Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation.
Cell
; 185(16): 2879-2898.e24, 2022 08 04.
Article
en En
| MEDLINE
| ID: mdl-35931020
ABSTRACT
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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Bacteriófagos
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Enfermedades Inflamatorias del Intestino
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Colitis
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Microbioma Gastrointestinal
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2022
Tipo del documento:
Article