Intestinal bacteria modify lymphoma incidence and latency by affecting systemic inflammatory state, oxidative stress, and leukocyte genotoxicity.
Cancer Res
; 73(14): 4222-32, 2013 Jul 15.
Article
in En
| MEDLINE
| ID: mdl-23860718
ABSTRACT
Ataxia-telangiectasia is a genetic disorder associated with high incidence of B-cell lymphoma. Using an ataxia-telangiectasia mouse model, we compared lymphoma incidence in several isogenic mouse colonies harboring different bacterial communities, finding that intestinal microbiota are a major contributor to disease penetrance and latency, lifespan, molecular oxidative stress, and systemic leukocyte genotoxicity. High-throughput sequence analysis of rRNA genes identified mucosa-associated bacterial phylotypes that were colony-specific. Lactobacillus johnsonii, which was deficient in the more cancer-prone mouse colony, was causally tested for its capacity to confer reduced genotoxicity when restored by short-term oral transfer. This intervention decreased systemic genotoxicity, a response associated with reduced basal leukocytes and the cytokine-mediated inflammatory state, and mechanistically linked to the host cell biology of systemic genotoxicity. Our results suggest that intestinal microbiota are a potentially modifiable trait for translational intervention in individuals at risk for B-cell lymphoma, or for other diseases that are driven by genotoxicity or the molecular response to oxidative stress.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphoma, B-Cell
/
Inflammation
/
Intestines
/
Lactobacillus
/
Leukocytes
Type of study:
Incidence_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Cancer Res
Year:
2013
Document type:
Article