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Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis.

Publication ,  Journal Article
Ichikawa, M; Nakamoto, N; Kredo-Russo, S; Weinstock, E; Weiner, IN; Khabra, E; Ben-Ishai, N; Inbar, D; Kowalsman, N; Mordoch, R; Nicenboim, J ...
Published in: Nature communications
June 2023

Primary sclerosing cholangitis (PSC) is characterized by progressive biliary inflammation and fibrosis. Although gut commensals are associated with PSC, their causative roles and therapeutic strategies remain elusive. Here we detect abundant Klebsiella pneumoniae (Kp) and Enterococcus gallinarum in fecal samples from 45 PSC patients, regardless of intestinal complications. Carriers of both pathogens exhibit high disease activity and poor clinical outcomes. Colonization of PSC-derived Kp in specific pathogen-free (SPF) hepatobiliary injury-prone mice enhances hepatic Th17 cell responses and exacerbates liver injury through bacterial translocation to mesenteric lymph nodes. We developed a lytic phage cocktail that targets PSC-derived Kp with a sustained suppressive effect in vitro. Oral administration of the phage cocktail lowers Kp levels in Kp-colonized germ-free mice and SPF mice, without off-target dysbiosis. Furthermore, we demonstrate that oral and intravenous phage administration successfully suppresses Kp levels and attenuates liver inflammation and disease severity in hepatobiliary injury-prone SPF mice. These results collectively suggest that using a lytic phage cocktail shows promise for targeting Kp in PSC.

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Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

June 2023

Volume

14

Issue

1

Start / End Page

3261

Related Subject Headings

  • Phage Therapy
  • Mice
  • Liver
  • Klebsiella pneumoniae
  • Inflammation
  • Cholangitis, Sclerosing
  • Animals
 

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Ichikawa, M., Nakamoto, N., Kredo-Russo, S., Weinstock, E., Weiner, I. N., Khabra, E., … Kanai, T. (2023). Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis. Nature Communications, 14(1), 3261. https://doi.org/10.1038/s41467-023-39029-9
Ichikawa, Masataka, Nobuhiro Nakamoto, Sharon Kredo-Russo, Eyal Weinstock, Iddo Nadav Weiner, Efrat Khabra, Noa Ben-Ishai, et al. “Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis.Nature Communications 14, no. 1 (June 2023): 3261. https://doi.org/10.1038/s41467-023-39029-9.
Ichikawa M, Nakamoto N, Kredo-Russo S, Weinstock E, Weiner IN, Khabra E, et al. Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis. Nature communications. 2023 Jun;14(1):3261.
Ichikawa, Masataka, et al. “Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis.Nature Communications, vol. 14, no. 1, June 2023, p. 3261. Epmc, 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 P-S, Taniki N, Morikawa R, Kasuga R, Tabuchi T, Sugimoto S, Mikami Y, Shiota A, Bassan M, Kanai T. Bacteriophage therapy against pathological Klebsiella pneumoniae ameliorates the course of primary sclerosing cholangitis. Nature communications. 2023 Jun;14(1):3261.

Published In

Nature communications

DOI

EISSN

2041-1723

ISSN

2041-1723

Publication Date

June 2023

Volume

14

Issue

1

Start / End Page

3261

Related Subject Headings

  • Phage Therapy
  • Mice
  • Liver
  • Klebsiella pneumoniae
  • Inflammation
  • Cholangitis, Sclerosing
  • Animals