Getachew Bruk, Tizabi Yousef
Department of Pharmacology, Howard University College of Medicine, Washington, DC, USA.
Clin Pharmacol Transl Med. 2019;3(2):152-159. Epub 2019 Oct 12.
BACKGROUND/AIMS: It is now well established that imbalance or dysbiosis in the gut microbiota (GM) plays a significant role in neuropsychiatric/neurodegenerative disorders. Recently it has been reported that the C-terminal domain of the heavy chain of tetanus toxin (Hc-TeTx) may not only act as a neuroprotectant but may also exhibit antidepressant effects in Wistar-Kyoto (WKY) rats, a putative animal model of treatment-resistant depression. The aim of this study was to determine whether Hc-TeTx may also interact with GM implicated in mood regulation in these rats.
Adult male WKY rats (5/group) were injected intramuscularly (IM) with 60 μg/kg Hc-TeTx or saline. Twenty-four hours after the injection, the animals were sacrificed, intestinal stools were collected and stored at -80°C. DNA was extracted from the samples for 16S rRNA gene-based microbiota analysis using 16S Metagenomics application.
Abundance of several bacteria at different taxonomic levels were distinguished between Hc-TeTx group and the control. At species-level, 11 operational taxonomic units (OTUs), particularly , a bacterium with a strong ability to degrade resistant starch, were enriched (69 fold) in the Hc-TeTx group. In addition, 5 species of probiotic , two butyrate-forming species S a, were enhanced by a minimum of 2-fold in Hc-TeTx group. In contrast, 24 species including five species of pathogenic (5-14 fold), two mucin-degrading , and four species of pathogenic were reduced by a minimum of 2-fold by Hc-TeTx treatment.
Hc-TeTx enhanced probiotic species and suppressed the opportunistic pathogens. Since overall effect of Hc-TeTx appears to be promoting GM associated with mood enhancement (e.g. ) and suppressing GM associated with mood dysregulation (e.g. ) a novel mechanism of beneficial effects of Hc-TeTx may involve normalization of dysbiosis.
背景/目的：现已明确，肠道微生物群（GM）的失衡或失调在神经精神/神经退行性疾病中起重要作用。最近有报道称，破伤风毒素重链的C末端结构域（Hc-TeTx）不仅可能作为一种神经保护剂，还可能在Wistar-Kyoto（WKY）大鼠（一种难治性抑郁症的假定动物模型）中表现出抗抑郁作用。本研究的目的是确定Hc-TeTx是否也可能与这些大鼠中参与情绪调节的GM相互作用。
成年雄性WKY大鼠（每组5只）肌肉注射（IM）60μg/kg Hc-TeTx或生理盐水。注射后24小时，处死动物，收集肠道粪便并储存在-80°C。从样本中提取DNA，使用16S宏基因组学应用进行基于16S rRNA基因的微生物群分析。
Hc-TeTx组和对照组在不同分类水平上的几种细菌丰度有所不同。在物种水平上，11个可操作分类单元（OTU），特别是一种具有强大抗性淀粉降解能力的细菌，在Hc-TeTx组中富集（69倍）。此外，5种益生菌，包括两种产丁酸盐的物种，在Hc-TeTx组中至少提高了2倍。相比之下，24种物种，包括5种致病菌（5-14倍）、两种粘蛋白降解菌和4种致病菌，经Hc-TeTx处理后至少减少了2倍。
Hc-TeTx增强了益生菌种类并抑制了机会致病菌。由于Hc-TeTx的总体作用似乎是促进与情绪增强相关的GM（例如）并抑制与情绪失调相关的GM（例如），Hc-TeTx有益作用的一种新机制可能涉及失调的正常化。
