The Importance of the Mucosal Antimicrobial Peptide Expression and Gut Microbiota in Anti-TNF Therapy Response in Ulcerative Colitis

Anti-TNF therapy is a treatment for ulcerative colitis (UC) patients but only 50-70% responds to treatment. Our aim was to determine antimicrobial peptides (AMP) and microbiota profiles in UC patients before start of anti-TNF therapy and correlate this to therapy outcome evaluated after 14 weeks of therapy.

Proteomic analysis of biopsies taken before therapy start, showed that therapy responders, but not non-responders, expressed Defensin 5 (Def5) and eosinophilic cationic protein (ECP). Def5, ECP and 9 other AMPs were analysed by rtPCR in mucosal biopsies. Multivariate factor analysis discriminated responders and non-responders according to the expression of the 11 genes. The most important nominators for response were increased expression of Def5 (p=0.006) and ECP (p=0.03), whereas non-responders were defined by increased expression of cathelicidin (p=0.05). Responders also had higher serum levels of ECP than non-responders (p=0.03).      

Microbiota analysis (GA-map™ Dysbiosis Test) revealed higher dysbiosis indexes and lower levels of Faecalibacterium prausnitzii in non-responders compared to responders.

In conclusion, anti-TNF therapy responders and non-responders display different patterns of mucosal AMP expression and gut microbiota before start of therapy. This indicates that anti-TNF treatment response might be predicted by antimicrobial peptides and the gut microbiota.