School of Biological Sciences, National Institute of Science Education and Research (NISER), P.O. Jatni, Khurda, Odisha, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, India.
School of Biological Sciences, National Institute of Science Education and Research (NISER), P.O. Jatni, Khurda, Odisha, India; Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai, India.
Biomed J. 2023 Apr;46(2):100519. doi: 10.1016/j.bj.2022.03.004. Epub 2022 Mar 16.
During the early postnatal life, gut microbiota development experiences dynamic changes in their structural and functional composition. The postnatal period is the critical window to develop a host defense mechanism. The maturation of intestinal mucosal barrier integrity is one of the essential defense mechanisms to prevent the entry of pathogens. However, the co-development of intestinal microbial colonization, formation of barrier integrity, and intestinal epithelial cell layer is not entirely understood.
We studied the gut microbial composition and diversity using 16S rRNA marker gene-based sequencing in mice to understand postnatal age-dependent association kinetics between gut microbial and intestinal development. Next, we assessed the intestinal development by in vivo gut permeability assay, mRNA gene expression of different tight junction proteins and intestinal epithelial cell markers, goblet cells population, villus length, and cecal IgA quantification.
Our results showed a significant shift in gut microbial structural and functional composition from postnatal day 14 onwards with early life Proteobacteria abundance. Relative abundance of Verrucomicrobia was maximum at postnatal day 14 and showed a gradual decrease over time. We also observed an age-dependent biphasic pattern in barrier integrity improvement and differentiation of intestinal epithelial cells (IECs). A significant improvement in barrier integrity between days 1 and 7 showed the host factor contribution, while that beyond day 14 revealed an association with changes in microbiota composition. Our temporal correlation analysis associated Bacteroidetes phylum with the mucosal barrier formation during postnatal development.
The present study revealed the importance and interplay of host factors and the microbiome in gut development and intestinal mucosal homeostasis.
在生命早期，肠道微生物群的结构和功能组成经历动态变化。出生后时期是宿主防御机制发展的关键窗口。肠道黏膜屏障完整性的成熟是防止病原体进入的重要防御机制之一。然而，肠道微生物定植、屏障完整性形成和肠上皮细胞层的共同发育还不完全清楚。
我们使用 16S rRNA 标记基因测序研究了小鼠肠道微生物的组成和多样性，以了解肠道微生物与肠道发育之间的年龄依赖性关联动力学。接下来，我们通过体内肠道通透性测定、不同紧密连接蛋白和肠上皮细胞标志物的 mRNA 基因表达、杯状细胞群体、绒毛长度和盲肠 IgA 定量评估肠道发育情况。
我们的结果表明，从第 14 天开始，肠道微生物的结构和功能组成发生了显著变化，早期生命中 Proteobacteria 的丰度增加。Verrucomicrobia 的相对丰度在第 14 天达到最大值，随后逐渐减少。我们还观察到，屏障完整性的改善和肠上皮细胞 (IEC) 的分化呈年龄依赖性双相模式。第 1 天至第 7 天之间屏障完整性的显著改善显示了宿主因素的贡献，而第 14 天之后的改善则与微生物群落组成的变化有关。我们的时间相关性分析将厚壁菌门与出生后发育过程中的黏膜屏障形成联系起来。
本研究揭示了宿主因素和微生物组在肠道发育和肠道黏膜稳态中的重要性和相互作用。
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