RT Journal Article
SR Electronic
T1 Intestinal Bacteria Modify Lymphoma Incidence and Latency by Affecting Systemic Inflammatory State, Oxidative Stress, and Leukocyte Genotoxicity
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 4222
OP 4232
DO 10.1158/0008-5472.CAN-13-0022
VO 73
IS 14
A1 Yamamoto, Mitsuko L.
A1 Maier, Irene
A1 Dang, Angeline Tilly
A1 Berry, David
A1 Liu, Jared
A1 Ruegger, Paul M.
A1 Yang, Jiue-in
A1 Soto, Phillip A.
A1 Presley, Laura L.
A1 Reliene, Ramune
A1 Westbrook, Aya M.
A1 Wei, Bo
A1 Loy, Alexander
A1 Chang, Christopher
A1 Braun, Jonathan
A1 Borneman, James
A1 Schiestl, Robert H.
YR 2013
UL http://cancerres.aacrjournals.org/content/73/14/4222.abstract
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.