Evidence map›Paper›PMID 33769187›Full record

ArticleGut microbes

Extracellular vesicles of Fusobacterium nucleatum compromise intestinal barrier through targeting RIPK1-mediated cell death pathway.

Le Liu, Liping Liang, Chenghai Yang, Youlian Zhou, Ye Chen

Open access · goldAbstract read
In one paragraph

Article in Gut microbes. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
116citing papers in PubMed, 2 pooled it
8.6field-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

116 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Live AirwayEnvironment & health (Washington, D.C.) · 2026
    Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Frontiers in bacterial outer membrane vesicles: From basic characteristics to cancer therapy.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026
    Article
  11. Review
  12. Review
  13. Review
  14. [The Impact of Oral Microecology on the Development of Inflammatory Bowel Disease].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026
    Review
  15. [Recent Research Progress and Prospects on Periodontitis Affecting Systemic Comorbidities via the Oral-Gut Axis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026
    Review
  16. Review
  17. Review
  18. Review
  19. Extracellular vesicles as indicators of environmental stress response inExtracellular vesicles and circulating nucleic acids · 2026
    Article
  20. Review

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

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

5 authors at 1 institution in 1 country.

Le LiuDepartment of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Liping LiangDepartment of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Chenghai YangDepartment of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Youlian ZhouDepartment of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Ye ChenDepartment of Gastroenterology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.ORCID 0000-0002-7964-7899
Nanfang Hospital · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Microbial factors that mediate microbes-host interaction in ulcerative colitis (UC), a chronic disease seriously affecting human health, are not fully known. The emerging oncobacterium Fusobacterium nucleatum (Fn) secretes extracellular vesicles carrying several types of harmful molecules in the intestine which can alter microbes-host interaction, especially the epithelial homeostasis in UC. However, the mechanism is not yet clear. Previously, we isolated EVs by the ultracentrifugation of Fn culture media and characterized them as the potent inducer of pro-inflammatory cytokines. Here, we examined the mechanism in detail. We found that in macrophage/Caco-2 co-cultures, FnEVs significantly promoted epithelial barrier loss and oxidative stress damage, which are related to epithelial necroptosis caused by the activation of receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein kinase 3 (RIPK3). Furthermore, FnEVs promoted the migration of RIPK1 and RIPK3 into necrosome in Caco2 cells. Notably, these effects were reversed by TNF-α neutralizing antibody or Necrostatin-1 (Nec-1), a RIPK1 inhibitor. This suggested that FADD-RIPK1-caspase-3 signaling is involved in the process. Moreover, the observed effects were verified in the murine colitis model treated with FnEVs or by adoptive transfer of FnEVs-trained macrophages. In conclusion, we propose that RIPK1-mediated epithelial cell death promotes FnEVs-induced gut barrier disruption in UC and the findings can be used as the basis to further investigate this disease.

Indexed as

ApoptosisAnimalsCaco-2 CellsCoculture TechniquesColitis, UlcerativeEpithelial CellsExtracellular VesiclesFusobacterium nucleatumHumansInflammationIntestinal MucosaMacrophagesMaleMiceMice, Inbred C57BLOxidative StressReceptor-Interacting Protein Serine-Threonine KinasesRIPK1 protein, humanRipk1 protein, mouseextracellular vesiclesFusobacterium nucleatummacrophagesnecroptosisoncobacteriumulcerative colitis

Identifiers

PMID33769187
PMCPMC8007154
OpenAlexW3135922797

What OpenQuestion holds

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LicenceCC BY
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.