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

近年来的科学研究表明，肠道微生物群及其结构和代谢可能是神经系统神经生物学和生理功能的主要促进因素。精神益生菌是有益细菌（益生菌）或支持这种细菌（益生元），可以积极调节微生物-肠道-大脑的相互作用。肠道神经系统和免疫系统是微生物群-大脑的交流通道，而精神生物通过这些通道发挥作用。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作用并调节肠道微生物群的机制远未被阐明，并且仍然是非常假设的。我们假设报道的效果可能是通过基于微生物内分泌的机制（即益生菌产生神经化学物质）。共生肠道细菌通过代谢不可消化纤维产生一系列神经递质，包括双歧杆菌产生γ-氨基丁酸（GABA），乳酸杆菌产生GABA和乙酰胆碱，芽孢杆菌产生多巴胺和去甲肾上腺素，肠球菌和链球菌产生血清素，埃希氏菌产生去甲肾上腺素和血清素。其中一些神经递质可以调节肠道的许多生理功能，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乙酰胆碱的释放来调节小肠和结肠的运动。肠道细菌在体内产生GABA可能影响微生物群-肠-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携带负责产生神经活性分子的基因。因此，对特定细菌菌株在多大程度上协调微生物-肠道-脑轴的理解仍然有限。此外，对这种微生物-神经系统串扰以及这些微生物如何影响神经生物学功能的机制理解仍然缺乏。我们假设肠道菌群和益生菌具有神经分泌作用，对神经系统有潜在的影响。该项目旨在(i)确立微生物群作为人类肠道关键生物功能的外神经内分泌作用，（ii）研究精神生物制剂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，（iii）开发并执行具有神经生物学功能的下一代益生菌的概念验证分析。了解心理抗生素对肠道菌群结构、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-肠-脑的交流。

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 microbiota–gut–brain interactions. Microbiota–brain 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 γ-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 microbiota–gut–brain 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 microbiota–nervous 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 microbiota–gut–brain communication.