Chronic constipation is one of the most common gastrointestinal complaints worldwide, yet it remains one of the least well understood. Depending on how it is defined, studies estimate that anywhere from two to 35 percent of adults experience constipation at some point, often with significant impacts on quality of life, mental health, and healthcare costs. Clinically, constipation has long been framed as a disorder of lifestyle, diet, or bowel motility — blamed on low fiber intake, physical inactivity, medications, aging, or sluggish intestinal movement. But for millions of patients, these explanations fall short.
That gap is especially stark in chronic idiopathic constipation (CIC), where symptoms persist despite the absence of an identifiable cause, and in Parkinson’s disease (PD), where severe constipation can emerge 10 to 20 years before tremors or movement problems appear. In both groups, standard therapies — including fiber supplements, laxatives, and pro-motility drugs — often provide little relief. These therapeutic limitations highlight the need to explore alternative mechanisms underlying constipation, with growing attention to the role of gut microbiota.
Now, researchers at Nagoya University have turned their attention to the colonic mucus layer, a protective lining that keeps stool hydrated and mobile. Their findings, published in Gut Microbes, suggest that chronic constipation may, in many cases, be driven by a cooperative microbial process that strips the colon of its lubricating barrier — reframing constipation as a disease of mucus loss and microbial imbalance rather than simple slow transit.
A problem with the microbiome
Both A. muciniphila and B. thetaiotaomicron were significantly more abundant in patients with Parkinson's disease and chronic idiopathic constipation compared to healthy controls.
—Tomonari Hamaguchi, Nagoya University.
The team focused on two gut bacteria that appear to play a central role in mucus degradation: Akkermansia muciniphila and Bacteroides thetaiotaomicron. A. muciniphila is consistently elevated in Parkinson’s patients across multiple countries, and has been linked to firmer stool and slower colonic transit, as well as gut dysbiosis in constipation cohorts. Likewise, Bacteroides species are often abundant in the colonic mucosa of constipated patients, though their fecal abundance varies across studies.
“Both A. muciniphila and B. thetaiotaomicron were significantly more abundant in patients with Parkinson's disease and chronic idiopathic constipation compared to healthy controls,” Tomonari Hamaguchi, lead author and microbiologist at Nagoya University, told DDN. “We also found that individuals with higher A. muciniphila had lower fecal mucin and moisture — hallmarks of constipation.”
Colonic mucus isn’t easy to break down. Unlike mucus in the stomach or small intestine, colonic mucin carries terminal sulfate groups — chemical modifications that act as a protective shield, preventing most gut bacteria from digesting it. However, the researchers discovered that this defense can be overcome when the two bacteria act in sequence to dismantle the mucus barrier.
In this two-step process, B. thetaiotaomicron produces sulfatase enzymes that strip away the terminal sulfate groups protecting colonic mucin. Once they’re removed, the underlying mucin structure is exposed — creating an opening for A. muciniphila, which can then consume the mucin.
“Akkermansia muciniphila is the key player. It specializes in degrading mucin, the protective mucus layer of the colon,” said Hamaguchi. “However, it needs a sulfatase-producing partner to remove these sulfates first. In our study, Bacteroides thetaiotaomicron served this role, but other Bacteroides species, such as B. caccae and B. uniformis, also possess sulfatases and could potentially substitute. So, the mechanism is cooperative: A. muciniphila is the driver, while the sulfatase-providing partner may vary between individuals.”
A therapeutic opportunity
While there’s a clear connection between these bacteria and mucus degradation, it still wasn’t clear whether their elevated levels in PD and CIC patients were causing constipation or were simply a consequence of it. To find out, the team induced constipation in healthy mice using loperamide, a drug that slows bowel movement, and with a fiber-deprived diet. In both models, stool output decreased as expected, confirming constipation. However, neither approach reproduced the bacterial overgrowth seen in patients, suggesting that constipation alone does not drive the expansion of these microbes.
Next, the researchers asked whether treatments could be responsible. They compared constipation patients who responded to laxatives with those who did not — and found no differences in bacterial levels between the two groups.
“When we induced constipation in mice or looked at laxative use in patients, we didn’t see the same bacterial overgrowth,” Hamaguchi said. “That tells us these bacteria are unlikely to be a secondary effect of constipation, diet, or medication. Their enrichment is likely an independent factor contributing to constipation.”
Finally, the team tested whether blocking the bacteria’s ability to degrade mucus could prevent constipation altogether. They genetically modified B. thetaiotaomicron so it could no longer activate sulfatase, the enzyme that removes protective sulfate groups from colonic mucin. Remarkably, when these modified bacteria were introduced into germ-free mice alongside A. muciniphila, the mice did not develop constipation, and their colonic mucus remained intact.
The experiment showed that blocking sulfatase activity alone was enough to prevent mucus degradation, even in the presence of a mucin-hungry bacterium like A. muciniphila. This finding points to sulfatase as a promising drug target — one that could stop constipation at its source rather than treating symptoms downstream.
Future possibilities
This evidence opens the door to entirely new ways of treating and diagnosing chronic constipation, in both PD and CIC patients. By targeting the bacteria responsible for breaking down the colon’s protective mucus layer, researchers could preserve the natural lubrication of the gut, keeping stool hydrated and easier to pass. Potential strategies might include drugs that block bacterial sulfatase enzymes, therapies that selectively reduce mucus-degrading bacteria, or probiotics that restore a healthier microbial balance.
Beyond treatment, these findings could also improve diagnosis and patient stratification. Measuring levels of A. muciniphila in stool could help identify individuals whose constipation is driven by microbial activity rather than slow gut movement, allowing doctors to tailor interventions more precisely.
For patients who have struggled for years with standard therapies, this research represents a shift in thinking and could finally offer them tangible relief by addressing the root cause of their condition rather than just managing symptoms.
