Marques de Souza Patricia Rodrigues, Keenan Catherine M, Wallace Laurie E, Habibyan Yasaman Bahojb, Davoli-Ferreira Marcela, Ohland Christina, Vicentini Fernando A, McCoy Kathy D, Sharkey Keith A
Department of Health Education, Federal University of Sergipe, Aracaju, SE, Brazil.
Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Gut Microbes. 2025 Dec;17(1):2442528. doi: 10.1080/19490976.2024.2442528. Epub 2024 Dec 20.
How the gut microbiota and immune system maintain intestinal homeostasis in concert with the enteric nervous system (ENS) remains incompletely understood. To address this gap, we assessed small intestinal transit, enteric neuronal density, enteric neurogenesis, intestinal microbiota, immune cell populations and cytokines in wildtype and T-cell deficient germ-free mice colonized with specific pathogen-free (SPF) microbiota, conventionally raised SPF and segmented filamentous bacteria (SFB)-monocolonized mice. SPF microbiota increased small intestinal transit in a T cell-dependent manner. SPF microbiota increased neuronal density in the myenteric and submucosal plexuses of the ileum and colon, similar to conventionally raised SPF mice, independently of T cells. SFB increased neuronal density in the ileum in a T cell-dependent manner, but independently of T cells in the colon. SPF microbiota stimulated enteric neurogenesis (Sox2 expression in enteric neurons) in the ileum in a T cell-dependent manner, but in the colon this effect was T cell-independent. T cells regulated nestin expression in the ENS. SPF colonization increased Th17 cells, RORγT Treg cells, and IL-1β and IL-17A levels in the ileum and colon. By neutralizing IL-1β and IL-17A, we observed that they control microbiota-mediated enteric neurogenesis but were not involved in the regulation of motility. Together, these findings provide new insights into the microbiota-neuroimmune dialog that regulates intestinal physiology.
肠道微生物群和免疫系统如何与肠神经系统（ENS）协同维持肠道内稳态仍未完全明确。为填补这一空白，我们评估了野生型和T细胞缺陷的无菌小鼠（定殖有特定病原体-free（SPF）微生物群、常规饲养的SPF小鼠以及单一定殖分节丝状菌（SFB）的小鼠）的小肠转运、肠神经元密度、肠神经发生、肠道微生物群、免疫细胞群体和细胞因子。SPF微生物群以T细胞依赖的方式增加小肠转运。SPF微生物群增加回肠和结肠肌间神经丛和黏膜下神经丛中的神经元密度，类似于常规饲养的SPF小鼠，且不依赖于T细胞。SFB以T细胞依赖的方式增加回肠中的神经元密度，但在结肠中不依赖于T细胞。SPF微生物群以T细胞依赖的方式刺激回肠中的肠神经发生（肠神经元中Sox2表达），但在结肠中这种作用不依赖于T细胞。T细胞调节ENS中的巢蛋白表达。SPF定殖增加回肠和结肠中的Th17细胞、RORγT调节性T细胞以及IL-1β和IL-17A水平。通过中和IL-1β和IL-17A，我们观察到它们控制微生物群介导的肠神经发生，但不参与运动调节。总之，这些发现为调节肠道生理的微生物群-神经免疫对话提供了新的见解。
