Restoring gut health in ulcerative colitis through microbiome-based therapy

The human gut is home to trillions of bacteria that play vital roles in digestion, immunity, and overall health. When this microbial balance is disturbed, it can contribute to the development of chronic diseases like ulcerative colitis (UC), an inflammatory condition of the large intestine. For some patients, current treatments offer limited relief or carry significant risks, including immune suppression. Researchers are now exploring alternative ways to restore gut health, focusing on the microbiome's ability to heal the intestinal lining.

One of the hallmarks of UC is a deficiency in certain bile acids, molecules that help digest fats and regulate gut health. These molecules aren't just produced by the liver—they are further processed by gut bacteria into forms that support intestinal healing. UC patients often show lower levels of these microbial bile acids, suggesting that their restoration could promote recovery.

The research teams led by Kristina Schoonjans and Rizlan Bernier-Latmani at EPFL, have identified Clostridium scindens, a bacterium that converts primary bile acids into 7α-dehydroxylated bile acids, as a key player in gut healing. Their study shows that supplementing the gut with this bacterium could improve recovery from colonic injury, offering a new potential therapy for UC and related disorders.

The researchers tested their hypothesis in mice with colitis, a disease model that mimics UC. They introduced Clostridium scindens into some mice while leaving others untreated. The team then monitored the animals' recovery by measuring weight loss, colon inflammation, and markers of intestinal healing.

Mice that received Clostridium scindens recovered more quickly, showing reduced inflammation and enhanced regeneration of the gut lining. The researchers found that these effects were dependent on TGR5, a receptor that responds to 7α-dehydroxylated bile acids, which stimulates the proliferation and differentiation of intestinal stem cells. When they tested the therapy in mice lacking this receptor, the benefits disappeared, confirming that bile acid metabolism is essential for healing.

To further validate their findings, they analyzed patient data to determine whether similar mechanisms were at play in humans. They found that in UC patients, the lower levels of 7α-dehydroxylated bile acids strongly correlated with impaired intestinal cell renewal. This reinforces the link between bile acid metabolism and intestinal healing.

Our findings highlight the potential of microbiome-targeted strategies to modulate bile acid metabolism and promote gut healing."

Antoine Jalil, the first author of the study

Unlike conventional treatments that focus on suppressing inflammation, this approach targets the underlying issue: the impaired ability of the gut to heal itself. By restoring natural bile acid balance through beneficial bacteria, this strategy could provide an alternative and more sustainable treatment option for UC patients. While further research is needed to explore its clinical applications, the findings highlight the therapeutic potential of microbiome-based interventions.