It has become known why treatment of chronic constipation often fails

Scientists from Nagoya University have discovered two species of gut bacteria that appear to work together to destroy the protective mucus layer of the colon, thereby contributing to the development of chronic constipation. These are Akkermansia muciniphila and Bacteroides thetaiotaomicron. The study was published in the journal Gut Microbes.

The mucus layer lines the walls of the colon and is also a component of fecal matter. It retains moisture, facilitates the movement of intestinal contents, and protects the epithelium from bacteria. When this barrier thins, stool becomes dry and dense.

As the study showed, the destruction occurs in stages. First, B. thetaiotaomicron produces the enzyme sulfatase, which removes sulfate groups from mucin. Normally, these groups protect the mucus from breakdown. After this "protection" is removed, A. muciniphila begins to actively digest the mucin.

As a result, the amount of mucus decreases, stool loses moisture and becomes hard, which leads to constipation. According to the authors, in such cases the problem lies not in slowed peristalsis, as is commonly believed, but in the loss of the mucus barrier. This is precisely why standard laxatives and medications that stimulate intestinal motility often prove ineffective.

The researchers also discovered a connection with Parkinson's disease. In patients with this diagnosis, who often suffer from constipation decades before the onset of tremor, levels of mucus-destroying bacteria were elevated. Previously, such symptoms were mainly attributed to nervous system damage.

"We genetically modified B. thetaiotaomicron so that it could not activate the sulfatase enzyme that removes sulfate groups from mucin," said lead author Tomonari Hamaguchi from Nagoya University. "When we placed these modified bacteria together with Akkermansia muciniphila in the intestines of germ-free mice, the animals did not develop constipation: the mucin remained protected and intact."

The experiment showed that blocking sulfatase activity prevents destruction of the mucus layer. According to the authors, this opens up the possibility of developing drugs targeting specifically bacterial enzymes.