Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, United States.
Department of Food Science and Technology, University of Nebraska, Lincoln, NE, United States.
Front Immunol. 2021 Feb 16;11:585431. doi: 10.3389/fimmu.2020.585431. eCollection 2020.
The intestinal microbiota is a critical component of mucosal health as evidenced by the fact that alterations in the taxonomic composition of the gastrointestinal microbiota are associated with inflammatory bowel diseases. To better understand how the progression of inflammation impacts the composition of the gastrointestinal microbiota, we used culture independent taxonomic profiling to identify temporal changes in the cecal microbiota of C3Bir IL-10 mice concomitantly with the onset and progression of colitis. This analysis revealed that IL-10 mice displayed a biphasic progression in disease severity, as evidenced by histopathological scores and cytokine production. Beginning at 4 weeks of age, pro-inflammatory cytokines including TNF-α, IFN-γ, IL-6, G-CSF, and IL-1α as well as chemokines including RANTES and MIP-1α were elevated in the serum of IL-10 mice. By 19 weeks of age, the mice developed clinical signs of disease as evidenced by weight loss, which was accompanied by a significant increase in serum levels of KC and IL-17. While the overall diversity of the microbiota of both wild type and IL-10 were similar in young mice, the latter failed to increase in complexity as the mice matured and experienced changes in abundance of specific bacterial taxa that are associated with inflammatory bowel disease in humans. Collectively, these results reveal that there is a critical time in young mice between four to six weeks of age when inflammation and the associated immune responses adversely affect maturation of the microbiota.
肠道微生物群是黏膜健康的关键组成部分，这一事实证明，胃肠道微生物群的分类组成发生改变与炎症性肠病有关。为了更好地了解炎症的进展如何影响胃肠道微生物群的组成，我们使用非培养分类分析来鉴定 C3Bir IL-10 小鼠结肠炎发病和进展过程中盲肠微生物群的时间变化。这项分析表明，IL-10 小鼠的疾病严重程度呈双相进展，这可通过组织病理学评分和细胞因子产生来证明。从 4 周龄开始，包括 TNF-α、IFN-γ、IL-6、G-CSF 和 IL-1α 在内的促炎细胞因子以及 RANTES 和 MIP-1α 在内的趋化因子在 IL-10 小鼠的血清中升高。到 19 周龄时，小鼠出现了疾病的临床症状，表现为体重减轻，这伴随着 KC 和 IL-17 血清水平的显著增加。虽然年轻小鼠中野生型和 IL-10 微生物群的整体多样性相似，但后者在成熟过程中未能增加复杂性，并且特定细菌类群的丰度发生变化，这些细菌类群与人类炎症性肠病有关。总的来说，这些结果表明，在 4 到 6 周龄之间的年轻小鼠中有一个关键时期，炎症和相关的免疫反应会对微生物群的成熟产生不利影响。
