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

Abstract

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.

Dietary Microbes Modulate Transgenerational Cancer Risk

“…Subsets of CD-1 mice who had been treated with NWD in-utero subsequently received in their drinking water an anti-inflammatory strain of Lactobacillus reuteri ATCC-PTA-6475 cultivated as described elsewhere (8,9), with live organisms supplied at a starting dosage of 3.5×10 5 organisms/mouse/day in drinking water (4). Live bacterial counts in water bottles were calculated to be 1.4×10 6 colony forming units (CFU) per mouse on day 1, 4.1×10 5 CFU on day 2, and 1.1×10 5 CFU on day 3, and L reuteri was detectable by PCR in feces and bowel of mice undergoing the dosing regimen, as described in detail in Lakritz et al (2014) (4). Control mice received regular drinking water.…”

“…Impaired regulatory capacity leads to uncontrolled immune inflammatory responses, obesity and cancer later in life (2, 3). Our recent studies in mice have shown that Westernized diet (NWD)-associated obesity and cancer coincide with changes in gastrointestinal (GI) tract microbial communities and immune regulatory capacity preventable by dietary enrichment with beneficial bacteria(4–7). We test here whether these postulated effects of gut microbes transcend generations.…”

The microbiome modulates the tumor macroenvironment

“…Oxytocin modulates interferon- γ (IFNγ) and CD25 expression culminating in robust yet tightly regulated immunity. As a consequence of eating probiotic organisms, aged mice displayed superb wound healing capacity 7 , 8 . In this setting, mice were also resistant to both western diet-induced and ErbB2 oncogene overexpression-associated mammary carcinogenesis 8 …”

Modification in the diet can induce beneficial effects against breast cancer

“…This effect was caused by the elevation of the pro-inflammatory cytokines IFN-γ, TNF-α and IL-2 levels and increased NK cell activity [115] . cells by LAB and their beneficial effect against mammary carcinoma was analyzed using two mice models [116] . In one model, mice were fed a Westernized chow increasing risk for development of mammary tumors.…”