Yeast β-glucan improves insulin sensitivity and hepatic lipid metabolism in mice humanized with obese type 2 diabetic gut microbiota
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Date
2022-08-29
Authors
Mitchelson, Kathleen A. J.
Tran, Tam T. T.
Dillon, Eugene T.
Vlckova, Klara
Harrison, Sabine M.
Ntemiri, Alexandra
Cunningham, Katie
Gibson, Irene
Finucane, Francis M.
O'Connor, Eibhlís M.
Journal Title
Journal ISSN
Volume Title
Publisher
John Wiley & Sons, Inc.
Published Version
Abstract
Scope: Gut microbiota alterations are associated with obesity and type 2 diabetes. Yeast β-glucans are potential modulators of the innate immune-metabolic response, by impacting glucose, lipid and cholesterol homeostasis. We examined whether yeast β-glucan interacts differentially with either an obese healthy or obese diabetic gut microbiome, to impact metabolic health through hepatic effects under high-fat dietary challenge. Methods and results: Male C57BL/6J mice were pre-inoculated with gut microbiota from obese healthy (OBH) or obese type 2 diabetic (OBD) subjects, in conjunction with a high-fat diet (HFD) with/without yeast β-glucan. OBD microbiome colonization adversely impacted metabolic health compared to OBH microbiome engraftment. OBD mice were more insulin resistant and displayed hepatic lipotoxicity compared to weight matched OBH mice. Yeast β-glucan supplementation resolved this adverse metabolic phenotype, coincident with increasing the abundance of health-related bacterial taxa. Hepatic proteomics demonstrated that OBD microbiome transplantation increased HFD-induced hepatic mitochondrial dysfunction, disrupted oxidative phosphorylation, and reduced protein synthesis, which were partly reverted by yeast β-glucan supplementation. Conclusions: Hepatic metabolism was adversely affected by OBD microbiome colonization with high-fat feeding, but partially resolved by yeast β-glucan. More targeted dietary interventions that encompass the interactions between diet, gut microbiota and host metabolism may have greater treatment efficacy.
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Keywords
High-fat diet , Type 2 diabetes , Gut microbiota , Hepatic triacylglycerol (TAG) , Yeast β-glucan
Citation
Mitchelson, K. A. J., Tran, T. T. T., Dillon, E. T., Vlckova, K., Harrison, S. M., Ntemiri, A., Cunningham, K., Gibson, I., Finucane, F. M., O'Connor, E. M., Roche, H. M. and O'Toole, P. W. (2022) 'Yeast β-glucan improves insulin sensitivity and hepatic lipid metabolism in mice humanized with obese type 2 diabetic gut microbiota', Molecular Nutrition and Food Research, 2100819. doi: 10.1002/mnfr.202100819
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Copyright
© 2022, John Wiley & Sons Ltd. This is the accepted version of the following item: Mitchelson, K. A. J., Tran, T. T. T., Dillon, E. T., Vlckova, K., Harrison, S. M., Ntemiri, A., Cunningham, K., Gibson, I., Finucane, F. M., O'Connor, E. M., Roche, H. M. and O'Toole, P. W. (2022) 'Yeast β-glucan improves insulin sensitivity and hepatic lipid metabolism in mice humanized with obese type 2 diabetic gut microbiota', Molecular Nutrition and Food Research, 2100819, doi: 10.1002/mnfr.202100819, which has been published in final form at: https://doi.org/10.1002/mnfr.202100819. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.