New way to prevent unfavorable intestinal microbiota

October 25, 2017, Hokkaido University
The administration of R -Spondin1 resulted in the increased secretion of α-defensin (right) compared to the control experiment (left). Credit: Hokkaido University

The trillions of microbes living in a mammal's intestine play an important role in the host's metabolism and immunity. The composition of microbiota is maintained by antimicrobial proteins secreted from intestinal cells. However, unfavorably altered microbiota, also known as dysbiosis, is seen in various diseases, often exacerbating the underlying disease and thus creating a vicious cycle between the host and the microbiota.

In order to restore microbiota to a normal state, researchers are exploring bacteriotherapy such as fecal microbiota transplantation and the use of probiotics, but no physiological approach has yet been developed so far.

In experiments using mice, a team of scientists led by Professor Takanori Teshima of Hokkaido University discovered that the molecule R-Spondin1 stimulates to differentiate to Paneth cells which secrete . The peptides are called α-defensins and are known to have strong and selective antimicrobial activities against pathological bacteria.

When they administered R-Spondin1 into healthy mice, they detected a remarkable increase in the number of Paneth cells and amount of α-defensin secretion, finding no significant changes in . This indicated that α-defensin does not kill symbiotic microbes in a healthy gut.

The team then used mice with graft-versus-host-disease (GVHD), an inflammatory complication that occurs after allogenic hematopoietic stem cell transplantation. The team has previously shown that GVHD leads to the loss of Paneth cells and induces intestinal dysbiosis. They have now found that the administration of R-Spondin1 prevents the GVHD-mediated depletion of Paneth and the decreased secretion of α-defensins. Importantly, the composition of intestinal microbiota was largely restored by the administration of R-Spondin1. The team also found evidence that α-defensin has similar effects on GVHD-mediated abnormalities when orally administered.

"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 . So our results suggest a novel and physiological approach to restore the gut's ecosystem and homeostasis while avoiding adverse effects," says Takanori Teshima.

R-Spondin1 protects Paneth cells against GVHD and ameliorates intestinal dysbiosis. The images show rolled intestines after hematopoietic stem cell transplantation with (right) or without (middle) R-Spondin1. (Hayase E. et al., Journal of Experimental Medicine, Oct. 24, 2017) Credit: Hayase E. et al., Journal of Experimental Medicine, October 24, 2017

Explore further: Changes in gut microbiota after unhealthy diet may protect from metabolic disease

More information: Eiko Hayase et al, R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease, The Journal of Experimental Medicine (2017). DOI: 10.1084/jem.20170418

Related Stories

Changes in gut microbiota after unhealthy diet may protect from metabolic disease

March 17, 2017
An unhealthy diet changes the composition of the gut flora and it is generally assumed that this maladaptation called "dysbiosis" triggers disease. A study by Matteo Serino and his colleagues at the Université Paul Sabatier ...

Immune cells support good gut bacteria in fight against harmful bacteria

April 21, 2015
An immune cell protein, ID2, is critical for the maintenance of healthy gut microbiota and helps these good bacteria fight off harmful bacteria, report scientists from the University of Chicago. The study, published in Immunity ...

Researchers find unhealthy gut microbes a cause of hypertension

February 3, 2017
Researchers have found that the microorganisms residing in the intestines (microbiota) play a role in the development of high blood pressure in rats. The study is published in Physiological Genomics. It was chosen as an APSselect ...

The gut microbiota plays a key role in treatment with classic diabetes medication

June 1, 2017
A clearer picture of how the classic diabetes medication metformin works has emerged. A recent study at Sahlgrenska Academy and University of Girona indicates that the clinical effect – control of blood glucose – is achieved ...

Prolonged military-style training causes changes to intestinal bacteria, increases inflammation

May 5, 2017
A new study finds that long periods of physiological stress can change the composition of microorganisms residing in the intestines (intestinal microbiota), which could increase health risks in endurance athletes and military ...

Recommended for you

Gradual release of immunotherapy at site of tumor surgery prevents tumors from returning

March 21, 2018
A new study by Dana-Farber Cancer Institute scientists suggests it may be possible to prevent tumors from recurring and to eradicate metastatic growths by implanting a gel containing immunotherapy during surgical removal ...

Immune cells in the retina can spontaneously regenerate

March 21, 2018
Immune cells called microglia can completely repopulate themselves in the retina after being nearly eliminated, according to a new study in mice from scientists at the National Eye Institute (NEI). The cells also re-establish ...

Cold can activate body's 'good' fat at a cellular level, study finds

March 21, 2018
Lower temperatures can activate the body's 'good' fat formation at a cellular level, a new study led by academics at The University of Nottingham has found.

Switch discovered to convert blood vessels to blood stem cells in embryonic development

March 20, 2018
A switch has been discovered that instructs blood vessel cells to become blood stem cells during embryonic development in mice. Using single-cell technology, researchers from the Wellcome Sanger Institute in Cambridge and ...

Don't blame adolescent social behavior on hormones

March 19, 2018
Reproductive hormones that develop during puberty are not responsible for changes in social behavior that occur during adolescence, according to the results of a newly published study by a University at Buffalo researcher.

Stem cells treat macular degeneration

March 19, 2018
In July 2015, 86-year-old Douglas Waters developed severe age-related macular degeneration (AMD). He struggled to see things clearly, even when up close.


Adjust slider to filter visible comments by rank

Display comments: newest first

not rated yet Nov 16, 2017
Holy crap ! No but seriously seems a pretty important nugget!
not rated yet Nov 17, 2017
I think it is good when deficiencies are fixed with natural substances already present in body. But as they are not patentable and less profitable, these may get buried with all the other good cures.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.