Evidence map›Paper›PMID 39541261›Full record

Observational studyInflammatory bowel diseases2025

Why Symptoms Linger in Quiescent Crohn's Disease: Investigating the Impact of Sulfidogenic Microbes and Sulfur Metabolic Pathways.

Jonathan Golob, Krishna Rao, Jeffrey A Berinstein, Prashant Singh, William D Chey, Chung Owyang, Nobuhiko Kamada, Peter D R Higgins, Vincent Young, Shrinivas Bishu and 1 more

Abstract readMulticenter StudyObservational Study
In one paragraph

Observational study in Inflammatory bowel diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Jonathan GolobDivision of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Krishna RaoDivision of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Jeffrey A BerinsteinDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-7631-9665
Prashant SinghDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
William D CheyDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Chung OwyangDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Nobuhiko KamadaDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Peter D R HigginsDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Vincent YoungDivision of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Shrinivas BishuDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0003-4823-5805
Allen A LeeDivision of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-4861-7646

Funding

Training Program in Gastrointestinal EpidemiologyT32DK062708 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Peter D.R. Higgins, Elliot Tapper · 2003 to 2026
$3.9M
Measuring Molecular and Mechanical Outcomes of Endoscopic Dilation of Fibrotic StricturesR01DK125687 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Peter D.R. Higgins, Guan Xu · 2020 to 2026
$3.3M
Inhibiting Bcl-2-regulated intestinal fibrosis in models of Crohn’s DiseaseR01DK118154 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HIGGINS, PETER D.R. · 2018 to 2022
$2.3M
CD4+ Tissue resident memory T-cells in Crohn's DiseaseK08DK123403 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BISHU, SHRINIVAS · 2020 to 2024
$848k
A Systems Biology Approach Using Fecal Microbiota and Metabolomics to Identify Novel Subtypes in Irritable Bowel Syndrome.K23DK124567 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LEE, ALLEN A · 2021 to 2023
$729k
The role of sulfidogenic microbes in quiescent Crohn’s disease with persistent symptomsR03DK139095 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LEE, ALLEN A · 2024 to 2025
$234k
AHRQ HHS R01 HS027431CCFNIDDK NIH HHS K08 DK123403NIDDK NIH HHS K23 DK124567NIDDK NIH HHS R01 DK118154NIDDK NIH HHS R01 DK125687NIDDK NIH HHS R03 DK139095NIDDK NIH HHS T32 DK062708NIH HHS DK124567
6 · The paper itself

Abstract

introductionEven in the absence of inflammation, persistent symptoms in patients with Crohn's disease (CD) are prevalent and worsen quality of life. We previously demonstrated enrichment in sulfidogenic microbes in quiescent Crohn's disease patients with (qCD + S) vs without persistent GI symptoms (qCD-S). Thus, we hypothesized that sulfur metabolic pathways would be enriched in stool while differentially abundant microbes would be associated with important sulfur metabolic pathways in qCD + S.

methodsWe performed a multicenter observational study nested within SPARC IBD. Quiescent inflammation was defined by fecal calprotectin level < 150 mcg/g. Persistent symptoms were defined by CD-PRO2. Active CD (aCD) and non-IBD diarrhea-predominant irritable bowel syndrome (IBS-D) were included as controls.

resultsThirty-nine patients with qCD + S, 274 qCD-S, 21 aCD, and 40 IBS-D underwent paired shotgun metagenomic sequencing and untargeted metabolomic profiling. The fecal metabolome in qCD + S was significantly different relative to qCD-S and IBS-D but not aCD. Patients with qCD + S were enriched in sulfur-containing amino acid pathways, including cysteine and methionine, as well as serine, glycine, and threonine. Glutathione and nicotinate/nicotinamide pathways were also enriched in qCD + S relative to qCD-S, suggestive of mitochondrial dysfunction, a downstream target of H2S signaling. Multi-omic integration demonstrated that enriched microbes in qCD + S were associated with important sulfur metabolic pathways. Bacterial sulfur metabolic genes, including CTH, isfD, sarD, and asrC, were dysregulated in qCD + S. Finally, sulfur metabolites with and without sulfidogenic microbes showed good accuracy in predicting the presence of qCD + S. DISCUSSION: Microbial-derived sulfur pathways and downstream mitochondrial function are perturbed in qCD + S, which implicate H2S signaling in the pathogenesis of this condition. Future studies will determine whether targeting H2S pathways results in improved quality of life in qCD + S.

Indexed as

Crohn DiseaseGastrointestinal MicrobiomeMetabolic Networks and PathwaysSulfurAdultCase-Control StudiesFecesFemaleHumansIrritable Bowel SyndromeMaleMetabolomeMetabolomicsMiddle AgedQuality of LifeSulfurhydrogen sulfideinflammatory bowel diseasemetabolomicsmicrobiomequality of life

Identifiers

PMID39541261
PMCPMC11879174

What OpenQuestion holds

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Registered trials

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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.