Integration of Urine Proteomic and Metabolomic Profiling Reveals Novel Insights Into Neuroinflammation in Autism Spectrum Disorder
Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders whose etiology and pathogenesis are not fully understood. To gain insight into the molecular basis of ASD, we performed comparative integrated proteomic and metabolomic analyses of urine samples from children diagnosed...
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| Format: | Article |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Psychiatry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fpsyt.2022.780747/full |
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| author | Wenlong Liu Liming Li Xiaochun Xia Xulan Zhou Yukai Du Zhaoqing Yin Juan Wang |
| author_facet | Wenlong Liu Liming Li Xiaochun Xia Xulan Zhou Yukai Du Zhaoqing Yin Juan Wang |
| author_sort | Wenlong Liu |
| collection | DOAJ |
| description | Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders whose etiology and pathogenesis are not fully understood. To gain insight into the molecular basis of ASD, we performed comparative integrated proteomic and metabolomic analyses of urine samples from children diagnosed with ASD and healthy children. All 160 samples underwent proteomics analysis and 60 were analyzed by liquid chromatography-mass spectrometry to obtain metabolite profiles. We identified 77 differentially expressed proteins (DEPs; 21 downregulated and 56 upregulated) and 277 differentially expressed metabolites; 31 of the DEPs including glutathione, leukocyte antigens, glycoproteins, neural adhesion factors, and immunoglobulins, have been implicated in neuroinflammation. The proteomic analysis also revealed 8 signaling pathways that were significantly dysregulated in ASD patients; 3 of these (transendothelial leukocyte migration, antigen processing and presentation, and graft vs. host disease) were associated with the neuroimmune response. The metabolism of tryptophan, which is also related to the neuroimmune response, has been found to play a potential role in ASD. Integrated proteome and metabolome analysis showed that 6 signaling pathways were significantly enriched in ASD patients, 3 of which were correlated with impaired neuroinflammation (glutathione metabolism, metabolism of xenobiotics by cytochrome P450 and transendothelial migration of leukocyte). We also found a correlation between prostaglandin (PG) E2 levels and the inflammatory response in ASD. These results underscore the prominent role of the neuroimmune response in ASD and provide potential biomarkers that can be used for diagnosis or as targets for early intervention. |
| first_indexed | 2024-04-13T08:50:39Z |
| format | Article |
| id | doaj.art-14db5effc2184810ab50b502ae9241f8 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-04-13T08:50:39Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-14db5effc2184810ab50b502ae9241f82022-12-22T02:53:29ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402022-05-011310.3389/fpsyt.2022.780747780747Integration of Urine Proteomic and Metabolomic Profiling Reveals Novel Insights Into Neuroinflammation in Autism Spectrum DisorderWenlong Liu0Liming Li1Xiaochun Xia2Xulan Zhou3Yukai Du4Zhaoqing Yin5Juan Wang6Department of Child Development and Behavior, School of Medicine, Women and Children's Hospital, Xiamen University, Xiamen, ChinaDepartment of Public Health and Medical Technology, Xiamen Medical College, Xiamen, ChinaDepartment of Public Health and Medical Technology, Xiamen Medical College, Xiamen, ChinaDepartment of Public Health and Medical Technology, Xiamen Medical College, Xiamen, ChinaDepartment of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDivision of Neonatology, The People's Hospital of Dehong Autonomous Prefecture, Mangshi, ChinaDepartment of Public Health and Medical Technology, Xiamen Medical College, Xiamen, ChinaAutism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders whose etiology and pathogenesis are not fully understood. To gain insight into the molecular basis of ASD, we performed comparative integrated proteomic and metabolomic analyses of urine samples from children diagnosed with ASD and healthy children. All 160 samples underwent proteomics analysis and 60 were analyzed by liquid chromatography-mass spectrometry to obtain metabolite profiles. We identified 77 differentially expressed proteins (DEPs; 21 downregulated and 56 upregulated) and 277 differentially expressed metabolites; 31 of the DEPs including glutathione, leukocyte antigens, glycoproteins, neural adhesion factors, and immunoglobulins, have been implicated in neuroinflammation. The proteomic analysis also revealed 8 signaling pathways that were significantly dysregulated in ASD patients; 3 of these (transendothelial leukocyte migration, antigen processing and presentation, and graft vs. host disease) were associated with the neuroimmune response. The metabolism of tryptophan, which is also related to the neuroimmune response, has been found to play a potential role in ASD. Integrated proteome and metabolome analysis showed that 6 signaling pathways were significantly enriched in ASD patients, 3 of which were correlated with impaired neuroinflammation (glutathione metabolism, metabolism of xenobiotics by cytochrome P450 and transendothelial migration of leukocyte). We also found a correlation between prostaglandin (PG) E2 levels and the inflammatory response in ASD. These results underscore the prominent role of the neuroimmune response in ASD and provide potential biomarkers that can be used for diagnosis or as targets for early intervention.https://www.frontiersin.org/articles/10.3389/fpsyt.2022.780747/fullautism spectrum disorderproteomicsmetabolomicsintegrated analysisurineneuroinflammation |
| spellingShingle | Wenlong Liu Liming Li Xiaochun Xia Xulan Zhou Yukai Du Zhaoqing Yin Juan Wang Integration of Urine Proteomic and Metabolomic Profiling Reveals Novel Insights Into Neuroinflammation in Autism Spectrum Disorder Frontiers in Psychiatry autism spectrum disorder proteomics metabolomics integrated analysis urine neuroinflammation |
| title | Integration of Urine Proteomic and Metabolomic Profiling Reveals Novel Insights Into Neuroinflammation in Autism Spectrum Disorder |
| title_full | Integration of Urine Proteomic and Metabolomic Profiling Reveals Novel Insights Into Neuroinflammation in Autism Spectrum Disorder |
| title_fullStr | Integration of Urine Proteomic and Metabolomic Profiling Reveals Novel Insights Into Neuroinflammation in Autism Spectrum Disorder |
| title_full_unstemmed | Integration of Urine Proteomic and Metabolomic Profiling Reveals Novel Insights Into Neuroinflammation in Autism Spectrum Disorder |
| title_short | Integration of Urine Proteomic and Metabolomic Profiling Reveals Novel Insights Into Neuroinflammation in Autism Spectrum Disorder |
| title_sort | integration of urine proteomic and metabolomic profiling reveals novel insights into neuroinflammation in autism spectrum disorder |
| topic | autism spectrum disorder proteomics metabolomics integrated analysis urine neuroinflammation |
| url | https://www.frontiersin.org/articles/10.3389/fpsyt.2022.780747/full |
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