Evidence map›Paper›PMID 42116295›Full record

ArticleMedicine2026

Association between 1400 metabolites mediated gut microbiota and frozen shoulder: An exploratory 2-step mendelian randomization study.

Rong Shen, Ji-Ang Li, Han-Dan Xiao, Chen-Han Zhou, Yi Zhang

Abstract read
In one paragraph

Article in Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

5 authors.

Rong ShenDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ji-Ang LiDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Han-Dan XiaoDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Chen-Han ZhouDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yi ZhangDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.ORCID 0000-0002-4475-5769

Funding

FuQing Postdoc Program of Xiangya Hospital, Central South University 176National Postdoctoral Science Foundation of China 2021M693562Provincial Natural Science Foundation of Hunan 2022JJ40843Provincial Outstanding Postdoctoral Innovative Talents Program of Hunan 2021RC2020Young Investigator Grant of Xiangya Hospital, Central South University 2020Q14
6 · The paper itself

Abstract

This study aimed to elucidate the causal relationship between gut microbiota (GM) and frozen shoulder (FS) and explore the potential mediating function of metabolites. Using pooled data from genome-wide association studies, we first performed bidirectional univariable Mendelian Randomization (MR) analysis to examine the relationship between GM and FS, avoiding any possible reverse causal influences. Exposure-related genetic variants that are independent of each other, were rigorously screened for use as instrumental variables. Further investigation of potential mediator pathways of the metabolites was conducted using a 2-step MR analysis. In this study, we primarily employ the inverse variance weighted method to assess the causal relationships among GM, metabolites, and FS, as well as to evaluate the potential mediating effect of metabolites. Heterogeneity and horizontal pleiotropy tests were conducted to assess the robustness of the results, such as MR-PRESSO, MR-Egger, Cochran Q. MR analysis identified 27 potential GM links associated with FS. In particular, 15 of them displayed positive associations with FS, while other microbiota showed negative associations. There was no significant correlation between GM and FS on reverse MR Analysis. Metabolites, including X-12844 levels, serve a mediating function in the development of FS. X-12844 levels mediate the effect of Eubacterium F sp000434115 on FS, with an indirect effect size of -0.016, accounting for 15.09% of the total effect size. For glycine to serine ratio, the mediation proportion was 8.19%. When examining 3-indoleglyoxylic acid levels, the mediating effect proportion is observed to be 11.66%. Our results provide evidence for a causal relationship between GM and FS as well as a metabolite-mediated pathway. These biomarkers may contribute to the detection, diagnosis, and treatment of FS, while providing fresh perspective on its underlying mechanism.

Indexed as

BursitisGastrointestinal MicrobiomeMendelian Randomization AnalysisGenome-Wide Association StudyHumanscausal relationshipfrozen shouldergut microbiotamendelian randomization studymetabolites

Identifiers

PMID42116295
PMCPMC13166831

What Socratic holds

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LicenceCC BY-NC
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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 Socratic graph.