Division of Pediatric Surgery, Department of Surgery, Yale University, New Haven, Connecticut, United States of America.
PLoS One. 2022 Mar 29;17(3):e0266251. doi: 10.1371/journal.pone.0266251. eCollection 2022.
Previous work demonstrated enhanced enterocyte proliferation and mucosal growth in gnotobiotic mice, suggesting that intestinal flora participate in mucosal homeostasis. Furthermore, broad-spectrum enteral antibiotics are known to induce near germ-free (GF) conditions in mice with conventional flora (CONV). We hypothesized that inducing near GF conditions with broad-spectrum enteral antibiotics would cause ordered small intestinal mucosal growth in CONV mice but would have no effect in GF mice with no inherent microbiome. C57BL/6J CONV and GF mice received either an antibiotic solution (Ampicillin, Ciprofloxacin, Metronidazole, Vancomycin, Meropenem) or a vehicle alone. After treatment, small intestinal villus height (VH), crypt depth (CD), mucosal surface area (MSA), crypt proliferation index (CPI), apoptosis, and villus and crypt cell types were assessed. Antibiotic-treated CONV (Abx-CONV) mice had taller villi, deeper crypts, increased CPI, increased apoptosis, and greater MSA compared to vehicle-treated CONV mice. Minor differences were noted in enterocyte and enterochromaffin cell proportions between groups, but goblet and Paneth cell proportions were unchanged in Abx-CONV mice compared to vehicle-treated CONV mice (p>0.05). Antibiotics caused no significant changes in VH or MSA in GF mice when compared to vehicle-treated GF mice (p>0.05). Enteral administration of broad-spectrum antibiotics to mice with a conventional microbiome stimulates ordered small intestinal mucosal growth. Mucosal growth was not seen in germ-free mice treated with antibiotics, implying that intestinal mucosal growth is associated with change in the microbiome in this model.
先前的工作表明，无菌动物中的肠上皮细胞增殖和黏膜生长增强，提示肠道菌群参与黏膜稳态。此外，广谱肠内抗生素已知可诱导具有常规菌群（CONV）的小鼠接近无菌（GF）状态。我们假设，用广谱肠内抗生素诱导接近 GF 状态会导致 CONV 小鼠的小肠黏膜有序生长，但在没有固有微生物组的 GF 小鼠中没有影响。C57BL/6J CONV 和 GF 小鼠分别接受抗生素溶液（氨苄西林、环丙沙星、甲硝唑、万古霉素、美罗培南）或单独的载体。治疗后，评估小肠绒毛高度（VH）、隐窝深度（CD）、黏膜表面积（MSA）、隐窝增殖指数（CPI）、凋亡以及绒毛和隐窝细胞类型。与接受载体处理的 CONV 小鼠相比，接受抗生素处理的 CONV（Abx-CONV）小鼠的绒毛更高、隐窝更深、CPI 增加、凋亡增加且 MSA 更大。各组之间的肠细胞和肠嗜铬细胞比例存在较小差异，但与接受载体处理的 CONV 小鼠相比，Abx-CONV 小鼠的杯状细胞和潘氏细胞比例没有变化（p>0.05）。与接受载体处理的 GF 小鼠相比，抗生素对 GF 小鼠的 VH 或 MSA 没有显著影响（p>0.05）。在该模型中，广谱抗生素的肠内给药可刺激具有常规微生物组的小鼠的小肠黏膜有序生长。抗生素治疗的无菌小鼠未出现黏膜生长，这表明黏膜生长与微生物组的变化有关。
