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Synthesis and breakdown of universal metabolic precursors promoted by iron

Muchowska KB, Varma SJ, Moran J

Nature. 2019 May;569(7754):104-107. PDF

Recommended by Dr. Paolo Arosio


A possible non-biological reaction framework for metabolic processes on early Earth

Pascal R.

Nature. 2019 May;569(7754):47-49.PDF

Ironing the Gut

It is well known that iron is not only an essential nutrient for mammals but also serves as a growth factor for most bacteria, including those residing in the intestine, known as the microbiome. Accordingly, intestinal bacteria compete for iron within the gut by different mechanisms. That  provides a growth advantage to those microbes which have more sophisticated strategies to acquire the metal needed for their proliferation and pathogenicity1. In addition, increased iron availability in the intestine severely changes the composition of the gut microbiome with the expansion of more virulent, potentially pathogenic bacteria2. The struggle for iron is now well appreciated as a central mechanism in host pathogen interaction and the outcome of infections3.  In a recent paper published in Cell Metabolism, Das and co-workers (2020) add a new facet to this picture as they provide novel evidence that the gut microbiome affects host iron homeostasis by modulating iron absorption4.  They noted that germ free (GF) but not specific pathogen free C57BL6 mice developed anemia when fed an iron poor diet, which already implied that bacteria in the gut may compete with host iron uptake. Mechanistically, this could be attributed to inhibition of hypoxia inducible factor 2 alpha (HIF2alpha) expression in the intestine by Lactobacilli with subsequent alterations of HIF2alpha mediated effects on transmembrane iron transfer from the intestinal lumen to the circulation.  Das and co-workers found that intestinal microbes sense iron deficiency and produce metabolites, namely, 1,3-diaminopropane (DAP) and reuterin, which block HIF2 heterodimerisation and thus its biological activity resulting in dietary iron accumulation within enterocyte ferritin. These data first suggest, that mice kept under SPF conditions may not be an ideal model to study host iron homeostasis as effects of intestinal microbes and their secreted products will be missed. Secondly, modulation of intestinal bacterial composition may open a new therapeutic avenue, as specific compositions of probiotics  could affect dietary iron absorption in either direction, for treatment of iron overload conditions (more Lactobacilli) or to ameliorate iron absorption (bacteria outcompeting Lactobacilli, antibiotics) in subjects with iron deficiency.    

1.            Skaar EP, Raffatellu M. Metals in infectious diseases and nutritional immunity. Metallomics. 2015;7(6):926-928.

2.            Jaeggi T, Kortman GA, Moretti D, et al. Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut. 2015;64(5):731-742.

3.            Nairz M, Schroll A, Sonnweber T, Weiss G. The struggle for iron – a metal at the host-pathogen interface. Cell Microbiol. 2010;12(12):1691-1702.

4.            Das NK, Schwartz AJ, Barthel G, et al. Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis. Cell Metab. 2020;31(1):115-130 e116.

Günter Weiss, Medical University of Innsbruck, Austria  (guenter.weiss@i-med.ac.at)

Iron transport and regulation in pregnancy: the fourth musketeer of iron homeostasis

The past two decades have witnessed increasing understanding of the molecular pathways and regulation of the three large iron flows in the body: intestinal iron absorption, macrophage-mediated recycling of iron from senescent erythrocytes, and the uptake of iron and its retrieval from storage in hepatocytes.  Often forgotten is another large iron flow, the transfer of iron during pregnancy from the mother through the placenta to the fetus. Understanding how the placenta transports iron and how the placental-fetal unit responds to maternal iron stresses is of more than academic interest, as iron deficiency during pregnancy is a major global problem, too often compounded by maternal infection and inflammation. In this context, the recent contributions of Sangkhae et al. JCI 2020 (and the associated commentary by Parrow et al. JCI 2020) and Fisher et al. JCI Insight 2020 are particularly noteworthy.

Reincarnation or Atavism in the Iron Field? By Ioav Cabantchik


The medieval practice of bloodletting was based on the Moslem medical writers who emphasized revulsion (bleeding from a site located as far from the ailment as possible). This position was attacked in 1514 by Pierre Brissot (1478-1522), a Paris physician, who stressed the importance of bleeding near the locus of the disease (derivative bleeding). He was declared a medical heretic by the Paris Faculty of Medicine and derivative bleeding was forbidden by an act of the French parliament. In 1518, Brissot was exiled to Spain and Portugal. In 1539, the celebrated anatomist, Andreas Vesalius, continued the controversy with his famous Venesection Letter, which came to the support of Brissot“. 

From T.A. Appel and A.B. Davis  “Bloodletting Instruments in the National Museum of History and Technology” 1–103, 1979  https://doi.org/10.5479/si.00810258.41.1

That venesection runs in the veins of our Pierre Brissot (former President of Bioiron and leading authority in hemochromatosis) may not come as a surprise to our members, but is the profession an hereditary trait or is that an atavistic feature of PR?….

In fact, Pierre Brissot is not only aware of his distinguished ancestry profession but also shared that information publically in his recently published historical article in the Revue du Praticien ( Vol. 67 _ Décembre 2017 ) titled “LA SAIGNÉE EN MÉDECINE : une très longue histoire qui n’est pas encore terminée”  (“Bleeding in medicine: a very long story that is not over yet”).


Renal Iron Handling In Health and Disease

Invitation to submit research and review articles related to Renal Iron Handling in Health and Disease.

While iron is a pre-requisite for life, it also initiates a cascade of pathological events that lead to parenchymal damage and activation of immune cells. Iron-dependent regulated cell death, namely ferroptosis, potentiates kidney injury and ironically, delivery of iron (or iron-loaded macrophages) to the kidney reduces the severity of the disease. Clearly, this represents our incomplete understanding iron metabolism in kidney health and pathology.

              We invite investigators to contribute original research articles as well as review articles that will aid in the understanding of iron metabolism and trafficking in the initiation and outcomes of kidney injury and chronic kidney disease.

Potential topics include, but are not limited to:

• Characterization and determination of the role of the kidney in iron trafficking and metabolism
• Effects of disorders of systemic iron metabolism (e.g. iron deficiency and iron overload) on the kidney, including new techniques to measure iron content (free or protein-bound) in tissue, plasma and cells
– Iron homeostasis in kidney disease (proteinuria, glomerulopathy and chronic kidney disease)
• Mechanism of iron-mediated kidney injury;
• Modulation of iron and hepcidin levels as therapeutic strategies to overcome injury and/or promote recovery 

Please use the following link to access the submission page