Vicentini Fernando A, Fahlman Tanner, Raptis Stephanie G, Wallace Laurie E, Hirota Simon A, Sharkey Keith A
Hotchkiss Brain Institute, Calgary, AB, Canada.
Snyder Institute for Chronic Diseases, Calgary, AB, Canada.
Adv Exp Med Biol. 2022;1383:55-69. doi: 10.1007/978-3-031-05843-1_6.
Propulsive gastrointestinal (GI) motility is critical for digestive physiology and host defense. GI motility is finely regulated by the intramural reflex pathways of the enteric nervous system (ENS). The ENS is in turn regulated by luminal factors: diet and the gut microbiota. The gut microbiota is a vast ecosystem of commensal bacteria, fungi, viruses, and other microbes. The gut microbiota not only regulates the motor programs of the ENS but also is critical for the normal structure and function of the ENS. In this chapter, we highlight recent research that has shed light on the microbial mechanisms of interaction with the ENS involved in the control of motility. Toll-like receptor signaling mechanisms have been shown to maintain the structural integrity of the ENS and the neurochemical phenotypes of enteric neurons, in part through the production of trophic factors including glia-derived neurotrophic factor. Microbiota-derived short-chain fatty acids and/or single-stranded RNA regulates the synthesis of serotonin in enterochromaffin cells, which are involved in the initiation of enteric reflexes, among other functions. Further evidence suggests a crucial role for microbial modulation of serotonin in maintaining the integrity of the ENS through enteric neurogenesis. Understanding the microbial pathways of enteric neural control sheds new light on digestive health and provides novel treatment strategies for GI motility disorders.
推进性胃肠(GI)动力对消化生理和宿主防御至关重要。胃肠动力由肠神经系统(ENS)的壁内反射通路精细调节。而ENS又受腔内因素调节:饮食和肠道微生物群。肠道微生物群是一个由共生细菌、真菌、病毒和其他微生物组成的庞大生态系统。肠道微生物群不仅调节ENS的运动程序,而且对ENS的正常结构和功能也至关重要。在本章中,我们重点介绍了最近的研究,这些研究揭示了参与控制动力的与ENS相互作用的微生物机制。Toll样受体信号机制已被证明可维持ENS的结构完整性和肠神经元的神经化学表型,部分是通过产生包括胶质细胞源性神经营养因子在内的营养因子。微生物群衍生的短链脂肪酸和/或单链RNA调节肠嗜铬细胞中血清素的合成,肠嗜铬细胞参与肠道反射的启动以及其他功能。进一步的证据表明,血清素的微生物调节在通过肠神经发生维持ENS完整性方面起着关键作用。了解肠道神经控制的微生物途径为消化健康提供了新的思路,并为胃肠动力障碍提供了新的治疗策略。