Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.
Molecular Virology and Microbiology, Department of Education, Innovation and Technology, Baylor College of Medicine, Houston, Texas, USA.
Neurogastroenterol Motil. 2023 Nov;35(11):e14676. doi: 10.1111/nmo.14676. Epub 2023 Sep 29.
Early-life events impact maturation of the gut microbiome, enteric nervous system, and gastrointestinal motility. We examined three regions of gastric tissue to determine how maternal separation and gut microbes influence the structure and motor function of specific regions of the neonatal mouse stomach.
Germ-free and conventionally housed C57BL/6J mouse pups underwent timed maternal separation (TmSep) or nursed uninterrupted (controls) until 14 days of life. We assessed gastric emptying by quantifying the progression of gavaged fluorescein isothiocyanate (FITC)-dextran. With isolated rings of forestomach, corpus, and antrum, we measured tone and contractility by force transduction, gastric wall thickness by light microscopy, and myenteric plexus neurochemistry by whole-mount immunostaining.
Regional gastric sampling revealed site-specific differences in contractile patterns and myenteric plexus structure. In neonatal mice, TmSep prolonged gastric emptying. In the forestomach, TmSep increased contractile responses to carbachol, decreased muscularis externa and mucosa thickness, and increased the relative proportion of myenteric plexus nNOS+ neurons. Germ-free conditions did not appreciably alter the structure or function of the neonatal mouse stomach and did not impact the changes caused by TmSep.
A regional sampling approach facilitates site-specific investigations of murine gastric motor physiology and histology to identify site-specific alterations that may impact gastrointestinal function. Delayed gastric emptying in TmSep is associated with a thinner muscle wall, exaggerated cholinergic contractile responses, and increased proportions of inhibitory myenteric plexus nNOS+ neurons in the forestomach. Gut microbes do not profoundly affect the development of the neonatal mouse stomach or the gastric pathophysiology that results from TmSep.
生命早期事件会影响肠道微生物群、肠神经系统和胃肠道动力的成熟。我们研究了胃组织的三个区域，以确定母体分离和肠道微生物如何影响新生小鼠胃的特定区域的结构和运动功能。
无菌和常规饲养的 C57BL/6J 幼鼠经历定时的母体分离（TmSep）或不间断哺乳（对照），直到 14 天龄。我们通过定量胃内荧光素异硫氰酸酯（FITC）-葡聚糖的推进来评估胃排空。通过分离前胃、胃体和胃窦的环形组织，我们通过力转换测量张力和收缩性，通过光显微镜测量胃壁厚度，通过全组织免疫染色测量肌间神经丛神经化学。
区域性胃采样揭示了收缩模式和肌间神经丛结构的特定部位差异。在新生小鼠中，TmSep 延长了胃排空。在前胃中，TmSep 增加了对卡巴胆碱的收缩反应，减少了外肌层和黏膜厚度，并增加了肌间神经丛 nNOS+神经元的相对比例。无菌条件没有明显改变新生小鼠胃的结构或功能，也没有影响 TmSep 引起的变化。
区域性采样方法有助于对小鼠胃动力生理学和组织学进行特定部位的研究，以确定可能影响胃肠道功能的特定部位改变。TmSep 导致的胃排空延迟与前胃壁更薄、胆碱能收缩反应过度、抑制性肌间神经丛 nNOS+神经元比例增加有关。肠道微生物对新生小鼠胃的发育或 TmSep 引起的胃病理生理学没有显著影响。
