Evidence map›Paper›PMID 31708445›Full record

ArticleCell metabolism2020

Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis.

Nupur K Das, Andrew J Schwartz, Gabrielle Barthel, Naohiro Inohara, Qing Liu, Amanda Sankar, David R Hill, Xiaoya Ma, Olivia Lamberg, Matthew K Schnizlein and 7 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
192citing papers in PubMed, 6 pooled it
16.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

192 citing papers in PubMed, 6 syntheses or guidelines pooled it, 319 citations in OpenAlex.

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132 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Nupur K DasDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Andrew J SchwartzDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Gabrielle BarthelDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Naohiro InoharaDepartment of Pathology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Qing LiuDepartment of Veterinary and Biomedical Sciences, the Pennsylvania State University, University Park, PA 16802, USA.
Amanda SankarDepartment of Pediatrics, Division of Hematology-Oncology, University of Michigan, Ann Arbor, MI 48109, USA.
David R HillDepartment of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA.
Xiaoya MaDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Olivia LambergDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
Matthew K SchnizleinDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA.
Juan L ArquésDepartamento Tecnología de Alimentos, INIA, Carretera de La Coruña Km 7, Madrid 28040, Spain.
Jason R SpenceDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA.
Gabriel NunezDepartment of Pathology and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA.
Andrew D PattersonDepartment of Veterinary and Biomedical Sciences, the Pennsylvania State University, University Park, PA 16802, USA.
Duxin SunCollege of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
Vincent B YoungDepartment of Internal Medicine, Division of Infectious Disease, University of Michigan, Ann Arbor, MI 48109, USA; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA.
Yatrik M ShahDepartment of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: shahy@umich.edu.
University of Michigan–Ann Arbor · USPennsylvania State University · USMichigan Center for Translational Pathology · US

Funding

University of Michigan Center for Gastrointestinal ResearchP30DK034933 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI OWYANG, CHUNG · 1986 to 2021
$22.5M
Translational Research in GI CancerP50CA130810 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BRENNER, DEAN E. · 2010 to 2016
$11.8M
Systems biology of Clostridium difficile infectionU01AI124255 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SCHLOSS, PATRICK DAVID, YOUNG, VINCENT B · 2016 to 2020
$9.8M
Training Program in Molecular HematologyT32HL007622 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SUNG WON CHOI, Jordan A. Shavit · 1986 to 2026
$9.2M
Stem Cell Differentiation CoreU19AI116482 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI TAKAYAMA, SHUICHI · 2015 to 2019
$6.4M
Control of iron absorption by intestinal HIF2 in iron and hematological disordersR01DK095201 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHAH, YATRIK M · 2012 to 2025
$5.7M
The role of HIF2alpha in colon carcinogenesisR01CA148828 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHAH, YATRIK M · 2010 to 2025
$5.2M
NCI NIH HHS P50 CA130810NCI NIH HHS R01 CA148828NHLBI NIH HHS T32 HL007622NIAID NIH HHS U01 AI124255NIAID NIH HHS U19 AI116482NIDDK NIH HHS P30 DK034933NIDDK NIH HHS R01 DK095201
6 · The paper itself

Abstract

Iron is a central micronutrient needed by all living organisms. Competition for iron in the intestinal tract is essential for the maintenance of indigenous microbial populations and for host health. How symbiotic relationships between hosts and native microbes persist during times of iron limitation is unclear. Here, we demonstrate that indigenous bacteria possess an iron-dependent mechanism that inhibits host iron transport and storage. Using a high-throughput screen of microbial metabolites, we found that gut microbiota produce metabolites that suppress hypoxia-inducible factor 2α (HIF-2α) a master transcription factor of intestinal iron absorption and increase the iron-storage protein ferritin, resulting in decreased intestinal iron absorption by the host. We identified 1,3-diaminopropane (DAP) and reuterin as inhibitors of HIF-2α via inhibition of heterodimerization. DAP and reuterin effectively ameliorated systemic iron overload. This work provides evidence of intestine-microbiota metabolic crosstalk that is essential for systemic iron homeostasis.

Indexed as

Gastrointestinal MicrobiomeAdolescentAnimalsAnti-Bacterial AgentsBasic Helix-Loop-Helix ProteinsCell LineCell ProliferationDiaminesDimerizationDuodenumEndothelial PAS Domain-Containing Protein 1FecesFemaleFerritinsGlyceraldehydeHomeostasis3-hydroxypropionaldehydeAnti-Bacterial AgentsBasic Helix-Loop-Helix ProteinsDiaminesEndothelial PAS Domain-Containing Protein 1FerritinsGlyceraldehydeIronPropanetrimethylenediamineanemiaEPAS1ferritinhemochromatosisHIFHIF-2ahypoxiahypoxia-inducible factorironmetabolitesmicrobiota

Identifiers

PMID31708445
PMCPMC6949377
OpenAlexW2986330148

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.