Abstract Body
Introduction: GWAS of microbial data have highlighted significant host-microbiome interactions based on microbiome heritability .
Objectives: Establishing causal relationships between specific gut microbiota and autism spectrum disorder (ASD) .
Methods: We analyzed gut microbiota data from a GWAS involving 5,959 participants and ASD summary statistics from 46,351 individuals. The inverse variance-weighted method was employed as the primary bidirectional Mendelian randomization (MR) analysis. To ensure the robustness of our findings, we performed several sensitivity analyses. Additionally , a reverse MR analysis was conducted to explore potential reverse causation. Finally , single nucleotide polymorphisms were annotated using GWAS4D to identify genes associated with these genetic variants, and enrichment analyses were performed to investigate their biological functions.
Results: We discovered that 17 gut microbial taxa were causally related to ASD risk. Among them, class Fimbriimonadia, order Fibrobacterales, family Acetobacteraceae, family Planococcaceae, genus Saccharomonospora, species Prevotellamassilia, species Ruminococcus E sp900314705, species UBA5394 sp002409725, species Faecalicoccus pleomorphus, species V9D3004, and species Desulfovibrio piger were positively correlated with ASD. Conversely , genus Pandoraea, genus UBP9, species CAG-81 sp000435795, species GCA- 900066755, species Acidaminococcus fermentans, and species Bacillus U were negatively correlated with ASD. The robustness of these associations was confirmed through sensitivity analyses. Moreover, reverse MR analysis revealed that ASD was associated with species Desulfovibrio piger and species Bacillus U. Lastly , we identified 10 novel host-microbiome shared genes in ASD through biological annotation.
Conclusions: Overall, this study provides evidence supporting a potential causal relationship between gut microbiota and ASD risk while also uncovering novel host-microbiome shared genes relevant to ASD.