Objective: Adrenocorticotropic hormone (ACTH) is the first‐line treatment of infantile epileptic spasm syndrome (IESS). Its reported effectiveness varies, and our current understanding regarding the role of gut microbiota composition in IESS treatment response is limited. This study assessed the microbiome–metabolome association to understand the role and mechanism of gut microbiota composition in IESS treatment outcomes.Methods: Children with IESS undergoing ACTH treatment were enrolled. Pre‐treatment stool and serum samples were collected for 16S rRNA gene sequencing and liquid chromatography–tandem mass spectrometry, respectively. The children were divided into “responsive” and “non‐responsive” groups, and gut microbiota and serum metabolome differences were analyzed.Results: Of the 30 patients with IESS, 14 responded to ACTH and 16 did not. The “non‐responsive” group had larger maleficent Clostridioides and Peptoclostridium_phage_p630P populations (linear discriminant analysis >2; false discovery rate q < 0.05). Ten metabolites were upregulated (e.g., xanthurenic acid) and 15 were downregulated (e.g., vanillylmandelic acid) (p < 0.05). Association analysis of the gut microbiome and serum metabolome revealed that Clostridioides and Peptoclostridium_phage_p630P2 were positively correlated with linoleic and xanthurenic acids, while Clostridioides was negatively correlated with vanillylmandelic acid (p < 0.05). A classifier using differential gut bacteria and metabolites achieved an area under the receiver operating characteristic curve of 0.906 to distinguish responders from non‐responders.Conclusion: This study found significant differences in pre‐treatment gut microbiota and serum metabolome between children with IESS who responded to ACTH and those who did not. Additional exploration may provide valuable information for treatment selection and potential interventions. Our results suggest that varying ACTH responses in patients with IESS may be associated with increased gut Clostridioides bacteria and kynurenine pathway alteration, but additional experiments are needed to verify this association.

Autism spectrum disorder (ASD) has been associated with disrupted brain connectivity, yet a comprehensive understanding of the dynamic neural underpinnings remains lacking. This study employed concurrent electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) techniques to investigate dynamic functional connectivity (dFC) patterns and neurovascular characteristics in children with ASD. We also explored associations between neurovascular characteristics and the developmental trajectory of adaptive behavior in individuals with ASD. Resting-state EEG and fNIRS data were simultaneously recorded from 58 ASD and 63 TD children. We implemented a k-means clustering approach to extract the dFC states for each modality. In addition, a multimodal covariance network (MCN) was constructed from the EEG and fNIRS dFC features to capture the neurovascular characteristics linked to ASD. EEG analyses revealed atypical properties of dFC states in the beta and gamma bands in children with ASD compared to TD children. For fNIRS, the ASD group exhibited atypical properties of dFC states such as duration and transitions relative to the TD group. The MCN analysis revealed significantly suppressed functional covariance between right superior temporal and left Broca's areas, alongside enhanced right dorsolateral prefrontal-left Broca covariance in ASD. Notably, we found that early neurovascular characteristics can predict the developmental progress of adaptive functioning in ASD. The multimodal investigation revealed distinct dFC patterns and neurovascular characteristics associated with ASD, elucidating potential neural mechanisms underlying core symptoms and their developmental trajectories. Our study highlights that integrating complementary neuroimaging modalities may aid in unraveling the complex neurobiology of ASD.

Objective: Employing whole‐exome sequencing (WES) technology to investigate the etiology of infantile epileptic spasm syndrome (IESS), and determining whether different etiologies exhibit phenotypic variations, while elucidating the potential associated factors, might improve short‐term responses to first‐line treatment.Methods: We retrospectively evaluated patients with IESS admitted for treatment between January 2018 and June 2023. Clinical phenotypic differences among etiological classifications and clinical manifestations were analyzed. Variable selection using the best subset method was performed, followed by logistic regression analysis to identify the factors influencing treatment response.Results: A total of 577 patients were included; 412 completed trio‐WES. Magnetic resonance imaging abnormalities were detected in 387 patients (67.1%). Patients with etiology as structural abnormalities were likelier to have non‐spasms at the initial seizure onset. A total of 532 patients completed the first‐line treatment; 273 patients received it for the first time at our hospital (initial response rates: 30.1% and 42.1%, respectively). The response group had a lower proportion of early‐onset seizures (≤3 months) than the no‐response group (11.3% vs. 23.7%, p < 0.01 and 11.3% vs. 21.5%, p = 0.03, respectively). Logistic regression analysis indicated that earlier initiation of first‐line treatment was associated with a higher likelihood of an initial response. However, the etiological classification did not have a significant impact on the initial response.Interpretation: IESS patients with structural abnormalities are more likely to present with non‐spasm seizures at initial onset. Early initiation of first‐line treatment is crucial; however, initial responses may be less favorable when seizures occur in early infancy.