2022-028 – Treating Leaky Gut by Targeting Bacteria and Snail Pathway

Background:
Tight junctions (TJs) are essential components of intestinal barrier integrity and protect the epithelium against passive paracellular flux and microbial translocation. Dysfunctional TJs lead to increased intestinal permeability, or “leaky gut”, a condition associated with gut microbial dysbiosis such as Inflammatory Bowel disease (IBD), irritable bowel syndrome (IBS), Parkinson’s disease, and metabolic syndrome. Sulfate-reducing bacteria (SRB) are minor residents of the gut microbiome in humansIncreased number of Desulfovibrio vulgaris (DSV), the most predominant SRB, is observed in IBD and extra-intestinal disorders such as Parkinson’s disease, suggesting a broad association of these gut bacteria with disparate diseases. This leads to the question whether SRB are the cause or effect of leaky gut in these diseases. Snail is a transcription factor that is also responsible for increased intestinal permeability through negatively regulating TJ proteins as well as adheren junction (AJ) proteins. Thus, to treat increased intestinal permeability, the relationship between targeting bacteria and the snail pathway needs to be explored.

Technology Description:
Researchers at the University of New Mexico, the Biomedical Research Institute of New Mexico, and the Department of Veterans Affairs have collaborated to demonstrate that leaky gut could be treated by targeting bacteria and the Snail Pathway.DSV-induced increased permeability can be monitored by an increase in the flux of a fluorescent probe in vitro. The translocation of the fluorescent probe from one side to the other side of the intestinal layer demonstrates the adverse effect of microbial translocation when the intestinal barrier function is impaired. This finding demonstrates that leaky gut could be treated by targeting these bacteria and the Snail Pathway.

It was also found that exogenous intestinal alkaline phosphatase (IAP) can reverse DSV- induced increase in snail protein expression and DSV-induced increase in intestinal permeability. IAP is a protein secreted by small intestinal cells and is found in stool and blood and throughout the intestinal lumen. IAP is known for its many protective roles such a detoxification of lipopolysaccharide (LPS), regulating gut microbiome, as well as maintaining barrier integrity. It is shown that IAP reversed DSV-mediated FITC-flux, inhibited DSV-induced snail expression and the translocation of Snail into the nucleus resulting in the reversal of DSV-induced leaky gut.

Website:

https://unm.flintbox.com/technologies/8C9575ACD2C341A7BCB2B0601E1A0A64

Advantages:

  • Maintains intestinal barrier integrity
  • Reverses DSV-induced leaky gut
  • Helps regulate gut microbiome
  • Provides a novel therapeutic intervention for correcting SRB-induced leaky gut via inhibition of the snail pathway

Potential Applications:

  • Gastroenterology
  • Microbiome Research
  • Microbial Dysbiosis
    • Inflammatory Bowel Disease (IBD)
    • Irritable Bowel Syndrome (IBS)
    • Parkinson's Disease
    • Metabolic Syndrome

Contact Information:

Name: Gregg Banninger

Email: GBanninger@innovations.unm.edu

Phone: 505-272-7908