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. 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.