Early-Life Environmental Variation Affects Intestinal Microbiota and Immune Development in New-Born Piglets

BackgroundEarly-life environmental variation affects gut microbial colonization and immune competence development; however, the timing and additional specifics of these processes are unknown. The impact of early-life environmental variations, as experienced under real life circumstances, on gut microbial colonization and immune development has not been studied extensively so far. We designed a study to investigate environmental variation, experienced early after birth, to gut microbial colonization and intestinal immune development.Methodology/Principal FindingsTo investigate effects of early-life environmental changes, the piglets of 16 piglet litters were divided into 3 groups per litter and experimentally treated on day 4 after birth. During the course of the experiment, the piglets were kept with their mother sow. Group 1 was not treated, group 2 was treated with an antibiotic, and group 3 was treated with an antibiotic and simultaneously exposed to several routine, but stressful management procedures, including docking, clipping and weighing. Thereafter, treatment effects were measured at day 8 after birth in 16 piglets per treatment group by community-scale analysis of gut microbiota and genome-wide intestinal transcriptome profiling. We observed that the applied antibiotic treatment affected the composition and diversity of gut microbiota and reduced the expression of a large number of immune-related processes. The effect of management procedures on top of the use of an antibiotic was limited.Conclusions/SignificanceWe provide direct evidence that different early-life conditions, specifically focusing on antibiotic treatment and exposure to stress, affect gut microbial colonization and intestinal immune development. This reinforces the notion that the early phase of life is critical for intestinal immune development, also under regular production circumstances.

背景：生命早期环境变化可影响肠道微生物定植与免疫功能发育，但该过程的发生时序与具体调控细节仍未明晰。迄今为止，针对真实生活环境中早期环境波动对肠道微生物定植及免疫发育的影响，相关研究尚未得到充分开展。本研究旨在探究出生后早期经历的环境变化对肠道微生物定植与肠道免疫发育的调控效应。
研究方法与主要结果：为探究生命早期环境变化的影响，16窝仔猪每窝均分为3组，并于出生后第4天实施实验处理。实验全程仔猪均与母猪同栏饲养。第1组不作任何处理；第2组给予抗生素干预；第3组在接受抗生素干预的同时，暴露于数项常规但具有应激性的饲养管理操作，包括断尾、剪牙与称重。随后，于出生后第8天，通过肠道微生物组群落水平分析与全基因组肠道转录组谱分析，对每个处理组的16头仔猪的处理效应进行检测。结果显示，本次施加的抗生素干预可改变肠道微生物组的组成与多样性，并下调大量免疫相关通路的基因表达；在此基础上叠加的饲养管理应激操作的影响较为有限。
结论与意义：本研究直接证实，不同的生命早期环境条件——尤其是抗生素干预与应激暴露——会显著影响肠道微生物定植与肠道免疫发育。该结果进一步强化了“生命早期阶段对肠道免疫发育至关重要”这一学术观点，即使在常规养殖生产环境中亦是如此。