Baker's yeast (1→3)-β-D-glucan Influences Insulin Sensitivity in Mice with Humanized Obese Diabetic Microbiome in High-Fat Diet-Induced Obesity

Abstract

AbstractIntroductionβ-glucans are naturally occurring polysaccharides which have isoform specific immunomodulatory and metabolic properties(1). Certain yeast (1→3)-β-D-glucan isoforms improve cholesterol(2), glucose(3) and lipid homeostasis(4). Feeding (1→3)-β-D-glucan alters the microbiome of high-fat diet (HFD) induced obese (DIO)/type 2 diabetic (T2D) mice(5). Here we investigated the potential impact of baker's yeast (1→3)-β-D-glucan in mice humanized with gut microbiomes from either obese healthy versus obese diabetic subjects on immune-metabolism within the context of high-fat feeding.MethodsC57Bl/6J male mice received an antibiotic cocktail of Ampicillin, Metronidazole, Vancomycin, Imipenem and Ciprofloxacin HCl in their drinking water for 6 weeks to diminish the endogenous gut microbiota. Mice were inoculated with microbiota samples obtained from obese healthy (OBH) or diabetic (OBD) humans twice daily for 3 days by oral dosing. Mice were fed a low-fat diet (LFD) (10% kcal) for 4 weeks followed by HFD (45% kcal) with/without baker's yeast (1→3)-β-D-glucan (βG), for 9 weeks. Weight, feed intake, glucose tolerance (1.5g/kg), insulin tolerance (0.5U/kg), hepatic and skeletal lipid levels were examined. Tissue specific molecular markers of metabolism and inflammation, and gut microbiome analysis are being determined to compliment the phenotypic data.ResultsOBH mice were more glucose tolerant and insulin sensitive than OBD mice, despite equal weight gain and adipose tissue mass. Fasting HOMA-IR, attributable to higher insulin concentrations, was higher in OBD compared to OBH mice. βG supplementation reduced HOMA-IR in OBD mice (P < 0.0611). Hepatic triacylglycerol (TAG) and cholesterol levels were also higher in OBD mice, which were prevented by βG supplementation. Hepatic proteomic, caecal microbiomic and metabolomic analysis is on-going in order to ascertain the impact of the OBD versus OBH dysbosis with/without βG supplementation with specific attention on immune-metabolism.