Mechanisms of Action of Biotherapeutic Agents

Abstract

Although crude mixtures of microorganisms (e.g., fermented milk products or poultices of moldy bread) have been used since antiquity to treat infections, the first scientific description of a biotherapeutic effect was made at the beginning of this century by the Russian Metchnikoff for which he received the Nobel Prize in 1908. Metchnikoff demonstrated that certain species of bacteria were able to enhance the proliferation of Vibrio cholerae, whereas other species inhibited its growth (1). A preliminary, but fundamental distinction needs to be made between the concept of “prebiotic” and “probiotic.” A “prebiotic” can be defined as a nonmetabolized, nonabsorbed substrate that is useful for the host by selectively enhancing the growth and/or the metabolic activity of a bacterium or of a group of bacteria (e.g., lactulose effect on the colonic flora) (2). A “probiotic” or a “biotherapeutic agent” (BTA) is a living microorganism administered to promote the health of the host by treating or preventing infections owing to strains of pathogens (3,4). Both terms of “probiotic” and “biotherapeutic agent” have been used in the literature to describe microorganisms that exert antagonistic activity against pathogens in vivo (4,5). BTA seems to be the more appropriate term, because it denotes a microorganism having therapeutic properties (3). Ideally, BTA should be innocuous, act against pathogens by multiple mechanisms to minimize the development of resistance (Table 1), and marshal host defenses to destroy the invading pathogen. An additional desirable property would be an immediate onset of action (in contrast to a vaccine that takes several weeks to stimulate antibody production).