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

Area of Science:

• Neuroscience
• Genetics
• Microbiology

Background:

• Autism spectrum disorder (ASD) often presents with malnutrition and gut dysbiosis, but the mechanisms are unclear.
• Understanding the interplay between ASD, diet, and gut microbiota is crucial for developing targeted interventions.
• Previous research has not fully elucidated the causal relationships between genetic susceptibility to ASD, dietary patterns, and gut microbial composition.

Purpose of the Study:

• To profile dietary intake differences in individuals with ASD compared to non-ASD individuals.
• To investigate the causal relationships between genetic susceptibility to ASD and dietary preferences using a bi-directional Mendelian Randomization approach.
• To identify ASD-associated gut microbial species and assess the mediating role of the gut microbiota in ASD-related dietary preferences.

Main Methods:

• Cross-sectional analysis of dietary records from 210,874 participants in the UK Biobank (232 with ASD).
• Bi-directional Mendelian Randomization (MR) leveraging genome-wide association data from iPSYCH-PGC (ASD) and UK Biobank (dietary traits).
• Mediation analyses to evaluate the role of gut microbiota in the association between ASD and dietary preferences.

Main Results:

• Individuals with ASD showed higher consumption of cheese, processed meat, and oily fish, with lower fruit intake, preferring high-fat/salt and energy-dense foods.
• Depletion of specific gut bacteria—*Turicibacter*, *Streptococcus*, and *Lachnospiraceae NK4A136*—was causally linked to ASD (FDR < 0.05).
• Gut microbiota significantly mediated the association between ASD and a preference for high-fat/salt foods.

Conclusions:

• ASD is associated with distinct dietary preferences, characterized by increased intake of certain processed foods and a preference for high-fat/salt options.
• The gut microbiome appears to mediate the relationship between ASD and specific eating behaviors, particularly the preference for high-fat/salt foods.
• Targeting the gut microbiome may offer a novel therapeutic avenue for addressing eating disorders and modifying dietary habits in individuals with ASD.