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Cerebrospinal Fluid Metabolites Mediate the Impact of Gut Microbiota on Amyotrophic Lateral Sclerosis: Novel Insights From Mendelian Randomization.

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Title: Cerebrospinal Fluid Metabolites Mediate the Impact of Gut Microbiota on Amyotrophic Lateral Sclerosis: Novel Insights From Mendelian Randomization.
Authors: Fu, Yuxin (AUTHOR), Su, Tengfei (AUTHOR), Cao, Jie (AUTHOR), Lang, Yue (AUTHOR), Yin, Xiang (AUTHOR), Shao, Jie (AUTHOR), Cui, Li (AUTHOR), Fee, Dominic B. (AUTHOR)
Source: Acta Neurologica Scandinavica. 11/10/2025, Vol. 2025, p1-17. 17p.
Subjects: Cerebrospinal fluid, Gut microbiota, Causal inference, Therapeutics, Amyotrophic lateral sclerosis, Mendelian randomization, Metabolites, Disease progression
Abstract: Background: Previous studies have noted changes in the gut microbiota of amyotrophic lateral sclerosis patients, with some assessing its impact through metabolites or inflammatory factors. However, most of these are observational, and peripheral systems may not accurately reflect central nervous system pathology. This study uniquely explores the influence of gut microbiota on amyotrophic lateral sclerosis by metabolites in cerebrospinal fluid, which is directly connected to the central nervous system. Methods: Data on gut microbiota, cerebrospinal fluid metabolites, and amyotrophic lateral sclerosis were derived from large‐scale genome‐wide association studies. We employed two‐sample and mediation Mendelian randomization to examine the causal effects of gut microbiota and cerebrospinal fluid metabolites on amyotrophic lateral sclerosis, as well as the mediating role of cerebrospinal fluid metabolites between gut microbiota and disease progression. Furthermore, the results were validated through various sensitivity analyses. Results: Two‐sample Mendelian randomization analysis revealed significant associations between three gut microbiota and four cerebrospinal fluid metabolites and amyotrophic lateral sclerosis. Notably, mediation Mendelian randomization analysis indicated that cyanobacteria may promote the onset of amyotrophic lateral sclerosis by increasing the levels of 3‐methoxytyramine sulfate in cerebrospinal fluid. Additionally, the sensitivity analysis confirmed the robustness of the Mendelian randomization results. Conclusions: This study addresses the gap in causal inference within the research on the relationship between gut microbiota, cerebrospinal fluid metabolomics, and amyotrophic lateral sclerosis, thereby advancing our understanding of the molecular mechanisms underlying the disease. The findings will provide a scientific basis for early intervention and precision treatment of the disease. [ABSTRACT FROM AUTHOR]
Copyright of Acta Neurologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Cerebrospinal Fluid Metabolites Mediate the Impact of Gut Microbiota on Amyotrophic Lateral Sclerosis: Novel Insights From Mendelian Randomization.
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  Data: <searchLink fieldCode="AR" term="%22Fu%2C+Yuxin%22">Fu, Yuxin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Su%2C+Tengfei%22">Su, Tengfei</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cao%2C+Jie%22">Cao, Jie</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lang%2C+Yue%22">Lang, Yue</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yin%2C+Xiang%22">Yin, Xiang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shao%2C+Jie%22">Shao, Jie</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cui%2C+Li%22">Cui, Li</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Fee%2C+Dominic+B%2E%22">Fee, Dominic B.</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Acta+Neurologica+Scandinavica%22">Acta Neurologica Scandinavica</searchLink>. 11/10/2025, Vol. 2025, p1-17. 17p.
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  Data: <searchLink fieldCode="DE" term="%22Cerebrospinal+fluid%22">Cerebrospinal fluid</searchLink><br /><searchLink fieldCode="DE" term="%22Gut+microbiota%22">Gut microbiota</searchLink><br /><searchLink fieldCode="DE" term="%22Causal+inference%22">Causal inference</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%22">Therapeutics</searchLink><br /><searchLink fieldCode="DE" term="%22Amyotrophic+lateral+sclerosis%22">Amyotrophic lateral sclerosis</searchLink><br /><searchLink fieldCode="DE" term="%22Mendelian+randomization%22">Mendelian randomization</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolites%22">Metabolites</searchLink><br /><searchLink fieldCode="DE" term="%22Disease+progression%22">Disease progression</searchLink>
– Name: Abstract
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  Data: Background: Previous studies have noted changes in the gut microbiota of amyotrophic lateral sclerosis patients, with some assessing its impact through metabolites or inflammatory factors. However, most of these are observational, and peripheral systems may not accurately reflect central nervous system pathology. This study uniquely explores the influence of gut microbiota on amyotrophic lateral sclerosis by metabolites in cerebrospinal fluid, which is directly connected to the central nervous system. Methods: Data on gut microbiota, cerebrospinal fluid metabolites, and amyotrophic lateral sclerosis were derived from large‐scale genome‐wide association studies. We employed two‐sample and mediation Mendelian randomization to examine the causal effects of gut microbiota and cerebrospinal fluid metabolites on amyotrophic lateral sclerosis, as well as the mediating role of cerebrospinal fluid metabolites between gut microbiota and disease progression. Furthermore, the results were validated through various sensitivity analyses. Results: Two‐sample Mendelian randomization analysis revealed significant associations between three gut microbiota and four cerebrospinal fluid metabolites and amyotrophic lateral sclerosis. Notably, mediation Mendelian randomization analysis indicated that cyanobacteria may promote the onset of amyotrophic lateral sclerosis by increasing the levels of 3‐methoxytyramine sulfate in cerebrospinal fluid. Additionally, the sensitivity analysis confirmed the robustness of the Mendelian randomization results. Conclusions: This study addresses the gap in causal inference within the research on the relationship between gut microbiota, cerebrospinal fluid metabolomics, and amyotrophic lateral sclerosis, thereby advancing our understanding of the molecular mechanisms underlying the disease. The findings will provide a scientific basis for early intervention and precision treatment of the disease. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
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  Data: <i>Copyright of Acta Neurologica Scandinavica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1155/ane/5582939
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        Text: English
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        Type: general
      – SubjectFull: Gut microbiota
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      – SubjectFull: Causal inference
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      – SubjectFull: Therapeutics
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      – SubjectFull: Amyotrophic lateral sclerosis
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      – SubjectFull: Mendelian randomization
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      – SubjectFull: Metabolites
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      – SubjectFull: Disease progression
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              Text: 11/10/2025
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