Long-term alteration of intestinal microbiota in patients with ulcerative colitis by antibiotic combination therapy

• Published in: PloS one 2014-01, Vol.9 (1), p.e86702-e86702
• Main Authors: Koido, Shigeo, Ohkusa, Toshifumi, Kajiura, Takayuki, Shinozaki, Junko, Suzuki, Manabu, Saito, Keisuke, Takakura, Kazuki, Tsukinaga, Shintaro, Odahara, Shunichi, Yukawa, Toyokazu, Mitobe, Jimi, Kajihara, Mikio, Uchiyama, Kan, Arakawa, Hiroshi, Tajiri, Hisao
• Format: Article
• Language: English
• Subjects: Actin; Actins - metabolism; Adolescent; Adult; Aged; Amoxicillin; Amoxicillin - therapeutic use; Anti-Bacterial Agents - therapeutic use; Antibiotics; Bacteria; Biology; Biopsy; Clinical trials; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - microbiology; Colon; Combination therapy; Double-Blind Method; Drug Therapy, Combination; Female; Fusobacterium - genetics; Fusobacterium - isolation & purification; Fusobacterium Infections - drug therapy; Fusobacterium Infections - microbiology; Fusobacterium varium; Gastroenterology; Hepatology; Humans; Inflammatory bowel disease; Internal medicine; Intestinal microflora; Intestinal Mucosa - drug effects; Intestinal Mucosa - microbiology; Intestine; Laboratories; Male; Mathematics; Medical research; Medical schools; Medicine; Metronidazole; Metronidazole - therapeutic use; Microbiota; Microbiota (Symbiotic organisms); Microbiota - genetics; Middle Aged; Mucosa; Muscle proteins; Patients; Pharmaceuticals; Phylogenetics; Polymorphism; Remission; Restriction fragment length polymorphism; Similarity; Tetracycline - therapeutic use; Therapy; Ulcerative colitis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0086702

Previous work has demonstrated that intestinal bacteria, such as Fusobacterium varium (F. varium), contribute to the clinical activity in ulcerative colitis (UC); thus, an antibiotic combination therapy (amoxicillin, tetracycline, and metronidazole (ATM)) against F. varium can induce and maintain UC remission. Therefore, we investigated whether ATM therapy induces a long-term alteration of intestinal microbiota in patients with UC. Patients with UC were enrolled in a multicenter, randomized, double-blind, placebo-controlled study. Biopsy samples at the beginning of the trial and again at 3 months after treatment completion were randomly obtained from 20 patients. The terminal restriction fragment length polymorphism (T-RFLP) in mucosa-associated bacterial components was examined to assess the alteration of the intestinal microbiota. Profile changes of T-RFLP in mucosa-associated bacterial components were found in 10 of 12 patients in the treatment group and in none of 8 in the placebo group. Dice similarity coefficients using the unweighted pair group method with arithmetic averages (Dice-UPGMA) confirmed that the similarity of mucosal microbiota from the descending colon was significantly decreased after the ATM therapy, and this change was maintained for at least 3 months. Moreover, at 3 months after treatment completion, the F. varium/β-actin ratio, examined by real-time PCR using nested PCR products from biopsy samples, was reduced less than 40% in 8 of 12 treated patients, which was higher, but not significantly, than in 4 of 8 patients in the placebo group. Together, these results suggest that ATM therapy induces long-term alterations in the intestinal microbiota of patients with UC, which may be associated, at least in part, with clinical effects of the therapy.