A review on preventive role of ketogenic diet (KD) in CNS disorders from the gut microbiota perspective

Abstract The gut microbiota plays an important role in neurological diseases via the gut–brain axis. Many factors such as diet, antibiotic therapy, stress, metabolism, age, geography and genetics are known to play a critical role in regulating the colonization pattern of the microbiota. Recent studies have shown the role of the low carbohydrate, adequate protein, and high fat “ketogenic diet” in remodeling the composition of the gut microbiome and thereby facilitating protective effects in various central nervous system (CNS) disorders. Gut microbes are found to be involved in the pathogenesis of various CNS disorders like epilepsy, Parkinson’s disease (PD), Alzheimer’s disease (AD), autism spectrum disorders (ASDs), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and stress, anxiety and depression. In vivo studies have shown an intricate link between gut microbes and KD and specific microbes/probiotics proved useful in in vivo CNS disease models. In the present review, we discuss the gut–brain bidirectional axis and the underlying mechanism of KD-based therapy targeting gut microbiome in in vivo animal models and clinical studies in neurological diseases. Also, we tried to infer how KD by altering the microbiota composition contributes towards the protective role in various CNS disorders. This review helps to uncover the mechanisms that are utilized by the KD and gut microbiota to modulate gut–brain axis functions and may provide novel opportunities to target therapies to the gut to treat neurologic disorders.