Ketogenic diet influences the microbiome-immune axis with therapeutic potential in ASD

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Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting social interaction and communication, associated with increased levels of inflammation and mitochondrial dysfunction. The ketogenic diet has neuroprotective affects and decreases the severity of inflammation related conditions. A cohort of 7 children aged 7 to 19 diagnosed with ASD have improved behavioral symptoms following the ketogenic diet. This study aims to identify changes to the gut microbiome and inflammatory markers that are associated with improved prognosis. Stool and plasma samples were collected before starting the diet and up to twelve months after starting the diet. Stool samples were sequenced for microbiome data and plasma samples were analyzed for inflammation factors, ketone bodies, and miRNA presence. Butyrate kinase (Buk) DNA and RNA levels were elevated in stool samples suggesting changes to the microbiome significantly affected butyrate kinase levels in the patient’s digestive tract. Metabolomic data identified the cohort had elevated butyrate levels following the ketogenic diet further characterizing the importance of butyrate kinase producing bacteria, including Roseburia. Changes to inflammatory factors identified a decrease in IL-1B, IL-12p70, and BDNF. Decreases in BDNF, an activator of the NF-kB pathway, identifies a potential pathway for decrease in IL-1B and IL-12p70. Correlation analysis identified that Roseburia species elevated Buk DNA and decreased inflammation. While limited in sample size, these findings provide important insight into key molecular changes in the microbiome-immune axis linked to brain function that could be targeted for treatment of ASD and warrants further investigation. Supported by grants from NIH (P20GM113134)

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