Evidence map›Paper›PMID 26044703›Full record

ArticleHepatology (Baltimore, Md.)2016

Absence of the intestinal microbiota exacerbates hepatobiliary disease in a murine model of primary sclerosing cholangitis.

James H Tabibian, Steven P O'Hara, Christy E Trussoni, Pamela S Tietz, Patrick L Splinter, Taofic Mounajjed, Lee R Hagey, Nicholas F LaRusso

Open access · greenAbstract read
In one paragraph

Article in Hepatology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.

0numbers the graph read from it
0cells of the map it votes in
111citing papers in PubMed
12.6field-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

111 citing papers in PubMed, 214 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Review
  5. Dysbiosis in the Gut-Liver Axis Is Associated With Low Bone Mass During Murine Cholestasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  6. Review
  7. Review
  8. Article
  9. Gut microbiome in biliary atresia.World journal of pediatric surgery · 2026
    Review
  10. Review
  11. Review
  12. Primary sclerosing cholangitis.Nature reviews. Disease primers · 2025
    Review
  13. Review
  14. Article
  15. The gut-liver axis in hepatobiliary diseases.Inflammation and regeneration · 2024
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

James H TabibianDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Steven P O'HaraDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Christy E TrussoniDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Pamela S TietzDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Patrick L SplinterDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Taofic MounajjedDivision of Anatomic Pathology, Mayo Clinic, Rochester, MN.
Lee R HageyDivision of Gastroenterology, University of California San Diego, La Jolla, CA.
Nicholas F LaRussoDivision of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
Mayo Clinic in Arizona · USMayo Clinic · USUniversity of California, San Diego · US

Funding

PILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI GREGORY J. GORES · 2009 to 2026
$22.2M
Pathophysiology of Biliary DiseaseR01DK057993 · NIDDK · MAYO CLINIC ROCHESTER · PI LARUSSO, NICHOLAS F., O'HARA, STEVEN P · 2001 to 2025
$7.1M
Pathophysiology of cholangiocyte responses to microbial pathogensR01AI089713 · NIAID · MAYO CLINIC ROCHESTER · PI O'HARA, STEVEN P · 2011 to 2015
$1.8M
NIAID NIH HHS AI089713NIAID NIH HHS R01 AI089713NIDDK NIH HHS DK57993NIDDK NIH HHS P30 DK084567NIDDK NIH HHS P30DK084567NIDDK NIH HHS R01 DK057993
6 · The paper itself

Abstract

unlabelledPrimary sclerosing cholangitis (PSC) is a chronic, idiopathic, fibroinflammatory cholangiopathy. The role of the microbiota in PSC etiopathogenesis may be fundamentally important, yet remains obscure. We tested the hypothesis that germ-free (GF) mutltidrug resistance 2 knockout (mdr2(-/-) ) mice develop a distinct PSC phenotype, compared to conventionally housed (CV) mdr2(-/-) mice. Mdr2(-/-) mice (n = 12) were rederived as GF by embryo transfer, maintained in isolators, and sacrificed at 60 days in parallel with age-matched CV mdr2(-/-) mice. Serum biochemistries, gallbladder bile acids, and liver sections were examined. Histological findings were validated morphometrically, biochemically, and by immunofluorescence microscopy (IFM). Cholangiocyte senescence was assessed by p16(INK4a) in situ hybridization in liver tissue and by senescence-associated β-galactosidase staining in a culture-based model of insult-induced senescence. Serum biochemistries, including alkaline phosphatase, aspartate aminotransferase, and bilirubin, were significantly higher in GF mdr2(-/-) (P < 0.01). Primary bile acids were similar, whereas secondary bile acids were absent, in GF mdr2(-/-) mice. Fibrosis, ductular reaction, and ductopenia were significantly more severe histopathologically in GF mdr2(-/-) mice (P < 0.01) and were confirmed by hepatic morphometry, hydroxyproline assay, and IFM. Cholangiocyte senescence was significantly increased in GF mdr2(-/-) mice and abrogated in vitro by ursodeoxycholic acid (UDCA) treatment.

conclusionsGF mdr2(-/-) mice exhibit exacerbated biochemical and histological features of PSC and increased cholangiocyte senescence, a characteristic and potential mediator of progressive biliary disease. UDCA, a commensal microbial metabolite, abrogates senescence in vitro. These findings demonstrate the importance of the commensal microbiota and its metabolites in protecting against biliary injury and suggest avenues for future studies of biomarkers and therapeutic interventions in PSC.

Indexed as

AnimalsCholangitis, SclerosingDisease Models, AnimalDisease ProgressionFemaleGastrointestinal MicrobiomeMaleMiceMice, Knockout

Identifiers

PMID26044703
PMCPMC4670294
OpenAlexW1945590693

What OpenQuestion holds

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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.