Protein from probiotic bacteria may alleviate inflammatory bowel disorders

May 23, 2011, Vanderbilt University Medical Center

A protein isolated from beneficial bacteria found in yogurt and dairy products could offer a new, oral therapeutic option for inflammatory bowel disorders (IBD), suggests a study led by Vanderbilt University Medical Center researcher Fang Yan, M.D., Ph.D.

The study, published May 23 in the , shows that the protein, called p40, was effective as an intervention in animal models of colitis (colon inflammation). The investigators demonstrated that the protein supports intestinal epithelial cell growth and function, and reduces inflammatory responses that can cause to die. Importantly, the investigators showed that oral consumption of p40 by mice in a protective delivery system prevents and treats colitis in multiple models of the disease.

Many of the hundreds of that live in our gut (known as the "human microbiome") are helpful to us: they help us digest certain substances, produce vitamins and fight off more dangerous bacteria. But miscommunication between these bacteria and our gut lining can lead to conditions like ulcerative colitis and . According to the Centers for Disease Control and Prevention, as many as 1.4 million persons in the United States alone may suffer from these diseases.

One type of helpful bacteria often used in yogurt production and in nutritional supplements, Lactobacillus rhamnosus GG (LGG), has been used in attempts to prevent intestinal disorders such as IBD and diarrhea, as well as other conditions such as dermatitis (). However, results generated using whole bacteria have been mixed.

Yan began studying LGG in 2001 while working in the lab of D. Brent Polk, M.D., the former director of the Division of Pediatric Gastroenterology, Hepatology and Nutrition at Vanderbilt.

This research was sparked when a colleague in Pediatric Infectious Diseases asked him, "Is there anything to this probiotic stuff?" said Polk, co-author on the study and currently director the Saban Research Institute of Children's Hospital Los Angeles.

"Probiotic bacterial function is not very clear right now," said Yan, a research associate professor of Pediatrics at Vanderbilt.

Polk and Yan showed that LGG prevented epithelial cells from inflammation-induced apoptosis – a kind of cell suicide. They then isolated and characterized two specific proteins secreted by LGG (which they called p75 and p40) responsible for the bacterium's beneficial effects.

In the current study, Yan investigated the mechanisms by which one of these proteins, p40, prevents and treats colitis.

In cell experiments, Yan and colleagues showed that p40 activates the epidermal growth factor receptor (EGFR), a protein critical for cell survival and growth.
Activation of EGFR protected epithelial cells in two ways: by preventing both apoptosis and inflammation-induced disruption of the "tight junctions" between , which form a barrier to keep toxic substances and pathogens out of the bloodstream.

To test the isolated protein's effectiveness in animal models of disease, the investigators developed a gel bead system to deliver the protein specifically to the colon while protecting the protein from being degraded by stomach acid and digestive enzymes.

In three different mouse models of intestinal inflammation, they showed that p40 prevented and treated intestinal injury and acute colitis.

This study is one of the few to identify and use individual molecules from beneficial microbes as potential therapeutics. In clinical applications, Yan says that the isolated could provide at least two advantages to using whole bacteria.

"One is bioavailability," she said. "Even if you eat live bacteria (as in yogurt), that does not mean 100 percent of will still be alive (and active) in your body."

Another advantage is safety. Although LGG is generally safe for most people, "in patients with immune deficiency, it could be a problem because it may induce an abnormal immune response," she noted.

As for the question that initiated these studies, Polk said, "Dr. Yan has answered this with a resounding 'yes.'"

"It has been my privilege to collaborate with Dr. Yan on this exciting work."

Related Stories

Recommended for you

Anemia discovery offers new targets to treat fatigue in millions

January 22, 2018
A new discovery from the University of Virginia School of Medicine has revealed an unknown clockwork mechanism within the body that controls the creation of oxygen-carrying red blood cells. The finding sheds light on iron-restricted ...

More surprises about blood development—and a possible lead for making lymphocytes

January 22, 2018
Hematopoietic stem cells (HSCs) have long been regarded as the granddaddy of all blood cells. After we are born, these multipotent cells give rise to all our cell lineages: lymphoid, myeloid and erythroid cells. Hematologists ...

How metal scaffolds enhance the bone healing process

January 22, 2018
A new study shows how mechanically optimized constructs known as titanium-mesh scaffolds can optimize bone regeneration. The induction of bone regeneration is of importance when treating large bone defects. As demonstrated ...

Researchers illustrate how muscle growth inhibitor is activated, could aid in treating ALS

January 19, 2018
Researchers at the University of Cincinnati (UC) College of Medicine are part of an international team that has identified how the inactive or latent form of GDF8, a signaling protein also known as myostatin responsible for ...

Bioengineered soft microfibers improve T-cell production

January 18, 2018
T cells play a key role in the body's immune response against pathogens. As a new class of therapeutic approaches, T cells are being harnessed to fight cancer, promising more precise, longer-lasting mitigation than traditional, ...

Weight flux alters molecular profile, study finds

January 17, 2018
The human body undergoes dramatic changes during even short periods of weight gain and loss, according to a study led by researchers at the Stanford University School of Medicine.

0 comments

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.