Early diabetes-like phenotypes in germ-free mice induced by gut microbiota from patients with type 2 diabetesOA
Background:The contribution of gut microbiota to the early stage of type 2 diabetes(T2D)remains incompletely understood.This study established a germ-free mouse model colonized with gut microbiota from donors with T2D to determine whether diabetes-associated microbiota could induce early diabetes-like phenotypes.Methods:Human fecal samples were collected from 18 healthy donors and 14 donors with T2D for microbiota profiling.Based on these features,samples from 12 healthy donors and 3 donors with T2D were selected,pooled within each group,and transplanted into germ-free mice,generating a healthy microbiota recipient group(HM,n=14)and a diabetes-associated microbiota recipient group(DM,n=13).Glucose homeostasis was assessed over 10 weeks using fasting blood glucose and intraperitoneal glucose tolerance tests.Gut microbial succession was analyzed by 16S rRNA sequencing.Fecal and plasma metabolomics were performed to identify metabolic and their associations with microbial changes.Results:DM mice developed an early diabetes-like phenotype characterized by progressive impairment of glucose tolerance,reduced insulin levels,and mild renal alterations,without sustained overt fasting hyperglycemia.Microbial divergence emerged before stable metabolic dysfunction and was accompanied by persistent dysbiosis in DM mice.Integrated metabolomic analysis identified coordinated alterations in fecal and plasma metabolites,with cholic acid and L-Dopa decreased in both compartments.L-Dopa showed consistent associations with altered genera,particularly Ruminococcus and Sellimonas.Conclusions:Transplanting diabetes-associated human gut microbiota effectively induced early glucose dysregulation in germ-free recipient mice.This model provides a framework for studying microbiota-associated events during early T2D-related metabolic deterioration.
Jianghao Feng;Xing Liu;Hua Zhu;Yun Yang;Wei Liu;Xiaoliang Jiang;Zhiwei Yang
Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,P.R.China China-Japan Friendship Hospital(Institute of Clinical Medical Sciences),Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,P.R.ChinaInstitute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,P.R.ChinaInstitute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,P.R.ChinaTaihe County People''s Hospital,The Taihe Hospital of Wannan Medical College,Fuyang,Anhui Province,P.R.ChinaDepartment of Cardiology,The First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei Province,P.R.ChinaInstitute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,P.R.ChinaInstitute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,P.R.China China-Japan Friendship Hospital(Institute of Clinical Medical Sciences),Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,P.R.China
医药卫生
germ-free micemetabolomicsmicrobiomicsmicrobiota transplantationtype 2 diabetes
《Animal Models and Experimental Medicine》 2026 (6)
P.1202-1216,15
National Key Research and Development Program of China,Grant/Award Number:2022YFF0710600Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,Grant/Award Number:2021-1-I2M-035Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2023-PT180-01National High-level Innovation and Entrepreneurship Talents Program for Young Backbone Talents(SpringBuds Project),Grant/Award Number:20250333。
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