One Month of Classic Therapeutic Ketogenic Diet Decreases Short Chain Fatty Acids Production in Epileptic Patients.

Erika Meroni,Anna Tagliabue,Maria Cristina Casiraghi,Daniela Erba,Valentina De Giorgis,Cinzia Ferraris

doi:10.3389/fnut.2021.613100

Abstract

Ketogenic diet (KD), a high fat and very low carbohydrates diet, is used worldwide for the treatment of drug resistant epilepsy but, due to its composition, it might exert an impact on gut health. Even though data of KD effects on intestinal microbiota changes are recently emerging, its influence on the gut environment has been scarcely addressed so far. The aim of this study was to investigate whether 1 month of KD affects the gut environment in epileptic patients, by analyzing short chain fatty acids (SCFA) production and fecal water toxicity. A total of seven patients were enrolled. Stool samples were collected before (T0) and after 1 month of KD (4:1 ketogenic ratio) (T1). SCFA were determined by GC-FID and fecal water toxicity in Caco-2 cell culture by comet assay. Concentrations of SCFA significantly decreased after KD (p < 0.05): in particular, we found a 55% reduction of total SCFA level, a 64% reduction of acetate, 33% of propionate, and 20% of butyrate (p < 0.05). Cytotoxicity of fecal water extracted from stool samples was not significantly altered by diet, while genotoxicity was slightly decreased after KD (p < 0.05). Genotoxicity values were consistent with data previously obtained from a healthy Italian population. The present study suggests that 1 month of KD significantly reduce SCFA production. Since SCFA produced by gut microbiota exert many health promoting effects on either the gut environment or human metabolism, these results open a new branch of investigation into KD effects.

Highlights

The classic ketogenic diet (KD) is a normocaloric high-fat very low-carbohydrate diet, used worldwide for the treatment of drug-resistant epilepsy (DRE) for its anticonvulsant effect [1]
A rich microbial ecology promotes the fundamental cross-talk and cross-feeding between species that guarantees the resilience of the gut ecosystem; one of the features of intestinal dysbiosis is the loss of diversity [27]
Our study evaluated the effect of KD on short chain fatty acids (SCFA) and fecal water toxicity in seven patients, by collecting fecal samples before and after 1 month of dietary treatment

Summary

Introduction

The classic ketogenic diet (KD) is a normocaloric high-fat very low-carbohydrate diet, used worldwide for the treatment of drug-resistant epilepsy (DRE) for its anticonvulsant effect [1]. KD is typically composed of a 4:1 ratio of fat (in grams) to protein plus carbohydrates (in grams), shifting the predominant caloric source from carbohydrates to fat [2] This diet induces changes in gut microbiota that have been addressed in vivo in animal [3,4,5] and human [6,7,8,9,10] studies. Several studies have shown that propionate and acetate can modulate the glycol-lipid metabolism, by inhibiting the hepatic synthesis of cholesterol and improving insulin sensitivity [16] With these multiple actions in mind, it is possible that altered SCFA production can negatively affect host’s health either in the gut or at a systemic level

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