Evidence map›Paper›PMID 41632030›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Gut Microbiota-Derived Anandamide Mediates the Therapeutic Effects of Urolithin A on Alcohol-Induced Cognitive and Social Dysfunction via CB1R-DRD2-RAP1 Signaling Axis.

Hongbo Zhang, Zibin Li, Yao Xiao, Ji Bian, Caian He, Chao Liu, Lan Gong, Lin Han, Zhigang Liu, Min Wang

Abstract read
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In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

Hongbo ZhangDepartment of Nutrition and Health, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Zibin LiDepartment of Nutrition and Health, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Yao XiaoDepartment of Nutrition and Health, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Ji BianKolling Institute, Sydney Medical School, Royal North Shore Hospital, University of Sydney, St. Leonards, NSW, Australia.
Caian HeDepartment of Nutrition and Health, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Chao LiuKey Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, Jinan, P. R. China.
Lan GongUNSW Microbiome Research Centre, St George and Sutherland Clinical Campus, University of New South Wales, Sydney, NSW, Australia.
Lin HanDepartment of Nutrition and Health, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Zhigang LiuDepartment of Nutrition and Health, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.
Min WangDepartment of Nutrition and Health, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China.

Funding

financial support provided by the China Agriculture Research System CARS-07-E-2Natural Science Foundation of China 32001701
6 · The paper itself

Abstract

Chronic alcohol consumption disrupts the gut microbiome, exacerbating alcohol-induced cognitive and social dysfunction (AICSD), which constitutes a primary etiology of early-onset dementia. Urolithin A (UA) has been well-reported as an effective intervention for neurodegenerative diseases. However, the protective efficacy of UA against AICSD, and its underlying mechanisms remain largely elusive. First, our study demonstrates that UA significantly enhances work memory (60.43%), short-term memory (12-fold), long-term memory (50.32%), social ability (10-fold), and social novelty (12-fold), while concurrently reducing synaptic impairments and neuroinflammation. Moreover, UA restores AICSD by upregulating the dopamine D2 receptor (DRD2) via RAP1 signaling. Furthermore, antibiotic treatment and fecal microbiota transplantation experiments confirm the causality between the host microbiota and behavioral alterations. Treatment with UA-enriched Bacteroids sartorii and Parabacteroids distasonis, or their derived endocannabinoid-anandamide (AEA), also ameliorates AICSD. Finally, AEA inhibits the Rap1 signaling through cannabinoid receptor 1 (CB1R) and DRD2 interaction, eventually ameliorating AICSD. Collectively, our study elucidates that microbiota-derived AEA mediates the therapeutic effects of UA on AICSD through the CB1R-DRD2-RAP1 signaling axis, providing valuable insights for UA and microbiome-targeted endocannabinoid interventions against AICSD.

Indexed as

Arachidonic AcidsEndocannabinoidsGastrointestinal MicrobiomePolyunsaturated AlkamidesReceptor, Cannabinoid, CB1Receptors, Dopamine D2AnimalsEthanolMaleMiceMice, Inbred C57BLSignal TransductionanandamideArachidonic AcidsCNR1 protein, mouseDRD2 protein, mouseEndocannabinoidsEthanolPolyunsaturated AlkamidesReceptor, Cannabinoid, CB1Receptors, Dopamine D2alcohol‐induced cognitive and social dysfunctionanandamideBacteroids sartorii and Parabacteroids distasonisdopamine D2 receptor and cannabinoid receptor 1urolithin A

Identifiers

PMID41632030
PMCPMC13067832

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Registered trials

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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.