Type-2 Diabetics Reduces Spatial Variation of Microbiome Based on Extracellular Vesicles from Gut Microbes across Human Body

Abstract

AbstractAs a result of advances in sequencing technology, the role of gut microbiota in the mechanism of type-2 diabetes mellitus (T2DM) has been revealed. Studies showing wide distribution of microbiome throughout the human body, even in the blood, have motivated the investigation of the dynamics in gut microbiota across the humans. Particularly, extracellular vesicles (EVs), lipid bilayer structures secreted from the gut microbiota, have recently come into the spotlight because gut microbe-derived EVs affect glucose metabolism by inducing insulin resistance. Recently, intestine hyper-permeability linked to T2DM has also been associated with the interaction between gut microbes and leaky gut epithelium, which increases the uptake of macromolecules like lipopolysaccharide from the membranes of microbes leading to chronic inflammation. In this article, we firstly investigate the co-occurrence of stool microbes and microbe-derived EVs across serum and urine in human subjects (N = 284), showing the dynamics and stability of gut derived EVs. Stool EVs are intermediate, while the bacterial composition in both urine and serum EVs is distinct from the stool microbiome. The co-occurrence of microbes was compared between patients with T2DM (N = 29) and matched in healthy subjects (N = 145). Our results showed significantly higher correlations in patients with T2DM compared to healthy subjects across stool, serum, and urine, which could be interpreted as the dysfunction of intestinal permeability in T2DM. Therefore, the significant correlation of EVs might give insight into the pathophysiological mechanisms of T2DM, as well as the role of EVs as a biomarker in the intestinal permeability of T2DM.