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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757079
• 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.

最近的科学研究报道，肠道微生物区系及其结构和代谢，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。心理生素是有益的细菌(益生菌)或支持这种细菌的益生菌(益生菌)，可以积极地调节微生物与大脑的相互作用。微生物通过肠道神经系统和免疫系统发挥作用。尽管有一些研究，但这些益生菌能够对消化道产生这些有益影响并调节肠道微生物区系的机制远未被阐明，而且仍然是非常假设的。我们假设，所报道的影响可能是通过基于微生物内分泌学的机制(即，神经化学物质的益生菌生产)。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氨基丁酸(GABA)，乳杆菌产生的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，以及大肠杆菌产生的去甲肾上腺素和5-羟色胺。其中一些神经递质可以调节许多肠道生理功能，包括肠液分泌、血液循环和溃疡。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。在体内，肠道细菌产生的GABA可能会影响微生物脑轴，并可能对健康有潜在的好处。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区系-肠道-脑轴的程度仍有有限的了解。此外，对这种微生物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仍然缺乏了解。我们假设肠道微生物区系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)确定微生物区系的外神经内分泌作用作为人体肠道的关键生物学功能，(Ii)调查精神生物群及其细菌素对肠道微生物区系多样性、新陈代谢和神经分泌功能的影响，以及(Iii)开发和进行具有神经生物学功能的下一代益生菌的概念验证分析。了解心理生物制剂对肠道微生物区系结构、代谢和功能的影响、机制和生物学效应，有助于更好地理解微生物脑内沟通。