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- Title
Microbiota-indole 3-propionic acid-brain axis mediates abnormal synaptic pruning of hippocampal microglia and susceptibility to ASD in IUGR offspring.
- Authors
Wang, Tingting; Chen, Beidi; Luo, Mingcui; Xie, Lulu; Lu, Mengxi; Lu, Xiaoqian; Zhang, Shuai; Wei, Liyi; Zhou, Xinli; Yao, Baozhen; Wang, Hui; Xu, Dan
- Abstract
Background: Autism spectrum disorder (ASD) has been associated with intrauterine growth restriction (IUGR), but the underlying mechanisms are unclear. Results: We found that the IUGR rat model induced by prenatal caffeine exposure (PCE) showed ASD-like symptoms, accompanied by altered gut microbiota and reduced production of indole 3-propionic acid (IPA), a microbiota-specific metabolite and a ligand of aryl hydrocarbon receptor (AHR). IUGR children also had a reduced serum IPA level consistent with the animal model. We demonstrated that the dysregulated IPA/AHR/NF-κB signaling caused by disturbed gut microbiota mediated the hippocampal microglia hyperactivation and neuronal synapse over-pruning in the PCE-induced IUGR rats. Moreover, postnatal IPA supplementation restored the ASD-like symptoms and the underlying hippocampal lesions in the IUGR rats. Conclusions: This study suggests that the microbiota-IPA-brain axis regulates ASD susceptibility in PCE-induced IUGR offspring, and supplementation of microbiota-derived IPA might be a promising interventional strategy for ASD with a fetal origin. 21xhjpDoyB4JmdH7kH-NGn Video Abstract
- Subjects
FETAL growth retardation; ARYL hydrocarbon receptors; HIPPOCAMPUS (Brain); AUTISM spectrum disorders; MICROGLIA; INDOLE; MICROBIAL metabolites; TRIMETHYLAMINE oxide
- Publication
Microbiome, 2023, Vol 11, Issue 1, p1
- ISSN
2049-2618
- Publication type
Article
- DOI
10.1186/s40168-023-01656-1