Frith Mary E, Kashyap Purna C, Linden David R, Theriault Betty, Chang Eugene B
bioRxiv. 2023 Nov 13:2023.11.08.566304. doi: 10.1101/2023.11.08.566304.
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. RNAseq 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。鉴于成年中枢神经系统功能取决于出生后发育关键期所接收的刺激，我们推测成年肠神经系统功能，即运动能力，在类似的关键期依赖于微生物刺激。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测序显示，在生命早期接触肠道微生物的小鼠中，神经元发育途径富集，而后期接触（或根本未接触）的小鼠则表现出炎症途径的过度表达。这些发现突出了肠神经系统发育中微生物群依赖的敏感期，指出了生命早期微生物群在后期生活中运动障碍的潜在作用。
