title: Gut microbial metabolism shifts towards a more toxic profile with supplementary iron in a kinetic model of the human large intestine
organism: metagenome
description: Safety of oral iron administration in African children has been questioned as it is associated with an increased burden of infectious disease. However, it remains unclear to which extent oral iron administration affects the intestinal microbiome. Therefore, we here investigated the impact of multiple iron preparations and doses on the growth and metabolism of a human gut microbiota in a well-controlled in vitro model of the large intestine. Microbiome analysis showed clear iron-induced changes and prominent shifts included a decrease of Bifidobacteriaceae and Lactobacillaceae under iron-rich conditions, paralleled by an increase of Roseburia and Prevotella. Metagenomic analyses showed a general enrichment of bacterial motility-chemotaxis systems under iron-rich conditions. Metabolome profiling showed that gut microbial activity markedly shifted from a saccharolytic to a proteolytic profile in response to iron. Levels of branched chain fatty acids and ammonia increased significantly, in particular under ferrous sulfate-rich conditions. Importantly, cell viability tests showed increased cytotoxicity of metabolite-containing effluent from iron-rich conditions. We also identified microbial metabolites with siderophoric activity that were specifically produced under low-iron conditions. Our data indicate that in the absence of host influences, iron induces a more hostile intestinal environment characterized by i) reduction of beneficial microbes and increase of certain bacterial species with pathogenic potential, ii) increased levels of bacterial metabolites that can impair the barrier function of the gut wall, and iii) increase of virulence-associated pathways of enteric pathogens. It can be envisaged that these in vitro phenomena also contribute to an increased risk for enteric infections in vivo.
attributes.tag: ENA first public
attributes.value: 2015-12-17
attributes.tag: ENA last update
attributes.value: 2016-10-21
attributes.tag: External Id
attributes.value: SAMEA2629424
attributes.tag: INSDC center alias
attributes.value: SDSU
attributes.tag: INSDC center name
attributes.value: San Diego State University
attributes.tag: INSDC first public
attributes.value: 2015-12-17T13:48:31Z
attributes.tag: INSDC last update
attributes.value: 2016-10-21T09:43:21Z
attributes.tag: INSDC status
attributes.value: public
attributes.tag: Submitter Id
attributes.value: TIM2_iron_study_16S_4
attributes.tag: collection date
attributes.value: 2011-09-05
attributes.tag: environment (biome)
attributes.value: terrestrial biome
attributes.tag: environment (feature)
attributes.value: anaerobic bioreactor
attributes.tag: environment (material)
attributes.value: feces
attributes.tag: geographic location (country and/or sea)
attributes.value: Netherlands
attributes.tag: geographic location (latitude)
attributes.value: 52.0905865
attributes.tag: geographic location (longitude)
attributes.value: 5.2332316
attributes.tag: investigation type
attributes.value: mimarks-culture
attributes.tag: miscellaneous environmental package
attributes.value: miscellaneous natural or artificial environment
attributes.tag: project name
attributes.value: TIM2_iron_study
attributes.tag: sample name
attributes.value: TIM2_iron_study_16S_4
attributes.tag: sequencing method
attributes.value: 454 flx