Vitamin D Receptor Emerges As A Key Player Amid The Murk Of 'Gut Flora'

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Vitamin D Receptor Emerges As A Key Player Amid The Murk Of 'Gut Flora'

Within the human digestive tract is a teeming mass of hundreds of types of

bacteria, a potpourri of microbes numbering in the trillions that help us

digest food and keep bad bacteria in check.

Now scientists have found that the vitamin

<http://www.medicalnewstoday.com/articles/161618.php> D receptor is a key

player amid the gut bacteria - what scientists refer to matter-of-factly

as

the "gut flora" - helping to govern their activity, responding to their

cues, and sometimes countering their presence. The work was published online

recently in the American Journal of Pathology.

The findings deliver a new lead to scientists investigating how bacteria

might play a role in the development of inflammatory bowel diseases such

as

Crohn's disease <http://www.medicalnewstoday.com/articles/151620.php> or

ulceractive colitis. The work complements studies suggesting that Salmonella

infection can increase the risk of inflammatory bowel disease.

"Vitamin D deficiency is a known factor in the pathology of inflammatory

bowel disease and colon cancer

<http://www.medicalnewstoday.com/articles/150496.php> ," said microbiologist

Jun Sun, Ph.D., of the University of Rochester Medical Center, "but there

have been very few reports about how bacteria might play a role by targeting

the vitamin D receptor. Our work suggests one possible mechanism, by working

through the vitamin D receptor, a sensor and regulator for the majority of

functions of vitamin D."

Sun specializes in the actions of bacteria in the body and how their

interactions within the body contribute to disease. She has shown that

bacteria often found in the human intestine affect molecular signals known

to contribute to inflammatory response and cell growth.

Her work with the vitamin D receptor takes place at a time when the molecule

is coming under increasing scrutiny. Scientists have associated vitamin D

and the receptor with many types of cancer

<http://www.medicalnewstoday.com/info/cancer-oncology/whatiscancer.php> , as

well as osteoporosis <http://www.medicalnewstoday.com/articles/155646.php> ,

heart disease, diabetes

<http://www.medicalnewstoday.com/info/diabetes/whatisdiabetes.php> ,

inflammatory bowel disease, and infection.

Sun's team took a close look at the vitamin D receptor in mice and its

interactions with bacteria in the colon. The team studied normal mice; mice

in which the vitamin D receptor had been knocked out; and mice that were

completely free of any germs. Scientists observed how the mice responded

to

infection with either a harmless strain of E. coli

<http://www.medicalnewstoday.com/articles/68511.php> or a pathogenic strain

of Salmonella Typhimurium.

The team found that Salmonella is able to regulate the vitamin D receptor,

increasing its activity and determining where in the colon the receptor is

active. In the presence of Salmonella, the receptor was more prevalent than

usual deep within folded intestinal structures known as crypts.

Sun's team also discovered that the vitamin D receptor plays a key role in

defending the body from assault by Salmonella and squelching inflammation.

The receptor stops a molecule known as NF-Kappa B, a well-known master

player in the world of inflammation, by binding to it and preventing it from

activating other inflammatory molecules. While scientists have known that

the receptor interacts with NF-Kappa B, details of the interaction modulated

by bacteria in the colon are new.

The scientists found that Salmonella was much more virulent and aggressive

in mice in which the vitamin D receptor had been turned off. These mice

showed higher levels of activity of inflammatory molecules, and they lost

weight more quickly and were much more likely to die in response to

infection.

"We live together in a mutually beneficial state with most of the bacteria

in our gut," said Sun, assistant professor in the Gastroenterology and

Hepatology Division of the Department of Medicine. "They help us digest

foods like fruits and vegetables, and we provide them a place to live and

thrive. We co-exist peacefully - most of the time.

"But we aren't able to culture most of these bacteria in the laboratory,

and

we don't know what most of them are doing. We need to understand our gut

flora much more than we do. This is particularly important for understanding

how we might manipulate the natural gut flora to stop an invader like

Salmonella," added Sun, who also has appointments in the P. Wilmot

Cancer Center and the Department of Microbiology and Immunology.

Notes:

In addition to Sun, authors of the study from Rochester include the first

author, post-doctoral associate Shaoping Wu, Ph.D., of the Gastroenterology

and Hepatology Division; Jian-Dong Li, M.D., Ph.D., of the Department of

Microbiology and Immunology; former technician Anne P. Liao; and former

research assistant Yinglin Xia, Ph.D.

Other authors include Yan Chun Li, Ph.D., of the University of Chicago, who

supplied the vitamin D receptor "knockout" mice, and R. Balfour Sartor,

M.D., of the University of North Carolina at Chapel Hill, who supplied the

specialized germ-free mice through the Center for Gastrointestinal Biology

and Diseases Gnotobiotic Core Facility and the National Gnotobiotic Rodent

Resource Center.

This work was funded by the National Institute of Diabetes and Digestive

and

Kidney Diseases.

Source: University of Rochester Medical Center