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IntroductionAnxiety and cognitive dysfunction are frequent, difficult to treat and burdensome comorbidities in human and canine epilepsy. Fecal microbiota transplantation (FMT) has been shown to modulate behavior in rodent models by altering the gastrointestinal microbiota (GIM). This study aims to investigate the beneficial effects of FMT on behavioral comorbidities in a canine translational model of epilepsy.MethodsNine dogs with drug-resistant epilepsy (DRE) and behavioral comorbidities were recruited. The fecal donor had epilepsy with unremarkable behavior, which exhibited a complete response to phenobarbital, resulting in it being seizure-free long term. FMTs were performed three times, two weeks apart, and the dogs had follow-up visits at three and six months after FMTs. Comprehensive behavioral analysis, including formerly validated questionnaires and behavioral tests for attention deficit hyperactivity disorder (ADHD)- and fear- and anxiety-like behavior, as well as cognitive dysfunction, were conducted, followed by objective computational analysis. Blood samples were taken for the analysis of antiseizure drug (ASD) concentrations, hematology, and biochemistry. Urine neurotransmitter concentrations were measured. Fecal samples were subjected to analysis using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based Dysbiosis Index (DI) assessment, and short-chain fatty acid (SCFA) quantification.ResultsFollowing FMT, the patients showed improvement in ADHD-like behavior, fear- and anxiety-like behavior, and quality of life. The excitatory neurotransmitters aspartate and glutamate were decreased, while the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABA/glutamate ratio were increased compared to baseline. Only minor taxonomic changes were observed, with a decrease in Firmicutes and a Blautia_A species, while a Ruminococcus species increased. Functional gene analysis, SCFA concentration, blood parameters, and ASD concentrations remained unchanged.DiscussionBehavioral comorbidities in canine IE could be alleviated by FMT. This study highlights FMT’s potential as a novel approach to improving behavioral comorbidities and enhancing the quality of life in canine patients with epilepsy.

Emerging contaminants are produced globally at high rates and often ultimately find their way into the aquatic environment. These include substances contained in anti-seizure medication (ASM), which are currently appearing in surface waters at increasing concentrations in Germany. Unintentional and sublethal, chronic exposure to pharmaceuticals such as ASMs has unknown consequences for aquatic wildlife. Adverse effects of ASMs on the brain development are documented in mammals. Top predators such as Eurasian otters (Lutra lutra) are susceptible to the bioaccumulation of environmental pollutants. Still little is known about the health status of the otter population in Germany, while the detection of various pollutants in otter tissue samples has highlighted their role as an indicator species. To investigate potential contamination with pharmaceuticals, Eurasian otter brain samples were screened for selected ASMs via high-performance liquid chromatography and mass spectrometry. Via histology, brain sections were analyzed for the presence of potential associated neuropathological changes. In addition to 20 wild otters that were found dead, a control group of 5 deceased otters in human care was studied. Even though none of the targeted ASMs were detected in the otters, unidentified substances in many otter brains were measured. No obvious pathology was observed histologically, although the sample quality limited the investigations.