Metabolism and Glycemic control: the crosstalk between intestinal microbiota and immune system

The tight crosstalk between the intestinal immune system and the microbiota in glucose intolerance 

In this article, Pomié et al. study the importance of the tight crosstalk between the intestinal immune system and the microbiota in metabolic disorders:

→ The fractalkine receptor, CX3CR1, is involved in the surveillance of the gut microbiota by the intestinal immune system.

→ Compared to their WT counterparts, CX3CR1-deficient mice exhibited a specific gut microbiota signature associated with impaired glycemic control during fasting.

→ Impaired CX3CR1 activation could be one of the first steps impairing glucose metabolism by exaggerating bacterial translocation, which modifies tissue microbiome and increases tissue inflammation, here demonstrated in the liver.

→ Prebiotic supplementation or antibiotic treatment in CX3CR1-deficient mice improved glycemic control during fasting, while germ-free mice colonized with the microbiome of CX3CR1-deficient mice developed glucose intolerance.

→ These results reinforced the importance of the tight crosstalk between the intestinal immune system and the microbiota to prevent metabolic disorders.


Tissue microbiomes_1

CX3CR1 regulates gut microbiota and metabolism. A risk factor of type 2 diabetes

➔ In collaboration with Vaiomer

Pomié C, Servant F, Garidou L, Azalbert V, Waget A, Klopp P, Garret C, Charpentier J, Briand F, Sulpice T, Lelouvier B, Douin-Echinard V, Burcelin R. Acta Diabetol. 2021 Aug;58(8):1035-1049. doi: 10.1007/s00592-021-01682-1. Epub 2021 Mar 22. PMID : 33754166.

The intestinal microbiota to immune system crosstalk is a major regulator of metabolism and hence metabolic diseases. An impairment of the chemokine receptor CX3CR1, as a key regulator shaping intestinal microbiota under normal chow feeding, could be one of the early events of dysglycemia.

We studied the gut microbiota ecology by sequencing the gut and tissue microbiota. We studied its role in energy metabolism in CX3CR1-deficent and control mice using various bioassays notably the glycemic regulation during fasting and the respiratory quotient as two highly sensitive physiological features. We used antibiotics and prebiotics treatments, and germ-free mouse colonization.

We identify that CX3CR1 disruption impairs gut microbiota ecology and identified a specific signature associated to the genotype. The glycemic control during fasting and the respiratory quotient throughout the day are deeply impaired. A selected four-week prebiotic treatment modifies the dysbiotic microbiota and improves the fasting state glycemic control of the CX3CR1-deficent mice and following a glucose tolerance test. A 4-week antibiotic treatment also improves the glycemic control as well. Eventually, germ free mice colonized with the microbiota from CX3CR1-deficent mice developed glucose intolerance.

CX3CR1 is a molecular mechanism in the control of the gut microbiota ecology ensuring the maintenance of a steady glycemia and energy metabolism. Its impairment could be an early mechanism leading to gut microbiota dysbiosis and the onset of metabolic disease.

Key words: microbiota; metabolic diseases; germ free mice; intestinal immune system; fractalkine

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