Editors' ChoiceDiabetes

Fasting the microbiome to treat diabetes

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Science Translational Medicine  16 May 2018:
Vol. 10, Issue 441, eaat8529
DOI: 10.1126/scitranslmed.aat8529

Abstract

Intermittent fasting helps to reduce diabetes-associated retinopathy through changes in microbiome bile acid metabolism.

It is known that the microbiome has a role in diabetes pathophysiology, but more recently it has been suggested that the microbiome also moderates the efficacy of certain diabetes therapies. In an article by Beli et al., the authors demonstrate a potential link between the microbiome and the beneficial effects of dietary therapy. In contrast to chronic caloric restriction, intermittent fasting limits food intake to certain hours of the day, which is believed to benefit metabolic outcomes with relevance to diabetes.

Using the db/db mouse model of diabetes, the authors demonstrated that intermittent fasting improved survival and prevented the development of retinopathy. Each outcome was independent of glycated hemoglobin concentrations. So, the authors turned their attention to the intestinal microbiome to explain the benefit of intermittent fasting, Studies of fecal bacterial ecology demonstrated clear changes in phylogenetic distributions accompanied by differences in the mucosa, including increased goblet cells and villi length, and improved barrier function. To understand the mechanisms through which changes in microbial ecology might affect host phenotypes, the authors focused on the generation of secondary bile acids, which are dependent on microbial metabolism. Secondary bile acids are altered in patients with diabetes, and taurochenodeoxycholate (TUDCA) has been proposed as a treatment for diabetes due to its effect on pancreatic beta cells and on the retina. TUDCA and other secondary bile acids were increased by intermittent fasting and linked to changes in microbial biosynthetic pathways. TUDCA acts in part through the G protein–coupled receptor TGR5. In a second mouse model (induced by streptozotocin), the use of the TGR5-selective agonist INT-767 ameliorated the development of retinopathy.

With these results, researchers can now consider the use of targeted microbial therapies as a treatment for diabetes or to augment dietary therapy. Unfortunately, the authors did not demonstrate that microbiota are sufficient to prevent retinopathy by using a fecal transfer model or antibiotics to inhibit microbial biosynthesis. Future studies will be necessary to better define the overall contribution of the microbiome to the prevention of retinopathy and its therapeutic potential in diabetes.

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