Finding a new way to target ‘hidden’ bacteria in the gut

What the research looked at?

Crohn’s Disease may partly be caused by an altered immune response to bacteria found in the gut. There’s growing evidence that a bacteria called E.coli may be involved. E.coli can move across the gut lining and grow inside an immune cell called a macrophage. Researchers want to find a therapy that targets E.coli – as antibiotics aren’t good at killing bacteria which are ‘hiding’ inside macrophages. 

A medicine called hydroxychloroquine (originally developed for treating malaria) increases the ability of antibiotics to kill the E.coli hidden in the macrophages. The researchers ran a clinical trial to see if a combination of antibiotics with hydroxychloroquine could be an effective treatment for Crohn’s. They compared this combination treatment to a commonly used steroid treatment called budesonide. 

Conclusions 

The researchers looked at how many people with Crohn’s were in remission after taking these treatments at 10, 24 or 52 weeks. Remission rates were similar in both treatment groups, but there were slightly more people still in remission at 24 and 52 weeks if they were taking antibiotics with hydroxychloroquine (this difference wasn’t statistically significant). 

Interestingly, treatment seemed to be more effective in a small number of people who were initially taking budesonide but were later moved onto the combination treatment of antibiotics with hydroxychloroquine (not significantly significant). 

The researchers also looked at markers in the blood of those taking antibiotics with hydroxychloroquine, but weren’t able to find any that could predict who responded best to this treatment. 

What do the researchers think this could this mean for people with Crohn's Disease? 

Although treatment with antibiotics and hydroxychloroquine caused some side effects, these were mild and this treatment was considered safe for long-term use. The results justify a future study of antibiotics and hydroxychloroquine as a new longer-term treatment option for people with Crohn’s. The researchers suggest a larger clinical trial, or the possible investigation of antibiotics with hydroxychloroquine combined with another treatment, such as a biologic medicine, to boost effectiveness. 

Scientific publications 

The full research study and conclusions were published in July 2020: 

• Randomized Trial of Ciprofloxacin Doxycycline and Hydroxychloroquine Versus Budesonide in Active Crohn’s Disease (Abstract only available for free) 

Who is leading the research: Profs. Jon Rhodes and Chris Probert, Department of Gastroenterology, University of Liverpool 
Our funding: £50,993 over 24 months 
Official title of the application: Comparison of Combination Antibiotic and Hydroxychloroquine Therapy (Budesonide) in the treatment of active Crohn's Disease. 
Tags: Drugs