gut microbiota controls metabolism in CX3CR1nul mice
CX3CR1 controls glycemia through a gut microbiota-dependent mechanism
The intestinal microbiota and immune system are now considered major actors in the control of energy metabolism. Dysregulation of their interplay leads to the translocation of bacteria towards tissues, thereby inducing low grade tissue inflammation causal to dysmetabolism. Here we identify the chemokine receptor CX3CR1 as a key regulator shaping intestinal microbiota under normal chow feeding. CX3CR1 controls bacterial translocation to the liver while modifying the liver microbiota signature associated with a low grade tissue inflammation. Disrupting this early regulator has several impacts on energy metabolism in the corresponding CX3CR1-deficient mice. It promotes glucose intolerance with a slight reduction of insulin sensitivity, fed hyperinsulinemia, and a reduced respiratory quotient. This suggests that CX3CR1-deficient mice oxidize more lipids than glucose, thereby not reducing their glycemia during short term fasting. Modulation of the gut microbiota ecology of CX3CR1-deficent mice by pre-probiotic or antibiotic treatments caused a reversal of glucose intolerance and insulin secretion phenotypes. Finally, colonization of germ free mice with the ileum microbiota from CX3CR1 null mice resulted in a slight glucose intolerance. Therefore, we have identified CX3CR1-deficiency as causal to microbiota dysbiosis partly responsible for early impairment of glucose metabolism and triggering the onset of hyperglycemia.
The intestinal microbiota and immune system are now considered major actors in the control of energy metabolism. Dysregulation of their interplay leads to the translocation of bacteria towards tissues, thereby inducing low grade tissue inflammation causal to dysmetabolism. Here we identify the chemokine receptor CX3CR1 as a key regulator shaping intestinal microbiota under normal chow feeding. CX3CR1 controls bacterial translocation to the liver while modifying the liver microbiota signature associated with a low grade tissue inflammation. Disrupting this early regulator has several impacts on energy metabolism in the corresponding CX3CR1-deficient mice. It promotes glucose intolerance with a slight reduction of insulin sensitivity, fed hyperinsulinemia, and a reduced respiratory quotient. This suggests that CX3CR1-deficient mice oxidize more lipids than glucose, thereby not reducing their glycemia during short term fasting. Modulation of the gut microbiota ecology of CX3CR1-deficent mice by pre-probiotic or antibiotic treatments caused a reversal of glucose intolerance and insulin secretion phenotypes. Finally, colonization of germ free mice with the ileum microbiota from CX3CR1 null mice resulted in a slight glucose intolerance. Therefore, we have identified CX3CR1-deficiency as causal to microbiota dysbiosis partly responsible for early impairment of glucose metabolism and triggering the onset of hyperglycemia.