Cargando…

Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon

Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in...

Descripción completa

Detalles Bibliográficos
Autores principales: Kortman, Guus A. M., Dutilh, Bas E., Maathuis, Annet J. H., Engelke, Udo F., Boekhorst, Jos, Keegan, Kevin P., Nielsen, Fiona G. G., Betley, Jason, Weir, Jacqueline C., Kingsbury, Zoya, Kluijtmans, Leo A. J., Swinkels, Dorine W., Venema, Koen, Tjalsma, Harold
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701948/
https://www.ncbi.nlm.nih.gov/pubmed/26779139
http://dx.doi.org/10.3389/fmicb.2015.01481
_version_ 1782408562596642816
author Kortman, Guus A. M.
Dutilh, Bas E.
Maathuis, Annet J. H.
Engelke, Udo F.
Boekhorst, Jos
Keegan, Kevin P.
Nielsen, Fiona G. G.
Betley, Jason
Weir, Jacqueline C.
Kingsbury, Zoya
Kluijtmans, Leo A. J.
Swinkels, Dorine W.
Venema, Koen
Tjalsma, Harold
author_facet Kortman, Guus A. M.
Dutilh, Bas E.
Maathuis, Annet J. H.
Engelke, Udo F.
Boekhorst, Jos
Keegan, Kevin P.
Nielsen, Fiona G. G.
Betley, Jason
Weir, Jacqueline C.
Kingsbury, Zoya
Kluijtmans, Leo A. J.
Swinkels, Dorine W.
Venema, Koen
Tjalsma, Harold
author_sort Kortman, Guus A. M.
collection PubMed
description Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in vitro model of the large intestine (TIM-2). The model was inoculated with a human microbiota, without supplementary iron, or with 50 or 250 μmol/L ferrous sulfate, 50 or 250 μmol/L ferric citrate, or 50 μmol/L hemin. High resolution responses of the microbiota were examined by 16S rDNA pyrosequencing, microarray analysis, and metagenomic sequencing. The metabolome was assessed by fatty acid quantification, gas chromatography-mass spectrometry (GC-MS), and (1)H-NMR spectroscopy. Cultured intestinal epithelial Caco-2 cells were used to assess fecal water toxicity. Microbiome analysis showed, among others, that supplementary iron induced decreased levels of Bifidobacteriaceae and Lactobacillaceae, while it caused higher levels of Roseburia and Prevotella. Metagenomic analyses showed an enrichment of microbial motility-chemotaxis systems, while the metabolome markedly changed from a saccharolytic to a proteolytic profile in response to iron. Branched chain fatty acids and ammonia levels increased significantly, in particular with ferrous sulfate. Importantly, the metabolite-containing effluent from iron-rich conditions showed increased cytotoxicity to Caco-2 cells. Our explorations indicate that in the absence of host influences, iron induces a more hostile environment characterized by a reduction of microbes that are generally beneficial, and increased levels of bacterial metabolites that can impair the barrier function of a cultured intestinal epithelial monolayer.
format Online
Article
Text
id pubmed-4701948
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-47019482016-01-15 Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon Kortman, Guus A. M. Dutilh, Bas E. Maathuis, Annet J. H. Engelke, Udo F. Boekhorst, Jos Keegan, Kevin P. Nielsen, Fiona G. G. Betley, Jason Weir, Jacqueline C. Kingsbury, Zoya Kluijtmans, Leo A. J. Swinkels, Dorine W. Venema, Koen Tjalsma, Harold Front Microbiol Microbiology Oral iron administration in African children can increase the risk for infections. However, it remains unclear to what extent supplementary iron affects the intestinal microbiome. We here explored the impact of iron preparations on microbial growth and metabolism in the well-controlled TNO's in vitro model of the large intestine (TIM-2). The model was inoculated with a human microbiota, without supplementary iron, or with 50 or 250 μmol/L ferrous sulfate, 50 or 250 μmol/L ferric citrate, or 50 μmol/L hemin. High resolution responses of the microbiota were examined by 16S rDNA pyrosequencing, microarray analysis, and metagenomic sequencing. The metabolome was assessed by fatty acid quantification, gas chromatography-mass spectrometry (GC-MS), and (1)H-NMR spectroscopy. Cultured intestinal epithelial Caco-2 cells were used to assess fecal water toxicity. Microbiome analysis showed, among others, that supplementary iron induced decreased levels of Bifidobacteriaceae and Lactobacillaceae, while it caused higher levels of Roseburia and Prevotella. Metagenomic analyses showed an enrichment of microbial motility-chemotaxis systems, while the metabolome markedly changed from a saccharolytic to a proteolytic profile in response to iron. Branched chain fatty acids and ammonia levels increased significantly, in particular with ferrous sulfate. Importantly, the metabolite-containing effluent from iron-rich conditions showed increased cytotoxicity to Caco-2 cells. Our explorations indicate that in the absence of host influences, iron induces a more hostile environment characterized by a reduction of microbes that are generally beneficial, and increased levels of bacterial metabolites that can impair the barrier function of a cultured intestinal epithelial monolayer. Frontiers Media S.A. 2016-01-06 /pmc/articles/PMC4701948/ /pubmed/26779139 http://dx.doi.org/10.3389/fmicb.2015.01481 Text en Copyright © 2016 Kortman, Dutilh, Maathuis, Engelke, Boekhorst, Keegan, Nielsen, Betley, Weir, Kingsbury, Kluijtmans, Swinkels, Venema and Tjalsma. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Kortman, Guus A. M.
Dutilh, Bas E.
Maathuis, Annet J. H.
Engelke, Udo F.
Boekhorst, Jos
Keegan, Kevin P.
Nielsen, Fiona G. G.
Betley, Jason
Weir, Jacqueline C.
Kingsbury, Zoya
Kluijtmans, Leo A. J.
Swinkels, Dorine W.
Venema, Koen
Tjalsma, Harold
Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon
title Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon
title_full Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon
title_fullStr Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon
title_full_unstemmed Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon
title_short Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon
title_sort microbial metabolism shifts towards an adverse profile with supplementary iron in the tim-2 in vitro model of the human colon
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701948/
https://www.ncbi.nlm.nih.gov/pubmed/26779139
http://dx.doi.org/10.3389/fmicb.2015.01481
work_keys_str_mv AT kortmanguusam microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT dutilhbase microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT maathuisannetjh microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT engelkeudof microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT boekhorstjos microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT keegankevinp microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT nielsenfionagg microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT betleyjason microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT weirjacquelinec microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT kingsburyzoya microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT kluijtmansleoaj microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT swinkelsdorinew microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT venemakoen microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon
AT tjalsmaharold microbialmetabolismshiftstowardsanadverseprofilewithsupplementaryironinthetim2invitromodelofthehumancolon