Evidence map›Paper›PMID 40955046›Full record

ArticleCNS neuroscience & therapeutics2025

Gut Microbiota-Bile Acid-Brain Axis and TGR5-ERK1/2 Signaling Mediate ADT-Induced Cognitive Impairment.

Fan Yang, Yanbo Liu, Zhien Zhou, Dong Yang, Weigang Yan

Abstract read
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Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Emerging Roles of Bile Acids in Neuroinflammation.International journal of molecular sciences · 2025
    Review
  7. Article
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.

Fan YangDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID 0009-0001-3460-1379
Yanbo LiuDepartment of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID 0000-0002-1042-4961
Zhien ZhouDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Dong YangDepartment of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Weigang YanDepartment of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID 0000-0002-7406-4694

Funding

National HiLevel Hospital Clinical Research Funding 2022-PUMCH-B-009National Key Research and Development Program of China 2023YFC3605700
6 · The paper itself

Abstract

aimsAlthough a key intervention for advanced Prostate Cancer, Androgen Deprivation Therapy has been associated with cognitive dysfunction, a phenomenon that has been largely attributed to systemic metabolic alterations and neuroinflammation. Nonetheless, the precise role of gut microbiota in ADT-induced cognitive impairment remains unclear, forming the basis of this study. Our aim is to explore the correlation between changes in gut metabolism and cognitive dysfunction following ADT in prostate cancer.

methodsA subcutaneous PC3 tumor-bearing mouse model of ADT-induced cognitive dysfunction was established. Behavioral tests (OFT, NORT, and Y-maze) were conducted to assess cognitive performance. Gut microbiota composition, fecal, and hippocampal bile acid profiles were analyzed by 16S rRNA sequencing and targeted metabolomics. To investigate potential mechanisms, we further supplemented ADT-susceptible (ADT-su) mice with Taurodeoxycholic acid (TDCA) via oral gavage and inhibited ERK1/2 signaling with PD98059, followed by behavioral testing and Western blot analysis of hippocampal Takeda G-protein coupled Receptor 5 (TGR5) and ERK1/2 expression.

resultsHierarchical clustering analysis revealed ADT-induced cognitive impairment in a subset of mice (ADT-susceptible and ADT-unsusceptible). These mice exhibited gut microbiota dysbiosis, featuring the depletion of bile acid-transforming taxa, including Bacteroides spp. and Clostridium scindens. Additionally, FMT from ADT-su mice to pseudo-germ-free mice efficiently transferred cognitive deficits and altered hippocampal bile acid profiles, confirming gut microbiota's causal role in ADT-induced neurocognitive decline. Notably, both gut and hippocampal TDCA levels were significantly decreased in ADT-su mice. Mechanistically, TDCA supplementation improved cognitive performance and upregulated hippocampal TGR5 and p-ERK1/2 expression, while ERK1/2 inhibition by PD98059 partially reversed these effects.

conclusionOur findings suggest that gut microbiota-mediated bile acid dysregulation, particularly reduced TDCA, contributes to ADT-induced cognitive dysfunction via impaired TGR5-ERK1/2 signaling. Targeting this pathway may represent a novel therapeutic strategy to mitigate cognitive impairment in prostate cancer patients undergoing ADT.

Indexed as

Bile Acids and SaltsBrainCognitive DysfunctionGastrointestinal MicrobiomeMAP Kinase Signaling SystemReceptors, G-Protein-CoupledAnimalsCell Line, TumorHippocampusHumansMaleMiceMice, Inbred C57BLProstatic NeoplasmsBile Acids and SaltsGpbar1 protein, mouseReceptors, G-Protein-Coupledandrogen deprivation therapybile acid metabolic reprogrammingcognitive dysfunctiongut microbiotaprostate cancertaurodeoxycholic acidTGR5

Identifiers

PMID40955046
PMCPMC12436682

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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.