Microbiome, Год журнала: 2024, Номер 12(1)

Опубликована: Март 28, 2024

Abstract Background Microdeletion of the human chromosomal region 16p11.2 (16p11.2 $${}^{+/-}$$ + / - ) is a prevalent genetic factor associated with autism spectrum disorder (ASD) and other neurodevelopmental disorders. However its pathogenic mechanism remains unclear, effective treatments for syndrome are lacking. Emerging evidence suggests that gut microbiota metabolites inextricably linked to host behavior through gut-brain axis therefore implicated in ASD development. Despite this, functional roles microbial context yet be elucidated. This study aims investigate therapeutic potential indole-3-propionic acid (IPA), metabolite, addressing behavioral neural deficits , as well underlying molecular mechanisms. Results Mice showed dysbiosis significant decrease IPA levels feces blood circulation. Further, these mice exhibited social cognitive memory impairments, along hyperactivation hippocampal dentate gyrus neurons reduced inhibitory synaptic transmission this region. However, oral administration effectively mitigated histological electrophysiological alterations, thereby ameliorating mice. Remarkably, treatment significantly increased phosphorylation level ERK1, protein encoded by Mapk3 gene region, without affecting transcription translation gene. Conclusions Our reveals leads decline metabolite levels; however, supplementation notably reverses phenotypes These findings provide new insights into critical role pathogenesis present promising strategy deficit disorders, such microdeletion syndrome.

Язык: Английский