Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice

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...

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Veröffentlicht in:International journal of cancer 2014-08, Vol.135 (3), p.529-540
Hauptverfasser: Lakritz, Jessica R., Poutahidis, Theofilos, Levkovich, Tatiana, Varian, Bernard J., Ibrahim, Yassin M., Chatzigiagkos, Antonis, Mirabal, Sheyla, Alm, Eric J., Erdman, Susan E.
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container_issue 3
container_start_page 529
container_title International journal of cancer
container_volume 135
creator Lakritz, Jessica R.
Poutahidis, Theofilos
Levkovich, Tatiana
Varian, Bernard J.
Ibrahim, Yassin M.
Chatzigiagkos, Antonis
Mirabal, Sheyla
Alm, Eric J.
Erdman, Susan E.
description 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. What's new? Can eating fermented foods like yogurt ward off cancer? Recent studies have suggested it's possible. To find out how, these authors isolated the probiotic bacteria involved in fermentation and fed them to mice that were susceptible to mammary tumors. These mice either had genetic changes predisposing them to cancer or were fed a diet known to increase their likelihood of developing the tumors. Eating the lactic acid bacteria stimulated an immune response that delayed the onset of tumors in both models, suggesting a potential avenue to prevent the cancer in humans.
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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. What's new? Can eating fermented foods like yogurt ward off cancer? Recent studies have suggested it's possible. To find out how, these authors isolated the probiotic bacteria involved in fermentation and fed them to mice that were susceptible to mammary tumors. 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Obstetrics ; L. reuteri ; Lactobacillus reuteri ; Lactobacillus reuteri - physiology ; mammary cancer ; Mammary gland diseases ; Mammary Neoplasms, Animal - genetics ; Mammary Neoplasms, Animal - microbiology ; Mammary Neoplasms, Animal - prevention &amp; control ; Mast Cells - immunology ; Mast Cells - microbiology ; Medical research ; Medical sciences ; Mice ; Mice, Transgenic ; Multiple tumors. Solid tumors. Tumors in childhood (general aspects) ; Probiotics ; Probiotics - therapeutic use ; Rodents ; Tumors</subject><ispartof>International journal of cancer, 2014-08, Vol.135 (3), p.529-540</ispartof><rights>2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC</rights><rights>2015 INIST-CNRS</rights><rights>2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.</rights><rights>2013 The Authors. 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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. What's new? Can eating fermented foods like yogurt ward off cancer? Recent studies have suggested it's possible. To find out how, these authors isolated the probiotic bacteria involved in fermentation and fed them to mice that were susceptible to mammary tumors. 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Obstetrics</subject><subject>L. reuteri</subject><subject>Lactobacillus reuteri</subject><subject>Lactobacillus reuteri - physiology</subject><subject>mammary cancer</subject><subject>Mammary gland diseases</subject><subject>Mammary Neoplasms, Animal - genetics</subject><subject>Mammary Neoplasms, Animal - microbiology</subject><subject>Mammary Neoplasms, Animal - prevention &amp; control</subject><subject>Mast Cells - immunology</subject><subject>Mast Cells - microbiology</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Multiple tumors. Solid tumors. 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subjects Animals
Apoptosis
Bacteria
bacteria, inflammation
Biological and medical sciences
Breast cancer
Cancer
Carcinogenesis
CD4-Positive T-Lymphocytes - immunology
CD4-Positive T-Lymphocytes - microbiology
Diet, High-Fat - adverse effects
Disease Models, Animal
Female
Genetic Predisposition to Disease
Gynecology. Andrology. Obstetrics
L. reuteri
Lactobacillus reuteri
Lactobacillus reuteri - physiology
mammary cancer
Mammary gland diseases
Mammary Neoplasms, Animal - genetics
Mammary Neoplasms, Animal - microbiology
Mammary Neoplasms, Animal - prevention & control
Mast Cells - immunology
Mast Cells - microbiology
Medical research
Medical sciences
Mice
Mice, Transgenic
Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
Probiotics
Probiotics - therapeutic use
Rodents
Tumors
title Beneficial bacteria stimulate host immune cells to counteract dietary and genetic predisposition to mammary cancer in mice
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