resources

Probiotics: Medical Interest
New interest. Fresh interest in probiotics was prompted by reports in the popular press linking yogurt consumption with longevity. There were also grave concerns in the medical literature about a striking rise in antibiotic resistant bacteria as well as the destructive effects of antibiotics on the healthy gut flora. More recently, the presence of damaging bacteria residing in the gut (H. pylori) has been shown to be a primary cause of peptic ulcers, a disease that had previously been thought to be caused by too much acid or stress. Some scientists believe that infection with a yet-to-be microorganism may be an underlying factor leading to inflammatory bowel disease. These trends stimulated more research on strains of bacteria isolated from healthy gut flora as well as from the family of strains used to ferment foods and dairy products, resulting in the identification of a number of Lactobacillus, bifidobacteria, E. coli and yeast strains that had beneficial effects on human and animal health. 

Growing clinical evidence. The medical literature has reported positive results of the probiotics to:

• Prevent or treat antibiotic associated diarrhea, including that caused by Clostridium difficile
• Treat diarrhea, such as rotavirus in children
• Treat irritable bowel syndrome
• Prevent or treat infections in the urinary tract or female genital tract (e.g. vagina)
• Reduce recurrence of bladder cancer
• Treat or prevent pouchitis, a condition that follows removal of the colon to treat ulcerative colitis
• Treat or manage eczema, or atopic dermatitis, especially in children

The unmet need for better therapies for major GI diseases represents a large market opportunity for efficacy‐proven products, both in the prescription drug space as well as high value over‐the‐counter channel products. Many of these are chronic diseases that require life‐long management. Irritable bowel syndrome (IBS) afflicts as many as one in five Americans. One million Americans have inflammatory bowel disease, of which about half have Crohn's disease and the other half have ulcerative colitis. Both diseases have secondary complications, such as the pouchitis that may occur in ulcerative colitis patients after removal of their colons. There are also acute diseases, such as antibiotic‐associated diarrhea. Diarrhea occurs in 5% to 25% of individuals taking antibiotics, and 15% to 25% of these have the more serious form caused by C. difficile, especially problematic in the elderly. Today, there are no FDA‐approved probiotic products or live biotherapeutics for these diseases. In the future, probiotics may play an important role in new treatment approaches for these and other GI diseases.

Irritable Bowel Syndrome
Irritable bowel syndrome (IBS) is a chronic disorder without a known cause. Individuals may alternate between having periods of diarrhea or constipation, or may primarily suffer from only diarrhea or constipation. They have abdominal pain or discomfort, e.g. bloating, that may improve with a bowel movement or accompany a change in stool frequency or in stool form. Studies of gut function in affected individuals have shown alterations in gut motility and increased sensitivity and pain in response to gut distention. Some studies have shown an altered gut flora, including small bowel bacterial overgrowth. Symptoms may worsen with stress, anxiety or depression. IBS can interfere with quality of life. Most available treatments focus on controlling the primary symptoms of the individual sufferer, with variable success. Better understanding of the underlying cause of IBS and better treatments for IBS remain a high unmet need.

Inflammatory Bowel Disease
Unlike irritable bowel syndrome, inflammatory bowel diseases produce clear pathological changes in the gastrointestinal tract. Crohn's disease primarily affects the small intestine and shows inflammation through all of the tissue layers, while ulcerative colitis affects the large intestine or colon and the inflammation is restricted to the mucous lining. These are different diseases, but a disorder in immune system response is involved in both, resulting in the inflammation and accompanying symptoms, but the trigger for the abnormal response remains unknown. Treatments include antiinflammatory agents, corticosteroids, immune system modifier drugs, antibiotics and newer biologic drugs, including monoclonal antibodies that interrupt the abnormal responses in the immune system.

Pouchitis
While most individuals with ulcerative colitis are treated with medical therapy, about 25‐40 percent ultimately require surgery to provide adequate relief of their symptoms or because they develop a serious complication. The most common procedure is removal of the colon and rectum, which also requires an ileostomy. A newer procedure, called the ileoanal pouch anal anastomosis or restorative proctocolectomy, avoids the ileostomy and permits stool to pass through the anus. This is done by forming a small pouch from the small bowel to serve as a reservoir and connecting this to the anus. Typically this results in about six small bowel movements per day. Pouchitis is a complication that can occur after this restorative surgery. The pouch becomes inflamed, producing symptoms that may include diarrhea, abdominal pain, fever and more frequent, sometimes bloody stools. Pouchitis is treated with a course of antibiotics, but relapse occurs in some individuals, or the symptoms may become chronic, requiring long‐term antibiotic therapy or even removal of the pouch. Long‐term antibiotic use is undesirabacterial strains. There are presently no FDA‐approved therapies for this condition.

Antibiotic‐associated Diarrhea
Diarrhea that develops after or during a course of antibiotic treatment, typically at least 5‐10 days after starting the antibiotic, is called antibiotic‐associated diarrhea. The diarrhea can progress to pain, fever and bloody diarrhea. The cause is related to the effect of the antibiotic on the gastrointestinal tract's normal bacterial residents or the gut flora. Certain antibiotics are more frequently associated with this development. It can develop either in or out of the hospital setting, but hospital‐acquired illness can be more severe. A particularly serious form is caused by the bacterium Clostridium‐difficile, or C. difficile. Treatment includes stopping the causative antibiotic, but many individuals may require treatment with a second antibiotic, such as metronidazole, to eliminate the C. difficile. Unfortunately, resistant strains are becoming more and more prevalent, making development of alternate treatment approaches a necessity.

International Scientific Association for Probiotics and Prebiotics
Association of scientists involved in research on probiotics. Useful site for definitions, background materials and references related to potential health benefits, discussions of public policy regarding probiotics.

NIH NCCAM: An Introduction to Probiotics
National Center for Complementary and Alternative Medicine supports probiotics research through federal grants; this review provides good overview and additional references.

Probiotics and the Human Microbiome
Overview of NIH-funded research into the relationship between probiotics and the human microbiome. There are ten times as many bacterial cells in and on the human body as there are human cells; the microbiome is the community of all microorganisms (including bacteria, archaea, fungi, viruses, and phage) found on and in the human body. The Human Microbiome Project is exploring how these non-human microorganisms living in our body affect health and disease. The new techniques being applied offer a way to study the impact of probiotics on the types and numbers of bacteria and other microorganisms present in an individual.