Metagenomic Characterization of Gut Microbiota in Children with Autism Spectrum Disorder: Microbial Signatures and Modulation by Anti-Inflammatory Diet and Probiotics Original paper

What was studied?

This study examined gut microbiome signatures in autism spectrum disorder (ASD), focusing on how microbial composition and immune–microbial interactions differ between typically developing children and those with ASD, including subgroups with functional gastrointestinal disorders (FGIDs). The analysis incorporated the focus keyphrase ASD gut microbiome signatures by using shotgun metagenomics and cytokine profiling to understand microbiota diversity, taxonomic shifts, and immune correlations. The investigators also tested whether a 12-week anti-inflammatory diet or probiotic supplementation could modulate gut ecology or immune–microbial networks. According to figures and data throughout the manuscript, microbial taxa such as Clostridioides, Coprococcus, Alistipes, Parabacteroides, Romboutsia, Lachnospira, and SCFA-producing genera played central roles, and immune nodes such as IFN-γ, IL-8, MIP-1β, and MCP-1 served as major hubs linking microbial shifts to systemic inflammation.

Who was studied?

The study recruited Colombian children categorized into multiple cohorts: typically developing, ASD without FGIDs, ASD with FGIDs (ASD_FGIDs), and TD with FGIDs (TD_FGIDs). A subset of children with ASD completed a 12-week intervention phase divided into three arms: ASD_control (n=6), ASD_diet (n=5), and ASD_probiotics (n=6). Participants provided fecal and plasma samples to allow paired microbiome and cytokine profiling. The selection emphasized real-world clinical heterogeneity, enabling discrimination of microbial patterns associated with both ASD phenotype and gastrointestinal symptom burden.

Most important findings

The study revealed distinct ASD gut microbiome signatures. Children with ASD exhibited a higher Firmicutes/Bacteroidetes ratio and enrichment of genera such as Clostridioides, Thomasclavelia, Alistipes, and Coprococcus compared with TD children. In ASD_FGIDs, Parabacteroides, Bacteroides, Alistipes, Akkermansia, and Phascolarctobacterium were significantly increased, with Parabacteroides showing the strongest difference (p = 4.16×10⁻⁸). TD_FGIDs showed depletion of butyrate-producers such as Anaerobutyricum and Coprococcus, implying a link between FGID symptoms and loss of beneficial taxa.

Immune–microbial networks in ASD were fragmented, dominated by IFN-γ and MCP-1 with multiple pro-inflammatory associations, whereas TD networks were compact and dominated by balanced commensal-cytokine interactions. SCFA-producing genera such as Faecalibacterium, Roseburia, and Bifidobacterium showed positive correlations with IL-8 and IFN-γ in TD children but weaker or dysregulated patterns in ASD. Interventions showed targeted changes: the anti-inflammatory diet increased six genera (Moraxella, Eubacterium, Novisyntrophococcus, Sellimonas, Altererythrobacter, Adlercreutzia) with a shift toward integrated, positive immune–microbial networks. Probiotics increased Romboutsia and decreased Lachnospira, modifying networks toward regulatory cytokine involvement, including SDF-1α and Eotaxin.

Key implications

The findings underscore that ASD is associated with identifiable microbial and immune signatures, especially when gastrointestinal symptoms are present. These ASD gut microbiome signatures highlight potential biomarkers for stratification and therapeutic targeting. The limited changes in alpha diversity suggest that microbiota-directed therapies influence specific taxa and immune networks rather than broad ecological architecture. Both diet and probiotics partially remodeled immune–microbial connectivity, suggesting that precision nutritional interventions may offer meaningful adjunctive support for ASD management, particularly for subgroups with FGIDs or immune dysregulation.

Citation

García-Zambrano S, et al. Gut Microbiota, Immune–Microbial Networks, and Nutritional Interventions in Colombian Children with Autism Spectrum Disorder.Pharmaceuticals. 2025;18(9):1376. doi:10.3390/ph18091376