The intestinal tract is a multifaceted environment where commensal bacteria both influence and are affected by the intestinal epithelium and underlying gut immune cells and the enteric nervous system. Recent studies have implicated gut microbes in having a role in brain development as well as in cognitive function and stress and anxiety-related behaviours. Gut microbes can influence this gut-microbial-brain axis via a number of pathways, including through the central nervous system, via the innate and adaptive immune system, and by modulating the hypothalamic-pituitary-adrenal axis (HPA). A major form of communication between gut microbes and the host comes from the production of a large number of metabolites and neuroactive compounds through microbial metabolic activity. For example, complex carbohydrates can be fermented in the colon by bacteria to produce short-chain fatty acids including butyrate, acetate, and propionate; these compounds are essential for gut health and they can also enter the blood and act in the brain through specific receptors. Certain microbes can generate neurotransmitters and neuromodulators, such as gamma-aminobutyric acid (GABA), norepinephrine, dopamine, acetylcholine, and serotonin. While ~90% of human serotonin is synthesized in enteric enterochromaffin cells in the gut and some strains of commensal bacteria produce serotonin, this neurotransmitter cannot cross the blood-brain barrier. However, its precursor, tryptophan can enter the brain. Tryptophan is an essential amino acid that is obtained from the diet. Tryptophan is metabolized by tryptophan hydroxylase to serotonin in the brain and the intestinal tract, or alternatively by indoleamine 2,3-dioxygenase to form kynurenine. Alterations in metabolic pathways related to tryptophan conversion can be induced by diet and result in alterations in tryptophan/serotonin ratios in the brain. The types of metabolic products that are produced by microbes are dependent upon the substrate available; thus, altering diet can have significant effects on gut microbial production of specific metabolites. Western-style diets that are high in fat and sugar and low in dietary fiber have been shown to have significant effects on stress- and anxiety-related behaviours, as well as altering cognitive function. These types of diets are associated with specific alterations in gut microbes and microbial function, including increases in Proteobacteria and reductions in production of short chain fatty acids. Another interesting finding is that the type of diet consumed by the host can significantly alter the ability of probiotics to modulate host physiological function, suggesting that production of certain metabolites may be critical for probiotic efficacy. Overall, it is clear that diet and commensal microbes interact at several different levels to alter host physiology through both direct and indirect mechanisms.