Crohn’s disease sustained remission achieved by targeting mycobacteria, says Prof Borody

IBD

By Michael Woodhead

23 Apr 2020

Prolonged remission from Crohn’s disease has been achieved for between three and 23 years using antibiotics targeting Mycobacteria and faecal microbiota transplant (FMT), according to Sydney clinicians.

The sustained remission results are reported in a case series of 10 patients who received anti-Mycobacterium avium spp paratuberculosis (anti-MAP) antibiotic combination therapy and in some cases infliximab and FMT at Professor Thomas Borody’s Centre for Digestive Disease.

Published in Gut Pathogens the report by Dr Gaurav Agrawal says that the anti-MAP treated patients with CD were induced into remission, and the remission was sustained with FMT, enabling reduction of medications.

The rationale for using anti-MAP therapy is based on the notion that Mycobacteria species cause a similar to IBD in animals, and human studies using antibiotics have shown short term resolution of symptoms and mucosal healing Crohn’s disease.

In the case series, seven of ten patients took anti-MAP therapy comprising combinations of antibiotics such as from rifabutin, metronidazole, ciprofloxacin, clarithromycin, clofazimine and clofazimine for a median 36 months.

After stopping AMAT, five patients received an average of four infusions of FMT, and four also received infliximab.

The researchers report that following treatment all 10 patients were clinically asymptomatic with a CDAI of < 30. They had endoscopic resolution as well as histologically complete, deep mucosal healing and had ceased all Crohn’s disease treatments

One patient achieved deep mucosal healing with AMAT alone. Of the 3/10 patients not prescribed AMAT, one had a combination of anti-inflammatory agents and a single antibiotic (metronidazole) followed by FMT. The other two received only FMT for C. difficile infection.

Overall, the median duration of treatment free remission was 8.5 years (

The researchers said there were several other patients treated with anti-MAP therapy who were in long-term remission but had been unable to completely cease medication without relapse, but were typically be on lower dose ‘maintenance’ AMAT or 5-ASA anti-inflammatory treatment.

They said their case series results “concur with our notion that Crohn’s disease occurs as the result of a primary infection with MAP, or a similar pathogen, and a resulting disruption of the protective mechanisms of the gut microbiome (dysbiosis).”

The proposed that the inability to clear MAP and the resulting dysbiosis from viable Mycobacteria, leads to granulomas and the relapsing, remitting behaviour observed in Crohn’s disease.

“Targeting both steps is likely key to higher eradication and recovery rates and a reason as to why efficacy of FMT alone is currently sub-optimal in remission of Crohn’s,” they wrote.

The acknowledged that case series may be biased by many variables  – including antibiotic resistance – and said a RCT is needed to compare therapy with AMAT and FMT versus current ‘standard of care’ therapy in Crohn’s disease.

Professor Borody declared a pecuniary interest in the Centre for Digestive Disease and  patents filed for antibiotic therapies in Crohn’s disease and FMT.

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