Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites.
Science
; 378(6618): eabm3233, 2022 10 28.
Article
en En
| MEDLINE
| ID: mdl-36302024
ABSTRACT
Microbiota-derived metabolites that elicit DNA damage can contribute to colorectal cancer (CRC). However, the full spectrum of genotoxic chemicals produced by indigenous gut microbes remains to be defined. We established a pipeline to systematically evaluate the genotoxicity of an extensive collection of gut commensals from inflammatory bowel disease patients. We identified isolates from divergent phylogenies whose metabolites caused DNA damage and discovered a distinctive family of genotoxins-termed the indolimines-produced by the CRC-associated species Morganella morganii. A non-indolimine-producing M. morganii mutant lacked genotoxicity and failed to exacerbate colon tumorigenesis in mice. These studies reveal the existence of a previously unexplored universe of genotoxic small molecules from the microbiome that may affect host biology in homeostasis and disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_neglected_diseases
/
3_zoonosis
Asunto principal:
Daño del ADN
/
Neoplasias Colorrectales
/
Enfermedades Inflamatorias del Intestino
/
Morganella morganii
/
Microbioma Gastrointestinal
/
Indoles
/
Mutágenos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos