@article{5aadfb6e72d94ddcb7e1cf7948ff49cd,
title = "Restructuring of the gut microbiome by intermittent fasting prevents retinopathy and prolongs survival in db/db mice",
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.",
author = "Eleni Beli and Yuanqing Yan and Leni Moldovan and Vieira, {Cristiano P.} and Ruli Gao and Yaqian Duan and Ram Prasad and Ashay Bhatwadekar and White, {Fletcher A.} and Townsend, {Steven D.} and Luisa Chan and Ryan, {Caitlin N.} and Daniel Morton and Moldovan, {Emil G.} and Chu, {Fang I.} and Oudit, {Gavin Y.} and Hartmut Derendorf and Luciano Adorini and Wang, {Xiaoxin X.} and Carmella Evans-Molina and Mirmira, {Raghavendra G.} and Boulton, {Michael E.} and Yoder, {Mervin C.} and Qiuhong Li and Moshe Levi and Busik, {Julia V.} and Grant, {Maria B.}",
note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2018 by the American Diabetes Association.",
year = "2018",
month = sep,
day = "1",
doi = "10.2337/db18-0158",
language = "English (US)",
volume = "67",
pages = "1867--1879",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "9",
}