R-Spo1 protein rebalances gut microbiota


In the human gut, there is a complex community of microorganisms, collectively known as the gut microbiota. It is well-established that the gut microbiota has a huge impact on people body health. The balance of the gut microbiota is highly regulated by a type of cells in the small intestine: Paneth cells. Paneth cells synthesize and secrete a variety of antimicrobial molecules, including α-defensins, to modulate host-microbe interactions.

Diseases like graft-versus-host disease (GVHD) impair the normal function of Paneth cells, leading to harmful alterations in the gut microbiota (namely dysbiosis), which further deteriorates the disease. At present, the common approaches to rebalance the gut microbiota are microbiota transplantation and probiotics treatment. However, so far no physiological approach is available.

Now, a study carried out by researchers at Hokkaido University, Kyushu University, National Institute of Genetics, and Kyowa Hakko Kirin in Japan has revealed an innovative approach to restoring the gut microbiota. The approach involves the use of the protein R-Spondin1 (R-Spo1) or recombinant α-defensin. You can read the full paper (R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease) in the Journal of Experimental Medicine.

Lead researcher of the study, Professor Takanori Teshima from Hokkaido University, has been studying hematopoietic stem cell transplantation. Professor Teshima has previously shown that GVHD -- a medical complication following allogeneic hematopoietic stem cell transplantation -- reduces the number of Paneth cells and their expression of α-defensins, leading to intestinal dysbiosis and blood infection. Additionally, his recent research has demonstrated for the first time that the R-Spo1 protein is a growth factor of Paneth cells.

In the current study, Professor Teshima and colleagues further investigated the effect of R-Spo1 treatment. In healthy mice treated with R-Spo1, they found that both Paneth cells and α-defensin secretion were highly increased, whereas the gut microbiota did not change much, suggesting that α-defensins do not affect a healthy gut microbiota. In another set of experiments, the researchers tested R-Spo1 in mice with GVHD, and discovered that the protein prevented the loss of Paneth cells, the reduced secretion of α-defensins, and intestinal dysbiosis. Furthermore, recombinant α-defensin therapy was as beneficial as R-Spo1 therapy.

In summary, these data demonstrate the beneficial effect of R-Spo1 and recombinant α-defensin on restoring the balance of the intestinal microbiota.
 
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