GPR109A expressed in immune cells as well as in colonic tissue is necessary for protection against colitis and colon carcinogenesis. Niacin suppresses colitis and colon cancer in a GPR109A-dependent manner. GPR109A is key in mediating the beneficial effects of gut microbiota and dietary fiber in colon. Niacin suppresses atherosclerosis by activating GPR109A in immune cells. GPR109A mediates butyrate effects in colon and is a critical molecular link between colonic bacteria and dietary fiber and the host.