Featured Research

from universities, journals, and other organizations

Gut Protein Found To Protect Against Infection And Intestinal Breakdown

Date:
February 8, 2006
Source:
UT Southwestern Medical Center
Summary:
A protein that binds to bile in the small intestine may hold the key to preventing infection and intestinal breakdown in people with conditions such as obstructive jaundice or irritable bowel syndrome, researchers at UT Southwestern Medical Center have discovered.

UT Southwestern researchers led by Dr. Steven Kliewer (right), professor of molecular biology, and including Dr. Takeshi Inagaki, postdoctoral research fellow in pharmacology, have identified one of the mechanisms for how the body keeps the number of bacteria low in the small intestine, and how it prevents them from getting into other organs.
Credit: Image courtesy of UT Southwestern Medical Center

A protein that binds to bile in the small intestine may hold the key to preventing infection and intestinal breakdown in people with conditions such as obstructive jaundice or irritable bowel syndrome, researchers at UT Southwestern Medical Center have discovered.

"What we've identified is one of the mechanisms for how the body keeps the number of bacteria low in the small intestine, and how it prevents them from getting into other organs," said Dr. Steven Kliewer, professor of molecular biology and the study's senior author. The study is available this week online and in an upcoming issue of the Proceedings of the National Academy of Sciences.

Bile, which is generated by the liver and flows into the small intestine via a duct, contains harsh acids that help the body absorb nutrients, kill certain bacteria and help keep intact the lining of the intestine, a major barrier against the infiltration of infectious microorganisms. That's no small task; if the innermost lining of the small intestine alone were unfolded, it would be the size of a tennis court.

When there's no bile in the intestine, as happens in people with obstructive jaundice or in those who rely on feeding tubes for nourishment, the lining breaks down and bacteria pass through it into the body, sometimes causing the massive blood infection known as sepsis. Simply giving bile acids orally as a substitute isn't a good solution because they can cause liver damage, Dr. Kliewer said.

The researchers focused on a molecule — FXR — in the wall of the lining, which binds to bile acids. When FXR was activated by a synthetic binding chemical called GW4064, it was found to activate several genes that are known to protect the intestinal lining or attack bacteria.

The research team also found that FXR molecules heavily lined the inside folds of the intestine in adult mice.
"It's perfectly positioned," Dr. Kliewer said. "It's expressed in just the right place to protect us from the environment."

When the bile ducts of mice were tied off, preventing bile from reaching the intestine, adding GW4064 prevented damage to the intestines, showing that it can replace bile in protecting the small intestine.

Genetically engineered mice that lacked FXR showed overall damage to the intestines, "strong evidence that this protein is crucial," Dr. Kliewer said. Drugs that bind to FXR, he said, could eventually become useful in treating various conditions of the small intestine.

Other UT Southwestern researchers involved in the study were Drs. Takeshi Inagaki and Guixiang Zhao, postdoctoral research fellows in molecular biology; Dr. Antonio Moschetta, postdoctoral research fellow in pharmacology and a research associate in the Howard Hughes Medical Institute; Youn-Kyoung Lee, student research assistant in molecular biology; Li Peng, senior research associate in molecular biology; John Shelton, senior research scientist in internal medicine; Dr. James Richardson, professor of pathology; Dr. Joyce Repa, assistant professor of physiology; and Dr. David Mangelsdorf, professor of pharmacology and biochemistry and an HHMI investigator. Drs. Ruth Yu and Michael Downes of the Salk Institute for Biological Studies in La Jolla, Calif., also participated in the study.

The work was supported by the National Institutes of Health, the HHMI and The Welch Foundation.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

UT Southwestern Medical Center. "Gut Protein Found To Protect Against Infection And Intestinal Breakdown." ScienceDaily. ScienceDaily, 8 February 2006. <www.sciencedaily.com/releases/2006/02/060207232927.htm>.
UT Southwestern Medical Center. (2006, February 8). Gut Protein Found To Protect Against Infection And Intestinal Breakdown. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2006/02/060207232927.htm
UT Southwestern Medical Center. "Gut Protein Found To Protect Against Infection And Intestinal Breakdown." ScienceDaily. www.sciencedaily.com/releases/2006/02/060207232927.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
China's Ageing Millions Look Forward to Bleak Future

China's Ageing Millions Look Forward to Bleak Future

AFP (July 24, 2014) China's elderly population is expanding so quickly that children struggle to look after them, pushing them to do something unexpected in Chinese society- move their parents into a nursing home. Duration: 02:07 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins