行为之间存在显着相关性。总而言之，我们发现了ADNP缺乏症与共肠肠道菌群组成的变化有关，ADNP综合征及以后的性别依赖性生物标志物。令人惊讶的是，我们发现在肠道菌群中快速检测到NAP（CP201）依赖治疗的生物标记。