Kortman Guus A M, Reijnders Dorien, Swinkels Dorine W
Department of Laboratory Medicine - Translational Metabolic Laboratory-830, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
Hemodial Int. 2017 Jun;21 Suppl 1:S28-S36. doi: 10.1111/hdi.12553. Epub 2017 Mar 22.
Patients with chronic kidney disease (CKD) and loss of kidney function are at increased risk for morbidity and mortality. The risks of CKD are attributed to "uremia," an increased concentration of uremic retention solutes (toxins) in the plasma. Recently, a colo-renal axis became clearly apparent and uremia has been associated with an altered gut microbiome composition and metabolism. There is a high prevalence of anemia in patients with CKD, for which patients are often treated with oral or intravenous iron. Recent in vivo and in vitro studies have reported adverse effects of oral iron supplementation on the gut microbiota composition, gut metabolome, and intestinal health, which in turn may result in an increased production of uremic toxins. It may also affect circulating levels of other microbe-derived molecules, that can act as mediators of immune regulation. Changes in body iron levels have also been reported to exert subtle effects on host immune function by modulating immune cell proliferation and differentiation, and by directly regulating cytokine formation and antimicrobial immune effector mechanisms. Based on the foregoing it is conceivable that oral iron supplementation in iron deficient predialysis CKD patients adversely changes gut microbiota composition, the gut and systemic metabolome, and host immunity and infection. Future studies are needed to confirm these hypotheses and to assess whether, compared to IV iron supplementation, oral iron supplementation negatively impacts on morbidity of CKD, and whether these adverse effects depend on the iron bioavailability of the iron formulation to the microbiota.
慢性肾脏病（CKD）患者以及肾功能丧失患者的发病和死亡风险会增加。CKD的风险归因于“尿毒症”，即血浆中尿毒症潴留溶质（毒素）浓度升高。最近，结肠-肾脏轴已清晰显现，且尿毒症与肠道微生物群组成及代谢的改变有关。CKD患者贫血患病率很高，对此患者常接受口服或静脉补铁治疗。最近的体内和体外研究报告了口服补铁对肠道微生物群组成、肠道代谢组和肠道健康的不良影响，这反过来可能导致尿毒症毒素产生增加。它还可能影响其他微生物衍生分子的循环水平，这些分子可作为免疫调节介质。据报道，体内铁水平的变化也会通过调节免疫细胞增殖和分化，以及直接调节细胞因子形成和抗菌免疫效应机制，对宿主免疫功能产生微妙影响。基于上述情况，可以想象，缺铁的透析前CKD患者口服补铁会对肠道微生物群组成、肠道和全身代谢组以及宿主免疫和感染产生不利影响。需要进一步的研究来证实这些假设，并评估与静脉补铁相比，口服补铁是否会对CKD的发病率产生负面影响，以及这些不良反应是否取决于铁制剂对微生物群的铁生物利用度。
