Gut Microbiome Mediates the Causal Link Between Autism Spectrum Disorder and Dietary Preferences: A Mendelian Randomization Study.

Subjects with ASD exhibit distinct dietary consumption patterns compared to non-ASD individuals in the UK Biobank cohort.

• Cross-sectional study profiled dietary intake differences using dietary records from 210,874 participants (ASD = 232; non-ASD = 210,642; median age = 56.18) from the UK Biobank.
• ASD subjects showed higher consumption of cheese, processed meat, and oily fish.
• ASD subjects showed lower intake of fruits.
• ASD subjects demonstrated a preference for high-fat/salt and energy-dense foods.

Depletion of three gut microbial taxa was causally related to ASD based on Mendelian Randomization analysis.

• Turicibacter, Streptococcus, and Lachnospiraceae NK4A136 were all causally depleted in association with ASD.
• All associations met a false discovery rate threshold of < 0.05.
• Effect sizes were β = -0.15 for Turicibacter, β = -0.10 for Streptococcus, and β = -0.093 for Lachnospiraceae NK4A136.
• A bi-directional Mendelian Randomization approach was used, leveraging genome-wide association metadata from iPSYCH-PGC (ASD) and UK Biobank (dietary intake/food-liking traits).

Gut microbiota significantly mediates the association between ASD and elevated preference for high-fat/salt foods.

• Mediation analyses were implemented to assess the role of gut microbiota in the association between ASD and dietary preferences.
• The depletion of Turicibacter, Streptococcus, and Lachnospiraceae NK4A136 significantly mediated the ASD-associated elevated preference for high-fat/salt foods.
• The study used genome-wide association metadata from iPSYCH-PGC for ASD and UK Biobank for dietary intake and food-liking traits.

A bi-directional Mendelian Randomization approach was used to dissect causal relationships between ASD genetic susceptibility, dietary preferences, and gut microbial species.

• Genome-wide association metadata were sourced from iPSYCH-PGC for ASD and UK Biobank for dietary intake and food-liking traits.
• The same MR strategy was implemented to identify ASD-associated gut microbial species.
• Mediation analyses further assessed the role of gut microbiota in the association between ASD and dietary preferences.
• The study design was cross-sectional with MR used to infer causal directions.

ASD frequently co-occurs with malnutrition and gut dysbiosis, yet the underlying mechanisms remain poorly understood prior to this study.

• The paper identifies this co-occurrence as a key motivation for the study.
• The study aims to address the gap in understanding mechanisms linking ASD to dietary and microbiome alterations.
• The findings highlight the future potential of gut microbiome-based therapeutics to modify eating disorders in ASD.