Could serologic anti-microbial antibodies predict Crohn’s disease?

Inflammatory bowel disease (IBD) is a family of intestinal disorders including Crohn’s disease (CD) and ulcerative colitis (UC) that are characterized by chronic and recurring periods of severe colonic (UC) or intestinal (CD) inflammation and extraintestinal symptoms. While the pathogenesis is unknown and seen as controversial, among others a dysregulated immune response in genetically susceptible individuals is discussed. It has also been suggested that the gut microbiota, barrier function, and immune system contribute in a mutually interdependent manner to IBD onset and exacerbation. Recently it has been proposed that host genetics and the microbiome interact to regulate susceptibility to IBD.

Several hypotheses, including the hygiene hypothesis (reduced childhood exposure to microorganisms increases susceptibility to allergic diseases by altering immune development), have been proposed as explanation for the increasing incidence of IBD in many parts of the world. Gut parasites are thought to promote expansion of bacteria that reduce inflammatory responses in IBD.

Recent research has focused on finding markers that can predict CD before disease diagnosis. A recent study, led by Dr. Jean-Frederic Colombel from The Henry D. Janowitz Division of Gastroenterology at Icahn School of Medicine at Mount Sinai, New York, has found that circulating anti-microbial antibodies years before CD diagnosis were associated with complicated CD at, or shortly after, diagnosis.

Sera from 100 US military personnel with CD had been prospective obtained (from the PREDICTS -Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects- Study). For each patient, four samples were obtained at different time points before and around disease diagnosis, and presence of 6 microbiota-directed antibodies was assessed: anti-Saccharomyces cerevisiae (ASCA)-Immunoglobulin A (ASCA-IgA), ASCA-IgG, anti-Escherichia coli outer membrane porin C (anti-OmpC), anti-bacterial flagellin (anti-CBir 1), anti-flagellin A4-Fla2 (anti-A4-Fla2) and anti-flagellin FlaX (anti-FlaX). The researchers also evaluated associations between the presence of CD anti-microbial antibodies before diagnosis and the later development of complications.

At a median of 6 years before CD diagnosis, 65 patients were positive for at least one CD associated anti-microbial antibody and the proportion of positive antibodies increased up to the time of CD diagnosis. Around the time of diagnosis, complicated disease developed in 24 patients. The proportion of positive antimicrobial antibodies before diagnosis was higher in patients with complicated CD as compared to those with non-complicated CD. Thus, an increased number of CD-associated antibodies against commensal microorganisms could allow identification of CD phenotypes that prove complicated at, or shortly after, clinical diagnosis.

In conclusion, antibodies against commensal microorganisms can help predict the progression towards complicated CD, which could open up a new diagnosis direction for IBD.

References:

Choung RS, Princen F, Stockfisch TP, et al. Serologic microbial associated markers can predict Crohn’s disease behaviour years before disease diagnosis. Aliment Pharmacol Ther. 2016; 43(12):1300-10. doi:10.1111/apt.13641.

Chu H, Khosravi A, Kusumawardhani IP, et al. Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease. Science. 2016; 352(6289):1116-20. doi:10.1126/science.aad9948.

Vindigni SM, Zisman TL, Suskind DL, Damman CJ. The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions. Therap Adv Gastroenterol. 2016; 9(4):606-25. doi:10.1177/1756283X16644242.

Paul Enck

Prof. Dr. Paul Enck, Director of Research, Dept. of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Germany. His main interests are gut functions in health and disease, including functional and inflammatory bowel disorders, the role of the gut microbiota, regulation of eating and food intake and its disorders, of nausea, vomiting and motion sickness, and the psychophysiology and neurobiology of the placebo response, with specific emphasis on age and gender contributions. He has published more than 170 original data paper in scientific, peer-reviewed journals, and more than 250 book chapters and review articles. He is board member/treasurer of the European Society of Neurogastroenterology and Motility and of the German Society of Neurogastroenterology and Motility, and has served as reviewer for many international journals and grant agencies.