Gut Microbiome-Based Analysis of Lipid A Biosynthesis in Individuals with Autism Spectrum Disorder: An In Silico Evaluation

The link between autism spectrum disorder (ASD) and the gut microbiome has received much attention, with special focus on gut–brain-axis immunological imbalances. Gastrointestinal problems are one of the major symptoms of ASD and are thought to be related to immune dysregulation. Therefore, in silico analysis was performed on mined data from 36 individuals with ASD and 21 control subjects, with an emphasis on lipid A endotoxin-producing bacteria and their lipopolysaccharide (LPS) metabolic pathways. Analysis of enzyme distribution among the 15 most abundant genera in both groups revealed that almost all these genera utilized five early-stage enzymes responsible for catalyzing the nine conserved lipid A synthesis steps. However, Haemophilus and Escherichia, which were significantly more abundant in individuals with ASD than in the control subjects, possess a complete set of essential lipid A synthesis enzymes. Furthermore, the 10 genera with the greatest increase in individuals with ASD showed high potential for producing late-stage lipid A products. Collectively, these results suggested that the synthesis rate of immunogenic LPS end products is likely to increase in individuals with ASD, which may be related to their gastrointestinal symptoms and elevated inflammatory conditions.