NIH Develops First Research Plan to Decrease Burden of Digestive Diseases

Laurie Barclay, MD

April 03, 2009

April 3, 2009 — The National Commission on Digestive Diseases of the National Institutes of Health (NIH) yesterday released a research plan designed to reduce the burden of digestive diseases, which range from food-borne gastrointestinal infections to cancer and liver failure.

Designated research priorities for the next decade include focusing on multidisciplinary study of causes, diagnostic strategies, and treatment of digestive diseases, which affect up to 70 million individuals in the United States annually. Appropriate areas for study include advances in bioengineering, biotechnology, and imaging to improve patient outcomes and treatments.

"NIH-funded research has led to tremendous discoveries in peptic ulcer disease, viral hepatitis, and colorectal cancer," Griffin P. Rodgers, MD, director of the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), said in a news release "To build on these advances and break new ground, we'll be looking for investigator-initiated projects and developing new initiatives that respond to the commission's recommendations. Of course, bringing in new investigators and utilizing NIH's peer review system to identify projects with high scientific merit will continue to be high priorities."

Symptoms of digestive disease, including abdominal pain, diarrhea, nausea, and vomiting, result in approximately 105 million physician visits and about $100 billion in direct US medical costs annually. In the United States, prescription medications for digestive diseases such as gastroesophageal reflux are among the most frequently prescribed drugs.

In fiscal year 2008, NIH research costs for digestive diseases exceeded $1.4 billion, involving approximately 20 institutes, centers, and offices. Current basic, translational, and clinical research at NIH is exploring mechanisms of digestive system development and function in normal and pathological states.

Breakthrough developments in research that have translated into improvements in clinical care and in outcomes of digestive diseases include the discovery of Helicobacter pylori as a major etiology of ulcer disease, discovery of multiple forms of viral hepatitis, development of curative treatments and prophylactic vaccines, and designing and implementing effective screening programs for colorectal cancer.

Current Strategies Ineffective, Expensive

Despite these advances, currently available strategies to prevent, diagnose, or treat digestive diseases are often incompletely effective and expensive. Progress has been slow for many conditions including functional gastrointestinal disorders and pancreatitis. The obesity epidemic has caused an increase in conditions such as nonalcoholic steatohepatitis.

Motivated by the morbidity and healthcare costs associated with digestive diseases, Elias A. Zerhouni, former director of NIH, established the commission in 2005 to review current evidence and to identify knowledge gaps to be filled by future research on digestive diseases. The commission includes 16 appointed members from academia, medical research, healthcare professions, and patient-advocacy groups, as well as 18 nonvoting ex officio members from the NIH and other federal agencies involved in digestive diseases research.

Recommendations from the commission encompassed many broad areas of scientific research including fundamental biology of the digestive system and disease-oriented topics, such as epidemiology; pertinent environmental exposures; genetic predispositions and mechanisms; diagnostic tools; potential treatment strategies; behavioral, social, and psychological factors affecting response to illness; disparities in healthcare access; prevention; and cures.

Recommended Research Priorities

Research priorities recommended by the National Commission on Digestive Diseases include the following:

  • Elucidate the biology and physiology of the digestive system, including manipulation of gastrointestinal stem cells and studying the fundamental mechanisms of digestion to develop treatment strategies for disorders of nutrient and fluid absorption, secretion, and metabolism. Other avenues for biological research include the enteric nervous system, intestinal microflora, and mucosal immune system.

  • Clarify the mechanisms underlying irritable bowel syndrome and other functional gastrointestinal and motility disorders. Areas for study include brain–gut interactions, the enteric nervous system, interstitial cells of Cajal and smooth muscle cells, pain and sensory mechanisms, the gut mucosa and musculature, intestinal microflora, immune and inflammatory responses, patient-specific factors determining susceptibility, and the effects of diabetes.

  • Identify additional pathogenic microbes causing harmful infections, including bacteria, viruses, protozoa, and helminths.

  • Develop more efficient diagnostic tools to predict and detect gastrointestinal and digestive cancers.

  • Use findings from comprehensive genetic and other studies to develop objective criteria for diagnosis and risk evaluation of inflammatory bowel diseases, allowing reliable subclassification of patients and their diverse constellations of symptoms.

  • Develop new therapeutic strategies to address intestinal failure and regeneration, nutritional disorders, nutritional support, surgically modified gut or stomach after bariatric surgery, and hepatic transplantation.

  • Clarify the neuromuscular biology of diseases involving the oropharynx and esophagus, which is critical to developing treatments for conditions such as swallowing disorders secondary to stroke, premature birth, and nonerosive reflux disease, as well as gastroesophageal reflux disease.

  • Improve therapeutic regimens for the wide range of diseases affecting the stomach and small intestine. This includes determining triggers for peptic ulcer disease in addition to H pylori and developing new approaches to preventing and treating ulcers, especially those associated with nonsteroidal anti-inflammatory drugs. Research is needed on effective treatments for diarrhea, other maldigestive/malabsorptive diseases, celiac disease and other autoimmune and allergic diseases affecting the digestive tract, and diseases of unknown origin, such as necrotizing enterocolitis and eosinophilic gastrointestinal diseases.

  • Identify more efficient categorization into subgroups of colon and rectal diseases, as well as treatment for these conditions, including diverticular disease, colonic ischemia, angioectasias, anal fistulas, hemorrhoids, fecal incontinence, radiation injury of the colon, and appendicitis.

  • Discover biologic and genetic triggers precipitating attacks of acute pancreatitis and promoting development of chronic pancreatitis. Research is also needed on pancreatic pain and pancreatic cancer.

  • Test and validate new techniques for recognition, prevention, and treatment of hepatic and biliary system diseases, including viral hepatitis, drug-induced liver disease, autoimmune diseases of the liver, hereditary liver diseases, cirrhosis, liver cancers, and gallstones. Improved procedures for liver transplantation are also needed.

"The commission's recommendations provide a guidepost for digestive diseases research to be addressed over the next decade," said commission chair Stephen P. James, MD, NIDDK director of the Division of Digestive Diseases and Nutrition. "We hope that this broad-based research plan leads to new findings that help reduce the pain and suffering experienced by the millions who suffer from digestive diseases."

National Institutes of Health. Published online April 2, 2009.

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