The role of the intestine in human health and disease has historically been neglected and was mostly attributed to digestive and absorptive functions. In the past two decades, however, discoveries related to human nutrition and intestinal host-microbe reciprocal interaction have established the essential role of intestinal health in the pathogenesis of chronic diseases and the overall wellbeing. That transfer of gut microbiota could be a means of disease phenotype transfer has revolutionized our understanding of chronic disease pathogenesis. This narrative review highlights the major concepts related to intestinal microbiota, metabolism, and metabolome (3M) that have facilitated our fundamental understanding of the association between the intestine, and human health and disease. In line with increased interest of microbiota-dependent modulation of human health by dietary phytochemicals, we have also discussed the emerging concepts beyond the phytochemical bioactivities which emphasizes the integral role of microbial metabolites of parent phytochemicals at extraintestinal tissues. Finally, this review concludes with challenges and future prospects in defining the 3M interactions and has emphasized the fact that, it takes 'guts' to stay healthy.
