Clinical Trials Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2016; 22(23): 5415-5421
Published online Jun 21, 2016. doi: 10.3748/wjg.v22.i23.5415
Intestinal-borne dermatoses significantly improved by oral application of Escherichia coli Nissle 1917
Elina Manzhalii, Daniel Hornuss, Wolfgang Stremmel
Elina Manzhalii, Department of Propedeutics of Internal Medicine 2, Bogomolets National Medical University, 02097 City of Kiev, Ukraine
Daniel Hornuss, Wolfgang Stremmel, Department of Gastroenterology, University Hospital of Heidelberg, 69120 Heidelberg, Germany
Author contributions: Manzhalii E is the responsible author, designed the study and performed the experiments; Hornuss D contributed by his expertise in colonic microbiota and Stremmel W wrote the manuscript.
Institutional review board statement: The study was reviewed and approved by the National Review Board of the Bogomolets National Medical University of Kiev, following the rules of the Helsinki Declaration.
Clinical trial registration statement: This registration policy applies to prospective, randomized, controlled trials only.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Authors do not have any conflict of interest to declare.
Data sharing statement: No additional data are included.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Elina Manzhalii, MD, Department of Propedeutics of Internal Medicine 2, Bogomolets National Medical University, 02097 City of Kiev, Ukraine.
Telephone: + 49-6221-568700 Fax: + 49-6221-564116
Received: January 7, 2016
Peer-review started: January 8, 2016
First decision: March 7, 2016
Revised: April 8, 2016
Accepted: May 4, 2016
Article in press: May 4, 2016
Published online: June 21, 2016

AIM: To evaluate the effect of oral Escherichia coli (E. coli) Nissle application on the outcome of intestinal-borne dermatoses.

METHODS: In a randomized, controlled, non-blinded prospective clinical trial 82 patients with intestinal-borne facial dermatoses characterized by an erythematous papular-pustular rash were screened. At the initiation visit 37 patients entered the experimental arm and 20 patients constituted the control arm. All 57 patients were treated with a vegetarian diet and conventional topical therapy of the dermatoses with ointments containing tetracycline, steroids and retinoids. In the experimental arm patients received a one month therapy with oral E. coli Nissle at a maintenance dose of 2 capsules daily. The experimental group was compared to a non-treatment group only receiving the diet and topical therapy. The primary outcome parameter was improvement of the dermatoses, secondary parameters included life quality and adverse events. In addition the immunological reaction profile (IgA, interleucin-8 and interferon-α) was determined. Furthermore the changes of stool consistency and the microbiota composition over the time of intervention were recorded.

RESULTS: Eighty-nine percent of the patients with acne, papular-pustular rosacea and seborrhoic dermatitis responded to E. coli Nissle therapy with significant amelioration or complete recovery in contrast to 56% in the control arm (P < 0.01). Accordingly, in the E. coli Nissle treated patients life quality improved significantly (P < 0.01), and adverse events were not recorded. The clinical improvement was associated with a significant increase of IgA levels to normal values in serum as well as suppression of the proinflammatory cytokine IL-8 (P < 0.01 for both parameters). In the E. coli Nissle treated group a shift towards a protective microbiota with predominance of bifidobacteria and lactobacteria (> 107 CFU/g stool) was observed in 79% and 63% of the patients, respectively (P < 0.01), compared to no change in the control group without E. coli Nissle. Moreover, the detection rate of a pathogenic flora dropped from 73% to 14 % of the patients in the experimental arm (P < 0.01) with no significant change in the control arm (accounting 80% before and 70% after the observation period, P > 0.05). Accordingly, stool consistency, color and smell normalized in the E. coli Nissle treated patients.

CONCLUSION: E. coli Nissle protects the mucus barrier by overgrowth of a favorable gut microbiota with less immunoreactive potential which finally leads to clinical improvement of intestinal borne dermatoses.

Keywords: Intestinal-borne dermatoses, Escherichia coli Nissle 1917, Immunological response, IgA, Interleukin-8, Interferon-α, Gut microbiota

Core tip: The occurrence of facial dermatoses with erythematous papular-pustular exanthemas is often linked to intestinal inflammation. However, the underlying mechanism remains unclear, and innovative treatment options are missing. Here we show that patients with these dermatoses carry a more aggressive microbiota associated with suppressed serum IgA levels, but increase of the proinflammatory cytokines interleukin-8 and interferon-α. Clinical manifestation, microbiota and inflammatory parameters are significantly improved by application of Escherichia coli Nissle. It indicates the usefulness of this probiotic therapy in a neglected patient population in desperate need for effective help.