Addition of Prebiotics to the Ketogenic Diet Improves Metabolic Profile but Does Not Affect Seizures in a Rodent Model of Infantile Spasms Syndrome

Abstract

The ketogenic diet (KD) is an effective treatment for infantile spasms syndrome (IS). However, the KD has implications for somatic growth, development, and the gut microbiota. The impact of incorporating a prebiotic fiber (PRE, oligofructose-enriched inulin, 0.8 g/dL) into a KD diet on spasms, developmental milestones, fecal gut microbiota, metabolites, and hippocampal mitochondrial metabolism were examined. Following IS induction, animals were randomized to KD or KD + PRE diets. A third group without IS and suckled by dams was included as a normally developing reference group (R). PRE inclusion decreased ketones and increased circulating glucose levels but had no impact on spasms. In the liver, PRE increased triglyceride concentrations, decreased carnitine levels, and downregulated genes encoding enzymes responsible for ketogenesis. In the hippocampus, PRE increased glutathione levels but did not affect the maximal respiratory capacity of mitochondria. Analysis of the gut microbiota showed that KD + PRE increased microbial richness and the relative abundance of Bifidobacterium pseudolongum and Lactobacillus johnsonii. No differences in developmental milestones (i.e., surface righting, negative geotaxis, and open field behavior) were observed between KD and KD + PRE, except for ultrasonic vocalizations that were more frequent in KD + PRE. In summary, PRE did not impact spasms or developmental outcomes, but was effective in improving both metabolic parameters and gut microbiota diversity.