Wang Mei, Donovan Sharon M
Mei Wang, PhD, is a research specialist and Sharon M. Donovan, PhD, RD, is a professor in the Department of Food Science & Human Nutrition, University of Illinois, Urbana, Illinois.
ILAR J. 2015;56(1):63-73. doi: 10.1093/ilar/ilv006.
Gnotobiotic (GN) rodent models have provided insight into the contributions of the gut microbiota to host health and preventing disease. However, rodent models are limited by several important physiological and metabolic differences from humans, and many rodent models do not dependably replicate the clinical manifestations of human diseases. Due to the high degree of similarity in anatomy, physiology, immunology and brain growth, the domestic pig (Sus scrofa) is considered a clinically relevant model to study factors influencing human gastrointestinal, immune, and brain development. Gnotobiotic piglet models have been developed and shown to recapitulate key aspects of GN rodent models. Human microbiota-associated (HMA) piglets have been established using inocula from infants, children, and adults. The gut microbiota of recipient HMA piglets was more similar to that of the human donor than that of conventionally reared piglets harboring a pig microbiota. Moreover, Bifidobacterium and Bacteroides, two predominant bacterial groups of infant gut, were successfully established in the HMA piglets. Thus, the HMA pig model has the potential to be a valuable model for investigating how the gut microbiota composition changes in response to environmental factors, such as age, diet, vaccination, antibiotic use and infection. The HMA also represents a robust model for screening the efficacy of pre- and probiotic interventions. Lastly, HMA piglets can be an ideal model with which to elucidate microbe-host interactions in human health and disease due to the similarities to humans in anatomy, physiology, developmental maturity at birth, and the pathophysiology of many human diseases.
无菌(GN)啮齿动物模型有助于深入了解肠道微生物群对宿主健康和疾病预防的作用。然而,啮齿动物模型存在一些局限性,因为它们在生理和代谢方面与人类存在重要差异,而且许多啮齿动物模型无法可靠地复制人类疾病的临床表现。由于家猪(Sus scrofa)在解剖学、生理学、免疫学和脑发育方面与人类高度相似,因此被认为是研究影响人类胃肠道、免疫和脑发育因素的临床相关模型。无菌仔猪模型已经建立,并显示出能够概括GN啮齿动物模型的关键特征。已使用来自婴儿、儿童和成人的接种物建立了人类微生物群相关(HMA)仔猪模型。与携带猪微生物群的传统饲养仔猪相比,受体HMA仔猪的肠道微生物群与人类供体的更为相似。此外,婴儿肠道中两个主要细菌类群双歧杆菌和拟杆菌在HMA仔猪中成功定植。因此,HMA猪模型有潜力成为一种有价值的模型,用于研究肠道微生物群组成如何响应年龄、饮食、疫苗接种、抗生素使用和感染等环境因素而发生变化。HMA模型也是筛选益生元和益生菌干预效果的有力模型。最后,由于HMA仔猪在解剖学、生理学、出生时的发育成熟度以及许多人类疾病的病理生理学方面与人类相似,它们可以成为阐明人类健康和疾病中微生物与宿主相互作用的理想模型。