Anti-TNF Therapy Response in Patients with Ulcerative Colitis Is Associated with Colonic Antimicrobial Peptide Expression and Microbiota Composition

• Published in: Journal of Crohn's and colitis Vol. 10; no. 8; pp. 943 - 952
• Main Authors: Magnusson, Maria K., Strid, Hans, Sapnara, Maria, Lasson, Anders, Bajor, Antal, Ung, Kjell-Arne, Öhman, Lena
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 01.08.2016
• Subjects: Adalimumab - therapeutic use; Adolescent; Adult; Aged; Anti-Inflammatory Agents - therapeutic use; Anti-TNF; Antimicrobial Cationic Peptides - metabolism; antimicrobial peptides; Biomarkers - metabolism; Biopsy; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - metabolism; Colitis, Ulcerative - microbiology; Colitis, Ulcerative - pathology; Cytokines - blood; Faecalibacterium prausnitzii - isolation & purification; Feces - chemistry; Feces - microbiology; Female; Gastrointestinal Microbiome; Humans; Immunologi inom det medicinska området; Immunology in the medical area; Infliximab - therapeutic use; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Male; microbiota; Middle Aged; Proteome; Real-Time Polymerase Chain Reaction; Treatment Outcome; Young Adult; microbiota; Anti-TNF; antimicrobial peptides
• ISSN: 1873-9946; 1876-4479; 1876-4479
• DOI: 10.1093/ecco-jcc/jjw051

Background and Aims: Anti-tumour necrosis factor [TNF] therapy is used in patients with ulcerative colitis [UC], but not all patients respond to treatment. Antimicrobial peptides [AMPs] and the gut microbiota are essential for gut homeostasis and may be important for treatment outcome. The aim of this study was to determine AMP and microbiota profiles in patients with UC before anti-TNF therapy start and correlate these data to treatment outcome. Methods: Serum and biopsies were obtained from UC patients naïve to biological therapy [n = 56] before anti-TNF therapy start [baseline]. Fecal samples were taken at baseline and Weeks 2 and 6. Quantitative proteomic analysis was performed in mucosal biopsies. Expression of AMPs and cytokines was determined in biopsies and serum. Microbiota analysis of fecal samples was performed using GA-map™ Dysbiosis Test and real-time quantitative polymerase chain reaction [rtPCR]. Treatment response was evaluated 12–14 weeks after baseline. Results: At baseline, proteomic analysis of biopsies showed that treatment responders and non-responders had differential expression of AMPs. Eleven AMP and AMP-related genes were analysed by rtPCR in mucosal biopsies and could together discriminate responders from non-responders at baseline. The most important nominators for response were increased expression of defensin 5 and eosinophilic cationic protein. Microbiota analysis revealed lower dysbiosis indexes and higher abundance of Faecalibacterium prausnitzii in responders compared with non-responders at baseline. Also, abundance of F. prausnitzii increased during induction therapy in responders. Conclusions: Anti-TNF therapy responders and non-responders display distinctly separate patterns of mucosal AMP expression and gut microbiota before treatment start. This indicates that intestinal antimicrobial/microbial composition can influence treatment outcome.