A mechanism by which gut microbiota elevates permeability and inflammation in obese/diabetic mice and human gut

Area of Science:

• Microbiology
• Metabolic Syndrome
• Gastroenterology

Background:

• Obesity and diabetes are linked to chronic gut inflammation and increased intestinal permeability ('leaky gut').
• The precise mechanisms driving these gut dysfunctions in obesity and diabetes remain unclear.

Purpose of the Study:

• To elucidate the mechanism by which gut microbiota in obesity promotes intestinal permeability, inflammation, and glucose metabolism abnormalities.
• To investigate the therapeutic potential of restoring gut microbiota function.

Main Methods:

• Utilized fecal conditioned media and fecal microbiota transplantation in obese mice and human samples.
• Employed untargeted metabolomics and molecular biology techniques to identify key pathways.
• Investigated the role of ethanolamine metabolism, microRNA-101a-3p, and Zona Occludens-1 (Zo1) in regulating intestinal barrier function.

Main Results:

• Reduced microbial ethanolamine metabolism in obesity leads to ethanolamine accumulation, inducing intestinal permeability.
• Elevated ethanolamine increases miR-101a-3p via ARID3a binding, which decreases Zo1 mRNA stability, impairing the intestinal barrier.
• This molecular cascade results in gut permeability, inflammation, and glucose metabolic dysfunction.
• A novel probiotic therapy targeting ethanolamine metabolism reversed these pathological changes by correcting the ARID3a/miR-101a/Zo1 axis.

Conclusions:

• The gut microbiota's impaired capacity to metabolize ethanolamine is a key driver of gut permeability, inflammation, and metabolic dysfunction in obesity.
• Restoring microbial ethanolamine metabolism through probiotic intervention offers a promising therapeutic strategy to reverse these obesity-associated gut and metabolic abnormalities.