Frith Mary E, Kashyap Purna C, Linden David R, Theriault Betty, Chang Eugene B
Interdisciplinary Scientist Training Program, University of Chicago, Chicago, IL 60637, USA.
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
iScience. 2024 Sep 6;27(10):110895. doi: 10.1016/j.isci.2024.110895. eCollection 2024 Oct 18.
Gastrointestinal microbes modulate peristalsis and stimulate the enteric nervous system (ENS), whose development, as in the central nervous system (CNS), continues into the murine postweaning period. Given that adult CNS function depends on stimuli received during critical periods of postnatal development, we hypothesized that adult ENS function, namely motility, depends on microbial stimuli during similar critical periods. We gave fecal microbiota transplantation (FMT) to germ-free mice at weaning or as adults and found that only the mice given FMT at weaning recovered normal transit, while those given FMT as adults showed limited improvements. RNA sequencing (RNA-seq) of colonic muscularis propria revealed enrichments in neuron developmental pathways in mice exposed to gut microbes earlier in life, while mice exposed later-or not at all-showed exaggerated expression of inflammatory pathways. These findings highlight a microbiota-dependent sensitive period in ENS development, pointing to potential roles of the early-life microbiome in later-life dysmotility.
胃肠道微生物调节蠕动并刺激肠神经系统（ENS），其发育，如同中枢神经系统（CNS）一样，持续到小鼠断奶后时期。鉴于成年CNS功能取决于出生后发育关键期所接收的刺激，我们推测成年ENS功能，即运动性，取决于相似关键期内的微生物刺激。我们在断奶时或成年后给无菌小鼠进行粪便微生物群移植（FMT），发现只有断奶时接受FMT的小鼠恢复了正常转运，而成年后接受FMT的小鼠改善有限。结肠固有肌层的RNA测序（RNA-seq）显示，早年接触肠道微生物的小鼠中神经元发育途径富集，而晚年接触或根本未接触肠道微生物的小鼠炎症途径表达过度。这些发现突出了ENS发育中微生物群依赖的敏感期，表明生命早期微生物群在晚年运动障碍中的潜在作用。
