Probiotic-Derived Factors: Probiotaceuticals?

Abstract

Probiotics are broadly defined as living, nonpathogenic microorganisms (usually bacteria) which, when administered in sufficient numbers, exert a positive influence on host health. Mechanisms of probiotic action described to date include adhesion to the intestinal-lumen interface; competition with pathogens for nutrients, receptor binding, and colonization; enhancement of mucosal barrier function; promotion of innate and adaptive immune responses; elaboration of bacteriocins; and modulation of cell kinetics via alterations in the proliferation to apoptosis ratio, with further mechanisms of action gradually becoming elucidated (1). However, it is rare for any individual probiotic to act through a single mechanism, and its biological impact is further influenced by factors including dose, frequency of administration, and the composition of the enteric microflora. Perhaps not surprisingly, given the vast numbers of bacterial species, strains, and substrains in the microflora, the number of potential probiotics, and the complexity of their mechanism(s) of action, is equally diverse. Although Escherichia coli 1917, the first probiotic species to be described, was identified almost a hundred years ago, only recently has there been an upsurge in research into the properties of probiotic-derived factors. Such agents could potentially achieve therapeutic benefit while avoiding risks associated with the administration of live bacteria. It is in this context that Heuvelin et al. (2), in the January issue of this journal, explore the biological properties of factors released by the probiotic, Bifidobacterium breve C50. In a 2004 rodent study of experimental inflammatory bowel disease (IBD) utilizing VSL#3, a commercially available combination of 8 probiotic species, Rachmilewitz et al. (3) described protective effects mediated by probiotic DNA. Moreover, live microorganisms were not required to attenuate the colitis, as nonviable probiotics could mediate the antiinflammatory effect. Probiotic-derived factors have since been described as capable of exerting probiotic activities through each of the previously described mechanisms. However, it is important to distinguish between the concept of probiotic, which is necessarily based on the ingestion of live microorganisms, and the concept of microorganism-derived bioactive compounds that may have useful applications in nutrition and medicine. Bioactive compounds of bacterial or yeast origin, (antibiotics, for example), have been utilized in medicine for decades. Although there are many bacteria-derived products capable of inducing a health benefit, the concept of probiotic is only attributed to microorganisms administered as viable forms, providing the opportunity for a symbiotic relationship between the host, and resident, or in-transit, microorganisms.