{"doi":"10.1016/j.ajcnut.2025.09.011","title":"Magnesium treatment increases gut microbiome synthesizing vitamin D and inhibiting colorectal cancer: results from a double-blind precision-based randomized placebo-controlled trial","abstract":"BACKGROUND: 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. OBJECTIVES: We hypothesize that Mg treatment increases gut C. maltaromaticum and F. prausnitzii, and the effect differs by TRPM7 polymorphism. METHODS: The Personalized Prevention of Colorectal Cancer Trial is a double-blind, precision-based randomized controlled trial with 240 participants randomly assigned to both treatment and TRPM7 genotype. Stool, rectal swabs, and rectal mucosa were collected. RESULTS: Of 239 participants who 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 with placebo significantly increased abundance of C. maltaromaticum (0.217 ± 0.615 (23.01%) compared with -0.065 ± 0.588 (-6.30%); P = 0.006) and F. prausnitzii (0.105 ± 0.817 (2.13%) compared with -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 with placebo in rectal swabs [-0.065 ± 0.511 (-6.54%) compared with 0.133 ± 0.503 (13.30%); adjusted P = 0.04]. The effect did not remain after false discovery rate correction. Mg treatment's effect on C. maltaromaticum in rectal swabs primarily appeared in females, and the treatment-genotype interaction remained significant. CONCLUSIONS: In individuals with adequate TRPM7 function, Mg supplementation increases the abundance of C. maltaromaticum and F. prausnitzii. CLINICAL TRIAL REGISTRY: This trial was registered at 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.","journal":"American Journal of Clinical Nutrition","year":2025,"id":522047,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":5,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9499,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03265483","NCT01105169","NCT04229992"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":813592,"name":"Xiangzhu Zhu","orcid":"0000-0002-4462-8815","position":1,"is_corresponding":false},{"id":499224,"name":"Reid M. Ness","orcid":"0000-0002-1645-7393","position":2,"is_corresponding":false},{"id":381198,"name":"Harvey J. Murff","orcid":"0000-0002-4943-4665","position":3,"is_corresponding":false},{"id":404190,"name":"Shan Sun","orcid":"0000-0003-0349-2664","position":4,"is_corresponding":false},{"id":750862,"name":"Chang Sik Yu","orcid":"0000-0001-9401-9981","position":5,"is_corresponding":false},{"id":1131795,"name":"Lei Fan","orcid":"0000-0003-1091-7018","position":6,"is_corresponding":false},{"id":245450,"name":"M. Andrea Azcárate-Peril","orcid":"0000-0003-0325-1289","position":7,"is_corresponding":false},{"id":86858,"name":"Martha J. Shrubsole","orcid":"0000-0002-5591-7575","position":8,"is_corresponding":false},{"id":311058,"name":"Qi Dai","orcid":"0000-0003-1343-1494","position":9,"is_corresponding":false},{"id":605095,"name":"Elizabeth Sun","orcid":null,"position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:49:49.198144Z","pmid":"40946805","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}