Recent advancements in the treatment of inflammatory bowel disease have introduced new, promising therapies, but nearly half of patients still don’t respond to treatment. Now, researchers have found that a molecule produced by specific gut microbes boosts the effectiveness of a novel treatment for Crohn’s disease by modulating immune responses.

The study, published in Cell Metabolism, may pave the way for personalized approaches to treat the condition. The findings, the authors say, “suggest that targeting specific microbe-host metabolic pathways may improve the efficacy of inflammatory bowel disease treatments.”

New therapies for inflammatory bowel disease include infliximab and ustekinumab, which target inflammatory cytokines. Ustekinumab, which is approved for Crohn’s disease in several countries, has shown promise, but the drug isn’t effective or loses its effectiveness over time in about 40% of patients. 

Previous research suggests that gut microbes, through their metabolites, play a crucial role in the development of inflammatory bowel disease and a person’s response to treatment. So, researchers led by Zhenyu Wang at Shanghai Jiao Tong University in China analyzed stool samples and intestinal mucosal samples from people with Crohn’s disease who were undergoing treatment with ustekinumab. 

Treatment efficacy

Of 85 Crohn’s disease patients receiving ustekinumab, about half achieved clinical remission after 52 weeks. 

Patients in remission showed distinct microbial profiles, higher microbial diversity and increased levels of certain beneficial metabolites, including L-ornithine, which were linked to lower inflammation markers. Patients with active disease had a higher abundance of harmful bacterial species and increased levels of lipids, the researchers found.

Further analyses suggested that certain gut microbes, such as Faecalibacterium prausnitzii, produce L-ornithine and other metabolites that could boost the effectiveness of ustekinumab.

Clinical applications

In various mouse models of colitis, L-ornithine enhanced the anti-inflammatory effects of ustekinumab by inhibiting the activation of immune cells that play a key role in inflammation.

Giving L-ornithine to Crohn’s disease patients treated with ustekinumab improved clinical outcomes, reducing disease activity and inflammation, the researchers found.

These results suggest that probiotics producing L-ornithine can improve responses to ustekinumab treatment in people with Crohn’s disease, the authors say. The work, they add, highlights L-ornithine’s potential as an additional therapy for inflammatory bowel disease, providing a basis for future clinical applications.