Yeast β-glucan improves insulin sensitivity and hepatic lipid metabolism in mice humanized with obese type 2 diabetic gut microbiota

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dc.contributor.authorMitchelson, Kathleen A. J.
dc.contributor.authorTran, Tam T. T.
dc.contributor.authorDillon, Eugene T.
dc.contributor.authorVlckova, Klara
dc.contributor.authorHarrison, Sabine M.
dc.contributor.authorNtemiri, Alexandra
dc.contributor.authorCunningham, Katie
dc.contributor.authorGibson, Irene
dc.contributor.authorFinucane, Francis M.
dc.contributor.authorO'Connor, Eibhlís M.
dc.contributor.authorRoche, Helen M.
dc.contributor.authorO'Toole, Paul W.
dc.contributor.funderDepartment of Agriculture, Food and the Marine, Irelanden
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderSaolta University Health Care Groupen
dc.date.accessioned2022-09-07T12:05:52Z
dc.date.available2022-09-07T12:05:52Z
dc.date.issued2022-08-29
dc.date.updated2022-09-07T11:46:01Z
dc.description.abstractScope: 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.en
dc.description.sponsorshipDepartment of Agriculture, Food and the Marine, Ireland (14/F/828 ‘‘ImmunoMet’’ Programme); Science Foundation Ireland (18/SPP/3522; SFI 19/FFP/6625); Saolta University Health Care Group (Career Development Award)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid2100819en
dc.identifier.citationMitchelson, 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.202100819en
dc.identifier.doi10.1002/mnfr.202100819en
dc.identifier.eissn1613-4133
dc.identifier.issn1613-4125
dc.identifier.journaltitleMolecular Nutrition and Food Researchen
dc.identifier.urihttps://hdl.handle.net/10468/13546
dc.language.isoenen
dc.publisherJohn Wiley & Sons, Inc.en
dc.rights© 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.en
dc.subjectHigh-fat dieten
dc.subjectType 2 diabetesen
dc.subjectGut microbiotaen
dc.subjectHepatic triacylglycerol (TAG)en
dc.subjectYeast β-glucanen
dc.titleYeast β-glucan improves insulin sensitivity and hepatic lipid metabolism in mice humanized with obese type 2 diabetic gut microbiotaen
dc.typeArticle (peer-reviewed)en
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