Hess Mark W, de Baaij Jeroen H F, Gommers Lisanne M M, Hoenderop Joost G J, Bindels René J M
Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
PLoS One. 2015 Sep 23;10(9):e0138881. doi: 10.1371/journal.pone.0138881. eCollection 2015.
Proton-pump inhibitor-induced hypomagnesemia (PPIH) is the most recognized side effect of proton-pump inhibitors (PPIs). Additionally, PPIH is associated with hypocalcemia and hypokalemia. It is hypothesized that PPIs reduce epithelial proton secretion and thereby increase the pH in the colon, which may explain the reduced absorption of and Mg2+ and Ca2+. Fermentation of dietary oligofructose-enriched inulin fibers by the microflora leads to acidification of the intestinal lumen and by this enhances mineral uptake. This study aimed, therefore, to improve mineral absorption by application of dietary inulin to counteract PPIH.
Here, C57BL/J6 mice were supplemented with omeprazole and/or inulin. Subsequently, Mg2+ and Ca2+ homeostasis was assessed by means of serum, urine and fecal electrolyte measurements. Moreover, the mRNA levels of magnesiotropic and calciotropic genes were examined in the large intestine and kidney by real-time PCR.
Treatment with omeprazole significantly reduced serum Mg2+ and Ca2+ levels. However, concomitant addition of dietary inulin fibers normalized serum Ca2+ but not serum Mg2+ concentrations. Inulin abolished enhanced expression of Trpv6 and S100g in the colon by omeprazole. Additionally, intestinal and renal mRNA levels of the Trpm6 gene were reduced after inulin intake.
This study suggests that dietary inulin counteracts reduced intestinal Ca2+ absorption upon PPI treatment. In contrast, inulin did not increase intestinal absorption of Mg2+ sufficiently to recover serum Mg2+. The clinical potential of dietary inulin treatment should be the subject of future studies.
质子泵抑制剂诱导的低镁血症(PPIH)是质子泵抑制剂(PPIs)最广为人知的副作用。此外,PPIH与低钙血症和低钾血症有关。据推测,PPIs减少上皮质子分泌,从而增加结肠内的pH值,这可能解释了镁离子和钙离子吸收减少的原因。微生物群对富含低聚果糖的菊粉纤维进行发酵会导致肠腔酸化,从而增强矿物质吸收。因此,本研究旨在通过应用膳食菊粉来改善矿物质吸收,以对抗PPIH。
在此,给C57BL/J6小鼠补充奥美拉唑和/或菊粉。随后,通过血清、尿液和粪便电解质测量来评估镁离子和钙离子的稳态。此外,通过实时PCR检测大肠和肾脏中与镁离子和钙离子相关基因的mRNA水平。
用奥美拉唑治疗显著降低了血清镁离子和钙离子水平。然而,同时添加膳食菊粉纤维可使血清钙离子浓度恢复正常,但血清镁离子浓度未恢复正常。菊粉消除了奥美拉唑引起的结肠中Trpv6和S100g表达增强。此外,摄入菊粉后,Trpm6基因在肠道和肾脏中的mRNA水平降低。
本研究表明,膳食菊粉可对抗PPI治疗后肠道钙离子吸收减少的情况。相比之下,菊粉未能充分增加肠道对镁离子的吸收以恢复血清镁离子水平。膳食菊粉治疗的临床潜力应是未来研究的主题。