1: Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis.
Science of the Month - September 2023
Nat Commun
2023 Jun 5;14(1):3261. doi: 10.1038/s41467-023-39029-9.
Ichikawa M, Nakamoto N, Kredo-Russo S, Weinstock E, Weiner IN, Khabra E, Ben-Ishai N, Inbar D, Kowalsman N, Mordoch R, Nicenboim J, Golembo M, Zak N, Jablonska J, Sberro-Livnat H, Navok S, Buchshtab N, Suzuki T, Miyamoto K, Teratani T, Fujimori S, Aoto Y, Konda M, Hayashi N, Chu PS, Taniki N, Morikawa R, Kasuga R, Tabuchi T, Sugimoto S, Mikami Y, Shiota A, Bassan M, Kanai T.
Primary Sclerosing Cholangitis (PSC) is an intractable autoimmune disease that causes damage to the large and small bile ducts inside and outside the liver, leading to cholestasis. The etiology of PSC is still unknown, and there are no effective medical treatments; the only curative therapy is liver transplantation. In this study, we analyzed the gut microbiota of 45 PSC patients visiting our hospital and found that patients harboring both *Klebsiella pneumoniae* (Kp) and *Enterococcus gallinarum* had more rapid disease progression. While antibiotics to which these pathogens are susceptible are a potential therapeutic approach, the emergence of resistant bacteria due to long-term use is a concern. To overcome this problem, we initiated the development of bacteriophages, which can selectively kill specific pathogenic bacteria with a low frequency of resistance emergence. Through international collaboration, we successfully created a bacteriophage cocktail that specifically eliminates Kp isolated from PSC patients. We demonstrated that its administration reduces the Kp bacterial load and attenuates bile duct damage mediated by the Th17 immune response (Figure 1). This achievement clarifies the role of gut bacteria contributing to the pathophysiology of PSC and is expected to lead to the clinical application of phage therapy targeting gut microbiota in the future.
(Nobuhiro Nakamoto, Department of Gastroenterology and Hepatology, Class of '77)
Other Published Papers
1: Extracellular aaRSs drive autoimmune and inflammatory responses in rheumatoid arthritis via the release of cytokines and PAD4.
Annals of the Rheumatic Diseases.
2023 Sep;82(9):1153-1161. doi: 10.1136
Kimura A, Takagi T, Thamamongood T, Sakamoto S, Ito T, Seki I, Okamoto M, Aono H, Serada S, Naka T, Imataka H, Miyake K, Ueda T, Miyanokoshi M, Wakasugi K, Iwamoto N, Ohmagari N, Iguchi T, Nitta T, Takayanagi H, Yamashita H, Kaneko H, Tsuchiya H, Fujio K, Handa H, Suzuki H.