The microbiome located in the human gastrointestinal tract (GIT) comprises the largest community (diverse and dense) of bacteria, and in conjunction with a conducive internal milieu, promotes the development of regulated pro- and anti-inflammatory signals within the GIT that promotes immunological and metabolic tolerance. In addition, host-microbial interactions govern GIT inflammation and provide cues for upholding metabolic regulation in both the host and microbes. Failure to regulate inflammatory responses can increase the risk of developing inflammatory conditions in the GIT. Here, we review clinical studies regarding the efficacy of probiotics/prebiotics and the role they may have in restoring host metabolic homeostasis by rescuing the inflammatory response. The clinical studies reviewed included functional constipation, antibiotic-associated diarrhoea, Clostridium difficile diarrhoea, infectious diarrhoea/gastroenteritis, irritable bowel syndrome, inflammatory bowel diseases and necrotizing enterocolitis. We have demonstrated that there was an overall reduction in risk when probiotics were administered over placebo in the majority of GIT inflammatory conditions. The effect size of a cumulative reduction in relative risk for the GIT conditions/diseases investigated was 0.65 (0.61-0.70) (z = 13.3); p < 0.0001 that is an average reduction in risk of 35 % in favour of probiotics. We also progress a hypothesis that the GIT comprises numerous micro-axes (e.g. mucus secretion, Th1/Th2 balance) that are in operational homeostasis; hence probiotics and prebiotics may have a significant pharmacobiotic regulatory role in maintaining host GIT homeostasis in disease states partially through reactive oxygen species signalling.

Mental health is closely linked to physical health. Depression (e.g., major depression) is highly prevalent worldwide and a major cause of disability. In a subgroup with treatment-resistant depression, standard pharmacotherapy interventions provide small if any incremental improvement in patient outcomes and may also require the application of an alternate approach. Therefore, in addition to the standard pharmacotherapies prescribed, patients will also be advised on the benefits of psychological counseling, electroconvulsive therapy, and transcranial magnetic stimulation or increasing physical activity and reducing harmful substance consumption. Numerous nutraceuticals have a beneficial role in treatment-resistant depression and include, herbal medicines of which Hypericum perforatum is the best studied, omega-3 fatty acid preparations, S-Adenosyl-L-Methionine (SAMe), various mineral formulations (e.g., magnesium) and folate (singly or in combination with B group vitamins) are prescribed to a lesser extent. Furthermore, a largely neglected area of research activity has been the role of live probiotic cultures that contribute to repairing dysbiosis (a leaky gut barrier abnormality) in the gastrointestinal tract (GIT). In this commentary, we build a hypothesis that in addition suggests that GIT metabolites that are elaborated by the microbiome cohort may provide novel and significant avenues for efficacious therapeutic interventions for mood disorders. We posit that the microbiome in the gastrointestinal tract is implicit as an important participant for the amelioration of adverse mood conditions via the diverse metabolic activities provided by live beneficial bacteria (probiotics) as an active adjuvant treatment. This activity is in part triggered by a controlled release of reactive oxygen species (ROS) and hence further questions the antioxidant/oxidative stress postulate.

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. Drug Dev Res 74 : 353-359, 2013.