Abstract
Autism spectrum disorder (ASD) is associated with alteration of gut microbiome, but the influence of familial structure on it remains poorly understood. We investigate gut microbiota across 429 children from multiplex families with multiple affected children, simplex families with one affected child, and single-child ASD families, alongside typically developing controls. We found that children from multiplex families exhibit the most distinct microbiome compositions. Cohabiting siblings in ASD families display higher microbiome similarity than those in healthy families, with a clear gradient in strain-sharing rates that is highest in multiplex, intermediate in simplex, and lowest in healthy siblings. This increased sharing involves specific taxa with reported opportunistic pathogenic potential, such as Eubacterium rectale, alongside reduced sharing of the commensal bacterium Bacteroides xylanisolvens. This suggests that their gut microbiome configurations, which are potentially influenced by shared environmental and host factors, are associated with increased persistence or detectability of specific bacterial strains. Our results underscore the significant contribution of family type to microbial heterogeneity in ASD and provide a hypothesis-generating context for future studies to explore the role of the shared microbial environment in a familial context.