The gastrointestinal microbiota (GIM) is the new hot topic in neurology. This contractile organ, far distant from the brain is now considered a a possible source for drug resistant epilepsy in canine epilepsy research as well as a potential cause for behavioral disease in epileptic and non-epileptic dogs alike. A recent article by Watanangura et al highlighted the importance of the GIM in epilepsy.
The aim of their study was to investigate the effect of phenobarbital (monotherapy) on the composition of the GIM and to determine if it resulted in a change to behavior in a select group of dogs. To be included in this study, all dogs had to meet Tier II level of confidence for epilepsy (normal brain MRI, spinal tap, normal blood work and neurologic examination) and be naive on any anticonvulsant treatment. They had 12 dogs who meet these inclusion criteria. On day 1, they started phenobarbital at 2.5 mg/kg PO q12h and took fecal samples. The drug was continued without dose adjustment for 90 days at which time another fecal sample was taken. Behavioral questionnaires were submitted on day 1 and day 90 as well.
The results:
Serum phenobarbital concentrations ranged from 19.8-18.1 mg/L (day 30 and day 90)
Seven of 12 dogs were seizure free throughout the study and called responders.
Five of 12 dogs were not seizure free and were called non-responders.
Short chain fatty acids (SCFA) did increase significantly in the study, specifically propionate and butyrate.
Butyrate was significantly higher in the responder group compared to the non-responder group. Butyrate is an anti-inflammatory fatty acid which may benefit epileptic dogs, yielding better response to treatment. Perhaps this is due to the neuroprotective effects, or by providing an alternative energy source for the brain.
The behavior survey showed a significant decrease in stranger-directed fear, and non-social fear with an increase in trainability! Phenobarbital has been used as an anxiolytic for humans and veterinary patients, supporting this finding. An idiosyncratic hyperexcitability and aggression has been reported with phenobarbital however it is rare. (More commonly seen with levetiracetam.)
There was no difference in the bacterial taxa in this study except for a significant decrease in Clostridiales on day 90. The significance of this remains to be seen, however it may affect the distribution of MCFA and other products.
The Take Home Message
What do we do with this information? Well…we tuck it away in our heads and know that phenobarbital, or seizures themselves, might affect the GI microbiome and SCFA in the GI. Does this mean we should supplement? Not yet. I am not sure we know who, how and when to supplement based on this study. This was a critical step forward in our path towards understanding the GIM and I am excited to share additional information that comes forth in this area!
Have a wonderful week and enjoy what August has to offer us! I look forward to working with you soon.