Differential analysis of Short chain fatty acids incubation in autistic organoids based on transcriptome sequencing

by Zaixin Wu, Xinyi Liu, Xiaobo Han, Miao Li

Autism spectrum disorder (ASD) is characterized by difficulty with social communication and restricted, repetitive patterns of behavior, interest, or activities. We hypothesized that a dysregulation in short-chain fatty acid (SCFA) metabolism induces metabolic dysregulation and proinflammatory responses, which collectively contribute to the social behavioral deficits observed in early childhood. Herein, by high-throughput RNA sequencing (RNA-seq) of the whole transcriptome, including GO and KEGG enrichment analyses, we analyzed global gene expression differences in ASD cerebral organoids exposed to different SCFAs. The ASD cerebral organoids were divided into three groups: the ASD group (control), the acetate-treated group (Z group), and the butyrate-treated group (J group), with three biological replicates per group. Organoids were treated with 100 μM sodium acetate or 100 μM sodium butyrate from day 16 to day 23 of cortical differentiation, for a total duration of 7 days. GO functional annotation revealed that acetate treatment primarily altered gene expression related to differential regulation, whereas butyrate exposure activated immune-related processes. KEGG pathway analysis indicated that butyrate treatment was associated with enrichment of the TGF-β immune-related signaling pathway in ASD organoids, whereas acetate treatment primarily affected molecular functions such as transcriptional regulation, catalytic activity, and membrane permeability.