Recent advances in our ability to identify and characterize the human microbiota have transformed our appreciation of the function of the colon from an organ principally involved in the reabsorption of secretory fluids to a metabolic organ on a par with the liver. High-throughput technology has been applied to the identification of specific differences in microbial DNA, allowing the identification of trillions of microbes belonging to more than 1000 different species, with a metabolic mass of approximately 1.5 kg. The close proximity of these microbes with the mucosa and gut lymphoid tissue helps explain why a balanced microbiota is likely to preserve mucosal health, whereas an unbalanced composition, as seen in dysbiosis, may increase the prevalence of diseases not only of the mucosa but also within the body due to the strong interactions with the gut immune system, the largest immune organ of the body. Such abnormalities have been pinpointed as etiological factors in a wide range of diseases, including autoimmune disorders, allergy, irritable bowel syndrome, inflammatory bowel disease, obesity, and colon cancer. Recognition of the strong potential for food to manipulate microbiota composition has opened up new therapeutic strategies against these diseases based on dietary intervention.