Mind-brain-body-gene framework, including the role of chrononutrition, is probably implicated in the genesis of functional gastrointestinal diseases (FGIDs). Emphasis was placed on psychosocial dysregulation, the bridging of the Cartesian Gap, and chronobiology viz. the way circadian and other rhythmic structures of the brain, e.g. suprachiasmatic nucleus, and gastrointestinal tract interact partially explaining the phrase “we are what and when we eat”. Chronobiological concepts of strain and stress in the context of sensory pain and the time-qualified network of gut hormones and neuropeptides are discussed for melatonin, serotonin, ghrelin, leptin, vasoactive intestinal peptide, neuropeptide Y, orexins, and others. The Tsimtsoum evolutionary aspects of diet from Palaeolithic to modern man in the context of increased omega-3/omega-6 fatty acid ratio reduces proinflammatory responses, important in pre-metabolic syndrome and cardiovascular disease, and protects against neuropsychic disorders possibly (FGIDs). Gut micro-organisms either affect the lumen (food substrates) and mucosa, where they reflect immunological, metabolic and physiologic function and importance of these two ecosystems. The interaction between enteric and autonomic systems and associated regulatory effects on proliferative and secretary epithelial dynamics and optimization of permeability for food nutrients and possible modulation of inflammation is an active area of research. In summary, this paper has focussed on the need to understand the multifarious aspects of biological and environmental variability, principally hormones and neuropeptides, in the possible genesis of (FGIDs).