Oral iron supplementation: Potential implications for the gut microbiome and metabolome in patients with CKD

Abstract

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.

Clostridium difficile infection in hospitalized octogenarian patients

“…Bifidobacteriaceae ) and an increase of potentially pathogenic microbiota (e.g. Clostridium perfringens ) . Thus, the present results support the findings of other studies reporting the risk factors and outcome of CDI in octogenarians .…”

The Phosphate Binder Ferric Citrate Alters the Gut Microbiome in Rats with Chronic Kidney Disease

“…Patients with end-stage kidney disease show decreased numbers of gut bacteria such as Lactobacillaceae and Prevotellaceae that are able to produce the short-chain fatty acid butyrate, also an important nutrient source for host enterocytes (Vaziri et al, 2013a;Wong et al, 2014). It was recently proposed that the use of oral iron supplements might further contribute to gut microbiome alterations (Kortman et al, 2017), extrapolating from studies in African children where supplemental iron decreased the abundances of bacteria considered to be beneficial, such as Bifidobacteriaceae and Lactobacillaceae (Jaeggi et al, 2015), and increased gut permeability (Nchito et al, 2006). In an in vitro model of the human colon, where intestinal epithelial Caco-2 cells were inoculated with human microbiota, incubation with ferrous sulfate or ferric citrate altered the microbiome population and also decreased levels of Bifidobacteriaceae and Lactobacillaceae (Kortman et al, 2016).…”

Altered microbiome in chronic kidney disease: systemic effects of gut-derived uremic toxins

“…Therefore, the gut environment in CKD suffers from combined disruptions to the microbial framework and lack of fiber substrate, adversely impacting the local nutrient environment for enterocytes [3]. It was recently proposed that use of oral iron supplements might further contribute to gut microbiome alterations [27], extrapolating from studies in African children whereby supplemental iron led to decreased abundance of generally beneficial bacteria including Lactobacillus and Bifidobacterium species [28] as well as increased gut permeability [29].…”