Microbial programming: early postnatal microbial colonisation effects on subsequent health

动物的胃肠道在出生时是无菌的，但在产道和周围环境中存在的细菌几乎立即定植。最初只有一小部分不同的细菌在肠道中定居，然而，随着动物年龄的增长，人们认为有400多种不同的细菌在这种环境中生长。许多因素会影响新生动物早期肠道内的细菌类型。主要因素包括与母亲相关的细菌种类、环境中的细菌（例如，保温箱中的早产儿与足月婴儿）、饮食类型（母乳喂养与配方奶喂养）以及抗生素的使用。有证据表明，在新生儿肠道中定植的细菌种类的模式可以对生命后期的定植模式和肠道健康产生长期影响。例如，与发展中国家的儿童相比，发达国家儿童过敏、哮喘和湿疹的增加可能与他们相对“清洁”的无病原体环境有关。在本项目中，我们将使用新生仔猪来研究“微生物编程”的概念。这只小猪是人类婴儿的一个很好的模型，研究结果也将对我们如何管理小猪以改善健康产生影响。首先，我们将分析肠道内容物中的细菌DNA，以精确确定乳猪从出生到断奶的细菌定植模式。接下来，我们将获得无菌仔猪，将它们暴露在乳猪中鉴定的选定细菌中5天，然后正常饲养。然后，我们将确定猪早期接触的细菌是否会影响断奶时的肠道细菌数量和/或肠道健康。如果证明了微生物编程效应，就有可能开发出在生命早期修改肠道定植模式的策略，以促进以后肠道的健康。

The gastrointestinal tract of animals is sterile at birth but is colonised almost immediately by bacteria present in the birth canal and in the surrounding environment. Initially only a small number of different bacterial species colonise the intestine, however, as the animal ages more than 400 different species are thought grow in this enviroment. A number of factors can affect the type of bacteria that colonise the intestine of neonatal animals in early life. Major factors include the bacterial species associated with the mother, bacteria in the environment (e.g. premature infant in an incubator versus full term baby), the type of diet (breast-fed versus formula) and use of antibiotics. There is evidence that the pattern of bacterial species colonising the neonatal intestine can have long term effects "programming" colonisation patterns and intestinal health later in life. For example, the increases in allergy, asthma and eczema in children in developed countries may be associated with their relatively "clean" pathogen-free environment compared with children in developing countries. In this project we will use neonatal piglets to investigate this concept of "microbial programming". The piglet is an excellent model for human infants and the results will also have implications for how we manage baby pigs to improve health. First we will analyse the bacterial DNA in intestinal contents to precisely determine the pattern of bacteria colonizing suckling pigs from birth to weaning. Next we will obtain germ-free piglets, expose them for 5 days to selected bacterial species identified in the suckling pig and then raise them normally. We will then determine whether the bacteria the pigs were exposed to in early life affects their intestinal bacterial populations and/or intestinal health at weaning. If a microbial programming effect is demonstrated it may be possible to develop strategies to modify the intestinal colonisation pattern in early life to promote a healthier intestine later.