Microbiota, Immune System and Autism Spectrum Disorders: An Integrative Model towards Novel Treatment Options

Abstract

Background: Autism spectrum disorder (ASD) is a condition strongly associated with genetic predisposition and familial aggregation. Among ASD patients different levels of symptoms severity are detectable, while the presence of intermediate autism phenotypes in close relatives of ASD probands is also known in literature. Recently, increasing attention has been paid to environmental factors that might play a role in modulating the relationship between genomic risk and development and severity of ASD. Within this framework, an increasing body of evidence has stressed a possible role of both gut microbiota and inflammation in the pathophysiology of neurodevelopment. The aim of this paper is to review findings about the link between microbiota dysbiosis, inflammation and ASD. Methods: articles ranging from 1990 to 2018 were identified on PUBMED and Google Scholar databases, with keyword combinations as: microbiota, immune system, inflammation, ASD, autism, broad autism phenotype, adult. Results: recent evidence suggests that microbiota alterations, immune system and neurodevelopment may be deeply intertwined, shaping each other during early life. However, results from both animal models and human samples are still heterogeneous, while few studies focused on adult patients and ASD intermediate phenotypes. Conclusion: A better understanding of these pathways, within an integrative framework between central and peripheral systems, might not only shed more light on neural basis of ASD symptoms, clarifying brain pathophysiology, but it may also allow to develop new therapeutic strategies for these disorders, still poorly responsive to available treatments.

Subthreshold Autism Spectrum in a Patient with Anorexia Nervosa and Behçet’s Syndrome

“…In both ASD and BS, involvement of the immune system has been hypothesized. For example, dysregulation of immune function and neuroinflammation, as well as the presence of maternal autoantibodies directed against fetal brain tissue, have been involved in the pathophysiology of ASD [19,21]. Recently, some authors highlighted the potential role of maternal antibodies against stress-induced phosphoprotein 1 (STIP1) [51], a ligand of prion protein found in the developing brain that has been shown to mediate neurogenesis in cultured hippocampal neurons [52,53].…”

“…In the last decades, increasing literature highlighted several kinds of immune system alterations, such as altered levels of cytokines, in patients with ASD [57]. The authors suggested the presence of shared genetic underpinnings between ASD and autoimmune diseases, which would interact with early environmental factors, in particular during intrauterine life, in shaping neuroimmune patterns [19,21]. On the other hand, also AN has been linked with the presence of immune system alterations: while some authors stressed the presence of a higher vulnerability of patients with autoimmune diseases towards the development of AN, pointing out a possible role of the immune system in the pathogenesis of eating disorders [58], others highlighted the presence of immune system dysregulation in patients with AN, hypothesizing that it may be caused by the altered nutritional status [59].…”

“…On the other hand, also AN has been linked with the presence of immune system alterations: while some authors stressed the presence of a higher vulnerability of patients with autoimmune diseases towards the development of AN, pointing out a possible role of the immune system in the pathogenesis of eating disorders [58], others highlighted the presence of immune system dysregulation in patients with AN, hypothesizing that it may be caused by the altered nutritional status [59]. In this framework, recent researches on the role of gut microbiota in both immune and psychiatric disorders have further broadened the perspectives [19]. Microbiota composition has been reported to be altered in both ASD and AN, and several authors hypothesized a role of the so-called microbiota-gut-brain axis in the pathophysiology of these disorders [19,60].…”

“…On the other hand, among subjects with ASD has been reported a higher prevalence of immune diseases, as well as findings of altered immune functions [18,19]. Some studies highlighted also, among mothers of subjects with ASD, the presence of autoantibodies directed against fetal brain tissue [20,21].…”

“…Some studies highlighted also, among mothers of subjects with ASD, the presence of autoantibodies directed against fetal brain tissue [20,21]. While these reports seem to support an association between neurodevelopment alterations and immune system dysfunctions in ASD, the relationship between the immune system and the broader autism spectrum, including its subthreshold manifestations, has been poorly investigated [19]. In this case presentation, we aim to report and discuss the presence of autistic traits in a male patient with AN and Behçet's syndrome (BS).…”