An agent-based modeling framework for evaluating hypotheses on risks for developing autism: effects of the gut...

Area of Science:

• Microbiome research
• Neuroscience
• Computational biology

Background:

• Autism Spectrum Disorder (ASD) incidence is rising, with growing hypotheses linking gut microbiome dysbiosis to its development.
• An imbalance between inflammatory (Clostridia, Desulfovibrio) and anti-inflammatory (Bifidobacteria) gut microbes may cause a 'leaky gut,' leading to brain inflammation and ASD.
• Understanding these microbial dynamics is crucial for identifying potential therapeutic targets.

Purpose of the Study:

• To investigate how gut microbiome population dynamics influence the imbalanced microbial states associated with ASD.
• To model the interactions between Clostridia, Desulfovibrio, and Bifidobacteria under varying physiological conditions.
• To explore potential interventions for mitigating ASD risk through microbiome modulation.

Main Methods:

• Development of a novel agent-based model simulating gut microbial population dynamics.
• Simulation of bacterial interactions under different physiological conditions and initial population levels.
• Analysis of bacterial population stability and response to simulated interventions like prebiotics, antibiotics, and lysozymes.

Main Results:

• The agent-based model demonstrated robust achievement of a single steady-state microbial population despite initial perturbations.
• Simulations suggest transient effects of disturbances like prebiotics or antibiotics, but sustained prebiotic treatments may improve Bifidobacteria levels.
• Clostridia growth rate emerged as a critical factor determining ASD risk; supra-physiological lysozyme treatment showed potential to suppress Clostridia.

Conclusions:

• Gut microbiome composition and dynamics play a significant role in the potential development of ASD.
• Sustained interventions may be necessary to correct microbial imbalances, unlike transient disturbances.
• Targeting Clostridia growth, potentially with lysozymes, presents a promising avenue for reducing ASD risk in high-risk infants.