Abstract
Intermittent fasting (IF) protects against the development of metabolic diseases and cancer, but whether it can prevent diabetic microvascular complications is not known. In db/db mice, we examined the impact of long-term IF on diabetic retinopathy (DR). Despite no change in glycated hemoglobin, db/db mice on the IF regimen displayed significantly longer survival and a reduction in DR end points, including acellular capillaries and leukocyte infiltration. We hypothesized that IF-mediated changes in the gut microbiota would produce beneficial metabolites and prevent the development of DR. Microbiome analysis revealed increased levels of Firmicutes and decreased Bacteroidetes and Verrucomicrobia. Compared with db/db mice on ad libitum feeding, changes in the microbiome of the db/db mice on IF were associated with increases in gut mucin, goblet cell number, villi length, and reductions in plasma peptidoglycan. Consistent with the known modulatory effects of Firmicutes on bile acid.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1867-1879 |
| Number of pages | 13 |
| Journal | Diabetes |
| Volume | 67 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2018 |
Funding
Acknowledgments. The authors would like to thank Tatiana E. Salazar, Dung V. Nguyen, James M. Dominguez II, Matthew Richardson, Shakir Hasan Hindi, Harkeerat Dhami, Jared Andre Smith, Joshua Hayes Thomas, and Emily Francesca Hutchinson (Indiana University School of Medicine, Indianapolis, IN) for their technical help with the animal experiments. Funding. Studies were supported by the National Institutes of Health (EY07739, EY12601, EY025383, EY023629, EY023627, and HL110170 [to M.B.G.] and DK093954 to [C.E.-M.]) and by JDRF (3-APF-2017-396-A-N [to E.B.]). Author Contributions. E.B., Y.Y., J.V.B., and M.B.G. designed experiments. E.B., Y.Y., L.M., C.P.V., Y.D., R.P., and X.X.W. performed experiments. E.B., Y.Y., L.M., R.G., L.C., C.N.R., D.M., E.G.M., and F.-I.C. analyzed the data. A.B. and S.D.T. provided resources. E.B., Y.Y., L.M., F.A.W., G.Y.O., H.D., R.G.M., M.E.B., Q.L., M.L., J.V.B., and M.B.G. discussed the results and interpreted the data. E.B., Y.Y., L.M., F.A.W., G.Y.O., L.A., C.E.-M., M.E.B., M.C.Y., M.L., and M.B.G. wrote and revised the paper. M.B.G. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
