Magnesium Treatment Increases Gut Microbiome Synthesizing Vitamin D and Inhibiting Colorectal Cancer: Results from a Double-Blind Precision-based Randomized Placebo-Controlled Trial.

Carnobacterium maltaromaticum and Faecalibacterium prausnitzii induce de novo gut synthesis of vitamin D to inhibit colorectal carcinogenesis in mice. Magnesium (Mg) treatment increases circulating vitamin D and Mg homeostasis is dependent on TRPM7 genotype. We hypothesize that Mg treatment increases gut C. maltaromaticum and F. prausnitzii and the effect differs by TRPM7 polymorphism. The Personalized Prevention of Colorectal Cancer Trial is a double-blind, precision-based randomized controlled trial with 240 participants randomized by both treatment and TRPM7 genotype. Stool, rectal swabs, and rectal mucosa were collected. Of 239 participants that completed the trial, 226 with valid microbiome data were analyzed (treatment n=112, placebo n=114). The interaction between treatment and TRPM7 genotype was only significant for C. maltaromaticum (p=0.001) and F. prausnitzii (p=0.02) in rectal swabs. In a stratified analysis by TRPM7 genotype without the missense variant, Mg treatment compared to placebo significantly increased abundance of C. maltaromaticum (0.217±0.615 (23.01%) compared to -0.065±0.588 (-6.30%); P=0.006) and F. prausnitzii (0.105±0.817 (2.13%) compared to -0.095±0.856 (-1.92%); P =0.04) in rectal swabs. The effect on C. maltaromaticum remained after multiple comparisons (Q=0.05 for C. maltaromaticum across all sample types and genotypes). In those with the TRPM7 missense variant, Mg decreased C. maltaromaticum, but not F. prausnitzii, compared to placebo in rectal swabs (-0.065±0.511 (-6.54%) compared to 0.133±0.503 (13.30%); adjusted P=0.04). The effect did not remain after FDR correction. Mg treatment's effect on C. maltaromaticum in rectal swabs primarily appeared in females, and the treatment-genotype interaction remained significant. In individuals with adequate TRPM7 function, Mg supplementation increases abundance of C. maltaromaticum and F. prausnitzii. This trial was registered on ClinicalTrials.gov as NCT04229992 (https://clinicaltrials.gov/study/NCT04229992?term=NCT04229992&rank=1). The parent study is registered as NCT03265483, and another relevant study is registered as NCT01105169.