Adequacy of calcium and vitamin D reduces inflammation, beta-catenin signaling and dysbiotic Parasutterela bacteria in the colon of C57BL/6 mice fed a Western-style diet

Authors: Zeng, Huawei; Safratowich, Bryan; LIU, ZHENJUA - University Of Massachusetts; Bukowski, Michael; ISHAQ, SUZANNE - University Of Maine

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/2/2021
Publication Date: 3/8/2021
Citation: Zeng, H., Safratowich, B.D., Liu, Z., Bukowski, M.R., Ishaq, S. 2021. Adequacy of calcium and vitamin D reduces inflammation, beta-catenin signaling and dysbiotic Parasutterela bacteria in the colon of C57BL/6 mice fed a Western-style diet. Journal of Nutritional Biochemistry. 92. Article 108613. https://doi.org/10.1016/j.jnutbio.2021.108613.
DOI: https://doi.org/10.1016/j.jnutbio.2021.108613

Interpretive Summary: Colon cancer is a major public health issue in the US, with approximately 137,000 new cases and 50,000 deaths per year. Adoption of a diet that is high in fat and low in calcium and vitamin D is a global problem leading to increased obesity, colonic inflammation and cancer. However, the mechanisms underlying this relationship remains to be elucidated. In this study, we demonstrate that an adequate intake of calcium and vitamin D reduces colonic inflammation, cancer signaling and unhealthy gut bacteria in a mouse model in the context of a diet that is high in fat and low in calcium and vitamin D. These data provide novel insights into diet-related cancer risk and will be useful for scientists who are interested in diet and colon cancer prevention.

Technical Abstract: Adoption of an obesogenic diet low in calcium and vitamin D (CaD), prevalent in many Western countries, leads to increased obesity, colonic inflammation, and cancer. However, the mechanisms underlying this relationship remain to be elucidated. We tested the hypothesis that CaD supplementation (from inadequacy to adequacy) may reduce colonic inflammation, oncogenic signaling, and dysbiosis in the colon of C57BL/6 mice fed a Western diet. Male C57/BL6 mice (4-week old) were assigned to 3 dietary groups (n = 20/group) for 36 weeks: (1) AIN76A as a control diet (AIN); (2) a defined rodent “new Western diet” (NWD); or (3) NWD with CaD supplementation (NWD/CaD). Mice receiving the NWD or NWD/CaD exhibited more than 0.2-fold increase in the levels of plasma leptin, tumor necrosis factor alpha (TNF-alpha), and body weight when compared with those on the AIN diet. The levels of plasma interleukin 6 (IL-6), inflammatory cell infiltration, and beta-catenin/Ki67 protein (oncogenic signaling) were increased more than 0.8-fold in the NWD as compared to the AIN group; however, the levels were not increased in the NWD/CaD group compared to controls. Consistent with the inflammatory phenotype, colonic secondary bile acid (BA, inflammatory bacterial metabolite) levels increased more than 0.4-fold in the NWD group when compared with the NWD/CaD and AIN groups. Furthermore, the abundance of colonic Proteobacteria (e.g., Parasutterela), considered signatures of dysbiosis, was increased more than 4-fold; and the a diversity of colonic bacterial species, indicative of health, was decreased by 30% in the NWD group when compared with the AIN and NWD/CaD groups. Collectively, CaD adequacy reduces colonic inflammation, beta-catenin oncogenic signaling, secondary BAs, and bacterial dysbiosis in mice fed with a Western diet.