Bugs as Drugs: Prebiotics and Probiotics in Gastroenterology

Presenter: Eamonn Quigley, MD, National University of Ireland at Cork

Dr. Quigley’s lecture served as early notice that this year’s ACG was going to take prebiotics and probiotic therapies very seriously-this was one of many sessions the College programmed on the topic. Dr. Quigley summarized current promising research on prebiotics and probiotics as treatment for infectious, inflammatory, and even malignant conditions of the GI tract.

The human gut bacterial population (“microbiota” or “microflora”) is typically comprised of 300 to 500 species. This diversity is a marker for intestinal health, and it decreases in obese or infected persons and in those with inflammatory bowel disease (IBD). Most of us are aware that non-pathogenic bacteria prevent overgrowth of pathogens by out-competing them, but emerging research has documented a much broader functional role for the microbiota, which…

• Contributes nutrition by producing folate and vitamin K, and by converting unabsorbed dietary sugars and alcohols into short-chain fatty acids (SCFAs). SCFAs serve as an energy source for colonic mucosal cells.

• Modulates growth: SCFAs promote the growth of intestinal epithelial cells while controlling their proliferation and differentiation.

• Prevent invasive infection by maintaining the integrity of the epithelial barrier.

• Prevent infection above and beyond simple competition by:
      » Producing fatty acids and peroxides that are nonspecifically inhospitable to pathogenic bacteria
      » Inhibiting pathogenic bacteria’s movement across the gut wall (thereby preventing translocation)
      » Enhancing mucosal barrier function and adhering to mucosal surfaces
      » Signaling the epithelium and immune system to modulate immune and inflammatory responses
      » Producing highly specific bacteriocins that inhibit or kill pathogenic bacteria

The entire bacterium may not be needed to confer benefit-dead cells, bacterial components, peptides, metabolites, or even bacterial DNA may be biologically active. Current research has studied two approaches to “bugs as drugs:” prebiotics, and probiotics:

• Prebiotics are non-digestible but fermentable foods or preparations that stimulate growth or activity of beneficial bacteria. Examples include oligosaccharides in human breast milk, inulin-like fructans and fructo-oligosaccharides (FOS). Fiber and lactulose also have some prebiotic effect. Oligosaccharides in breast milk account for part of the immunologic benefits of breast-feeding. Fructans and FOS are found in wheat, onion, chicory, garlic, leeks, artichokes, and bananas. These reach the colon intact, where they undergo fermentation. Dr. Quigley notes that much of the evidence favoring prebiotics has been shown in experimental animal studies and small human trials, which have suggested some benefit for prebiotics in inflammatory bowel disease , IBS, and colon cancer. There are no high-quality prospective human studies to date.

• Probiotics are foods or preparations that contain live organisms thought to confer a health benefit to the host. Commercially-available probiotic preparations available in health food stores and supermarkets have not been subjected to high-quality study in humans. Concerns persist about the products’ stability over storage time, and whether they actually contain the viable bacteria as labeled. But good evidence for a role for probiotics exists in a number of areas:
      » Infectious and antibiotic associated diarrhea: Meta-analysis suggests value for Saccharomyces boulardii,  Lactobacillus acidophilus and bulgaricus, Enterococcus faecium SF68, Bifidobacterium longum, and Lactobacillus GG in preventing bacteria-associated diarrhea. There is not sufficient evidence to justify routine probiotics for high-risk persons starting antibiotics.
      » IBD: Several studies lend support for a role for probiotics in maintaining remission in ulcerative colitis (UC). There is weaker evidence for a role in inducing remission in mild-to-moderately active UC. The strongest evidence for a role in UC treatment is seen in a study of pouchitis (inflammation in the neo-rectum of UC patients post-total colectomy and ileo-anal pouch procedure). The probiotic used was VSL#3-mixture of eight different bacterial strains. There is currently no evidence base supporting the use of probiotics in Crohn’s disease.
      » Functional GI disorders: Minimal evidence base, but some promise in irritable bowel syndrome (IBS) has been seen for Bifidobacterium infantis 35624, which appears to improve both pain and global symptoms. Other strains tend to improve only one or two of the many symptoms experienced by IBS patients.

If ACG 2011 had a recurrent theme, it was nicely summed up in this lecture: probiotic treatments are coming. Scientific evidence is accumulating for this approach, and patients will likely embrace it as a “natural” remedy. Primary care physicians should carefully follow this emerging trend-it holds promise for some of our most challenging patients with chronic disease. The subject was a central topic at this national specialty conference, but if these modalities become the standard of care, it is likely that primary care offices will provide most of the treatment.