title: Efficacy of bacteriophage therapy against gut-derived sepsis caused by Pseudomonas aeruginosa in mice.
abstract: We evaluated the efficacy of bacteriophage (phage) therapy by using a murine model of gut-derived sepsis caused by Pseudomonas aeruginosa that closely resembles the clinical pathophysiology of septicemia in humans. Oral administration of a newly isolated lytic phage strain (KPP10) significantly protected mice against mortality (survival rates, 66.7% for the phage-treated group versus 0% for the saline-treated control group; P<0.01). Mice treated with phage also had lower numbers of viable P. aeruginosa cells in their blood, liver, and spleen. The levels of inflammatory cytokines (tumor necrosis factor alpha TNF-alpha, interleukin-1beta [IL-1beta], and IL-6) in blood and liver were significantly lower in phage-treated mice than in phage-untreated mice. The number of viable P. aeruginosa cells in fecal matter in the gastrointestinal tract was significantly lower in phage-treated mice than in the saline-treated control mice. We also studied the efficacy of phage treatment for intraperitoneal infection caused by P. aeruginosa and found that phage treatment significantly improved the survival of mice, but only under limited experimental conditions. In conclusion, our findings suggest that oral administration of phage may be effective against gut-derived sepsis caused by P. aeruginosa.
authors.affiliation: Third Department of Surgery, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Watanabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Go
authors.initials: G
authors.lastname: Sano
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Sumiyama
authors.forename: Jumpei
authors.initials: J
authors.lastname: Uchiyama
authors.forename: Shingo
authors.initials: S
authors.lastname: Sakurai
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Matsuzaki
authors.forename: Shosuke
authors.initials: S
authors.lastname: Imai
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001691:Biological Therapy; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000378:metabolism; D041741:Lower Gastrointestinal Tract / Q000382:microbiology; D051379:Mice; D008813:Mice, Inbred ICR; D011552:Pseudomonas Infections / Q000628:therapy*; D017105:Pseudomonas Phages; D011550:Pseudomonas aeruginosa; D018805:Sepsis / Q000097:blood / Q000382:microbiology / Q000401:mortality / Q000628:therapy*
chemical_list: D016207:Cytokines