Intravenous ferric carboxymaltose and ferric derisomaltose alter the intestinal microbiome in female iron-deficient anemic mice.

Iron deficiency anemia (IDA) is a leading global health concern affecting approximately 30% of the population. Treatment for IDA consists of replenishment of iron stores, either by oral or intravenous (IV) supplementation. There is a complex bidirectional interplay between the gut microbiota, the host's iron status, and dietary iron availability. Dietary iron deficiency and supplementation can influence the gut microbiome; however, the effect of IV iron on the gut microbiome is unknown. We studied how commonly used IV iron preparations, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), affected the gut microbiome in female iron-deficient anemic mice. At the phylum level, vehicle-treated mice showed an expansion in Verrucomicrobia, mostly because of the increased abundance of Akkermansia muciniphila, along with contraction in Firmicutes, resulting in a lower Firmicutes/Bacteroidetes ratio (indicator of dysbiosis). Treatment with either FCM or FDI restored the microbiome such that Firmicutes and Bacteroidetes were the dominant phyla. Interestingly, the phyla Proteobacteria and several members of Bacteroidetes (e.g., Alistipes) were expanded in mice treated with FCM compared with those treated with FDI. In contrast, several Clostridia class members were expanded in mice treated with FDI compared with FCM (e.g., Dorea spp., Eubacterium). Our data demonstrate that IV iron increases gut microbiome diversity independently of the iron preparation used; however, differences exist between FCM and FDI treatments. In conclusion, replenishing iron stores with IV iron preparations in clinical conditions, such as inflammatory bowel disease or chronic kidney disease, could affect gut microbiome composition and consequently contribute to an altered disease outcome.

Sodium phosphate cotransporter 2a inhibitors: potential therapeutic uses.

PURPOSE OF REVIEW: Targeting sodium phosphate cotransporter 2a (Npt2a) offers a novel strategy for treating hyperphosphatemia in chronic kidney disease (CKD). Here we review recent studies on the efficacy of Npt2a inhibition, its plasma phosphate (Pi)-lowering effects, as well as potential "off-target" beneficial effects on cardiovascular consequences. RECENT FINDINGS: Two novel Npt2a-selective inhibitors (PF-06869206 and BAY-767) have been developed. Pharmacological Npt2a inhibition shows a significant phosphaturic effect and consequently lowers plasma Pi and parathyroid hormone (PTH) levels regardless of CKD. However, plasma fibroblast growth factor 23 (FGF23), a master regulator of Pi homeostasis, shows inconsistent responses between these two inhibitors (no effect by PF-06869206 vs. reduction by BAY-767). In addition to the effects on Pi homeostasis, Npt2a inhibition also enhances urinary excretions of Na+, Cl-, and Ca2+, which is recapitulated in animal models with reduced kidney function. The effect of Npt2a inhibition by BAY-767 on vascular calcification has been studied, with positive results showing that oral treatment with BAY-767 (10 mg kg-1) attenuated the increases in plasma Pi and Ca2+ content in the aorta under the setting of vascular calcification induced by a pan-FGF receptor inhibitor. Together, Npt2a inhibition offers a promising therapeutic approach for treating hyperphosphatemia and reducing cardiovascular complications in CKD. SUMMARY: Npt2a inhibition significantly increases urinary Pi excretion and lowers plasma Pi and PTH levels; moreover, it exerts pleiotropic "off-target" effects, providing a novel treatment for hyperphosphatemia and exhibiting beneficial potential for cardiovascular complications in CKD.

Effects of Graded Levels of Chromium Methionine on Performance, Carcass Traits, Meat Quality, Fatty Acid Profiles of Fat, Tissue Chromium Concentrations, and Antioxidant Status in Growing-Finishing Pigs.

A 97-day feeding trial was conducted to investigate the effects of dietary chromium methionine (CrMet) on performance, carcass traits, meat quality, fatty acid profiles of fat, tissue chromium concentrations, and antioxidant status in growing-finishing pigs. A total of 180 crossbred pigs with a mean initial body weight (BW) 30.18 ± 0.28 kg were allotted to 5 treatments with 6 replicates per treatment and 6 pigs per pen in a randomized complete block design based on BW and sex. Treatments were added with 0 (control), 100, 200, 400, and 800 µg/kg chromium as CrMet. Blood samples were obtained from the anterior vena cava on days 97. Carcass characteristics, pork quality, and tissue chromium concentration data were collected from one pig per pen. The results indicated that supplemental CrMet did not significantly affect growth performance, carcass traits, or meat amino acid profiles. Chromium at 100, 400, and 800 µg/kg decreased drip loss but increased shear force (P < 0.05). Pigs fed 100 or 400 µg/kg had a higher 24-h pH than the control (P < 0.05). While meat color, muscle moisture, crude protein, or crude fat were not affected by CrMet. Supplemental 800 µg/kg chromium reduced C18:0 levels in belly fat (P < 0.05), and chromium supplementation increased cis-9, trans 11-conjugated linoleic acid levels linearly (P < 0.05). Dietary CrMet supplementation increased serum, kidney, and muscle chromium contents (P < 0.05) but did not affect liver chromium contents. Besides, tissue chromium concentrations were increased linearly with increased chromium dosage (P < 0.05). Chromium at 400 µg/kg increased serum glutathione peroxidase activities (P < 0.05), and chromium at 800 µg/kg decreased serum total antioxidant capacity levels (P < 0.05). Nevertheless, liver and kidney antioxidant status were not significantly affected by CrMet. These results indicated that dietary supplementation CrMet did not significantly influence growth and carcass traits, but improved meat quality at the expense of tenderness. Therefore, the long-term exposure to 800 µg/kg chromium affected fatty acid compositions and reduced serum antioxidant capacity.

Effects of chromium methionine supplementation on growth performance, serum metabolites, endocrine parameters, antioxidant status, and immune traits in growing pigs.

The effects of dietary chromium methionine (CrMet) on growth performance, serum metabolites, endocrine parameters, antioxidant status, and immune traits in growing pigs were investigated. A total of 180 crossbred pigs (30.18 ± 0.28 kg initial body mass) were randomly divided into five groups, each group with six pens, six pigs per pen. Pigs were fed on the same basal diet supplemented with 0 (control), 100, 200, 400, and 800 µg/kg Cr from CrMet for 35 days. The results showed that supplemental CrMet did not affect growth performance. Cr at 200-800 µg/kg significantly decreased serum glucose levels (P < 0.05), while other serum metabolites were unaffected by Cr supplementation. Serum growth hormone (GH) levels were significantly decreased by Cr addition (P < 0.05). Furthermore, serum insulin-like growth factor I (IGF-I) levels were linearly decreased with increased Cr dose, and a significant reduction was observed in pigs fed 800 µg/kg Cr diets (P < 0.05). Serum immunoglobulin A, G, and M concentrations were increased linearly with increased Cr dosage, and pigs fed 400 µg/kg Cr had greater serum immunoglobulin M contents (P < 0.05). Cr at 400 µg/kg significantly increased serum superoxide dismutase and total antioxidant capacity activities (T-AOC) (P < 0.05). However, Cr at 800 µg/kg increased serum catalase activities, while decreasing serum T-AOC contents (P < 0.05). Additionally, there was a significant increase in serum malondialdehyde levels for pigs fed 800 µg/kg Cr diets (P < 0.05). These results indicated that dietary supplementation CrMet decreased serum glucose, GH, and IGF-I levels. Besides, supplemental 400 µg/kg Cr as CrMet improved serum antioxidant status and immune responses, but additional 800 µg/kg Cr resulted in lipid peroxidation in growing pigs.