ArticleMedicine2026
Mendelian randomization study of lithocholate sulfate mediating the effect of MMP-1 on ischemic stroke.
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.
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.
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.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
This study aimed to investigate the potential causal relationship between the inflammatory factor matrix metalloproteinase-1 (MMP-1) and ischemic stroke (IS) using Mendelian randomization (MR), and to examine whether the gut microbiota-derived metabolite lithocholate sulfate (LSL) mediates this association. We performed a 2-sample MR analysis to assess the causal effect of genetically predicted MMP-1 levels (based on 14,744 individuals) on IS risk (39,818 cases and 2,71,817 controls). Genetic instruments were single nucleotide polymorphisms associated with the exposures, sourced from published genome-wide association studies. The causal direction was verified through reverse MR analysis. Furthermore, a multivariable MR analysis was conducted to quantify the mediating effect of LSL on the pathway from MMP-1 to IS. Genetically predicted higher MMP-1 levels were significantly associated with an increased risk of IS (inverse variance weighted odds ratio: 1.085, 95% confidence interval [CI]: 1.031-1.142, P = .002). In contrast, reverse MR analysis provided no evidence for a causal effect of IS on MMP-1 levels (inverse variance weighted odds ratio: 1.034, 95% CI: 0.954-1.120, P = .420). The mediation analysis revealed a significant indirect effect mediated by LSL, with an estimated proportion of 0.0071 (95% CI: 0.0027-0.0168). This MR study provides genetic evidence that elevated MMP-1 is causally associated with an increased risk of IS. Furthermore, we identify LSL as a protective mediator in this pathway. Our findings propose a novel MMP-1 → LSL → IS axis, suggesting a compensatory interaction where a pro-inflammatory signal may upregulate a protective metabolite. This highlights LSL as a potential target for future research into stroke mechanisms and prevention.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.