Inspired by a patient.
We know that our intestines hold over 100 trillion microbes,
including approximately 1,000 different species of bacteria. Our own DNA is
overwhelmed in a way by the DNA of these bacteria living happily along with us!
Probiotics, as well as bacteria in yogurts and other supplements, are very
popular nowadays to improve “gut health.” But what does this mean for epilepsy
in general and the ketogenic diet in specific?
What have studies found?
Two recent papers have raised awareness and excitement that
maybe a part of the ketogenic diet’s mechanism of action may rest in changes in
the population of several key bacteria in our intestines.
The first paper from UCLA was published in Cell in June. In
mice, it appeared that two bacteria, Akkermansia and Parabacteroides, were
important for protection from seizures. These mice did not have seizure control
when on the ketogenic diet if they were treated with antibiotics (which would
kill these bacteria) or were raised in a germ-free environment. Similarly,
putting (transplanting) these bacteria into the intestines of other mice would
protect them from seizures. The theory is that GABA (an inhibitory
neurotransmitter) goes up when these bacteria are in the gut. These results
were presented in a TEDx talk. Of note, a study from 2016 in Molecular Autism
from Calgary found that Akkermansia decreased in mice treated with the
ketogenic diet (the opposite finding).
In another study published in Epilepsy Research from Fudan
University in China, researchers looked at the fecal samples of 20 children
treated with the ketogenic diet. Again, there were changes in the gut
microbiota, with increased Bacteroidetes and decreased Firmicutes, with perhaps
hints of differences in those children who responded to the ketogenic diet.
These findings were actually very different from published work from Italy in
Clinical Nutrition ESPEN back in February 2017. These authors found NO changes
in 6 children with Glut1 Deficiency on the ketogenic diet in amounts of
Bacteroidetes and Firmicutes.
How do we interpret these often contradictory results?
Right now, we can say there is growing evidence that the
ketogenic diet appears to affect the bacteria in your intestines. Yet, we are
not certain if improving bacterial strains that affect seizures or possibly
reducing those that could have a negative effect could make a difference. For
now, it is too early to change probiotics or try to ingest any bacteria
intentionally.
More Study Needed
Absolutely this line of research is fascinating and begs for
more studies of children and adults on (and off) ketogenic diets. These studies
could help us learn
If there are definite trends in larger numbers of people
after many months
What these bacteria may be producing that could affect
epilepsy
If changes correlate with seizure control (or may only just
show a change based on the foods we eat that isn’t relevant for epilepsy)
Xie G, Zhou Q, Qiu CZ, Dai WK, Wang HP, Li YH, Liao JX, Lu
XG, Lin SF, Ye JH, Ma ZY, Wang WJ. Ketogenic diet poses a significant effect on
imbalanced gut microbiota in infants with refractory epilepsy. World J
Gastroenterol. 2017 Sep 7;23(33):6164-6171.
Abstract
AIM:
To investigate whether patients with refractory epilepsy and
healthy infants differ in gut microbiota (GM), and how ketogenic diet (KD)
alters GM.
METHODS:
A 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.
RESULTS:
After 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.
CONCLUSION:
GM 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.
Zhang Y, Zhou S, Zhou Y, Yu L, Zhang L, Wang Y. Altered gut
microbiome composition in children with refractory epilepsy after
ketogenic diet. Epilepsy Res. 2018 Sep;145:163-168.
Abstract
OBJECTIVE:
The aim of this study was to investigate the characteristics
and composition of intestinal microbiota in children with refractory epilepsy
after ketogenic diet (KD) therapy and to explore the bacterial biomarkers related
to clinical efficacy.
METHODS:
We prospectively analyzed 20 patients (14 males, 6 females)
treated with KD. Clinical efficacy, electroencephalogram (EEG) changes, and
laboratory tests were evaluated, and fecal specimens were obtained prior to and
6 months after therapy. The composition of gut microbiota was analyzed by 16S
rDNA sequencing, and we screened the possible flora associated with efficacy of
the KD.
RESULTS:
After 6 months of treatment, 2 patients were seizure free, 3
had ≥ 90% seizure reduction, 5 had a reduction of 50-89%, and 10 had < 50%
reduction. All 10 responders showed an improvement in EEG. Compared with
baseline, fecal microbial profiles showed lower alpha diversity after KD
therapy and revealed significantly decreased abundance of Firmicutes and
increased levels of Bacteroidetes. We also observed that Clostridiales,
Ruminococcaceae, Rikenellaceae, Lachnospiraceae, and Alistipes were enriched in
the non-responsive group.
CONCLUSIONS:
The results show that the KD can reduce the species richness
and diversity of intestinal microbiota. The changes of gut microbiota may be
associated with different efficacy after KD, and specific gut microbiota may
serve as an efficacy biomarker and a potential therapeutic target in patients
with refractory epilepsy.
Tagliabue A, Ferraris C, Uggeri F, Trentani C, Bertoli S, de
Giorgis V, Veggiotti P, Elli M. Short-term impact of a classical
ketogenic diet on gut microbiota in GLUT1 Deficiency Syndrome: A 3-month
prospective observational study. Clin Nutr ESPEN. 2017 Feb;17:33-37.
Abstract
BACKGROUND&AIMS:
The classical ketogenic diet (KD) is a high-fat, very
low-carbohydrate normocaloric diet used for drug-resistant epilepsy and Glucose
Transporter 1 Deficiency Syndrome (GLUT1 DS). In animal models, high fat diet
induces large alterations in microbiota producing deleterious effects on gut
health. We carried out a pilot study on patients treated with KD comparing
their microbiota composition before and after three months on the diet.
METHODS:
Six patients affected by GLUT1 DS were asked to collect
fecal samples before and after three months on the diet. RT - PCR analysis was
performed in order to quantify Firmicutes, Bacteroidetes, Bifidobacterium spp.,
Lactobacillus spp., Clostridium perfringens, Enterobacteriaceae, Clostridium
cluster XIV, Desulfovibrio spp. and Faecalibacterium prausnitzii.
RESULTS:
Compared with baseline, there were no statistically
significant differences at 3 months in Firmicutes and Bacteroidetes. However
fecal microbial profiles revealed a statistically significant increase in
Desulfovibrio spp. (p = 0.025), a bacterial group supposed to be involved in
the exacerbation of the inflammatory condition of the gut mucosa associated to
the consumption of fats of animal origin.
CONCLUSIONS:
A future prospective study on the changes in gut microbiota
of all children with epilepsy started on a KD is warranted. In patients with
dysbiosis demonstrated by fecal samples, it my be reasonable to consider an
empiric trial of pre or probiotics to potentially restore the «ecological
balance» of intestinal microbiota.
He Z, Cui BT, Zhang T, Li P, Long CY, Ji GZ, Zhang FM. Fecal
microbiota transplantation cured epilepsy in a case with Crohn's
disease: The first report. World J Gastroenterol. 2017 May 21;23(19):3565-3568.
Abstract
Fecal microbiota transplantation (FMT) is a promising
strategy that involves reconstruction of gut microbiota. Recently, it has been
considered as a treatment of Crohn's disease (CD) and certain neurological
diseases. Here, to the best of our knowledge, we report the first case that
used FMT to achieve remission of intestinal and neurological symptoms in a girl
with CD and a 17-year history of epilepsy. During the 20 mo of follow-up, FMT
has proved its efficacy in preventing relapse of seizures after withdrawing the
antiepileptic drugs. Furthermore, this finding highlights the role of microbiota-gut-brain
axis and inspires a novel treatment for epilepsy through remodeling gut
microbiota.
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