Let’s suppose your summer backpacking trip takes a disastrous turn and you’re lost, out of food, and desperate. You think those berries look OK so you swallow them down—even though they’re as bitter as anything you’ve eaten before. It’s not long before you regret ignoring your taste buds and suspect you’ve eaten something poisonous.
Unless you’re a molecular biologist, you’re probably not thinking at that moment about the biochemistry churning in your gut. But a cacophony of cellular signals is actually assembling a second line of defense to keep your digestive system from absorbing toxins into your bloodstream.
Of course, your body doesn’t always win. But Dr. Timothy Osborne’s lab at Sanford-Burnham’s Lake Nona campus has outlined how bitter taste-sensing receptors on enteroendocrine cells in the gut, called T2Rs, automatically kick into gear when confronted with bitter-tasting substances. You might disregard the taste buds in your mouth, but your digestive system knows better and tries to make up for your recklessness.
Dr. Osborne’s lab had previously proposed that T2Rs trigger a hormone that stimulates the digestion of fat and protein and limits the absorption of dietary toxins. But exactly how was unclear.
The new experiments suggest that the hormone in turn stimulates neighboring enterocytes—the intestinal cells that absorb nutrients—to produce more of a protein called ABCB1, which transports a variety of chemicals—and toxins—out of cells.
Dr. Osborne and his colleagues, led by staff scientist Dr. Tae-Il Jeon, explained the protective mechanism this way in a paper published May 19 in Biochemical Journal:
“Our results indicate that T2Rs and ABCB1 play important interconnected roles in intestinal host defense: potentially toxic bitter-food substances are ‘sensed’ by T2Rs expressed in enteroendocrine cells, which secrete [a hormone] in response. Then, [the hormone] acts on enterocytes to limit absorption of the dietary derived T2R agonist by increasing ABCB1 efflux activity.”
In other words, if you swallow something bitter, T2R signaling in your gut triggers a chain of events that ends with an attempt by the transporter protein ABCB1 to keep the perceived dietary toxin out of your intestinal cells and ultimately out of your body.
In this study, the researchers surveyed several intestinal cell lines and found that one derived from a human colorectal cancer expresses both bitter taste receptors and several efflux transporters (mechanisms that pump toxic substances out of the cell). They then treated these cells with a bitter compound, triggering a response by T2R receptors.
The idea that ABCB1 transporter proteins limit the absorption of toxins detected by T2R receptors makes sense. It’s already known that the transporter protein is responsible for pumping antibiotics and chemotherapeutic drugs out of the cell. (In fact, increased ABCB1 activity might help explain why many cancer cells become resistant to chemotherapy.) Now scientists better understand how taste receptors in the gut also work with ABCB1 to provide a second line of defense against toxins—like poisonous berries.
Left: Rhodamine (green) is a substrate for the ABCB1 efflux pump. Right: When a bitter compound is added, ABCB1 pumps rhodamine out.
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Original paper:
Jeon TI, Seo YK, & Osborne TF (2011). Gut Bitter Taste Receptor Signaling Induces ABCB1 through a Mechanism Involving CCK. The Biochemical journal PMID: 21592089
