First Author | Yamamoto ML | Year | 2013 |
Journal | Cancer Res | Volume | 73 |
Issue | 14 | Pages | 4222-32 |
PubMed ID | 23860718 | Mgi Jnum | J:199304 |
Mgi Id | MGI:5502254 | Doi | 10.1158/0008-5472.CAN-13-0022 |
Citation | Yamamoto ML, et al. (2013) Intestinal Bacteria Modify Lymphoma Incidence and Latency by Affecting Systemic Inflammatory State, Oxidative Stress, and Leukocyte Genotoxicity. Cancer Res 73(14):4222-4232 |
abstractText | 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. (c)2013 AACR. |