Evidence map›Paper›PMID 39905483›Full record

ArticleMicrobiome2025

Microbiota governs host chenodeoxycholic acid glucuronidation to ameliorate bile acid disorder induced diarrhea.

Zishen Lin, Yue Feng, Jinping Wang, Zhaoyue Men, Xi Ma

Abstract read
In one paragraph

Article in Microbiome, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Article
  3. mSystems · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
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.

Zishen LinState Key Laboratory of Animal Nutrition and Feeding, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China.
Yue FengState Key Laboratory of Animal Nutrition and Feeding, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China.
Jinping WangState Key Laboratory of Animal Nutrition and Feeding, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China.
Zhaoyue MenState Key Laboratory of Animal Nutrition and Feeding, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China.
Xi MaState Key Laboratory of Animal Nutrition and Feeding, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China. maxi@cau.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDisorder in bile acid (BA) metabolism is known to be an important factor contributing to diarrhea. However, the pathogenesis of BA disorder-induced diarrhea remains unclear.

methodsThe colonic BA pool and microbiota between health piglets and BA disorder-induced diarrheal piglets were compared. Fecal microbiota transplantation and various cell experiments further indicated that chenodeoxycholic acid (CDCA) metabolic disorder produced CDCA-3β-glucuronide, which is the main cause of BA disorder diarrhea. Non-targeted metabolomics uncovered the inhibition of the BA glucuronidation by Lactobacillus reuteri (L. reuteri) is through deriving indole-3-carbinol (I3C). In vitro, important gene involved in the reduction of BA disorder induced-diarrhea were screened by RNA transcriptomics sequencing, and activation pathway of FXR-SIRT1-LKB1 to alleviate BA disorder diarrhea and P53-mediated apoptosis were proposed in vitro by multifarious siRNA interference, CO-IP, immunofluorescence, and so on, which mechanism was also verified in a variety of mouse models.

resultsHere, we reveal for the first time that core microbiota derived I3C represses gut epithelium glucuronidation, particularly 3β-glucuronic CDCA production, which reaction is mediated by host UDP glucuronosyltransferase family 1 member A4 (UGT1A4) and necessary of BA disorder induced diarrhea. Mechanistically, L. reuteri derived I3C activates aryl hydrocarbon receptor to decrease UGT1A4 transcription and CDCA-3β-glucuronide content, thereby upregulating FXR-SIRT1-LKB1 signal. LKB1 binds with P53 based on protein interaction, ultimately resists to apoptosis and diarrhea. Moreover, I3C assists CDCA to attain the ameliorative effects of FXR activation in BA disorder diarrhea, through reversion of abnormal metabolism pathway, improving the outcomes of CDCA supplement.

conclusionThese findings uncover the crucial interplay between gut epithelial cells and microbes, highlighting UGT1A4-mediated conversion of CDCA-3β-glucuronide as a key target for ameliorating BA disorder-induced diarrhea. Video Abstract.

Indexed as

Bile Acids and SaltsChenodeoxycholic AcidDiarrheaGastrointestinal MicrobiomeGlucuronidesAnimalsColonDisease Models, AnimalFecal Microbiota TransplantationHumansIntestinal MucosaLimosilactobacillus reuteriMiceSirtuin 1SwineBile Acids and SaltsChenodeoxycholic AcidGlucuronidesSirtuin 1Bile acid diarrheaChenodeoxycholic acidGlucuronidationLiver kinase B1Microbiota

Identifiers

PMID39905483
PMCPMC11792533

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.