Researchers at the University of California, San Diego, have created a petri dish model for intestinal permeability. This condition, also known as “leaky gut,” leads to conditions associated with chronic inflammation such as atherosclerosis, dementia or inflammatory bowel disease. Although serious complications are best documented as a result of celiac disease, other researchers have found links between non-celiac permeability, microbiota imbalances and mood disorders such as anxiety or depression (Minerva Gastroenterologica e Dietologica, March 2017). Intestinal permeability has been difficult to treat, but now there is a treatment with promise for leaky gut.
A Model with Promise for Leaky Gut:
The UCSD scientists took stem cells from the intestines of patients with leaky gut syndrome. They grew these stem cells under special conditions that allowed them to form into miniature organs (Life Science Alliance, Feb. 10, 2020). These tiny balls of intestinal cells demonstrated that under certain types of stress, the tight junctions between intestinal cells start to disintegrate. Aging and tumor growth created such stress. So did certain types of bacteria. A stress-polarity signaling (SPS) pathway appears to be critical to this process.
The authors summarized:
“Using the combined synergy of patient-derived tissues and mouse and human organoid-based models, we showed that the SPS-pathway serves as a protective host response that is compromised in the aged gut and early during the initiation of colon cancers.”
The investigators identified a compound, occludin, that was a consistent marker for junction failure. Low occludin was linked to poor barrier function. They also found that the diabetes drug metformin can help reverse the permeability. Metformin-treated mini-guts produced six times more occludin than the untreated, stressed organoids. Since the mini-guts were created from different individuals’ stem cells, they offer the opportunity to test personalized medicines.
The Promise of Metformin:
For now, though, metformin looks very promising. The drug is already approved and has been prescribed for decades, to treat diabetes and for off-label uses such as prostate cancer, pulmonary fibrosis and thyroid nodules. Next, the team will want to test this medication in humans with leaky gut to see whether it helps relieve symptoms.
The researchers conclude:
“These findings reveal the importance of the SPS-pathway in the gut and highlights its therapeutic potential for treating gut barrier dysfunction in aging, cancer, and dysbiosis.”