Epidemiological studies show that ingestion of whole plant foods, vegetables, fruit and whole grain cereals, is inversely related with chronic disease. Conversely, poor diet, typified by the modern Western style diet, rich in refined carbohydrates, red meat, processed foods and low in whole plant foods and fiber is associated with increased disease risk. Aberrant gut microbiota profiles define the intestinal microbiota in obesity, diabetes (both type 1 and type 2), intestinal cancer and autoimmune disease. Similarly, microbial metabolites of red meat derived choline and L-carnitine have been directly linked with CVD. Importantly, the gut microbiota too is critical for rendering some of the most important plant food molecular components, non-digestible carbohydrates and polyphenols, into biologically available and biological active intermediates. This raises the intriguing possibility that not only is gut microbiota whole plant food metabolism associated with protection from chronic disease but that we may be able modulate the gut microbiota and their activities using whole plant foods. Our ecological studies examining the gut microbiota of children growing up in rural Africa with those in urban Italy show that diet and dietary transition can dramatically impact on the gut microbiome. Similarly, we have shown that dietary intervention with certain whole plant foods can improve recognised biomarkers of metabolic disease and concomitantly modulate gut microbiota profiles. Here we discuss how whole plant foods may be employed to modulate the gut microbiome giving specific examples from both in vitro models systems and human studies