Sugar preference isn’t just a matter of taste - it’s deeper than that
By Karl Leif
Bates for Duke Today
January 13.
2022 -- DURHAM, N.C. – Your taste buds may or may not be able to tell real
sugar from a sugar substitute like Splenda, but there are cells in your
intestines that can and do distinguish between the two sweet solutions. And
they can communicate the difference to your brain in milliseconds.
Not long after
the sweet taste receptor was identified in the mouths of mice 20 years ago,
scientists attempted to knock those taste buds out. But they were surprised to
find that mice could still somehow discern and prefer natural sugar to
artificial sweetener, even without a sense of taste.
The answer to
this riddle lies much further down in the digestive tract, at the upper end of
the gut just after the stomach, according to research led by Diego Bohórquez,
an associate professor of medicine and neurobiology in the Duke University
School of Medicine.
In a paper
appearing Jan. 13 in Nature Neuroscience, “we’ve identified the cells that make
us eat sugar, and they are in the gut,” Bohórquez said. Infusing sugar directly
into the lower intestine or colon does not have the same effect. The sensing
cells are in the upper reaches of the gut, he said.
Having
discovered a gut cell called the neuropod cell, Bohórquez with his research
team has been pursuing this cell’s critical role as a connection between what’s
inside the gut and its influence in the brain. The gut, he argues, talks
directly to the brain, changing our eating behavior. And in the long run, these
findings may lead to entirely new ways to treat diseases.
Originally
termed enteroendrocrine cells because of their ability to secrete hormones,
specialized neuropod cells can communicate with neurons via rapid synaptic
connections and are distributed throughout the lining of the upper gut. In
addition to producing relatively slow-acting hormone signals, the Bohórquez
research team has shown that these cells also produce fast-acting
neurotransmitter signals that reach the vagus nerve and then the brain within
milliseconds.
Bohórquez said
his group’s latest findings further show that neuropods are sensory cells of
the nervous system just like taste buds in the tongue or the retinal cone cells
in the eye that help us see colors.
“These cells
work just like the retinal cone cells that that are able to sense the
wavelength of light,” Bohórquez said. “They sense traces of sugar versus
sweetener and then they release different neurotransmitters that go into
different cells in the vagus nerve, and ultimately, the animal knows ‘this is
sugar’ or ‘this is sweetener.’”
Using
lab-grown organoids from mouse and human cells to represent the small intestine
and duodenum (upper gut), the researchers showed in a small experiment that
real sugar stimulated individual neuropod cells to release glutamate as a
neurotransmitter. Artificial sugar triggered the release of a different
neurotransmitter, ATP.
Using a
technique called optogenetics, the scientists were then able to turn the
neuropod cells on and off in the gut of a living mouse to show whether the
animal’s preference for real sugar was being driven by signals from the gut.
The key enabling technology for the optogenetic work was a new flexible
waveguide fiber developed by MIT scientists. This flexible fiber delivers light
throughout the gut in a living animal to trigger a genetic response that
silenced the neuropod cells. With their neuropod cells switched off, the animal
no longer showed a clear preference for real sugar.
“We trust our
gut with the food we eat,” Bohórquez said. “Sugar has both taste and nutritive
value and the gut is able to identify both.”
“Many people
struggle with sugar cravings, and now we have a better understanding of how the
gut senses sugars (and why artificial sweeteners don’t curb those cravings),”
said co-first author Kelly Buchanan, a former Duke University School of
Medicine student who is now an Internal Medicine resident at Massachusetts
General Hospital. “We hope to target this circuit to treat diseases we see every
day in the clinic.”
In future
work, Bohórquez said he will be showing how these cells also recognize other
macronutrients. “We always talk about ‘a gut sense,’ and say things like ‘trust
your gut,’ well, there’s something to this,” Bohórquez said.
“We can change
a mouse’s behavior from the gut,” Bohórquez said, which gives him great hope
for new therapies targeting the gut.
Support for
this study came from the National Institutes of Health (R21 AT010818, DP2
MH122402, R01 DK131112), the Howard Hughes Medical Institute, the Hartwell
Foundation and the MIT McGovern Institute.
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