TY - JOUR
T1 - Interactions between gut microbiota, host genetics and diet modulate the predisposition to obesity and metabolic syndrome
AU - Ussar, Siegfried
AU - Griffin, Nicholas W.
AU - Bezy, Olivier
AU - Fujisaka, Shiho
AU - Vienberg, Sara
AU - Softic, Samir
AU - Deng, Luxue
AU - Bry, Lynn
AU - Gordon, Jeffrey I.
AU - Kahn, C. Ronald
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice - obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic - plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome.
AB - Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice - obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic - plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome.
UR - http://www.scopus.com/inward/record.url?scp=85018193359&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2015.07.007
DO - 10.1016/j.cmet.2015.07.007
M3 - Article
C2 - 26299453
AN - SCOPUS:85018193359
VL - 22
SP - 516
EP - 530
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 3
ER -