Diverse Classes of Bitter Phytochemicals Modulate Carbohydrate Metabolism and Immune Responses through Gastrointestinal Bitter Taste Receptors

Plant foods are the primary source of both carbohydrates and bioactive phytochemicals in unprocessed diets, yet most of the latter compounds are bitter. Since bitter principles are often aversive to the consumer, the food industry routinely removes them from diet through selective breeding and debittering. Bitter taste type 2 receptors (T2Rs) were first identified in the oral cavity, however recent findings suggest that they are also expressed throughout the gut. We therefore hypothesized that T2Rs are capable of perceiving bitter tasting plant‐based phenols, flavonoids, isoflavones, terpenes, and glucosinolates, to subsequently regulate glucose metabolism in anticipation of the incoming carbohydrate load. Indeed, gavage with bitter tastants followed by a gavage of glucose to lean and diet‐induced obese mice improved oral glucose tolerance, glucose utilization, GLP‐1 and insulin secretion. Additionally, they modulated levels of glucose transporters, insulin signaling, bioenergetic profiles, and immune responses throughout the mouse gastrointestinal tract. Taken together, this data suggests the gastrointestinal system perceives most, if not all, bitter phytochemicals as external signals to prime uptake and utilization of plant based carbohydrates. If confirmed in humans, these findings may explain how structurally diverse phytonutrients modulate carbohydrate metabolism, and highlight a critical role of bitter tasting phytochemicals in our diet.