Mitsuharu Matsumoto1, Toshiya Ebata2, Junko Hirooka3, Ritsuko Hosoya4, Natsuhiko Inoue5, Satomi Itami6, Kazuo Tsuji7, Taketoshi Yaginuma8, Koji Muramatsu9, Atsuo Nakamura9, Ayako Fujita9, Toshikazu Nagakura10. 1. Dairy Science and Technology Institute, Kyodo Milk Industry Co Ltd, Hinode, Tokyo, Japan. Electronic address: m-matumoto@meito.co.jp. 2. Chitofuna Dermatology Clinic, Setagaya, Tokyo, Japan. 3. Hirooka Clinic, Shinjuku, Tokyo, Japan. 4. Hosoya Dermatology Clinic, Komae, Tokyo, Japan. 5. Inoue Clinic, Kawasaki, Kanagawa, Japan. 6. Itami Skin Clinic, Kashiwa, Chiba, Japan. 7. Tsuji Clinic, Shibuya, Tokyo, Japan. 8. Yaginuma Dermatology Clinic, Kashiwa, Chiba, Japan. 9. Dairy Science and Technology Institute, Kyodo Milk Industry Co Ltd, Hinode, Tokyo, Japan. 10. Yoga Allergy Clinic, Setagaya, Tokyo, Japan.
Abstract
BACKGROUND: Evidence suggests that intestinal microbiota play an important role in the pathogenesis of atopic dermatitis (AD) through induction of immunosuppression and immune tolerance; however, the exact underlying mechanism is unclear. Few studies to date have examined the effects of probiotics on adult-type AD. OBJECTIVE: To examine the effects of the probiotic Bifidobacterium animalis subsp lactis LKM512 on adult-type AD and the expression of metabolites that are known to be influenced by gut microbiota in fecal samples. METHODS:Forty-four patients were randomly assigned to receive LKM512 or a placebo and underwent medical examinations. Fecal microbiota were analyzed with real-time polymerase chain reaction. Metabolomic analysis was conducted to search for antipruritic metabolites produced by intestinal bacteria using feces derived from 3 patients whose itch scores had improved using capillary electrophoresis with time-of-flight mass spectrometry. Antipruritic effects of kynurenic acid were observed using AD-induced NC/Nga mice. RESULTS:LKM512 administration alleviated itch in AD patients compared with controls and improved the dermatology-specific quality-of-life scores when compared with the controls. Administration of LKM512 also increased the expression of the antipruritic and antinociceptive metabolite kynurenic acid (KYNA) in patients whose itch score had improved after LKM512 treatment. In mouse experiments, scratching behavior counts tended to be decreased by KYNA injection when compared with no treatment. CONCLUSION:LKM512 administration may exert antipruritic effects by increasing KYNA production. LKM512 could therefore be a potentially effective therapeutic candidate for the reduction of pruritus. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000005695.
RCT Entities:
BACKGROUND: Evidence suggests that intestinal microbiota play an important role in the pathogenesis of atopic dermatitis (AD) through induction of immunosuppression and immune tolerance; however, the exact underlying mechanism is unclear. Few studies to date have examined the effects of probiotics on adult-type AD. OBJECTIVE: To examine the effects of the probiotic Bifidobacterium animalis subsp lactis LKM512 on adult-type AD and the expression of metabolites that are known to be influenced by gut microbiota in fecal samples. METHODS: Forty-four patients were randomly assigned to receive LKM512 or a placebo and underwent medical examinations. Fecal microbiota were analyzed with real-time polymerase chain reaction. Metabolomic analysis was conducted to search for antipruritic metabolites produced by intestinal bacteria using feces derived from 3 patients whose itch scores had improved using capillary electrophoresis with time-of-flight mass spectrometry. Antipruritic effects of kynurenic acid were observed using AD-induced NC/Nga mice. RESULTS: LKM512 administration alleviated itch in ADpatients compared with controls and improved the dermatology-specific quality-of-life scores when compared with the controls. Administration of LKM512 also increased the expression of the antipruritic and antinociceptive metabolite kynurenic acid (KYNA) in patients whose itch score had improved after LKM512 treatment. In mouse experiments, scratching behavior counts tended to be decreased by KYNA injection when compared with no treatment. CONCLUSION: LKM512 administration may exert antipruritic effects by increasing KYNA production. LKM512 could therefore be a potentially effective therapeutic candidate for the reduction of pruritus. TRIAL REGISTRATION: umin.ac.jp/ctr Identifier: UMIN000005695.