1150-P: A Hyperhomocysteinemia-Inducing Diet Alters Gut Microbiome and Glucose Homeostasis

Abstract

Hyperhomocysteinemia (HHcy) is a risk factor for higher mortality in type 2 diabetic patients. A high methionine low folate (HMLF) diet chronically induces HHcy by causing homocysteine (Hcy) accumulation in systemic circulation. A higher systemic Hcy level is clinically associated with the incidence of diabetes mellitus. However, whether HHcy negatively impacts on glucose metabolism and insulin sensitivity remains inconclusive and contradictory. Meanwhile, very few studies have focused on the direct impact of HMLF diet on glucose homeostasis, and that on the gut flora. To understand the impact of HMLF diet, C57BL/6 mice were fed a HMLF diet for 8 consecutive weeks. HMLF diet feeding successfully induced HHcy, caused progressive body weight loss, and slightly impaired glucose homeostasis, as revealed by slight glucose intolerance and insulin resistance, in C57BL/6 mice. Of noted, HMLF diet feeding altered the gut microbiome profile that the relative abundance of porphyromonadaceae family of bacteria was enriched in diet-induced HHcy mice. Interestingly, a previous study correlated the higher frequency of porphyromonadaceae with the development of GLP-1 resistance, implying that HMLF diet might prompt the development of GLP-1 resistance. GLP-1 resistance results in the impairment on glucose-induced insulin secretion. These results provide novel insights into the roles of impaired glucose homeostasis and gut microbiome in the pathogenesis of HHcy-related complications. In short, an improper dietary pattern might impair glucose homeostasis by altering the gut microbiome profile. Disclosure C. Cheng: None. C. Wang: None. Y. Huang: None. Funding Chinese University of Hong Kong (4930709); Hong Kong Research Grants Council Senior Research Fellow Scheme 2020/21 (SRFS2021-4S04)