Investigator at The Saban Research Institute Leads Team That Discovers Mechanism of Action for Probiotics

Published on 
June 3, 2011

Findings May Lead to New Treatments for Inflammatory Bowel Disease

MEDIA CONTACT:  Ellin Kavanagh at 323-361-8505
Dr. Brent Polk
Brent Polk, MD, director of The Saban Research Institute at Children's Hospital Los Angeles.

LOS ANGELES (June 3, 2011) –  Probiotic bacteria in yogurt has long been suspected of having therapeutic qualities but little has been known about how and why these benefits occurred.  Brent Polk, MD, director of The Saban Research Institute, and colleagues at Vanderbilt University Medical Center have discovered a previously unknown mechanism for how probiotic-derived protein protects the intestine from injury and inflammation.

The research team identified a soluble protein, p40, derived from probiotic bacteria called Lactobacillus rhamnosus GG (LGG).  This protein was been shown to prevent experimentally- induced cell death in the intestine.  By inducing cell death, the researchers modeled what occurs in autoimmune gastrointestinal diseases like ulcerative colitis or Crohn’s disease, where the overactive immune system mistakenly attacks cells lining the intestine. 

In a series of studies the investigators demonstrated that p40 was able to prevent and treat acute colitis.

Using ex vivo intestinal cells, the researchers demonstrated that p40 stimulated the epidermal growth factor receptor, or EGFR, a protein required for normal cell function, growth and proliferation.  Activation of this receptor prevented apoptosis, or cellular suicide, of the intestinal epithelium while also strengthening the physical barrier between epithelial cells by preventing inflammation-induced injury.  This physical barrier, or tight junction between the cells, prevents toxins from leaving the intestine and gaining access to the blood stream.

To test the effect of p40 on intestinal disease, the investigators used in vivo models and a gel bead system that allowed protein protection from stomach acid while delivering it to the site of injury in the colon.  Administration of the p40-embedded beads reduced both apoptosis and alterations in the barrier function of intestinal epithelium in an EGFR-dependent manner.

“Dr. Yan and our other colleagues have shown that p40 can be delivered orally and that it protects against inflammation in the bowel.  With 1.4 million people in the US suffering from inflammatory bowel disease, the possibility of a biologically-relevant, oral therapeutic is very exciting,” said Dr Polk.

Brent Polk, MD, is also professor and chair of Pediatrics and professor of Biochemistry and Molecular Biology at the Keck School of Medicine of the University of Southern California and former director of the Division of Pediatric Gastroenterology, Hepatology and Nutrition at Vanderbilt.  Fang Yan, MD, PhD, Research Associate Professor of Pediatrics at Vanderbilt University Medical Center was first author on the study.

The work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Disorders, the Crohn’s and Colitis Foundation of America, the National Center for Complementary and Alternative Medicine, the National Cancer Institute and the Department of Veterans Affairs.

About Children’s Hospital Los Angeles
Children's Hospital Los Angeles has been named the best children’s hospital in California and among the best in the nation for clinical excellence with its selection to the prestigious US News & World Report Honor Roll.  Children’s Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States and is one of America's premier teaching hospitals, affiliated with the Keck School of Medicine of the University of Southern California since 1932.

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