How to repair your gut

How to repair your gut

In a world first, researchers have identified a key biomolecule that enhances the repair of your gut lining by prompting stem cells to regenerate damaged tissue.

A strong cellular lining is essential for a healthy gut as it provides a barrier to the billions of microbes and harmful toxins present in our intestinal tract. This barrier is often damaged by infection and inflammation, which causes many painful symptoms.

The study, published in Cell Stem Cell the authors investigated the environment that surrounds gut stem cells and used "mini gut" organoid methodology where tiny replicas of gut tissue were grown in a dish. The study defined key cells that reside in close proximity to stem cells in the gut that produce the biomolecule Neuregulin-1 that acts directly on stem cells to kick-start the repair process.

"Our really important discovery is that supplementation with additional Neuregulin-1 (NRG1) accelerates repair of the gut lining by activation of key growth pathways," the senior author said.

NRG1, but not EGF, is upregulated upon damage and is expressed in mesenchymal stromal cells, macrophages, and Paneth cells. NRG1 deletion reduces proliferation in intestinal crypts and compromises regeneration capacity. NRG1 robustly stimulates proliferation in crypts and induces budding in organoids, in part through elevated and sustained activation of mitogen-activated protein kinase (MAPK) and AKT.

Consistently, NRG1 treatment induces a proliferative gene signature and promotes organoid formation from progenitor cells and enhances regeneration following injury.
"Our findings open new avenues for the development of Neuregulin 1-based therapies for enhancing intestinal repair and supporting rapid restoration of the critical gut function."

Gastrointestinal disease, such as Crohn's disease and ulcerative colitis, is a major health issue worldwide and results in severe damage to the epithelial cell layer lining the gut. Under these conditions, the intestine has a limited capacity to repair efficiently to restore its main absorptive function and is associated with symptoms including diarrhoea, dehydration, loss of weight and malnutrition. Developing ways to support intestinal tissue repair will dramatically improve patient recovery.

"It was very exciting to observe that Neuregulin 1 can not only drive cells to divide but enhances stem cell properties which supercharges these cells into a repair program," another author said.
"This shortens the period of damage. The gut lining is injured during common chemotherapy treatment for cancer and we were also able to show recovery is significantly improved with application of Neuregulin-1 following chemotherapy.