Magnesium treatment increases gut microbiome synthesizing vitamin D and inhibiting colorectal cancer: results from a double-blind precision-based randomized placebo-controlled trial Original paper

What was studied?

This randomized, double-blind, precision-based placebo-controlled trial tested whether 12 weeks of personalized magnesium supplementation changes gut microbial features linked to vitamin D activity and colorectal cancer protection. The investigators targeted two microbes previously shown in animal work to support local vitamin D signaling and suppress colorectal carcinogenesis: Carnobacterium maltaromaticum and Faecalibacterium prausnitzii. They also tested whether responses differ by a functional magnesium-handling gene variant in TRPM7 and whether microbial changes explain shifts in circulating vitamin D metabolites.

Who was studied?

Researchers enrolled adults with a history of colorectal polyps in the Personalized Prevention of Colorectal Cancer Trial and randomized them to magnesium glycinate or placebo. The analysis included 226 participants with usable microbiome data, with a mean age around 60, and mostly White participants. They stratified randomization by TRPM7 genotype, comparing people with typical TRPM7 function (GG) versus carriers of a missense variant (GA). They profiled microbiomes from stool, rectal swabs, and rectal mucosal biopsies to capture different gut niches.

What were the most important findings?

Magnesium’s effect depended on TRPM7 genotype and sample niche, with the clearest signal in rectal swabs. In participants without the missense variant (GG), magnesium increased C. maltaromaticum and also increased F. prausnitzii in rectal swabs compared with placebo, supporting a genotype-specific microbial response. In carriers of the missense variant (GA), magnesium tended to move in the opposite direction for C. maltaromaticum in swabs and reduced F. prausnitzii in rectal mucosa. The treatment-genotype interaction stayed strongest for C. maltaromaticum, and the swab effect appeared mainly in females. Magnesium-driven microbial shifts did not mediate changes in circulating vitamin D metabolites, suggesting local gut effects rather than systemic vitamin D changes.

What are the greatest implications of this study?

This trial supports a precision-nutrition concept for microbiome modulation: magnesium can shift colorectal-adjacent microbial signatures, but the direction and location depend on TRPM7 genotype and sex. For clinicians, the key implication is that magnesium supplementation may not produce uniform microbiome benefits; it may selectively raise microbes tied to local vitamin D signaling in some patients while lowering certain taxa in others. This genotype-aware pattern matters for building microbiome signature databases and for designing prevention strategies in higher-risk groups, because rectal swab and mucosal niches can respond differently than stool.