Evidence map›Paper›PMID 39048073›Full record

ArticleJournal of advanced research2025

Disturbance of bile acids profile aggravates the diarrhea induced by capecitabine through inhibiting the Wnt/β-catenin pathway.

Zhipeng Wang, Zhijun Liu, Lili Cui, Jianguo Sun, Chen Bu, Mao Tang, Mingming Li, Shouhong Gao, Wansheng Chen, Xia Tao

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Zhipeng WangDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, PR China.
Zhijun LiuDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, PR China; Research and Development Center of Chinese Medicine Resources and Biotechnology, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China.
Lili CuiDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, PR China.
Jianguo SunDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, PR China; College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, 650500, PR China.
Chen BuDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, PR China.
Mao TangDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, PR China.
Mingming LiDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, PR China.
Shouhong GaoDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, PR China; College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, 650500, PR China. Electronic address: gaoshouhong@smmu.edu.cn.
Wansheng ChenDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, PR China; Research and Development Center of Chinese Medicine Resources and Biotechnology, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China. Electronic address: chenwansheng@smmu.edu.cn.
Xia TaoDepartment of Pharmacy, Second Affiliated Hospital of Naval Medical University, Shanghai 200003, PR China; College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, 650500, PR China. Electronic address: taoxia@smmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDiarrhea is the primary dose-limiting side effect of capecitabine(Cap) hindering its clinical application, but the mechanism is unclear. Clarifying this mechanism may enhance the patient compliance and improve the treatment outcome.

objectivesTo assess if the endogenous metabolic profile could prodict the diarrhea induced by Cap and explore and validate underlying mechanisms.

methodsUntargeted and targeted bile acids(BAs) metabolomics were performed to analyzed the metabolic profile of baseline samples from colorectal cancer(CRC) patients and the association with the diarrhea induced by Cap was assessed. The toxicity of BAs and Cap and its metabolites alone or their combinations to the human normal intestinal epithelial cell(HIEC) was assessed, and the key genes that mediated the BAs-enhanced toxicity of Cap were discovered by RNA-seq and then validated. A mouse model with high exposure levels of BAs was constructed and then treated with Cap to verify the Cap-induced diarrhea enhanced by BAs.

resultsThe baseline endogenous metabolic profile showed obviously difference between diarrhea and non-diarrhea CRC patients, and the differential metabolites mainly enriched in BAs metabolism; the deoxycholic acid(DCA) and lithocholic acid(LCA) were selected to be the key BAs that enhanced the toxicity of Cap metabolite 5-FU to the HIEC cell; the DCA and LCA could inhibit the Wnt/β-catenin signaling pathway, which then suppressed the P-glycoprotein and increased the exposure level of 5-FU in the HIEC cell. The results of animal experiment verified that the excessive DCA and LCA could aggravate the Cap-induced diarrhea through inhibiting Wnt/β-catenin-P-glycoprotein pathway.

conclusionsThe disordered BAs metabolic profile showed close relationship with diarrhea induced by Cap, and excessive DCA and LCA were proved to be the key BAs, which could aggravate the Cap-induced diarrhea through inhibiting Wnt/β-catenin-P-glycoprotein pathway.

Indexed as

Antimetabolites, AntineoplasticBile Acids and SaltsCapecitabineColorectal NeoplasmsDiarrheaWnt Signaling PathwayAnimalsbeta CateninDisease Models, AnimalFemaleHumansMaleMetabolomicsMiceMiddle AgedAntimetabolites, Antineoplasticbeta CateninBile Acids and SaltsCapecitabineBile acidsCapecitabineDiarrheaMetabolomicsWnt/β-catenin pathway

Identifiers

PMID39048073
PMCPMC12147608

What Socratic 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 Socratic graph.