Title: Intestinal bacteria modify lymphoma incidence and latency by affecting systemic inflammatory state, oxidative stress, and leukocyte genotoxicity.

Authors: Yamamoto, Mitsuko L; Maier, Irene; Dang, Angeline Tilly; Berry, David; Liu, Jared; Ruegger, Paul M; Yang, Jiue-In; Soto, Phillip A; Presley, Laura L; Reliene, Ramune; Westbrook, Aya M; Wei, Bo; Loy, Alexander; Chang, Christopher; Braun, Jonathan; Borneman, James; Schiestl, Robert H

Published In Cancer Res, (2013 Jul 15)

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.

PubMed ID: 23860718

MeSH Terms: No MeSH terms associated with this publication