Department of Life Sciences, Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, Republic of Korea.
ImmunoBiome Inc. POSTECH Biotech Center, Pohang, 37673, Republic of Korea.
Exp Mol Med. 2020 Sep;52(9):1383-1396. doi: 10.1038/s12276-020-0473-2. Epub 2020 Sep 10.
Considerable evidence points to the critical role of the gut microbiota in physiology and disease. The administration of live microbes as a therapeutic modality is increasingly being considered. However, key questions such as how to identify candidate microorganisms and which preclinical models are relevant to recapitulate human microbiota remain largely unanswered. The establishment of a humanized gnotobiotic mouse model through the fecal microbiota transplantation of human feces into germ-free mice provides an innovative and powerful tool to mimic the human microbial system. However, numerous considerations are required in designing such a model, as various elements, ranging from the factors pertaining to human donors to the mouse genetic background, affect how microbes colonize the gut. Thus, it is critical to match the murine context to that of human donors to provide a continuous and faithful progression of human flora in mice. This is of even greater importance when the need for accuracy and reproducibility across global research groups are taken into account. Here, we review the key factors that affect the formulation of a humanized mouse model representative of the human gut flora and propose several approaches as to how researchers can effectively design such models for clinical relevance.
大量证据表明，肠道微生物群在生理和疾病中起着关键作用。将活体微生物作为一种治疗方式越来越受到关注。然而，如何识别候选微生物以及哪些临床前模型与再现人类微生物群相关等关键问题仍未得到充分解答。通过将人类粪便中的粪便微生物群移植到无菌小鼠中，建立人源化无菌小鼠模型为模拟人类微生物系统提供了一种创新而强大的工具。然而，在设计此类模型时需要考虑许多因素，因为从人类供体相关因素到小鼠遗传背景等各种因素都会影响微生物在肠道中的定植。因此，将小鼠的背景与人类供体的背景相匹配以在小鼠中提供人类菌群的连续和忠实进展至关重要。当考虑到全球研究小组对准确性和可重复性的需求时，这一点尤为重要。在这里，我们回顾了影响人类肠道菌群代表性的人源化小鼠模型形成的关键因素，并提出了几种方法，说明研究人员如何为临床相关性有效地设计此类模型。
