Causal associations between gut microbiota and autism spectrum disorder and attention-deficit/hyperactivity disorder: a two-sample mendelian randomization study

Abstract

The gut microbiota have been implicated in the development of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, the precise causal relationships between the gut microbiota and ASD or ADHD remain unclear. We investigated potential causal associations between gut microbiota and two neurodevelopmental mental disorders (ASD and ADHD) via Mendelian randomization (MR) analyses. We used genome-wide association study (GWAS) summary datasets, including data from the MiBioGen consortium (N = 18,340), the Dutch Microbiome Project (N = 8,208), an ASD GWAS (N = 46,350), and an ADHD GWAS (N = 292,548). Our MR analysis identified 16 gut bacterial taxa associated with ASD. Seven taxa were associated with an increased risk (OR 1.03–1.10), while nine were associated with a decreased risk (OR 0.89–0.96). Conversely, 28 gut bacterial taxa were causally linked to ADHD: 16 were associated with an increased risk (OR 1.02–1.04), and 12 were associated with a decreased risk (OR 0.95–0.98). Both ASD and ADHD were causally influenced by the family “Clostridiales noname,” but with opposite effects. Our MR analysis revealed causal effects of specific gut microbiota on ASD and ADHD, suggesting that certain gut microbes may play a role in the development and treatment of these disorders, as well as in their differential diagnosis.