Dysbiosis of the Gut Microbiome in Individuals with ASD

Background: The gut microbiome, consisting of bacteria and their gene products, is an integral component of human health by contributing to host metabolism, immunity, and development and function of the nervous system. While a healthy microbiotic ecosystem promotes human health and prevents many chronic illnesses, dysbiosis has been implicated in a wide range of diseases including irritable bowel syndrome, anxiety depressive behaviors, autism spectrum disorder (ASD), mood disorders, obesity, and cancer.

Objectives: The purpose of this study was to identify disorder related dysbiosis in individuals diagnosed with ASD.

Methods: Participants with ASD and their undiagnosed, co-habiting siblings were recruited for the study. Participants were asked to complete a diet and lifestyle survey which helps identify environmental influences of their gut microbiome, as well as provide a stool sample. Bacterial DNA isolated from stool was used as a template for library construction using the Ion 16S Metagenomics Kit and sequencing on the Ion Gene Studio S5 Plus System. Data was analyzed with the Ion Reporter software Ion 16S Metagenomics Kit analyses module and the DESeq2 package in R.

Results: In this pilot study of 15 sibling pairs, we observed several differences in the composition of gut bacteria of individuals with ASD compared to their siblings. The relative ratio of the two main phyla, Firmicutes to Bacteroidetes, is ~3:1 in the sibling participants and ~8.5:1 in participants with ASD, respectively. There were four bacterial genus that were present in higher quantities in the ASD group (log₂ FC > 5, adj pvalue <0.05) and six bacterial genus that were present in lower quantities in the ASD group (log₂ FC < -5, adj pvalue <0.05). Finally, we observed an increase of the opportunistic pathogen, Citrobacter freundii, in participants with ASD when compared to their siblings.

Conclusions: Bacterial profiles are extremely variable (80-90%) between healthy adults, making it difficult to identify dysbiosis conditions that are relevant to disease. Using a co-habiting, sibling matched internal control, we anticipated that our ability to resolve disorder related dysbiosis in individuals with ASD would be improved. Since bacterial composition can be relatively easily manipulated, personalized treatment of gut-bacteria-related psychiatric disorders shows tremendous potential for improving human health and reducing the economic burden of mental health disorders on the health care system.