A systematic review of gut‐immune‐brain mechanisms in Autism Spectrum Disorder

Abstract

Despite decades of research, the etiological origins of Autism Spectrum Disorder (ASD) remain elusive. Recently, the mechanisms of ASD have encompassed emerging theories involving the gastrointestinal, immune, and nervous systems. While each of these perspectives presents its own set of supporting evidence, the field requires an integration of these modular concepts and an overarching view of how these subsystems intersect. In this systematic review, we have synthesized relevant evidences from the existing literature, evaluating them in an interdependent manner and in doing so, outlining their possible connections. Specifically, we first discussed gastrointestinal and immuno‐inflammation pathways in‐depth, exploring the relationships between microbial composition, bacterial metabolites, gut mucosa, and immune system constituents. Accounting for temporal differences in the mechanisms involved in neurodevelopment, prenatal and postnatal phases were further elucidated, where the former focused on maternal immune activation (MIA) and fetal development, while the latter addressed the role of immune dysregulation in contributing to atypical neurodevelopment. As autism remains, foremost, a neurodevelopmental disorder, this review presents an integration of disparate modules into a “Gut‐Immune‐Brain” paradigm. Existing gaps in the literature have been highlighted, and possible avenues for future research with an integrated physiological perspective underlying ASD have also been suggested.

Plasma and Fecal Metabolite Profiles in Autism Spectrum Disorder

“…Metabolic abnormalities have been reported in ASD (7), though most have measured a small subset of metabolites and many outcomes have not reproduced between cohorts. Mitochondrial dysfunction, which heavily influences systemic metabolism, is estimated to be higher in ASD than controls (5% vs ~0.01%) (8), and genes crucial for mitochondrial function are risk factors for ASD (9).…”

Effects of Probiotic Supplementation on Gastrointestinal, Sensory and Core Symptoms in Autism Spectrum Disorders: A Randomized Controlled Trial

“…The possible role of the gut microbiota in ASD has been conceptualized starting from several lines of evidence. First of all, the prevalence of gastrointestinal (GI) symptoms has been found to be higher in ASD subjects compared to typically developing (TD) peers ( 9 – 12 ). Then, several studies showed a significant dysbiosis and a change in the stability, diversity, composition and/or metabolism of the gut microbiota in ASD children compared to TD peers ( 13 , 14 ), while others reported disrupted intestinal permeability in ASD subjects ( 15 , 16 ), and evidence of a systemic and intestinal inflammation in ASD [i.e.…”

Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence

“…Although differentiation is mostly driven by immune signals such as chemokines or cytokines, the Treg/Th17 balance could be influenced by an altered microbiota. Indeed, differentiation into Treg can be induced by some species of Clostridiales and by Bacteroides fragilis, whereas the differentiation into Th17 cell can be induced by some segmented filamentous bacteria (SFB) [82].…”