Research Article: The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs

Date Published: January 26, 2017

Publisher: Public Library of Science

Author(s): Nick D. Jeffery, Andrew K. Barker, Cody J. Alcott, Jon M. Levine, Ilyssa Meren, Jane Wengert, Albert E. Jergens, Jan S. Suchodolski, Brenda A Wilson.

http://doi.org/10.1371/journal.pone.0170589

Abstract

Meningoencephalomyelitis of unknown origin (MUO) is a common, naturally-occurring, clinical disease of pet dogs. It is an immune-mediated condition that has many similarities with experimental autoimmune encephalitis (EAE) in rodents and so investigation of its pathogenesis may aid in understanding factors that contribute to development of multiple sclerosis in people. Gut microbiota are known to modulate immune responses that influence susceptibility to immune-mediated brain disease. In this study we aimed to compare abundance of specific constituents of the fecal microbiota, namely Faecalibacterium prausnitzii and Prevotellaceae, between dogs diagnosed with MUO and matched controls. Fecal samples were obtained from 20 dogs diagnosed with MUO and 20 control dogs matched for breed, age and gender. Bacterial abundance was measured using qPCR and 16S rRNA sequencing. We found that Prevotellaceae were significantly less abundant in cases compared with controls (p = 0.003) but there was no difference in abundance of F.prausnitzii. There was no evidence of other differences in gut microbiota between groups. These data, derived from this naturally-occurring canine clinical model, provide strong corroborative evidence that high abundance of Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease.

Partial Text

Disease in pet dogs treated by veterinarians forms a unique, frequently-overlooked, resource of biomedical translational data [1]. There are many advantages of these diseases as models of their human equivalents. First, they arise spontaneously, often through multifactorial etiologies similar to those that induce the parallel diseases in humans. Second, both pet dogs and humans share a common environment that may be a source of disease-causing risks. Third, diagnostic procedures and therapeutic interventions are broadly similar between humans and dogs with similar diseases. Within the field of neurology these features of similarity have been most extensively discussed in regard to spinal cord injury [2,3]. In this study we investigate possible etiologies for another canine disease: meningoencephalomyelitis of unknown origin (MUO), which models many aspects of multiple sclerosis in people.

Samples with adequate documentation of all variables were collected from a total of 70 dogs, of which 39 were Cases and 31 were Controls. As expected from previous studies [29], the majority were small breed dogs (<20kg bodyweight). There were 20 matched pairs of dogs (40 dogs in total); 5 pairs were male and 15 pairs were female; this gender predominance is also similar to that reported in previous studies [29]. The analysis presented here supports an association between low Prevotellaceae abundance and a diagnosis of MUO in dogs, which also corroborates previous observations of an association between this bacterial group and diagnosis of MS in people [18]. Such corroboration, especially in a different species, is important because investigation of such a complicated system as the gut microbiome carries an inherently high risk of false discovery. In this study, we specifically targeted only two bacterial populations in our primary pre-specified analysis implying that the risk of false discovery is low. Therefore, this evidence carries high value as corroboration of the importance of Prevotellaceae in reducing risk of immune-mediated CNS disease. Interestingly, low abundance of Prevotellaceae has also been associated with Parkinson’s disease in people [32]. The rigid case-control design has enabled us to minimize the possible confounding factors of age, gender and genetic variability.   Source: http://doi.org/10.1371/journal.pone.0170589

 

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