Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Cell Rep. 2024 Apr 23;43(4):113953. doi: 10.1016/j.celrep.2024.113953. Epub 2024 Mar 21.
The gastrointestinal (GI) tract is innervated by intrinsic neurons of the enteric nervous system (ENS) and extrinsic neurons of the central nervous system and peripheral ganglia. The GI tract also harbors a diverse microbiome, but interactions between the ENS and the microbiome remain poorly understood. Here, we activate choline acetyltransferase (ChAT)-expressing or tyrosine hydroxylase (TH)-expressing gut-associated neurons in mice to determine effects on intestinal microbial communities and their metabolites as well as on host physiology. The resulting multi-omics datasets support broad roles for discrete peripheral neuronal subtypes in shaping microbiome structure, including modulating bile acid profiles and fungal colonization. Physiologically, activation of either ChAT or TH neurons increases fecal output, while only ChAT activation results in increased colonic contractility and diarrhea-like fluid secretion. These findings suggest that specific subsets of peripherally activated neurons differentially regulate the gut microbiome and GI physiology in mice without involvement of signals from the brain.
胃肠道（GI）由肠神经系统（ENS）的内在神经元和中枢神经系统及外周神经节的外在神经元支配。胃肠道还拥有多样化的微生物组，但 ENS 与微生物组之间的相互作用仍知之甚少。在这里，我们在小鼠中激活表达胆碱乙酰转移酶（ChAT）或酪氨酸羟化酶（TH）的肠道相关神经元，以确定其对肠道微生物群落及其代谢物以及宿主生理学的影响。由此产生的多组学数据集支持离散的外周神经元亚型在塑造微生物组结构方面的广泛作用，包括调节胆汁酸谱和真菌定植。从生理学上讲，激活 ChAT 或 TH 神经元均可增加粪便排出量，而只有 ChAT 激活可导致结肠收缩性增加和类似腹泻的液体分泌。这些发现表明，在外周激活的特定神经元亚群在不涉及来自大脑信号的情况下，以不同的方式调节小鼠的肠道微生物组和 GI 生理学。
