Evidence map›Paper›PMID 38289995›Full record

ArticleInflammatory bowel diseases2024

Crohn's Disease-Associated Pathogenic Mutation in the Manganese Transporter ZIP8 Shifts the Ileal and Rectal Mucosal Microbiota Implicating Aberrant Bile Acid Metabolism.

Kristi Briggs, Vartika Tomar, Nicholas Ollberding, Yael Haberman, Arno R Bourgonje, Shixian Hu, Lara Chaaban, Laxmi Sunuwar, Rinse K Weersma, Lee A Denson and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Inflammatory bowel diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. A Developmental Perspective on the Intestinal Microbiota in Crohn's Disease.International journal of molecular sciences · 2026
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  4. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Kristi BriggsDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-0947-3686
Vartika TomarDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nicholas OllberdingDepartment of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Yael HabermanDepartment of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Arno R BourgonjeDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Shixian HuDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Lara ChaabanDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Laxmi SunuwarDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rinse K WeersmaDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Lee A DensonDepartment of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.ORCID 0000-0001-8045-7198
Joanna M P MeliaDivision of Gastroenterology and Hepatology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-0984-4600

Funding

Stem Cell/Organoid and Genome Editing CoreP30DK078392 · NIDDK · CINCINNATI CHILDRENS HOSP MED CTR · PI LEE ARMISTEAD DENSON · 2007 to 2026
$24.4M
Sex differences in the impact of frailty on vaccine-induced immune responses in community-dwelling older adultsU54AG062333 · NIA · JOHNS HOPKINS UNIVERSITY · PI KLEIN, SABRA L. · 2018 to 2022
$8.9M
Dosing and Pilot Efficacy of 2'-Fucosyllactose in Inflammatory Bowel DiseaseR01HD094862 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI LEE ARMISTEAD DENSON, Jeffrey Samuel Hyams · 2018 to 2026
$5.0M
Genetic variation in the metal transporter ZIP8 and impact on the innate immune response in the gutK08DK114478 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI MELIA, JOANNA MILLER PELOQUIN · 2019 to 2023
$971k
Johns Hopkins Specialized Center for Research Excellence in Sex Differences U54AG062333NIA NIH HHS U54 AG062333NICHD NIH HHS R01 HD094862NIDDK NIH HHS K08 DK114478NIDDK NIH HHS P30 DK078392NIH HHS DK114478
6 · The paper itself

Abstract

backgroundA pathogenic mutation in the manganese transporter ZIP8 (A391T; rs13107325) increases the risk of Crohn's disease. ZIP8 regulates manganese homeostasis and given the shared need for metals between the host and resident microbes, there has been significant interest in alterations of the microbiome in carriers of ZIP8 A391T. Prior studies have not examined the ileal microbiome despite associations between ileal disease and ZIP8 A391T.

methodsHere, we used the Pediatric Risk Stratification Study (RISK) cohort to perform a secondary analysis of 16S ribosomal RNA gene sequencing data obtained from ileal and rectal mucosa to study associations between ZIP8 A391T carrier status and microbiota composition.

resultsWe found sequence variants mapping to Veillonella were decreased in the ileal mucosa of ZIP8 A391T carriers. Prior human studies have demonstrated the sensitivity of Veillonella to bile acid abundance. We therefore hypothesized that bile acid homeostasis is differentially regulated in carriers of ZIP8 A391T. Using a mouse model of ZIP8 A391T, we demonstrate an increase in total bile acids in the liver and stool and decreased fibroblast growth factor 15 (Fgf15) signaling, consistent with our hypothesis. We confirmed dysregulation of FGF19 in the 1000IBD cohort, finding that plasma FGF19 levels are lower in ZIP8 A391T carriers with ileocolonic Crohn's disease.

conclusionsIn the search for genotype-specific therapeutic paradigms for patients with Crohn's disease, these data suggest targeting the FGF19 pathway in ZIP8 A391T carriers. Aberrant bile acid metabolism may precede development of Crohn's disease and prioritize study of the interactions between manganese homeostasis, bile acid metabolism and signaling, and complicated ileal Crohn's disease.

Indexed as

Bile Acids and SaltsCation Transport ProteinsCrohn DiseaseIleumIntestinal MucosaMutationAdolescentAnimalsChildDisease Models, AnimalFemaleGastrointestinal MicrobiomeHumansMaleManganeseMiceBile Acids and SaltsCation Transport ProteinsManganeseSLC39A8 protein, humanbile acidsCrohn’s diseasemanganeseVeillonellaZIP8

Identifiers

PMID38289995
PMCPMC11291615

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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.