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

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 composit...