Azathioprine and mesalazine-induced effects on the mucosal flora in patients with IBD colitis.
BACKGROUND
The impact of azathioprine and 5-aminosalicylic acid (5-ASA) on the innate immunity and mucosal flora is unknown. The study investigated the influence of IBD treatment on the concentrations and spatial organization of mucosal bacteria using fluorescence in situ hybridization with 16s r-RNA targeting probes.


METHODS
We prospectively investigated colonoscopic biopsies from five groups of 20 subjects each: patients with ulcerative or indeterminate colitis treated with azathioprine (group 1), azathioprine and 5-ASA (group 2), 5-ASA (group 3), untreated IBD (group 4), and healthy controls.


RESULTS
The elevated numbers of leukocytes in mucus of IBD patients were reduced nearly to norm in patients treated with azathioprine alone. In contrast, 5-ASA therapy had no influence on mucus leukocyte migration and was associated with the lowest concentrations of mucosal bacteria of all IBD groups. The suppressed migration of leukocytes in azathioprine-treated patients was accompanied by a 28-fold higher concentration of mucosal bacteria when compared with the 5-ASA group or a 1000-fold increase when compared with healthy controls. The percent of the epithelial surface covered with adherent bacteria (P < 0.001) and the amenability of mucosal bacteria (P = 0.01) were also significantly increased in the azathioprine-treated group compared with all other IBD groups. The patients receiving both 5-ASA and azathioprine did not differ statistically from untreated IBD patients either in mucus leukocyte migration or in bacterial concentrations.


CONCLUSIONS
Azathioprine and 5-ASA induce opposite effects on the mucus barrier. Concomitant therapy of 5-ASA and azathioprine mutually neutralizes the effects of both on the mucosal flora and the barrier function.
Swidsinski
Alexander
A
Humboldt University, Charité Hospital, CCM, Laboratory for Molecular Genetics, Polymicrobial Infections and Bacterial Biofilms, 10098 Berlin, Germany.
Loening-Baucke
Vera
V
Bengmark
Stig
S
Lochs
Herbert
H
Dörffel
Yvonne
Y
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use*; D001419:Bacteria / Q000302:isolation & purification*; D001422:Bacterial Adhesion; D003092:Colitis / Q000276:immunology / Q000382:microbiology; D003093:Colitis, Ulcerative / Q000276:immunology / Q000382:microbiology; D003106:Colon / Q000276:immunology / Q000382:microbiology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000382:microbiology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology*; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use*; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D019804:Mesalamine; D001379:Azathioprine