Given that the gastrointestinal tract (GIT) mucosa is one of the most metabolically active tissues, basic research spanning over the last three decades has also recognized that the idea that microbes are to be eliminated at all costs is flawed. This research has significantly redefined the exchanges between gut-dwelling microbes and vertebrates by recognizing that the microbial active cohort and its mammalian host have shared critical coevolutionary metabolic interactions that span millennia. As such, the GIT microbiome may also be the site for the production of novel molecules that exhibit therapeutic efficacy, realizing a long held notion that the GIT commensal cohort is a site for pharmacobiotic activity. Indeed basic and clinical research aimed at manipulating the GIT microbiota demonstrates the potential that exists in the microbiological production of nutra-pharmaceuticals. In this commentary/brief review we develop a hypothesis that multi-strain probiotics can influence the commensal microbiota in the GIT in a beneficial manner by upregulating the pharmacobiotic potential of the microbial cohort. Furthermore, we illustrate this with a biologically plausible posit for the beneficial use of a multi-strain probiotic to prevent and treat Clostridium difficile–associated diarrhea. As such we further posit in this review that microbial cohorts (e.g., in the GIT) present bacterial communities with an overwhelming accuracy at identifying pathogens/pathogenic states than do current diagnostic methodologies; this then plausibly leading to future microbe directed site-specific therapeutics.