Gut microbiota: neurosecretion, modulation by psychobiotics and bacteriocins, and mechanisms of action thereof

肠道微生物群：神经分泌、精神抗生素和细菌素的调节及其作用机制

• 批准号: RGPIN-2018-06059
• 负责人: Hammami, Riadh
• 金额: $ 1.75万
• 依托单位: University of Ottawa
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=679758
• 关键词: Gut; microbiota; neurosecretion; modulation; psychobiotics

Recent scientific studies have reported that intestinal microbiota, with its structure and metabolism, may be a major contributory factor to the neurobiological and physiological function of the nervous system. Psychobiotics are beneficial bacteria (probiotics) or support for such bacteria (prebiotics) that can positively modulate microbiotagutbrain interactions. Microbiotabrain communication channels through which psychobiotics exert effects include the enteric nervous system and the immune system. Despite some studies, the mechanisms by which these probiotics are able to exert these beneficial effects on the digestive tract and to modulate the intestinal microbiota are far from being elucidated and remain very hypothetical. We hypothesize that reported effects may be through a microbial endocrinology-based mechanism (i.e. probiotic production of a neurochemical). Commensal gut bacteria, through metabolism of non-digestible fibers, produce a range of neurotransmitters including -aminobutyric acid (GABA) by Bifidobacteria, GABA and acetylcholine by Lactobacilli, dopamine and noradrenalin by Bacillus, serotonin by Enterococcus and Streptococcus, and noradrenalin and serotonin by Escherichia. Some of these neurotransmitters could regulate many intestinal physiological functions, including intestinal fluid secretion, blood circulation and ulceration. The GABA receptor has been shown to regulate motility in the small intestine and colon by modulating the release of acetylcholine from enteric neurons. In vivo GABA production by intestinal bacteria may impact the microbiotagutbrain axis, and could have potential health benefits. It is not yet clear as to why certain bacteria harbour genes responsible for the production of neuroactive molecules. Therefore, there is still a limited understanding of the extent to which specific bacterial strains orchestrate the microbiota-gut-brain axis. In addition, the mechanistic understanding of this microbiotanervous system crosstalk and how theses microbes impact neurobiological functions is still lacking. We hypothesize that gut microbiota and probiotics have a neurosecretory role with a potential impact on the nervous system. The project aims to (i) establish the exo-neuroendocrine role of microbiota as a key biological function in human gut, (ii) investigate the impact of psychobiotics and their bacteriocins on the gut microbiota diversity, metabolism and neurosecretory function and (iii) develop and perform proof-of-concept analysis of next-generation probiotics with neuro-biological function. Understanding the impact, mechanisms, and biological effects of psychobiotics on gut microbiota architecture, metabolism and function could lead to better comprehension of microbiotagutbrain communication.

最近的科学研究已经报道，肠道微生物群及其结构和代谢可能是神经系统的神经生物学和生理功能的主要贡献因素。精神生物药是有益的细菌（益生菌）或支持这种细菌（益生元），可以积极调节微生物毒素与脑的相互作用。精神生物药发挥作用的微生物毒素通信渠道包括肠神经系统和免疫系统。尽管有一些研究，但这些益生菌能够对消化道发挥这些有益作用并调节肠道微生物群的机制远未阐明，仍然是非常假设的。我们假设，报告的影响可能是通过微生物内分泌学为基础的机制（即益生菌生产的神经化学物质）。共生肠道细菌通过代谢不可消化的纤维，产生一系列神经递质，包括双歧杆菌产生的γ-氨基丁酸（GABA）、乳酸杆菌产生的GABA和乙酰胆碱、芽孢杆菌产生的多巴胺和去甲肾上腺素、肠球菌和链球菌产生的5-羟色胺以及埃希氏菌产生的去甲肾上腺素和5-羟色胺。其中一些神经递质可调节肠道的许多生理功能，包括肠液分泌、血液循环和溃疡形成。GABA受体已被证明通过调节肠神经元释放乙酰胆碱来调节小肠和结肠的运动性。体内肠道细菌产生的GABA可能会影响微生物毒素脑轴，并可能具有潜在的健康益处。目前还不清楚为什么某些细菌含有负责产生神经活性分子的基因。因此，对特定细菌菌株协调微生物群-肠-脑轴的程度仍然有有限的了解。此外，对这种微生物与神经系统串扰的机制以及这些微生物如何影响神经生物学功能的理解仍然缺乏。我们假设肠道微生物群和益生菌具有神经分泌作用，对神经系统有潜在影响。该项目旨在（i）确定微生物群的外神经内分泌作用是人类肠道中的关键生物功能，（ii）研究精神生物素及其细菌素对肠道微生物群多样性，代谢和神经分泌功能的影响，以及（iii）开发和执行具有神经生物功能的下一代益生菌的概念验证分析。了解心理生物学对肠道微生物群结构，代谢和功能的影响，机制和生物学效应可以更好地理解微生物群-脑通信。