In lab, Mayo traces two gut signals linked to IBS-related constipation

In the Mayo Clinic Microbiomics Program laboratory, researchers worked through a chain that begins with bacterial chemistry and ends with gut movement. Their new study found that two microbial signals, hypoxanthine and butyrate, cooperate inside intestinal cells to regulate the process.

Hypoxanthine prompts enterochromaffin cells — specialized cells lining the intestine — to release serotonin, a chemical messenger that helps move food through the digestive tract. Butyrate takes a supporting role: it primes those cells to respond more strongly to hypoxanthine, amplifying the signal rather than replacing it.

The researchers tested the mechanism at several scales, using laboratory-grown intestinal cells, organoids — miniature gut models — intestinal tissue and genetically altered bacteria. They identified enterochromaffin cells as meeting points where several microbial messages can be combined before the gut responds. The findings were published in the Proceedings of the National Academy of Sciences.

The connection to constipation-predominant irritable bowel syndrome comes from earlier Mayo Clinic research, which found lower levels of both molecules in patients with the condition. That does not show that replacing them will treat patients. The current result is a laboratory mechanism, and the researchers still need to test whether restoring complementary signals improves intestinal movement.

And so what, concretely? The work points toward microbiome treatments designed around a patient’s missing combination of signals, rather than a single bacterium or molecule. For people with IBS-related constipation, that could eventually mean a more targeted way to restore gut function; for now, it is a research direction, not an available therapy.