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. 2021 Aug;58(8):1035-1049.
doi: 10.1007/s00592-021-01682-1. Epub 2021 Mar 22.

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

Celine Pomié  1   2   3 , Florence Servant  4 , Lucile Garidou  1   2 , Vincent Azalbert  1   2 , Aurélie Waget  1   2 , Pascale Klopp  1   2 , Céline Garret  1   2 , Julie Charpentier  1   2 , Francois Briand  5 , Thierry Sulpice  5 , Benjamin Lelouvier  4 , Victorine Douin-Echinard  6   7 , Rémy Burcelin  8   9
Affiliations

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

Celine Pomié et al. Acta Diabetol. 2021 Aug.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Fractalkine; Germ free mice; Intestinal immune system; Metabolic diseases; Microbiota.

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