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.