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Abstract：
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.
摘要：
活性依赖性神经保护蛋白（ADNP）及其蛋白片段NAP（候选药物CP201）调节突触形成和认知以及行为功能，在某种程度上,通过微管相互作用。考虑到微生物组和大脑功能之间的潜在相互作用，我们现在研究了ADNP缺陷基因型的潜在影响，在Adnp+/-小鼠模型中模拟ADNP综合征对微生物群组成的影响。我们已经发现了令人惊讶的强健的性二分法Adnp基因型效应和通过NAP(CP201)的校正如下。大多数测试的共生细菌微生物群受到Adnp基因型的影响，并以男性性别依赖的方式通过NAP治疗进行校正。以下列表包括以粗体标记的测试的所有细菌组,是通过NAP增加和校正(减少)的雄性Adnp基因型。（1）真细菌科（EubV3），（2）肠杆菌科（肠科），(3)肠球菌属(gEncocc),(4)乳酸菌群(Lacto),(5)双歧杆菌属(BIF),(6)拟杆菌属/普氏杆菌属(Bac)，(7)Clostridiumcoccoidesgroup(Coer),（8）Clostridiumleptum组（ClusterIV，sgClep),和(9)小鼠肠道拟杆菌(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之处。此外，在乳杆菌属组(Lacto)中观察到女性Adnp+/-基因型相关的降低(对比男性增加)。在特定的细菌组负荷与野外行为以及社会识别行为之间发现了显着的相关性。总之,我们发现ADNP缺乏与共生肠道菌群组成相关的变化，ADNP综合征及以后的性别依赖性生物标志物。引人注目的是，我们在肠道微生物群中发现了快速检测到的NAP(CP201)治疗依赖性生物标志物.
