# Calcium: magnesium balance, microbiota, and necroptosis and inflammation

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $660,589

## Abstract

Five US studies using the Mg tolerance test, the “gold standard” test of magnesium (Mg) status, indicated that
>50% of participants had Mg deficiency. In our ongoing US trial, we have found a similar result. In growing
recognition of the importance of Mg in human health, very recently, Mg was selected by the US Federal Dietary
Reference Intake (DRI) Committee to update the DRI. However, current available human data are not
conclusive. Further human studies are necessary to develop more accurate DRI and RDA for Mg. TNF (tumor
necrosis factor)-induced necroptosis, a newly discovered pathway of regulated necrosis, is more inflammatory
than apoptosis. Animal studies revealed very critical roles of necroptosis in inflammation and many human
inflammatory diseases. Recently, TRPM7 (i.e. Transient Receptor Potential Melastatin 7, an ion channel
essential to Mg absorption and homeostasis) was identified as a downstream effector of necroptosis.
Consistent with in vitro data, Mg affected the growth of Bifidobacterium and Lactobacillus, two major beneficial
bacteria in the gut, as well as systemic inflammation and metabolic disorders in mice. Our pilot findings from a
randomized trial suggest reducing the Ca/Mg ratio through Mg supplementation may increase Bifidobacterium
and Lactobacillus, accompanied by significant reductions in TRPM7 and COX-2 (cyclooxygenase 2)
expression in rectal tissues. In addition to microbiota-host interaction on inflammatory response, many
enzymes, including those involved in fermentation, transport and metabolism of carbohydrates, are dependent
on the Ca/Mg ratio or Mg concentrations. In our pilot metagenomic study, we found all the significantly
changed biologic functions within the microbial community caused by a reduction in the Ca/Mg ratio are
biologically dependent on the Ca/Mg ratio or Mg concentrations. It is striking that the functions with significant
changes in stool samples were centered on the fermentation of carbohydrates and energy metabolism while
the functions in rectal swabs were related to immune response. Rectal tissues had a distinct functional profile.
Our pilot data are highly novel and promising and have very broad clinical and public health significance for
many inflammation-related diseases or metabolic disorders. However, due to the small sample size in our pilot
study, these findings should be confirmed in larger studies which will also address many novel scientific
inquiries based on our pilot data, such as other biomarkers in necroptosis-induced inflammation as well as
microbial species and functions. In Aim 1, we will evaluate the effects of reducing the Ca/Mg ratio on colorectal
microbiota abundance (i.e. Bifidobacterium and Lactobacillus measured by high-throughput quantitative PCR)
and expression of biomarkers in necroptosis-related pathways in rectal tissue assayed by
immunohistochemistry and serum TNF-α in the “Personalized Prevention of Colorectal Cancer Trial [PPCCT,
R01CA149633; PI, Dai & Yu]...

## Key facts

- **NIH application ID:** 9853627
- **Project number:** 5R01DK110166-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** QI DAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $660,589
- **Award type:** 5
- **Project period:** 2017-05-05 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853627

## Citation

> US National Institutes of Health, RePORTER application 9853627, Calcium: magnesium balance, microbiota, and necroptosis and inflammation (5R01DK110166-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853627. Licensed CC0.

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