Akkermansia muciniphila administration ameliorates streptozotocin-induced hyperglycemia and muscle atrophy by promoting IGF2 secretion from mouse intestine

Abstract

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that can lead to severe diabetic complications. While the changes and correlations between gut microbiota and the pathogenesis of T1DM have been extensively studied, little is known about the benefits of interventions on gut bacterial communities, particularly using probiotics, for this disease. In the present study, we reported that the mice surviving after 5 months of streptozotocin (STZ) injection had reduced blood glucose level and recovered gut microbiota with increased Akkermansia muciniphila proportion. Gavage of heat-killed A. muciniphila increases the diversity of gut microbiota and elevated immune and metabolic signaling pathways in the intestine. Mechanistically, A. muciniphila treatment promoted the secretion of insulin-like growth factor 2 (IGF2) which subsequently activated IGF2 signaling in skeletal muscles and enhanced muscle and global metabolism. Our results suggest that the administration of heat-killed A. muciniphila could be a potential therapeutic strategy for T1DM and its associated hyperglycemia.