PT  - JOURNAL ARTICLE
AU  - Yamamoto, Mitsuko L.
AU  - Maier, Irene
AU  - Dang, Angeline Tilly
AU  - Berry, David
AU  - Liu, Jared
AU  - Ruegger, Paul M.
AU  - Yang, Jiue-in
AU  - Soto, Phillip A.
AU  - Presley, Laura L.
AU  - Reliene, Ramune
AU  - Westbrook, Aya M.
AU  - Wei, Bo
AU  - Loy, Alexander
AU  - Chang, Christopher
AU  - Braun, Jonathan
AU  - Borneman, James
AU  - Schiestl, Robert H.
TI  - Intestinal Bacteria Modify Lymphoma Incidence and Latency by Affecting Systemic Inflammatory State, Oxidative Stress, and Leukocyte Genotoxicity
AID  - 10.1158/0008-5472.CAN-13-0022
DP  - 2013 Jul 15
TA  - Cancer Research
PG  - 4222--4232
VI  - 73
IP  - 14
4099  - http://cancerres.aacrjournals.org/content/73/14/4222.short
4100  - http://cancerres.aacrjournals.org/content/73/14/4222.full
SO  - Cancer Res2013 Jul 15; 73
AB  - 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. Cancer Res; 73(14); 4222–32. ©2013 AACR.