Craig B. Webb,     Fort Collins, Colorado

Jan S. Suchodolski,     College Station, Texas

Definition

As defined by the World Health Organization, probiotics are “live microorganisms which when administered in adequate amounts confer a health benefit on the host” (FAO/WHO, 2001). Key components to this current definition are that the microorganisms are alive and that they are administered in sufficiently high amounts. Theoretically any bacterial strain that fulfills this definition can be classified as a probiotic. The microorganisms found most frequently in various products are lactic acid bacteria (i.e., Lactobacillus spp., Enterococcus spp., Streptococcus spp., and Bifidobacterium spp.). These traditionally have been associated with health benefits, although probiotic products feature a range of bacteria and yeasts (e.g., Escherichia coli strain Nissle 1917, Bacillus coagulans, Saccharomyces boulardii).

Many products on the market now are offered as a combination of probiotics and prebiotics (undigestible food ingredients added to diets to stimulate the growth of native probiotic bacteria). In such a case the product is named a symbiotic. The U.S. Food and Drug Administration does not regulate probiotics, and currently no governing agency oversees quality control, product content, or label claims.

Intestinal Microbiota

The intestinal microbiota constitutes a highly complex ecosystem composed of several hundreds to thousands of phylotypes. The total microbial load in the intestine is estimated to contain 10¹² to 10¹⁴ microbial cells. This bacterial population represents a huge degree of antigenic diversity containing approximately 100 times as many genes as the host genome. The microbiota is absolutely essential to the physiologic development and function of the GI tract. Studies of the GI tract in germ-free rodents show a decrease in vascularity, digestive enzyme concentration, and muscle wall thickness, decreased cytokine and immunoglobulin production, reduced lymphocyte numbers, and abnormal development of Peyer patches when compared with conventionally raised animals. In addition to normal development, the microbiota plays a key role in maintaining immunologic homeostasis within the GI tract, protecting the mucosa from pathogenic bacteria, and when necessary, coordinating the immunologic and inflammatory response to commensal and pathogenic organisms. It is this range of properties, central to maintaining GI health and function, that make the microbiota such a potent target for therapeutic intervention in cases of GI disease.

Mechanism of Action

Proper selection of probiotics requires an understanding that every bacterial strain, even if it is derived from the same bacterial species, can be different in its phenotypic, functional, and immunologic properties. This is one reason for the disparity in clinical reports: one study may report that a specific bacterial species caused clinical disease, whereas another study suggests that this same bacterial species may have beneficial properties. For example, Bifidobacterium animalis AHC7 significantly reduced duration of diarrhea in dogs (Kelley et al, 2009), whereas B. animalis ATCC 25527(T) caused duodenitis in interleukin-10–deficient mice (Moran et al, 2009). How probiotic strains impart beneficial effects remains poorly understood. Some probiotic strains have been shown to modulate the immune system and, in doing so, enhance IgA production and pathogen phagocytosis as well as stimulate the release of a variety of antiinflammatory cytokines. Other probiotic strains help restore or normalize the function of a leaky mucosal barrier and reduce abnormal intestinal permeability. Probiotics help protect the normal microbiota from pathogenic bacteria through the production of antimicrobial substances called bacteriocins and through competitive exclusion of pathogens by preventing adhesion, occupying binding sites, or consuming vital nutrients. Recent studies suggest that probiotics have no appreciable effect on the overall composition of the intestinal microbiota but are able to alter its metabolic function (Garcia-Mazcorro et al, 2011; McNulty et al, 2011).

To impart a health benefit to the host, a probiotic must be able to survive passage into the gut, be able to adhere to epithelial cells, and be able to proliferate within the GI tract. Even those probiotic strains that fulfill these criteria appear to colonize the GI tract for only relatively brief periods of time and usually are eliminated within a few days after the end of administration. Therefore, if the goal of therapy is to have a long-term impact on the patient, long-term daily administration of probiotics in high doses is required. Interestingly, colonization with probiotic strains does not occur in a subset of animals, most likely because of interindividual differences in microbiota composition at baseline that lead to competitive exclusion of probiotic strains and therefore potentially therapeutic failure.