J.R.L. and T.P. contributed equally to this work.
Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice
Article first published online: 10 JAN 2014
© 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
International Journal of Cancer
Volume 135, Issue 3, pages 529–540, 01 August 2014
How to Cite
Lakritz, J. R., Poutahidis, T., Levkovich, T., Varian, B. J., Ibrahim, Y. M., Chatzigiagkos, A., Mirabal, S., Alm, E. J. and Erdman, S. E. (2014), Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice. Int. J. Cancer, 135: 529–540. doi: 10.1002/ijc.28702
- Issue published online: 17 MAY 2014
- Article first published online: 10 JAN 2014
- Accepted manuscript online: 31 DEC 2013 04:24AM EST
- Manuscript Accepted: 23 DEC 2013
- Manuscript Received: 5 JUL 2013
- National Institutes of Health . Grant Numbers: P30-ES002109 , RO1CA108854; U01 CA164337
- mammary cancer;
- bacteria, inflammation;
- L. reuteri
Recent studies suggest health benefits including protection from cancer after eating fermented foods such as probiotic yogurt, though the mechanisms are not well understood. Here we tested mechanistic hypotheses using two different animal models: the first model studied development of mammary cancer when eating a Westernized diet, and the second studied animals with a genetic predilection to breast cancer. For the first model, outbred Swiss mice were fed a Westernized chow putting them at increased risk for development of mammary tumors. In this Westernized diet model, mammary carcinogenesis was inhibited by routine exposure to Lactobacillus reuteri ATCC-PTA-6475 in drinking water. The second model was FVB strain erbB2 (HER2) mutant mice, genetically susceptible to mammary tumors mimicking breast cancers in humans, being fed a regular (non-Westernized) chow diet. We found that oral supplement with these purified lactic acid bacteria alone was sufficient to inhibit features of mammary neoplasia in both models. The protective mechanism was determined to be microbially-triggered CD4+CD25+ lymphocytes. When isolated and transplanted into other subjects, these L. reuteri-stimulated lymphocytes were sufficient to convey transplantable anti-cancer protection in the cell recipient animals. These data demonstrate that host immune responses to environmental microbes significantly impact and inhibit cancer progression in distal tissues such as mammary glands, even in genetically susceptible mice. This leads us to conclude that consuming fermentative microbes such as L. reuteri may offer a tractable public health approach to help counteract the accumulated dietary and genetic carcinogenic events integral in the Westernized diet and lifestyle.