TY - JOUR
T1 - Yeast β-Glucan Improves Insulin Sensitivity and Hepatic Lipid Metabolism in Mice Humanized with Obese Type 2 Diabetic Gut Microbiota
AU - Mitchelson, Kathleen A.J.
AU - Tran, Tam T.T.
AU - Dillon, Eugene T.
AU - Vlckova, Klara
AU - Harrison, Sabine M.
AU - Ntemiri, Alexandra
AU - Cunningham, Katie
AU - Gibson, Irene
AU - Finucane, Francis M.
AU - O'Connor, Eibhlís M.
AU - Roche, Helen M.
AU - O'Toole, Paul W.
N1 - Publisher Copyright:
© 2022 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.
PY - 2022/11
Y1 - 2022/11
N2 - 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. The study examines 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 are 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 impacts metabolic health compared to OBH microbiome engraftment. OBD mice are more insulin resistant and display hepatic lipotoxicity compared to weight matched OBH mice. Yeast β-glucan supplementation resolves this adverse metabolic phenotype, coincident with increasing the abundance of health-related bacterial taxa. Hepatic proteomics demonstrates that OBD microbiome transplantation increases HFD-induced hepatic mitochondrial dysfunction, disrupts oxidative phosphorylation, and reduces protein synthesis, which are partly reverted by yeast β-glucan supplementation. Conclusions: Hepatic metabolism is 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.
AB - 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. The study examines 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 are 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 impacts metabolic health compared to OBH microbiome engraftment. OBD mice are more insulin resistant and display hepatic lipotoxicity compared to weight matched OBH mice. Yeast β-glucan supplementation resolves this adverse metabolic phenotype, coincident with increasing the abundance of health-related bacterial taxa. Hepatic proteomics demonstrates that OBD microbiome transplantation increases HFD-induced hepatic mitochondrial dysfunction, disrupts oxidative phosphorylation, and reduces protein synthesis, which are partly reverted by yeast β-glucan supplementation. Conclusions: Hepatic metabolism is 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.
KW - gut microbiota
KW - hepatic triacylglycerol (TAG)
KW - high-fat diet
KW - type 2 diabetes
KW - yeast β-glucan
UR - http://www.scopus.com/inward/record.url?scp=85139236128&partnerID=8YFLogxK
U2 - 10.1002/mnfr.202100819
DO - 10.1002/mnfr.202100819
M3 - Article
C2 - 36038526
AN - SCOPUS:85139236128
SN - 1613-4125
VL - 66
SP - e2100819
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 22
M1 - 2100819
ER -