Scientists finally explain why chronic constipation treatments often fail

The findings, published in Gut Microbes, help explain why common treatments often fail for millions of people living with persistent constipation.

The research also uncovered an important link to Parkinson's disease. Patients with Parkinson's, who often experience constipation decades before tremors begin, were found to have higher levels of these mucus-degrading bacteria. Constipation in Parkinson's has traditionally been blamed on nerve damage. However, the new results suggest that gut bacteria may also play a meaningful role in driving these early symptoms.

Gut Mucus and Its Role in Chronic Constipation

Constipation is one of the most common digestive complaints. It is typically attributed to slow movement in the intestines, meaning food and waste do not travel through the digestive tract quickly enough. But this explanation does not account for every case.

Some individuals develop constipation without a clear cause, a condition known as chronic idiopathic constipation (CIC). People with Parkinson's disease frequently suffer from severe, treatment-resistant constipation, although it is classified separately from CIC. In many cases, patients struggle with constipation for 20 or even 30 years before movement symptoms appear, leaving doctors without a clear explanation.

Rather than concentrating on nerve or muscle function, the researchers turned their attention to colonic mucin. This gel-like substance forms a protective coating along the walls of the large intestine and is also mixed within stool. Colonic mucin keeps stool moist, allows it to pass more easily, and shields the intestinal lining from bacteria.

The team discovered that the two bacteria dismantle this protective barrier in a step-by-step process. First, B. thetaiotaomicron produces enzymes that remove sulfate groups attached to mucin. These sulfate groups normally act as a defense, preventing bacteria from breaking it down. Once those protective groups are removed, A. muciniphila can digest the exposed mucin.

When mucin levels drop too low, stool loses moisture and becomes hard and dry, leading to constipation. Because the root problem is the loss of this protective mucus rather than sluggish intestinal movement, standard laxatives and drugs designed to stimulate gut motion may not provide relief.

Targeting a Bacterial Enzyme as a New Treatment Strategy

To test whether blocking this process could prevent constipation, the researchers altered one of the bacteria.

"We genetically modified B. thetaiotaomicron so it could no longer activate the enzyme sulfatase that removes sulfate groups from mucin," Tomonari Hamaguchi, lead author and lecturer from the Academic Research & Industry-Academia-Government Collaboration Office at Nagoya University, explained.

"We put these modified bacteria into germ-free mice together with Akkermansia muciniphila, and surprisingly the mice did not develop constipation; the mucin stayed protected and intact."

The experiment showed that when the sulfatase enzyme was disabled, the bacteria could no longer break down mucin. This suggests that medications designed to block sulfatase activity might help treat what researchers describe as bacterial constipation in people.

For the millions dealing with chronic, treatment-resistant constipation, including many living with Parkinson's disease, the findings point toward a new approach. Instead of focusing only on gut movement, future therapies may aim to protect the colon's mucus barrier and address the underlying microbial cause.