Low gut microbiota diversity and dietary magnesium intake are associated with the development of PPI‐induced hypomagnesemia

• DOI: 10.1096/fj.201900839r
• Publication Date: 2019-07-12T21:06:15Z
• Authors: Lisanne M. M. Gom...; Thomas H. A. Eder...; Jenny Wijst; Caro Overmars-Bos; Guus A. M. Kortman; Jos Boekhorst; René J. M. Bindels; Jeroen H. F. Baaij; Joost G. J. Hoend...
• Keywords: Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Male; 0301 basic medicine; Colon; CMBI - Radboud University Medical Center; Proton Pump Inhibitors; Radboudumc 11: Renal disorders RIMLS: Radboud Institute for Molecular Life Sciences; Diet; Gastrointestinal Microbiome; 3. Good health; Physiology - Radboud University Medical Center; Mice, Inbred C57BL; Lactobacillus; Mice; 03 medical and health sciences; RNA, Ribosomal, 16S; Animals; Magnesium; Bifidobacterium; Molecular Biology; Omeprazole

Proton pump inhibitors (PPIs) are used by millions of patients for the treatment of stomach acid-reflux diseases. Although PPIs are generally considered safe, about 13% of the users develop hypomagnesemia. Despite rising attention for this issue, the underlying mechanism is still unknown. Here, we examine whether the gut microbiome is involved in the development of PPI-induced hypomagnesemia in wild-type C57BL/6J mice. After 4 wk of treatment under normal or low dietary Mg2+ availability, omeprazole significantly reduced serum Mg2+ levels only in mice on a low-Mg2+ diet without affecting the mRNA expression of colonic or renal Mg2+ transporters. Overall, 16S rRNA gene sequencing revealed a lower gut microbial diversity in omeprazole-treated mice. Omeprazole induced a shift in microbial composition, which was associated with a 3- and 2-fold increase in the abundance of Lactobacillus and Bifidobacterium, respectively. To examine the metabolic consequences of these microbial alterations, the colonic composition of organic acids was evaluated. Low dietary Mg2+ intake, independent of omeprazole treatment, resulted in a 10-fold increase in formate levels. Together, these results imply that both omeprazole treatment and low dietary Mg2+ intake disturb the gut internal milieu and may pose a risk for the malabsorption of Mg2+ in the colon.-Gommers, L. M. M., Ederveen, T. H. A., van der Wijst, J., Overmars-Bos, C., Kortman, G. A. M., Boekhorst, J., Bindels, R. J. M., de Baaij, J. H. F., Hoenderop, J. G. J. Low gut microbiota diversity and dietary magnesium intake are associated with the development of PPI-induced hypomagnesemia.