Scientists find physiological approach to restoring intestinal health

Scientists at Hokkaido University have used antimicrobial peptides to restore the gut’s ecosystem without impacting healthy microbiota.

A mammal’s metabolism and immunity are affected by the microbes in their intestine, and this composition of microbiota is maintained by antimicrobial proteins secreted from intestinal cells. Dysbiosis, which are unfavourably altered microbiota, often exacerbate an underlying disease.

Controlling or restoring the microbiota can be achieved through ‘bacteriotherapy’ such as faecal microbiota transplantation and probiotics. Published in the Journal of Experimental Medicine, Professor Takanori Teshima and his team at Hokkaido University experimented on mice to discover a physiological approach.

They found that the molecule R-Spondin1 stimulates intestinal stem cells to differentiate to Paneth cells, which secrete antimicrobial peptides. The peptides, called α-defensins, act selectively against pathological bacteria, meaning healthy symbiotic microbes remain untouched.

After giving healthy mice R-Spondin1, they found the number of Paneth cells and amount of α-defensin secretion significantly increased without causing any substantial changes in gut microbiota.

“The two molecules we tested, R-Spondin1 and α-defensin, are both intrinsic to mammals, including humans, and found to have little effect on healthy microbiota. So, our results suggest a novel and physiological approach to restore the gut’s ecosystem and homeostasis while avoiding adverse effects,” Professor Teshima explained.

The team then used mice with graft-versus-host disease (GvHD), an inflammatory complication that occurs after allogenic haematopoietic stem cell transplantation. Previously, their research has shown that GvHD leads to the loss of Paneth cells and induces intestinal dysbiosis. However, the administration of R-Spondin1 can prevent the depletion of Paneth cells, prevent the decreased secretion of α-defensins and rebalance intestinal microbiota. Similar results were produced when the α-defensin was orally administered.