The intestinal microbiota is a group of bacteria living in the gut in a symbiotic relationship of both commensal and mutualistic types. The gut microbiota acts as a barrier versus detrimental microbes using competition for nutrients and ecological binding site occupancies and antimicrobial substances production. Microbiota composition in the gastrointestinal tract reflects the physiological properties in a given region and is stratified on both a transverse and longitudinal axis. Diet contributes to shaping the gut microbial structure and influences the metabolic functions of the host. Alteration of the microbial structure and function is related to the pathogenesis of various disorders. Fermentation occurs in the gut, and bacteria break down indigestible carbohydrates to acetate, lactate, short-chain fatty acids, and other metabolites. Butyrate and propionate can regulate intestinal physiology and immune function whereas acetate acts as a substrate for lipogenesis and gluconeogenesis. Overall, growing evidence suggests a contributing role of the gut microbiota in predicting the personalized host response to dietary interventions. However, further studies are needed to decipher downstream mechanisms by which microbe's sense and react to specific food-derived compounds and their downstream impact on the host. Additionally, integration of multi-omics strategies not only limited to microbiome analyses but in combination with proteomics, metabolomics, transcriptomics, and epigenomics are required to identify potential clinical predictors of person-specific response, using advanced machine-learning algorithms and accurate validation methods.