Gut microbial ‘TNFα-sphingolipids-steroid hormones’ axis in children with autism spectrum disorder: an insight from meta-omics analysis
Abstract Background Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder affecting brains of children. Mounting evidences support the associations between gut microbial dysbiosis and ASD, whereas detailed mechanisms are still obscure. Methods Here we probed the potential roles...
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BMC
2024-12-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-05973-3 |
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| author | Li Shao Guangyong Cai Jinlong Fu Weishi Zhang Yuefang Ye Zongxin Ling Shiwei Ye |
| author_facet | Li Shao Guangyong Cai Jinlong Fu Weishi Zhang Yuefang Ye Zongxin Ling Shiwei Ye |
| author_sort | Li Shao |
| collection | DOAJ |
| description | Abstract Background Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder affecting brains of children. Mounting evidences support the associations between gut microbial dysbiosis and ASD, whereas detailed mechanisms are still obscure. Methods Here we probed the potential roles of gut microbiome in ASD using fecal metagenomics and metabolomics. Results Children with ASD were found to be associated with augmented serum cytokines milieu, especially TNFα. Metagenomic analysis generated 29 differential species and 18 dysregulated functional pathways such as Bifidobacterium bifidum, Segatella copri, and upregulated ‘Sphingolipid metabolism’ in children with ASD. Metabolomics revealed steroid hormone dysgenesis in children with ASD with lower abundances of metabolites such as estriol, estradiol and deoxycorticosterone. A three-way association analysis showed positive correlations between TNFα and microbial function potentials such as ‘Bacterial toxins’ and ‘Lysosome’, indicating the contribution of microbial dysbiosis to neuroinflammation. TNFα also correlated positively with ‘Sphingolipid metabolism’, which further showed negative correlations with metabolites estriol and deoxycorticosterone. Such results, in consistent with current findings, revealed the contribution of increased TNFα to upregulated sphingolipid metabolism, which further impaired steroid hormone biosynthesis. Conclusion Our study proposed the gut microbial ‘TNFα-sphingolipids-steroid hormones’ axis in children with ASD, which may provide new perspectives for developing gut microbiome-based treatments in the future. |
| format | Article |
| id | doaj-art-dcdc1007c841423d8db537d4e7571a46 |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-dcdc1007c841423d8db537d4e7571a462025-01-05T12:44:30ZengBMCJournal of Translational Medicine1479-58762024-12-0122111010.1186/s12967-024-05973-3Gut microbial ‘TNFα-sphingolipids-steroid hormones’ axis in children with autism spectrum disorder: an insight from meta-omics analysisLi Shao0Guangyong Cai1Jinlong Fu2Weishi Zhang3Yuefang Ye4Zongxin Ling5Shiwei Ye6School of Clinical Medicine, Institute of Hepatology and Metabolic Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityDepartment of Acupuncture and Chinese Tuina, Lishui Second People’s HospitalSchool of Clinical Medicine, Institute of Hepatology and Metabolic Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityDepartment of Otolaryngology, Affiliated Hospital 2 of Nantong UniversitySchool of Clinical Medicine, Institute of Hepatology and Metabolic Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal UniversityState Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityLishui Key Laboratory of mental Health and brain Disorders, Lishui Second People’s HospitalAbstract Background Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder affecting brains of children. Mounting evidences support the associations between gut microbial dysbiosis and ASD, whereas detailed mechanisms are still obscure. Methods Here we probed the potential roles of gut microbiome in ASD using fecal metagenomics and metabolomics. Results Children with ASD were found to be associated with augmented serum cytokines milieu, especially TNFα. Metagenomic analysis generated 29 differential species and 18 dysregulated functional pathways such as Bifidobacterium bifidum, Segatella copri, and upregulated ‘Sphingolipid metabolism’ in children with ASD. Metabolomics revealed steroid hormone dysgenesis in children with ASD with lower abundances of metabolites such as estriol, estradiol and deoxycorticosterone. A three-way association analysis showed positive correlations between TNFα and microbial function potentials such as ‘Bacterial toxins’ and ‘Lysosome’, indicating the contribution of microbial dysbiosis to neuroinflammation. TNFα also correlated positively with ‘Sphingolipid metabolism’, which further showed negative correlations with metabolites estriol and deoxycorticosterone. Such results, in consistent with current findings, revealed the contribution of increased TNFα to upregulated sphingolipid metabolism, which further impaired steroid hormone biosynthesis. Conclusion Our study proposed the gut microbial ‘TNFα-sphingolipids-steroid hormones’ axis in children with ASD, which may provide new perspectives for developing gut microbiome-based treatments in the future.https://doi.org/10.1186/s12967-024-05973-3autism spectrum disordergut microbiomemetagenomicsmetabolomics |
| spellingShingle | Li Shao Guangyong Cai Jinlong Fu Weishi Zhang Yuefang Ye Zongxin Ling Shiwei Ye Gut microbial ‘TNFα-sphingolipids-steroid hormones’ axis in children with autism spectrum disorder: an insight from meta-omics analysis Journal of Translational Medicine autism spectrum disorder gut microbiome metagenomics metabolomics |
| title | Gut microbial ‘TNFα-sphingolipids-steroid hormones’ axis in children with autism spectrum disorder: an insight from meta-omics analysis |
| title_full | Gut microbial ‘TNFα-sphingolipids-steroid hormones’ axis in children with autism spectrum disorder: an insight from meta-omics analysis |
| title_fullStr | Gut microbial ‘TNFα-sphingolipids-steroid hormones’ axis in children with autism spectrum disorder: an insight from meta-omics analysis |
| title_full_unstemmed | Gut microbial ‘TNFα-sphingolipids-steroid hormones’ axis in children with autism spectrum disorder: an insight from meta-omics analysis |
| title_short | Gut microbial ‘TNFα-sphingolipids-steroid hormones’ axis in children with autism spectrum disorder: an insight from meta-omics analysis |
| title_sort | gut microbial tnfα sphingolipids steroid hormones axis in children with autism spectrum disorder an insight from meta omics analysis |
| topic | autism spectrum disorder gut microbiome metagenomics metabolomics |
| url | https://doi.org/10.1186/s12967-024-05973-3 |
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