Gut dysbiosis in neurodevelopmental disorders: linking microbiota signatures to cognitive rigidity in autism spectrum disorder

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Authors: Bhagavathi Sundaram Sivamaruthi, Periyanaina Kesika, Chaiyavat Chaiyasut, Durairaj Ragu Varman
Cited by: 4
References: 89

Abstract

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterised not only by social-communication difficulties but also by restricted interests, stereotyped behaviours, and marked cognitive rigidity. Over the past decade, converging lines of evidence have implicated gut dysbiosis, an imbalance in intestinal microbial composition and function, as a potentially important modulator of these behavioural phenotypes via the microbiota-gut-brain axis. In this narrative review, we integrate preclinical and clinical data to examine how specific microbial signatures, metabolic pathways, and immune and synaptic mechanisms may contribute to inflexible cognition in ASD. The manuscript outlines the organisation of the microbiota gut-brain axis in neurodevelopment and summarises reproducible microbial alterations reported in ASD cohorts. We then discuss how microbial metabolites, including short-chain fatty acids and tryptophan-derived neuroactive molecules, as well as immune mediators and neurotransmitter precursors, converge on pathways regulating excitatory-inhibitory balance, synaptic plasticity, and corticostriatal circuit function. Evidence from germ-free, genetic, and environmental rodent models provides causal support for microbiota-dependent modulation of repetitive and rigid behaviours, whilst clinical studies reveal associations between dysbiosis, metabolomic profiles, gastrointestinal symptoms, and ASD severity. Finally, we consider the translational landscape of microbiota-targeted interventions, probiotics, prebiotics, dietary strategies, and faecal microbiota transplantation and highlight key methodological and ethical challenges for moving toward precision microbiome-based therapies. Taken together, current data support gut dysbiosis as both a mechanistic contributor and a tractable therapeutic target for cognitive rigidity in ASD.

Fields of Study & Subjects

Gut microbiota and health Tryptophan and brain disorders Autism Spectrum Disorder Research

Publication details

Journal / source
Frontiers in Microbiology
Publisher
Frontiers Media SA
Volume
17
Pages
1760635–1760635
Publication date
27 January 2026
Language
EN