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.

Protocol for measuring respiratory function of mitochondria in frozen colon tissue from rats

“…In this protocol, 50 mg of frozen colon tissue was examined. The tissue amount needs to be determined for each tissue types such as cardiac fibers, 1 hippocampus 8 , 12 , 13 and epithelial cells. 2 The method is not able to measure proton leak-related respiration.…”

Dietary fiber content in clinical ketogenic diets modifies the gut microbiome and seizure resistance in mice

“…Moreover, differences in dietary formulation can have substantial impacts on microbiome-dependent host phenotypes -KDs with different fat ratio and/or source resulted in differential influences of the microbiome on host glucose and lipid metabolism, as well as immune function 8,9 . In addition, supplementation with dietary fiber, a key energy source for gut bacteria that modulates myriad host metabolic, immune, and neural functions, is incorporated into some clinical KD regimens to ease gastrointestinal symptoms 31 , but whether it alters seizure response is unclear 32 . Overall, increasing research indicating that the gut microbiome modifies seizure susceptibility and the antiseizure effects of the KD raises the important question of how variations in the formulation of medical KDs differentially shape the microbiome in ways that impact seizure outcome.…”