Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study
BackgroundAutism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long been recognized. Altered immune function and gut microbiota have been found in ASD populations. Immune dysfunction has be...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1100816/full |
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| author | Xin-Jie Xu Xin-Jie Xu Ji-Dong Lang Jun Yang Bo Long Xu-Dong Liu Xiao-Feng Zeng Xiao-Feng Zeng Geng Tian Xin You Xin You Xin You |
| author_facet | Xin-Jie Xu Xin-Jie Xu Ji-Dong Lang Jun Yang Bo Long Xu-Dong Liu Xiao-Feng Zeng Xiao-Feng Zeng Geng Tian Xin You Xin You Xin You |
| author_sort | Xin-Jie Xu |
| collection | DOAJ |
| description | BackgroundAutism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long been recognized. Altered immune function and gut microbiota have been found in ASD populations. Immune dysfunction has been hypothesized to involve in the pathophysiology of a subtype of ASD.MethodsA cohort of 105 ASD children were recruited and grouped based on IFN-γ levels derived from ex vivo stimulated γδT cells. Fecal samples were collected and analyzed with a metagenomic approach. Comparison of autistic symptoms and gut microbiota composition was made between subgroups. Enriched KEGG orthologues markers and pathogen-host interactions based on metagenome were also analyzed to reveal the differences in functional features.ResultsThe autistic behavioral symptoms were more severe for children in the IFN-γ-high group, especially in the body and object use, social and self-help, and expressive language performance domains. LEfSe analysis of gut microbiota revealed an overrepresentation of Selenomonadales, Negatiyicutes, Veillonellaceae and Verrucomicrobiaceae and underrepresentation of Bacteroides xylanisolvens and Bifidobacterium longum in children with higher IFN-γ level. Decreased metabolism function of carbohydrate, amino acid and lipid in gut microbiota were found in the IFN-γ-high group. Additional functional profiles analyses revealed significant differences in the abundances of genes encoding carbohydrate-active enzymes between the two groups. And enriched phenotypes related to infection and gastroenteritis and underrepresentation of one gut–brain module associated with histamine degradation were also found in the IFN-γ-High group. Results of multivariate analyses revealed relatively good separation between the two groups.ConclusionsLevels of IFN-γ derived from γδT cell could serve as one of the potential candidate biomarkers to subtype ASD individuals to reduce the heterogeneity associated with ASD and produce subgroups which are more likely to share a more similar phenotype and etiology. A better understanding of the associations among immune function, gut microbiota composition and metabolism abnormalities in ASD would facilitate the development of individualized biomedical treatment for this complex neurodevelopmental disorder. |
| first_indexed | 2024-04-10T15:01:51Z |
| format | Article |
| id | doaj.art-406edf056e9d4f61a5d248810c120018 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T15:01:51Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-406edf056e9d4f61a5d248810c1200182023-02-15T10:34:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.11008161100816Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary studyXin-Jie Xu0Xin-Jie Xu1Ji-Dong Lang2Jun Yang3Bo Long4Xu-Dong Liu5Xiao-Feng Zeng6Xiao-Feng Zeng7Geng Tian8Xin You9Xin You10Xin You11Medical Science Research Center, Research Center for Translational Medicine, Department of Scientific Research, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaPrecision Medicine Center, Geneis Beijing Co., Ltd., Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaMedical Science Research Center, Research Center for Translational Medicine, Department of Scientific Research, Peking Union Medical College Hospital, Beijing, ChinaMedical Science Research Center, Research Center for Translational Medicine, Department of Scientific Research, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, ChinaPrecision Medicine Center, Geneis Beijing Co., Ltd., Beijing, ChinaDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaKey Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, ChinaAutism Special Fund, Peking Union Medical Foundation, Beijing, ChinaBackgroundAutism Spectrum Disorders (ASD) are defined as a group of pervasive neurodevelopmental disorders, and the heterogeneity in the symptomology and etiology of ASD has long been recognized. Altered immune function and gut microbiota have been found in ASD populations. Immune dysfunction has been hypothesized to involve in the pathophysiology of a subtype of ASD.MethodsA cohort of 105 ASD children were recruited and grouped based on IFN-γ levels derived from ex vivo stimulated γδT cells. Fecal samples were collected and analyzed with a metagenomic approach. Comparison of autistic symptoms and gut microbiota composition was made between subgroups. Enriched KEGG orthologues markers and pathogen-host interactions based on metagenome were also analyzed to reveal the differences in functional features.ResultsThe autistic behavioral symptoms were more severe for children in the IFN-γ-high group, especially in the body and object use, social and self-help, and expressive language performance domains. LEfSe analysis of gut microbiota revealed an overrepresentation of Selenomonadales, Negatiyicutes, Veillonellaceae and Verrucomicrobiaceae and underrepresentation of Bacteroides xylanisolvens and Bifidobacterium longum in children with higher IFN-γ level. Decreased metabolism function of carbohydrate, amino acid and lipid in gut microbiota were found in the IFN-γ-high group. Additional functional profiles analyses revealed significant differences in the abundances of genes encoding carbohydrate-active enzymes between the two groups. And enriched phenotypes related to infection and gastroenteritis and underrepresentation of one gut–brain module associated with histamine degradation were also found in the IFN-γ-High group. Results of multivariate analyses revealed relatively good separation between the two groups.ConclusionsLevels of IFN-γ derived from γδT cell could serve as one of the potential candidate biomarkers to subtype ASD individuals to reduce the heterogeneity associated with ASD and produce subgroups which are more likely to share a more similar phenotype and etiology. A better understanding of the associations among immune function, gut microbiota composition and metabolism abnormalities in ASD would facilitate the development of individualized biomedical treatment for this complex neurodevelopmental disorder.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1100816/fullautism spectrum disordersgut microbiotametagenomicsinterferonimmune |
| spellingShingle | Xin-Jie Xu Xin-Jie Xu Ji-Dong Lang Jun Yang Bo Long Xu-Dong Liu Xiao-Feng Zeng Xiao-Feng Zeng Geng Tian Xin You Xin You Xin You Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study Frontiers in Immunology autism spectrum disorders gut microbiota metagenomics interferon immune |
| title | Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study |
| title_full | Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study |
| title_fullStr | Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study |
| title_full_unstemmed | Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study |
| title_short | Differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδT cells-derived IFN-γ Levels: A preliminary study |
| title_sort | differences of gut microbiota and behavioral symptoms between two subgroups of autistic children based on γδt cells derived ifn γ levels a preliminary study |
| topic | autism spectrum disorders gut microbiota metagenomics interferon immune |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1100816/full |
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