The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders

Abstract

Purpose of review: There is a growing body of evidence indicating the gut microbiota influence neurodevelopment and behavior. The purposes of this review are to provide an overview of studies analyzing the microbiota and their metabolites in autism spectrum disorders (ASD) and to discuss the possible mechanisms of action involved in microbial influence on the brain and behavior.

Recent findings: The microbiota-gut-brain (MGB) axis has been extensively studied in animal models, and it is clear that alterations in the composition of microbiota alter neurological and behavioral outcomes. However, findings in human studies are less abundant. Although there are several studies so far showing altered microbiota (dysbiosis) in ASD, the results are heterogeneous and often contradictory. Intervention studies such as fecal microbiota transplant therapies show promise and lend credence to the involvement of the microbiota in ASD. A role for the microbiota in ASD is likely; however, further studies elucidating microbial or metabolomic signatures and mechanisms of action are needed. Future research should focus on intervention studies that can identify specific metabolites and immune mediators that improve with treatment to help identify etiologies and pathological mechanisms of ASD.

Keywords: Autism; Behavior; Dysbiosis; Dysregulation; Microbiota; Neurodevelopment.

Fig. 1

Mechanisms of the microbiota-gut-brain axis. Possible mechanisms of the MGB-axis are being actively investigated and include neuroimmune pathways, neural communication through the vagus nerve, influence of metabolites produced by the microbiota, microbial-derived neurotransmitters, and the significant influence the microbiota have on tryptophan, kynurenine, and serotonin metabolism. Short-chain fatty acids (SCFA) can promote peripheral T regulatory (Treg) cell expansion as well as influence tight junction (TJ) proteins and intestinal barrier function. Microbiota regulate tryptophan (Trp) metabolites by degrading Trp to indole-derivatives or through kynurenine and serotonin pathways, such as increasing expression of tryptophan hydroxylase (Tph)1 in enterochromaffin (EC) cells. Dysbiosis can promote activation of immune cells, including macrophages that produce quinolinic acid (QA) through an alternative kynurenine pathway, a known excitotoxic N-methyl-D-aspartate (NMDA) receptor agonist. Activated immune cells also produce proinflammatory cytokines which can further disrupt microflora and impact intestinal barrier function. Neural communication can also occur through the vagus nerve via signaling from hormones and neurotransmitters release by gut endocrine cells and immune cells. Breech of the intestinal barrier would also allow direct pattern recognition sensing due to Toll-like receptor expression on afferent fibers