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Genetic evidence on chemical communication between gut microbiota and neurological and psychiatric disorders: a Mendelian randomization study.

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Title: Genetic evidence on chemical communication between gut microbiota and neurological and psychiatric disorders: a Mendelian randomization study.
Authors: Yu, Shiyao (AUTHOR), Ye, Zhijun (AUTHOR), Zhao, Wen (AUTHOR), Yu, Xinyi (AUTHOR), Qiu, Yuhui (AUTHOR), Lin, Keyi (AUTHOR), Lu, Ting (AUTHOR), Ge, Lijuan (AUTHOR), Sun, Jingbo (AUTHOR), Hua, Rong (AUTHOR)
Source: European Archives of Psychiatry & Clinical Neuroscience. Jun2026, Vol. 276 Issue 4, p1759-1773. 15p.
Subjects: Gut microbiota, Mendelian randomization, Neurological disorders, Anxiety, People with mental illness, Alzheimer's disease, Autism spectrum disorders
Abstract: Background: Accumulating evidence from clinical trials and preclinical studies revealed the importance of the microbiota-gut-brain axis (MGBA) in neurological and psychiatric disorders (NPDs). MGBA remains a blueprint for extended explorations. Methods: We examine the bidirectional association between 5 NPDs (late-onset Alzheimer's disease (AD), migraine, autism spectrum disorder (ASD), all anxiety disorder, depression) and gut microbiota (GM) via microbial-derived metabolites, neurotransmitter, and precursors including total branched-chain amino acids (BCAA), isoleucine, leucine, valine, acetate, tryptophan, kynurenine, glutamate, tyrosine, serotonin using two step Mendelian randomization. Five methods were performed, including inverse variance weighted, MR Egger regression, weighted median, weighted mode, and simple mode. The robustness of results was supported by Cochran's Q test, the MR-Egger regression, the MR pleiotropy residual sum and outlier, and the leave-one-out method. Results: After false discovery rate correction, we found elevated isoleucine in plasma as a risk factor for AD and elevated tyrosine in plasma as a risk factor for anxiety. Conversely, AD has genetically effect on a lower level of total BCAA, isoleucine, leucine, valine, glutamate, and tyrosine in plasma. We also found that Clostridia, Clostridiales, Sutterella, and Ruminococcus torques group were positively correlated with isoleucine. Elevated Sutterella abundance was found strongly positively correlated with ASD. Desulfovibrionales and Desulfovibrionaceae were found strongly positively correlated with AD. Pathways of Clostridia/Clostridiales/Ruminococcus torques group/Sutterella- isoleucine- AD were established with mediating percentages ranging from − 54.265% to 132.908%. Conclusion: Our study elucidates how chemical signalling bridges communication between GM and NPDs, paving avenues for microbiota-based treatment. [ABSTRACT FROM AUTHOR]
Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature 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.)
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  Data: Genetic evidence on chemical communication between gut microbiota and neurological and psychiatric disorders: a Mendelian randomization study.
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  Data: <searchLink fieldCode="AR" term="%22Yu%2C+Shiyao%22">Yu, Shiyao</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ye%2C+Zhijun%22">Ye, Zhijun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhao%2C+Wen%22">Zhao, Wen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yu%2C+Xinyi%22">Yu, Xinyi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Qiu%2C+Yuhui%22">Qiu, Yuhui</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lin%2C+Keyi%22">Lin, Keyi</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lu%2C+Ting%22">Lu, Ting</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Ge%2C+Lijuan%22">Ge, Lijuan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sun%2C+Jingbo%22">Sun, Jingbo</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hua%2C+Rong%22">Hua, Rong</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22European+Archives+of+Psychiatry+%26+Clinical+Neuroscience%22">European Archives of Psychiatry & Clinical Neuroscience</searchLink>. Jun2026, Vol. 276 Issue 4, p1759-1773. 15p.
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  Data: <searchLink fieldCode="DE" term="%22Gut+microbiota%22">Gut microbiota</searchLink><br /><searchLink fieldCode="DE" term="%22Mendelian+randomization%22">Mendelian randomization</searchLink><br /><searchLink fieldCode="DE" term="%22Neurological+disorders%22">Neurological disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Anxiety%22">Anxiety</searchLink><br /><searchLink fieldCode="DE" term="%22People+with+mental+illness%22">People with mental illness</searchLink><br /><searchLink fieldCode="DE" term="%22Alzheimer's+disease%22">Alzheimer's disease</searchLink><br /><searchLink fieldCode="DE" term="%22Autism+spectrum+disorders%22">Autism spectrum disorders</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Accumulating evidence from clinical trials and preclinical studies revealed the importance of the microbiota-gut-brain axis (MGBA) in neurological and psychiatric disorders (NPDs). MGBA remains a blueprint for extended explorations. Methods: We examine the bidirectional association between 5 NPDs (late-onset Alzheimer's disease (AD), migraine, autism spectrum disorder (ASD), all anxiety disorder, depression) and gut microbiota (GM) via microbial-derived metabolites, neurotransmitter, and precursors including total branched-chain amino acids (BCAA), isoleucine, leucine, valine, acetate, tryptophan, kynurenine, glutamate, tyrosine, serotonin using two step Mendelian randomization. Five methods were performed, including inverse variance weighted, MR Egger regression, weighted median, weighted mode, and simple mode. The robustness of results was supported by Cochran's Q test, the MR-Egger regression, the MR pleiotropy residual sum and outlier, and the leave-one-out method. Results: After false discovery rate correction, we found elevated isoleucine in plasma as a risk factor for AD and elevated tyrosine in plasma as a risk factor for anxiety. Conversely, AD has genetically effect on a lower level of total BCAA, isoleucine, leucine, valine, glutamate, and tyrosine in plasma. We also found that Clostridia, Clostridiales, Sutterella, and Ruminococcus torques group were positively correlated with isoleucine. Elevated Sutterella abundance was found strongly positively correlated with ASD. Desulfovibrionales and Desulfovibrionaceae were found strongly positively correlated with AD. Pathways of Clostridia/Clostridiales/Ruminococcus torques group/Sutterella- isoleucine- AD were established with mediating percentages ranging from − 54.265% to 132.908%. Conclusion: Our study elucidates how chemical signalling bridges communication between GM and NPDs, paving avenues for microbiota-based treatment. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
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  Data: <i>Copyright of European Archives of Psychiatry & Clinical Neuroscience is the property of Springer Nature 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: 10.1007/s00406-025-02147-0
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        Text: English
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      – SubjectFull: Gut microbiota
        Type: general
      – SubjectFull: Mendelian randomization
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      – SubjectFull: Neurological disorders
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      – SubjectFull: Anxiety
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      – SubjectFull: People with mental illness
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      – SubjectFull: Alzheimer's disease
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      – SubjectFull: Autism spectrum disorders
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      – TitleFull: Genetic evidence on chemical communication between gut microbiota and neurological and psychiatric disorders: a Mendelian randomization study.
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              Text: Jun2026
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