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Gut microbial 'TNFα-sphingolipids-steroid hormones' axis in children with autism spectrum disorder: an insight from
Li Shao1, Guangyong Cai2, Jinlong Fu1
1School of Clinical Medicine, Institute of Hepatology and Metabolic Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
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.
