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Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation
Open accessAbstract
Human gut commensals are increasingly suggested to impact non-communicable diseases, such as inflammatory bowel diseases (IBD), yet their targeted suppression remains a daunting unmet challenge. In four geographically distinct IBD cohorts (n = 537), we identify a clade of Klebsiella pneumoniae (Kp) strains, featuring a unique antibiotics resistance and mobilome signature, to be strongly associated with disease exacerbation and severity. Transfer of clinical IBD-associated Kp strains into colitis-prone, germ-free, and colonized mice enhances intestinal inflammation. Stepwise generation of a lytic five-phage combination, targeting sensitive and resistant IBD-associated Kp clade members through distinct mechanisms, enables effective Kp suppression in colitis-prone mice, driving an attenuated inflammation and disease severity. Proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers demonstrates gastric acid-dependent phage resilience, safety, and viability in the lower gut. Collectively, we demonstrate the feasibility of orally administered combination phage therapy in avoiding resistance, while effectively inhibiting non-communicable disease-contributing pathobionts.
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“Intestinal mucosal resurfacing (124) is a technique that targets the duodenal surface in order to improve the intestinal barrier.”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [124]
In the citing paper
“Federici et al. (124) demonstrated that oral compound phage-targeted therapy can inhibit human intestinal microbiota symbiosis, improve intestinal inflammation, and effectively avoid antibiotic resistance.”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [124]
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“This technique is currently used in patients with type 2 diabetes to improve the proliferation of enteroendocrine cells and endocrine cells, ultimately improving blood glucose levels.”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [124]
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Metadata
- Authors
- Federici, S., Kredo-Russo, S., Valdés-Mas, R., Kviatcovsky, D., Weinstock, E., Matiuhin, Y., Silberberg, Y., Atarashi, K., Furuichi, M., Oka, A., Liu, B., Fibelman, M., Weiner, I. N., Khabra, E., Cullin, N., Ben-Yishai, N., Inbar, D., Ben-David, H., Nicenboim, J., Kowalsman, N., Lieb, W., Kario, E., Cohen, T., Geffen, Y. F., Zelcbuch, L., Cohen, A., Rappo, U., Gahali-Sass, I., Golembo, M., Lev, V., Dori-Bachash, M., Shapiro, H., Moresi, C., Cuevas-Sierra, A., Mohapatra, G., Kern, L., Zheng, D., Nobs, S. P., Suez, J., Stettner, N., Harmelin, A., Zak, N., Puttagunta, S., Bassan, M., Honda, K., Sokol, H., Bang, C., Franke, A., Schramm, C., Maharshak, N., Sartor, R. B., Sorek, R., & Elinav, E.
- Affiliations
- Weizmann Institute of Science (IL)
- Keio University (JP)
- University of North Carolina at Chapel Hill (US)
- Tel Aviv University (IL)
- German Cancer Research Center (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Inserm (FR)
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Elinav, Eran
- ORCID
- Federici, Sara
- Kviatcovsky, Denise
- Matiuhin, Yulia
- Atarashi, Koji
- Furuichi, Munehiro
- Oka, Akihiko
- Liu, Bo
- Weiner, Iddo Nadav
- Cullin, Nyssa
- Lieb, Wolfgang
- Cohen, Tal
- Rappo, Urania
- Shapiro, Hagit
- Moresi, Claudia
- Kern, Lara
- Zheng, Danping
- Nobs, Samuel Philip
- Suez, Jotham
- Stettner, Noa
- Harmelin, Alon
- Honda, Kenya
- Sokol, Harry
- Bang, Corinna
- Schramm, Christoph
- Maharshak, Nitsan
- Sartor, Ryan Balfour
- Sorek, Rotem
- Elinav, Eran
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 185
- Issue
- 16
- Pages
- 2879-2898.e24
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W4289780574
- Cited by
- 542
- References
- 121
- Citations by year
- 2026: 124 · 2025: 152 · 2024: 130 · 2023: 108 · 2022: 27
- FWCI
- 56.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 368 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- HAL (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (20H05627)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- inflammatory bowel disease, Klebsiella pneumoniae, phage therapy, bacteriophages, gut commensals, intestinal inflammation, antibiotic resistance, mobilome, colitis, germ-free mice, gastric acid, pathobionts, disease severity
- MeSH terms
- Gastrointestinal Microbiome, Animals, Bacteriophages, Colitis, Humans, Inflammation, Klebsiella pneumoniae, Inflammatory Bowel Diseases, Mice
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