PSUN174 A Microbiome Targeted Nutraceutical that Induces Endogenous Glucoregulatory Peptide Hormones

Abstract

Abstract Maintaining a narrow and healthy blood glucose range is essential for preventing the progression of microvascular and macrovascular complications associated with glucose dysregulation. It has now been established that secondary metabolites derived from colonic microbiota potentially serve as endogenous secretagogues for glucoregulatory hormone peptides. Specifically, metabolites such as short and medium-chain fatty acids and indole derivatives trigger the secretion of GLP-1 and PYY from the colonic L cells that improve gut motility, modulate insulin, and promote anorexigenic effects. However, secondary metabolites are significantly down-regulated in diets that lack complex carbohydrates and polyphenols, leading to hormonal dysbiosis. To address this need, we developed structural, chemical, and cell-based functional assays to screen a library of prebiotic fibers, polyphenols, and probiotics aimed at the induction of glucoregulatory peptides. Precisely, these ingredients were put through a series of microbiological fermentation assays to produce postbiotic secondary metabolites and subsequently tested as secretagogues on specialized human primary enteroendocrine cells. Prebiotics that significantly induced GLP-1 and PYY in these functional cells were formulated into a lead cocktail: JAN-1000. As a proof of concept, JAN-1000 was tested against an equal dose of single fibers to demonstrate superiority in secondary metabolite production and the induction of key metabolic peptides. JAN-1000 increased SCFAs by 7.9-fold (p<0.0001), indoles by 28.4% (p<0.0001), GLP-1 by 4.7-fold (p<0.0001), and PYY by 3.3-fold (p<0.0001). Furthermore, we initiated a pilot clinical study with healthy volunteers to demonstrate tolerability and efficacy on glucose and lipid homeostasis. A one-month supplementation of JAN-1000 lowered fasting glucose by 10% (p<0.001), lowered iAUC postprandial glucose by 42% (p=n.s.), reduced hypo and hyper-glycemic events, and improved HDL cholesterol by 5% (p<0.01). These results suggest that JAN-1000 is an effective and safe nutrition-based intervention that mediates communication between the gut microbiome with colonic cells and effectively improves hallmarks of diabetes complications and comorbidities. Studies are underway to confirm and expand on these results in people with type 2 diabetes and pre-diabetes. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.