Scientists Uncover Why Chronic Constipation Treatments Often Fail

Scientists at Nagoya University have identified a previously unrecognized bacterial partnership in the gut that may contribute to chronic constipation. Their findings, published in Gut Microbes, show that two microbes, Akkermansia muciniphila and Bacteroides thetaiotaomicron, work together to degrade the protective mucus layer lining the colon.

This mucus, made largely of colonic mucin, acts as a lubricant that keeps stool soft and easy to pass while shielding the intestinal wall from bacterial invasion. The researchers discovered that the two bacteria dismantle this barrier in a coordinated, stepwise process. First, B. thetaiotaomicron produces an enzyme called sulfatase, which removes protective sulfate groups from mucin. Once these defenses are stripped away, A. muciniphila can digest the exposed mucus. When mucin levels drop too low, stool loses moisture, becomes dry and hard, and constipation develops.

The study also revealed a notable connection to Parkinson's disease. Patients with Parkinson’s—many of whom experience severe constipation decades before motor symptoms appear—were found to have elevated levels of these mucus-degrading bacteria. This suggests that microbial imbalance, not just nerve damage, may contribute to early digestive symptoms in the disease.

To test a potential solution, researchers genetically modified B. thetaiotaomicron so it could no longer produce the sulfatase enzyme. When introduced into germ-free mice alongside A. muciniphila, the animals did not develop constipation, and their mucus layer remained intact.

These findings suggest that targeting bacterial sulfatase activity could offer a new treatment strategy—one that focuses on protecting the colon’s mucus barrier rather than simply stimulating bowel movement.

REFERENCE: Tomonari Hamaguchi, Noriaki Gibo, Misuzu Ohara, Mikako Ito, Tomoyuki Ogura, Jun-Ichi Takeda, Hiroshi Nishiwaki, Fei Zhao, Ryo Kinoshita-Daitoku, Masashi Hattori, Koji Nonogaki, Tetsuya Maeda, Kenichi Kashihara, Yoshio Tsuboi, Masaaki Hirayama, Mitsuhiro Fujishiro, Hiroki Kawashima, Kinji Ohno. Bacterial constipation: Mucin-degrading intestinal commensal bacteria cause constipation. Gut Microbes, 2026; 18 (1) DOI: 10.1080/19490976.2025.2596809