Breast Cancer risk reduced if consume butyrate - Dec 2023

Intestinal vitamin D receptor protects against extraintestinal breast cancer tumorigenesis

Gut Microbes, 15:1,2202593, DOI: 10.1080/19490976.2023.2202593
Yong-Guo Zhang, Yinglin Xia, Jilei Zhang, Shreya Deb, Shari Garrett & Jun Sun

The microbiota plays critical roles in regulating the function and health of the intestine and extraintestinal organs. A fundamental question is whether an intestinal-microbiome-breast axis exists during the development of breast cancer. If so, what are the roles of host factors? Vitamin D receptor (VDR) involves host factors and the human microbiome. Vdr gene variation shapes the human microbiome, and VDR deficiency leads to dysbiosis. We hypothesized that intestinal VDR protects hosts against tumorigenesis in the breast. We examined a 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model in intestinal epithelial VDR knockout (VDRAIEC) mice with dysbiosis. We reported that VDRAIEC mice with dysbiosis are more susceptible to breast cancer induced by DMBA. Intestinal and breast microbiota analysis showed that VDR deficiency leads to a bacterial profile shift from normal to susceptible to carcinogenesis. We found enhanced bacterial staining within breast tumors. At the molecular and cellular levels, we identified the mechanisms by which intestinal epithelial VDR deficiency led to increased gut permeability, disrupted tight junctions, microbial translocation, and enhanced inflammation, thus increasing tumor size and number in the breast. Furthermore, treatment with the beneficial bacterial metabolite butyrate or the probiotic Lactobacillus plantarum reduced breast tumors, enhanced tight junctions, inhibited inflammation, increased butyryl-CoA transferase, and decreased levels of breast Streptococcus bacteria in VDRAIEC mice. The gut microbiome contributes to the pathogenesis of diseases not only in the intestine but also in the breast. Our study provides insights into the mechanism by which intestinal VDR dysfunction and gut dysbiosis lead to a high risk of extraintestinal tumorigenesis. Gut-tumor-microbiome interactions represent a new target in the prevention and treatment of breast cancer.
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Butyrate treatment reduced the breast tumor number, increased breast VDR expression, decreased proliferation, and increased apoptosis in VDRAIEC mice
Because butyrate synthesis-related transferase was decreased in the feces of VDRAIEC mice compared to VDRloxp mice, we then hypothe­sized that butyrate treatment in mice could reduce the formation of breast tumors. We also tested the role of butyrate because it is known to increase VDR expression in the intestine11. Female VDRloxp and VDRAIEC mice were treated with 2.5% butyrate in the drinking water starting at the age of 6-7 weeks and ending 18 weeks after the first DMBA treatment. The breast tumor number was significantly decreased in VDRAIEC mice treated with butyrate (Figure 5a). The breast tumor volume was significantly smaller in VDRAIEC mice treated with butyrate than in those without butyrate treatment (Figure 5b). Pathological analysis showed that the mammary glands were smaller in size in VDRAIEC mice treated with butyrate (Figure 5c). Increased pro­tein expressions of VDR and reduced ?? catenin (552) were observed in breast tumors of VDRAIEC mice treated with butyrate (Figure 5d). Increased VDR expression was confirmed by IHC staining of breast tumor tissue in VDRAIEC mice treated with butyrate (Figure 5e). In VDRAIEC mice trea­ted with butyrate, we found significantly reduced ??catenin (Ser552) in breast tumors (Figure 5f). Apoptosis-positive cells were also significantly increased in the breast tumors of VDRAIEC mice treated with butyrate, as shown by TUNEL staining (Figure 5g).

Vitamin D Life - Butyrate is one of 16+ activators of VDR

Vitamin D Life - 22 studies in both categories breast cancer and Vitamin D Receptor

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