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Introduction: Alterations in the composition and function of the gut microbiome have been reported in idiopathic epilepsy (IE), however, interactions of gut microbes with the enteric nervous system (ENS) in this context require further study. This pilot study examined how gastrointestinal microbiota (GIM), their metabolites, and nutrients contained in intestinal contents communicate with the ENS. Methods: Fecal supernatants (FS) from healthy dogs and dogs with IE, including drug-naïve, phenobarbital (PB) responsive, and PB non-responsive dogs, were applied to cultured myenteric neurons to test their activation using voltage-sensitive dye neuroimaging. Additionally, the concentrations of short-chain fatty acids (SCFAs) in the FS were quantified. Results: Our findings indicate that FS from all examined groups elicited neuronal activation. Notably, FS from PB non-responsive dogs with IE induced action potential discharge in a higher proportion of enteric neurons compared to healthy controls, which exhibited the lowest burst frequency overall. Furthermore, the highest burst frequency in enteric neurons was observed upon exposure to FS from drug-naïve dogs with IE. This frequency was significantly higher compared to that observed in PB non-responsive dogs with IE and showed a tendency to surpass that of healthy controls. Discussion: Although observed disparities in SCFA concentrations across the various FS samples might be associated with the induced neuronal activity, a direct correlation remains elusive at this point. The obtained results hint at an involvement of the ENS in canine IE and set the basis for future studies.
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Introduction: Anxiety 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. Methods: Nine 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. Results: Following 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. Discussion: Behavioral 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.
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In the last decade, nutrition has gained interest in the management of canine idiopathic epilepsy (IE) based on growing scientific evidence. Diets can serve their functions through many pathways. One potential pathway includes the microbiota-gut-brain axis, which highlights the relationship between the brain and the intestines. Changing the brain's energy source and a number of dietary sourced anti-inflammatory and neuroprotective factors appears to be the basis for improved outcomes in IE. Selecting a diet with anti-seizure effects and avoiding risks of proconvulsant mediators as well as interference with anti-seizure drugs should all be considered in canine IE. This literature review provides information about preclinical and clinical evidence, including a systematic evaluation of the level of evidence, suggested mechanism of action and interaction with anti-seizure drugs as well as pros and cons of each potential dietary adaptation in canine IE.
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Enfermedades de los Perros , Epilepsia , Perros , Animales , Epilepsia/veterinaria , Dieta/veterinariaRESUMEN
Phenobarbital (PB) is one of the most important antiseizure drugs (ASDs) to treat canine idiopathic epilepsy (IE). The effect of PB on the taxonomic changes in gastrointestinal microbiota (GIM) and their functions is less known, which may explain parts of its pharmacokinetic and pharmacodynamic properties, especially its antiseizure effect and drug responsiveness or drug resistance as well as its effect on behavioral comorbidities. Fecal samples of 12 dogs with IE were collected prior to the initiation of PB treatment and 90 days after oral PB treatment. The fecal samples were analyzed using shallow DNA shotgun sequencing, real-time polymerase chain reaction (qPCR)-based dysbiosis index (DI), and quantification of short-chain fatty acids (SCFAs). Behavioral comorbidities were evaluated using standardized online questionnaires, namely, a canine behavioral assessment and research questionnaire (cBARQ), canine cognitive dysfunction rating scale (CCDR), and an attention deficit hyperactivity disorder (ADHD) questionnaire. The results revealed no significant changes in alpha and beta diversity or in the DI, whereas only the abundance of Clostridiales was significantly decreased after PB treatment. Fecal SCFA measurement showed a significant increase in total fecal SCFA concentration and the concentrations of propionate and butyrate, while acetate concentrations revealed an upward trend after 90 days of treatment. In addition, the PB-Responder (PB-R) group had significantly higher butyrate levels compared to the PB-Non-Responder (PB-NR) group. Metagenomics of functional pathway genes demonstrated a significant increase in genes in trehalose biosynthesis, ribosomal synthesis, and gluconeogenesis, but a decrease in V-ATPase-related oxidative phosphorylation. For behavioral assessment, cBARQ analysis showed improvement in stranger-directed fear, non-social fear, and trainability, while there were no differences in ADHD-like behavior and canine cognitive dysfunction (CCD) scores after 90 days of PB treatment. While only very minor shifts in bacterial taxonomy were detected, the higher SCFA concentrations after PB treatment could be one of the key differences between PB-R and PB-NR. These results suggest functional changes in GIM in canine IE treatment.
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OBJECTIVE: To evaluate the feasibility of buccal mucosal graft urethroplasty for repairing complete urethral rupture in cats. ANIMALS: 15 male domestic shorthair cats with traumatic complete urethral rupture. PROCEDURES: In each cat, a section of buccal mucosa was harvested, sutured, and formed into a tubule by use of an 8F indwelling catheter as support. This tubular graft was connected to both ruptured ends of the urethra to renew the urinary passage. The catheter was left in place until the absence of leakage was confirmed by positive contrast retrograde urethrography. After spontaneous urination was confirmed, cats were discharged from the hospital. Six months later, urethrography was repeated and owners were asked to score their cats' urinary function and quality of life. RESULTS: 13 cats recovered well following surgery, with no complications in the oral cavity or surgical site and no signs of difficulty or discomfort when urinating. Urethrography 2 weeks and 6 months after surgery revealed no stricture or leakage in the abdominal cavity. The 2 remaining cats developed a urethral stricture and underwent second surgery with a successful outcome. At the 6-month follow-up, 14 cats had only mild urinary signs, and 1 cat had incontinency. Owners indicated they were delighted (n = 14) or pleased (1) with their cats' quality of life. CLINICAL RELEVANCE: Buccal mucosa was found to be a good source of graft tissue for performance of urethroplasty in male cats, yielding satisfactory outcomes with few postoperative complications. The described technique may be suitable for severe and complicated cases of urethral rupture in male cats.