Bacterial, Fungal Profiles Predict Infliximab Response, Study Reveals

Bacterial and fungal profiles found in fecal samples from people with inflammatory bowel disease (IBD) were able to predict the patients’ responses to the anti-inflammatory therapy infliximab, a study revealed.

These findings support the development of a predictive test that would help clinicians to choose the most effective treatment for their IBD patients.

The study, “Bacterial and Fungal Profiles as Markers of Infliximab Drug Response in Inflammatory Bowel Disease,” was published in the Journal of Crohn’s and Colitis.

IBD is a general term to describe disorders characterized by chronic inflammation of the digestive tract. The two most common forms of IBD are ulcerative colitis (UC), which is limited to the colon, and Crohn’s disease (CD), found anywhere along the digestive tract.

Anti-inflammatory medications are the standard treatment for IBD, and in some cases, surgery is required. If these therapies fail to control inflammation, then infliximab can be used as an alternative treatment.

Infliximab — sold as Remicade, among other brand names — is an antibody-based therapy that prevents TNF-alpha, a pro-inflammatory protein, from interacting with inflammatory cells in the intestine. Administered intravenously (into the vein), the treatment effectively reduces inflammation and controls the disease.

However, up to 40% of patients either fail to respond to infliximab or lose response over time. And there currently are no reliable biomarkers to predict who will respond positively to the treatment.

“A test for predicting responses would help to choose drug therapies and avoid unnecessary drug use, which would reduce potential adverse effects and save on drug expenses in the healthcare system,” Eija Nissilä, PhD, senior author of the study, said in a press release.

People with IBD have been found to have an altered state of gut microbiota, or the microorganisms living in the gut. Given that, researchers at the University of Helsinki, in Finland, now wondered if variations in bacterial and fungal communities found in the feces of IBD patients being treated with infliximab therapy could predict their treatment response.

A total of 72 IBD patients — 47 with colitis and 25 with Crohn’s — were followed for one year after starting infliximab treatment or until treatment was stopped.

DNA analysis was used to identify both bacteria and fungi to generate microbiota profiles isolated from fecal samples before infliximab treatment. The analysis was then done again after two, six, and 12 weeks, as well as one year after starting therapy.

The participants’ responses to infliximab were evaluated by colonoscopy and by clinical tests performed 12 weeks (three months) after treatment initiation.

The analysis revealed that bacterial and fungal profiles were significantly different — before infliximab therapy — between patients who responded and those who did not.

In non-responders, the team found a lower abundance of bacteria that produces a type of fat called short-chain fatty acids, particularly of the class of bacteria known as Clostridia.

Moreover, compared with responders, those who failed to respond to infliximab treatment had a higher abundance of bacteria and fungi associated with inflammation, in particular, the fungus Candida.

A statistical calculation supported these results, showing that bacteria profiles could predict responses to infliximab treatment in both UC and CD patients with an area under the curve (AUC) greater than 0.8, which is above the acceptable level as a good predictor of response.

The study also showed how infliximab treatment had a beneficial effect on the gut microbiota in these patients.

Based on the findings, “fecal bacterial and fungal microbiota composition could provide a predictive tool to estimate [infliximab] response in IBD patients,” the researchers concluded.

“Such a predictive test would make it possible to choose the appropriate therapy, providing savings in drug therapy costs in healthcare,” Nissilä said.

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