Abstract

INTRODUCTION: Studies have demonstrated antitumor or anti-inflammatory properties of calcium and vitamin D. Dietary calcium and vitamin D intake has been associated with lower risk of colorectal cancer. However, the effect of calcium and vitamin D intake on gut microbiota is not well understood. METHODS: This is a cross-sectional study of 99 colonic biopsies of 35 individuals (average age 62 years, 77% Caucasian and 1 woman) with poly-free colonoscopy between August 2013 and April 2017 at Michael E. DeBakey VA Medical Center. Microbial DNA was isolated and the V4 region of the16S rRNA gene was amplified then sequenced for microbiome profiling. A food frequency questionnaire was used to ascertain calorie-adjusted calcium and vitamin D intake. Median intake was used to dichotomize the intake to low vs. high. Sequencing data were analyzed using the UPARSE and SILVA database for operational taxonomic unit (OTU) classification. Alpha-diversity (Shannon index), beta-diversity (weighted UniFrac) and relative abundance of bacteria (Mann-Whitney test) were compared between low vs. high intake. Reported P-value was adjusted for multiple comparisons using false discovery rate (FDR). RESULTS: Compared with lower intake, higher dietary calcium and vitamin D intakes were both associated with greater richness and evenness (P value < 0.005). The community composition also differed by calcium and vitamin D intake (P = 0.001). In phylum level, the relative abundance of Verrucomicrobia was greater in individuals with higher calcium and vitamin D intake (P values < 0.005). In genus level, high consumption of both calcium and vitamin D were associated with a significantly higher relative abundance of Akkermansia, Faecalibacterium, Dialister, Haemophilus, Odoribacter, Fusicatenibacter, and Paraprevotella, but a lower abundance of Erysipelatoclostridium and Lachnoclostridium (FDR P values < 0.05). Higher intake of calcium, but not vitamin D, was also associated with lower abundance of Bacteroides and higher abundance of Parabacteroides (P values = 0.02). CONCLUSION: Higher intake of calcium and vitamin D was associated with a higher diversity of colonic microbiota and higher abundance of potentially beneficial bacteria and lower abundance of harmful bacteria in healthy individuals. Further metagenomics and metabolomics research are needed to understand whether and how the protective effect of calcium and vitamin D on colorectal cancer is partially mediated through gut microbiome.

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