Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy

Abstract

AIMTo investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota (GM), and how ketogenic diet (KD) alters GM.METHODSA total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded. Stool samples were collected for 16S rDNA sequencing using the Illumina Miseq platform. The composition of GM in each sample was analyzed with MOTHUR, and inter-group comparison was conducted by R software.RESULTSAfter being on KD treatment for a week, 64% of epileptic infants showed an obvious improvement, with a 50% decrease in seizure frequency. GM structure in epileptic infants (P1 group) differed dramatically from that in healthy infants (Health group). Proteobacteria, which had accumulated significantly in the P1 group, decreased dramatically after KD treatment (P2 group). Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups. Bacteroides increased significantly in the P2 group, in which Prevotella and Bifidobacterium also grew in numbers and kept increasing.CONCLUSIONGM pattern in healthy infants differed dramatically from that of the epileptic group. KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.

Fecal Microbiota Transplantation in Neurological Disorders

“…A difference in gut microbiota profiles between patients with different types of therapy refractory epilepsy and healthy controls was found in several studies. All these studies reported increased abundance of the phyla Firmicutes relative to Bacteroidetes in subjects with refractory epilepsy (Xie et al, 2017;Peng et al, 2018;Lindefeldt et al, 2019). Some bacteria of the phylum Firmicutes may alter neurotransmitter levels (Peng et al, 2018).…”

“…Some bacteria of the phylum Firmicutes may alter neurotransmitter levels (Peng et al, 2018). Further microbiota analysis outcomes differed considerably between these studies, including α-diversity measures (Xie et al, 2017;Peng et al, 2018;Lindefeldt et al, 2019). One study (Peng et al, 2018) found an increased Firmicutes/Bacteroidetes ratio and α-diversity in drug-resistant patients compared to drug-sensitive patients, with the latter being similar to healthy controls.…”

“…Several studies suggest an important role of the gut microbiota in the pathophysiology of neurological disorders. A different human gut microbiota composition compared to healthy controls has been reported for several neurological disorders, such as Parkinson's disease (Hasegawa et al, 2015;Keshavarzian et al, 2015;Scheperjans et al, 2015;Unger et al, 2016), multiple sclerosis (Miyake et al, 2015;Chen et al, 2016;Jangi et al, 2016;Cosorich et al, 2017), autism spectrum disorder (Finegold et al, 2002(Finegold et al, , 2010De Angelis et al, 2013Kang et al, 2013;Ma et al, 2019), Alzheimer's disease (Vogt et al, 2017;Zhuang et al, 2018;Haran et al, 2019;Li B. et al, 2019;Liu et al, 2019), neuromyelitis optica (Cree et al, 2016), Rett syndrome (Strati et al, 2016), epilepsy (Xie et al, 2017;Peng et al, 2018;Lindefeldt et al, 2019), amyotrophic lateral sclerosis (Fang et al, 2016;Rowin et al, 2017;Mazzini et al, 2018), cerebral infarction (Karlsson et al, 2012;Yin et al, 2015), spinal cord injury (Gungor et al, 2016), and multiple system atrophy (Tan et al, 2018). However, data on microbiota composition are frequently inconsistent and numerous potential confounders are involved.…”

Keto microbiota: A powerful contributor to host disease recovery

“…Gut microbiota profile is significantly different between healthy and epileptic individuals. KD treatment is able to reshape gut microbiota in humans and rodents [38,39]; and this keto microbiota is required to avoid seizures. In fact, mouse models of refractory epilepsy showed that those given antibiotics or reared in a germ-free environment were resistant to seizure protection from KD, while keto microbiota fecal transplant helped mice with seizure control.…”

Decreased abundance of Akkermansia muciniphila after adrenocorticotropic hormone therapy in patients with West syndrome

“…Research over the last decade on the brain-gut-microbiota axis, which has been shown to involve various regions of the nervous system, has mainly focused on psychiatric and neurologic pathologies, including chronic pain [5] , autism spectrum disorder [6] , Parkinson's disease [7], and multiple sclerosis [8] . Additionally, in recent years, the GM has been found to have an important role in the treatment of refractory epilepsy, especially regarding its effect in mediating the antiseizure effects of the ketogenic diet [9,10] .…”