Table_2_Donor Microbiota Composition and Housing Affect Recapitulation of Obese Phenotypes in a Human Microbiota-Associated Murine Model.pdf

Human microbiota-associated (HMA) mouse models offer a valuable approach to study the role of intestinal microbiota in the development of obesity. In this study, we used an HMA model to evaluate whether engraftment of human obese or lean microbiota, from each of three donors, could recapitulate host phenotypes under conventional and specific-pathogen-free housing. Microbiota engraftment was correlated with donor relative abundances of the class Bacteroidia (Spearman’s ρ = 0.73, P ≤ 0.001), and one obese donor resulted in significant weight gain (P ≤ 0.003) and compromised insulin sensitivity under conventional housing. SPF housing partially blunted phenotypic response. Results of this study indicate that our HMA model partially recapitulates obese phenotypes under conventional housing and highlights a need to consider donor-specific effects as well as housing conditions when studying the role of the microbiota in obesity.

人类菌群定植关联（Human microbiota-associated, HMA）小鼠模型为探究肠道菌群在肥胖发生发展中的作用提供了极具价值的研究途径。本研究采用该HMA小鼠模型，旨在验证来自3名供体的人类肥胖型或瘦型肠道菌群，在常规饲养与无特定病原体（specific-pathogen-free, SPF）饲养条件下，能否重现宿主相关表型。研究发现，菌群定植成功率与供体粪便菌群中拟杆菌纲（Bacteroidia）的相对丰度呈显著正相关（斯皮尔曼相关系数ρ=0.73，P≤0.001）；其中1名肥胖供体的菌群在常规饲养条件下可使宿主出现显著体重增长（P≤0.003），并损害其胰岛素敏感性。SPF饲养条件可部分削弱该表型反应。本研究结果表明，所构建的HMA小鼠模型可在常规饲养条件下部分重现肥胖相关表型，同时凸显了在研究菌群与肥胖的关联时，需同时考虑供体特异性效应与饲养环境因素的必要性。