Type 2 diabetes: treatment resistance due to microbiota


A new kind of treatment has been in use for several years for people with type 2 diabetes: GLP-1 analogues (glucagon-like peptide 1), which stimulate insulin secretion via the gut-brain axis. These medications offer many advantages (weight loss, low risk of hypoglycemia, etc.). However, not all patients respond in the same way, and some are completely resistant. Researchers in Toulouse, France, have recently explained this “biological injustice”, which they attribute to the intestinal microbiota.

Rémy Burcelin’s team at Paul Sabatier University demonstrated, through numerous experiments in mice, that intestinal dysbioses (particularly in the ileum) caused by a diet too high in fat, may reduce sensitivity of the enteric nervous system to GLP-1. In particular, the administration of antibiotics was found to reduce the response to GLP-1 in healthy mice and to improve it in those with dysbiosis. This suggests that certain bacteria promote the activation of the enteric nervous system by GLP-1, while others hamper it, potentially because of their variable capacity to metabolize certain amino acids or their influence on intestinal pH.

Researchers hope that their discovery will improve the future of treatment for type 2 diabetes, particularly in patients who are currently resistant to GLP-1 analogues.


Grasset E., et al. A Specific Gut Microbiota Dysbiosis of Type 2 Diabetic Mice Induces GLP-1 Resistance through an Enteric NO-Dependent and Gut-Brain Axis Mechanism. Cell Metabolism. 2 mai 2017.  http://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30218-8?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1550413117302188%3Fshowall%3Dtrue