title: Dietary iron depletion at weaning imprints low microbiome diversity and this is not recovered with oral Nano Fe(III).
abstract: Alterations in the gut microbiota have been recently linked to oral iron. We conducted two feeding studies including an initial diet-induced iron-depletion period followed by supplementation with nanoparticulate tartrate-modified ferrihydrite (Nano Fe(III): considered bioavailable to host but not bacteria) or soluble ferrous sulfate (FeSO4: considered bioavailable to both host and bacteria). We applied denaturing gradient gel electrophoresis and fluorescence in situ hybridization for study-1 and 454-pyrosequencing of fecal 16S rRNA in study-2. In study-1, the within-community microbial diversity increased with FeSO4 (P = 0.0009) but not with Nano Fe(III) supplementation. This was confirmed in study-2, where we also showed that iron depletion at weaning imprinted significantly lower within- and between-community microbial diversity compared to mice weaned onto the iron-sufficient reference diet (P < 0.0001). Subsequent supplementation with FeSO4 partially restored the within-community diversity (P = 0.006 in relation to the continuously iron-depleted group) but not the between-community diversity, whereas Nano Fe(III) had no effect. We conclude that (1) dietary iron depletion at weaning imprints low diversity in the microbiota that is not, subsequently, easily recovered; (2) in the absence of gastrointestinal disease iron supplementation does not negatively impact the microbiota; and (3) Nano Fe(III) is less available to the gut microbiota.
authors.affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom.
authors.forename: Dora I A
authors.initials: DI
authors.lastname: Pereira
authors.forename: Mohamad F
authors.initials: MF
authors.lastname: Aslam
authors.forename: David M
authors.initials: DM
authors.lastname: Frazer
authors.forename: Annemarie
authors.initials: A
authors.lastname: Schmidt
authors.forename: Gemma E
authors.initials: GE
authors.lastname: Walton
authors.forename: Anne L
authors.initials: AL
authors.lastname: McCartney
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gibson
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Anderson
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Powell
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics; D001682:Biological Availability; D005243:Feces / Q000382:microbiology; D005290:Ferric Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019266:Iron, Dietary / Q000378:metabolism*; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D051381:Rats; D017207:Rats, Sprague-Dawley; D014886:Weaning
chemical_list: D005290:Ferric Compounds; D019266:Iron, Dietary
keywords: Iron supplementation; microbiome; microbiota; nanoparticles; oral iron