Jonas Andre Lundekvam [1,2], Marte Lie Høivik [1,2], Dagmar Klotz [3], Carl August Munck [4], Ørjan Næss [5], Vibeke Strande [6], Dag Henrik Reikvam [7], Asle Wilhelm Medhus [1]

Affiliates

Department of Gastroenterology, Oslo University Hospital [1], University of Oslo, Institute of Clinical Medicine [2], Department of Pathology, Oslo University Hospital [3], Department of Gastroenterology, Vestre Viken Hospital Trust, Bærum Hospital [4], Division of Medicine, Diakonhjemmet Hospital [5], Division of Medicine, Lovisenberg Diaconal Hospital [6], Department of Infectious Diseases, Oslo University Hospital [7]

Abstract

Background
Anti-TNF drugs are often the first-line biologic treatment in patients with ulcerative colitis (UC), but many do not achieve sufficient clinical response. The gut microbial composition affect the expression of TNF in the mucosa, and anti-TNF treatment may produce a shift towards a healthy gut microbiome. In this ongoing proof of concept study, we assess safety and clinical/histological outcomes of probiotic supplementation in UC patients with insufficient response to anti-TNF treatment.
Methods
UC patients starting anti-TNF therapy were included at regular evaluation colonoscopy 6–12 months after onset of treatment. Main exclusion criteria were steroid use last 4 weeks, antibiotic or probiotic use last 12 weeks, or severe colitis. Patients with endoscopic Mayo score ≥2 received a probiotic compound containing 5 bacterial strains from the genera Lactobacillus, Bifidobacterium and Streptococcus, 4 tablets daily (12*10^9 colony-forming units/day) for 8 weeks. Partial Mayo Score (PMS), biochemical, endoscopic and histological outcomes were recorded at baseline and after 8 weeks of probiotic treatment. Biopsies were collected from all colonic segments. Histologic disease activity was assessed using the Robarts Histopathology Index (RHI) by a blinded histopathologist. Summary values are median (range). Analyses were performed using the Wilcoxon signed-rank test.
Results
Eight (6 male, median age 31.5 years, range 26–49) patients have completed the intervention including endoscopic evaluation after 8 weeks. No serious adverse events have been recorded. Values at baseline (W0) and at probiotic treatment evaluation (W8) are shown in the table. RHI decreased significantly from 17 (12-18) at W0 to 5 (0-17) at W8 (p=0.04). Five out of eight patients achieved histological improvement defined as ≥7 point reduction. Fecal calprotectin was 490 (26–4933) at W0 compared with 163 (38–1887) at W8 (p=0.2).
Conclusion
The present results indicate that supplementary treatment with a probiotic compound is safe and beneficial for UC patients on anti-TNF treatment.