Long-term alteration of intestinal microbiota in patients with ulcerative colitis by antibiotic combination therapy.
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.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Shigeo
S
Koido
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Toshifumi
T
Ohkusa
Frontier Research Laboratories, Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan ; Pharmaceutical Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
Takayuki
T
Kajiura
Frontier Research Laboratories, Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan ; Pharmaceutical Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
Junko
J
Shinozaki
Pharmaceutical Laboratories, Ajinomoto Co., Inc., Kawasaki, Japan.
Manabu
M
Suzuki
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Keisuke
K
Saito
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Kazuki
K
Takakura
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Shintaro
S
Tsukinaga
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Shunichi
S
Odahara
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Toyokazu
T
Yukawa
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Jimi
J
Mitobe
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Mikio
M
Kajihara
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Kan
K
Uchiyama
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Hiroshi
H
Arakawa
Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Hisao
H
Tajiri
D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000382:microbiology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005673:Fusobacterium / Q000235:genetics* / Q000302:isolation & purification; D005674:Fusobacterium Infections / Q000188:drug therapy / Q000382:microbiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000382:microbiology*; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D064307:Microbiota / Q000235:genetics*; D008875:Middle Aged; D013752:Tetracycline / Q000627:therapeutic use
D000199:Actins; D000900:Anti-Bacterial Agents; D008795:Metronidazole; D000658:Amoxicillin; D013752:Tetracycline