Kidney Week

Abstract: SA-PO307

Low Gut Microbiota Diversity and Dietary Magnesium Intake Are Associated with the Development of Proton Pump Inhibitor-Induced Hypomagnesemia

Session Information

• Fluid and Electrolytes: Basic - II
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Hoenderop, Joost, Radboud University Medical Center, Nijmegen, Netherlands

Joost Hoenderop,

• Gommers, Lisanne, Radboud University Medical Center, Nijmegen, Netherlands

Lisanne Gommers,

• Ederveen, Thomas, Radboud University Medical Center, Nijmegen, Netherlands

Thomas Ederveen,

• Van der wijst, Jenny, Radboud University Medical Center, Nijmegen, Netherlands

Jenny Van der wijst,

• Overmars-Bos, Caro, Radboud University Medical Center, Nijmegen, Netherlands

Caro Overmars-Bos,

• Boekhorst, Jos, NIZO, Ede, Netherlands

Jos Boekhorst,

• Bindels, René J., Radboud University Medical Center, Nijmegen, Netherlands

René J. Bindels,

• De Baaij, Jeroen H.F., Radboud University Medical Center, Nijmegen, Netherlands

Jeroen H.F. De Baaij,

Background

Proton pump inhibitors (PPIs) are used by millions of patients for the treatment of stomach acid-reflux diseases. Long-term PPI intake has been associated with serious adverse effects including enteric and respiratory infections, acute kidney injury (AKI) and chronic kidney disease (CKD). In addition, it has become increasingly evident that long-term PPI use induces hypomagnesemia (serum magnesium (Mg²⁺) levels < 0.7 mmol/L). Despite rising attention for this issue, the underlying mechanism is still unknown. Recent studies have identified associations between PPI use and gut microbiota. Here, we examined whether the gut microbiome is involved in the development of PPI-induced hypomagnesemia.

Methods

To assess the effects of the PPI omeprazole on Mg²⁺ homeostasis and gut microbiota, C57BL/6J mice were treated daily with omeprazole (20 mg/kg bodyweight) or placebo for four weeks under normal (0.22 % w/w) or low (0.05 % w/w) dietary Mg²⁺availability. Subsequently, Mg²⁺ homeostasis was assessed by means of serum, urine and faecal electrolyte measurements, RT-qPCR to evaluate renal and intestinal Mg²⁺-related genes, and gut microbiota composition was investigated by 16S rRNA gene sequencing.

Results

After four weeks of treatment, omeprazole significantly reduced serum Mg²⁺ levels in mice on a low Mg²⁺ diet. Renal Trpm6 expression was increased as compensation for the low Mg²⁺ diet in placebo-treated mice, but expression of this Mg²⁺ channel was not changed in the omeprazole-treated group. Moreover, these mice did not exhibit urinary Mg²⁺ wasting. Overall, 16S rRNA gene sequencing revealed a lower gut microbial diversity in omeprazole-treated mice. Omeprazole induced a shift in microbial composition that 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.

Conclusion

Our 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.

Funding

• Government Support - Non-U.S.