Researchers at Tohoku University Graduate School of Medicine uncovered an unexpected possibility involving a drug that has long been used to treat constipation. In a clinical trial, the medication lubiprostone appeared to slow the decline of kidney function in patients with moderate CKD, raising hopes for an entirely new approach to kidney disease treatment.

“We noticed that constipation is a symptom that often accompanies CKD, and decided to investigate this link further,” explains Abe. “Essentially, constipation disrupts the intestinal microbiota, which worsens kidney function. Working backwards, we hypothesized that we could improve kidney function by treating constipation.”

The Surprising Gut Kidney Connection

Doctors have increasingly focused on what researchers call the “gut kidney axis,” the complex relationship between intestinal bacteria and kidney health. People with CKD often experience constipation and imbalances in gut microbes, which can contribute to inflammation and the buildup of harmful compounds in the body.

Earlier research had hinted that improving gut health might help protect the kidneys, but evidence in humans remained limited. To explore the idea further, researchers launched the multicenter Phase II clinical trial known as the LUBI-CKD TRIAL across nine medical institutions in Japan.

The study enrolled 150 patients with moderate chronic kidney disease. Participants received either lubiprostone or a placebo, allowing scientists to compare how the treatment affected kidney function over time.

The results surprised the researchers. Patients who received either 8 µg or 16 µg doses of lubiprostone showed a slower decline in kidney function compared with those in the placebo group. Kidney performance was measured using estimated glomerular filtration rate (eGFR), one of the most widely used indicators of kidney health.

Researchers reported that the protective effect appeared dose dependent, meaning higher doses were linked to greater benefits. The 16 µg group showed particularly promising preservation of kidney function signals during the 24 week trial period.

How a Constipation Drug May Protect the Kidneys

Scientists then investigated why the drug appeared to help the kidneys.

Their analysis pointed to changes in the gut microbiome. Lubiprostone increased the production of spermidine, a naturally occurring compound tied to healthier mitochondrial activity. Mitochondria are often described as the power plants of cells because they generate the energy cells need to function properly.

The researchers found that improved mitochondrial function may help shield kidney tissue from further damage. They also identified changes in bacterial pathways connected to polyamine production, adding more evidence that gut microbes may directly influence kidney health.

Interestingly, the treatment did not significantly reduce certain uremic toxins that scientists originally expected to change. Instead, the kidney benefits seemed tied more closely to microbiome remodeling and mitochondrial support. That finding could reshape how researchers think about treating CKD in the future.

Why Researchers Are Excited About the Findings

The study has drawn attention because lubiprostone is already an approved medication for chronic constipation, potentially making future clinical use faster than developing a completely new drug from scratch.

Researchers also believe the discovery may have implications beyond kidney disease. Because mitochondrial dysfunction is involved in many chronic illnesses, scientists are exploring whether similar gut targeted approaches could eventually help other disorders as well.

The research team is now planning larger Phase 3 trials to confirm whether the benefits hold up in broader patient populations. Scientists are also searching for biomarkers that could predict which patients are most likely to respond to treatment.

Although more research is still needed, the findings have added momentum to a rapidly growing area of medicine focused on the connection between gut bacteria, cellular energy production, and chronic disease progression. For people living with CKD, even modest slowing of kidney decline could potentially delay dialysis and improve quality of life.

Inside the human mouth, bacteria are in near constant communication. Roughly 700 bacterial species live there, and many exchange chemical messages through a process called quorum sensing. Some of these microbes communicate using signaling molecules known as N-acyl homoserine lactones (AHLs).

Researchers from the College of Biological Sciences and the School of Dentistry set out to investigate how these bacterial signals shape the oral microbiome and whether interrupting those signals could help prevent harmful plaque buildup while preserving healthy bacteria. Their findings, published in npj Biofilms and Microbiomes, could eventually influence treatments far beyond dentistry.

Scientists Target Bacterial Communication

The research team discovered several important patterns in how mouth bacteria interact:

• Bacteria living in dental plaque produce AHL signals in aerobic environments (such as above the gumline), and those signals can still affect bacteria in anaerobic environments (beneath the gumline).
• Removing AHL signals using specialized enzymes called lactonases increased populations of bacteria associated with good oral health.
• The findings suggest that carefully selected enzymes may be able to reshape dental plaque communities and support a healthier oral microbiome.

“Dental plaque develops in a sequence, much like a forest ecosystem,” said Mikael Elias, associate professor in the College of Biological Sciences and senior author of the study. “Pioneer species like Streptococcus and Actinomyces are the initial settlers in simple communities — they’re generally harmless and associated with good oral health. Increasingly diverse late colonizers include the ‘red complex’ bacteria like Porphyromonas gingivalis, which are strongly linked to periodontal disease. By disrupting the chemical signals bacteria use to communicate, one could manipulate the plaque community to remain or return to its health-associated stage.”

Oxygen Levels Change Bacterial Behavior

The researchers also found that oxygen plays a surprisingly important role in determining how these bacterial messages influence plaque growth.

“What’s particularly striking is how oxygen availability changes everything,” said lead author Rakesh Sikdar. “When we blocked AHL signaling in aerobic conditions, we saw more health-associated bacteria. But when we added AHLs under anaerobic conditions, we promoted the growth of disease-associated late colonizers. Quorum sensing may play very different roles above and below the gumline, which has major implications for how we approach treatment of periodontal diseases.”

This discovery suggests that bacterial communication works differently depending on where bacteria live inside the mouth. That insight could help researchers design more targeted approaches to controlling gum disease and maintaining a healthier balance of microbes.

Future Treatments Could Protect Healthy Bacteria

The next phase of the research will examine how bacterial signaling differs across various areas of the mouth and in people with different stages of periodontal disease.

“Understanding how bacterial communities communicate and organize themselves may ultimately give us new tools to prevent periodontal disease — not by waging war on all oral bacteria, but by strategically maintaining a healthy microbial balance,” said Elias.

Researchers believe this strategy could eventually be expanded beyond oral health. Imbalances in the microbiome, known as dysbiosis, have been linked to numerous diseases throughout the body, including certain cancers. Scientists hope these findings could help lay the groundwork for future therapies that guide microbial communities toward healthier states rather than eliminating bacteria altogether.

Funding for the study was provided by the National Institutes of Health.