Preclinical studies involving large animal models aim to recapitulate the clinical situation as much as possible and bridge the gap from benchtop to bedside. To date, studies investigating intervertebral disc (IVD) degeneration and regeneration in large animal models have utilized a wide spectrum of methodologies for outcome evaluation. This paper aims to consolidate available knowledge, expertise, and experience in large animal preclinical models of IVD degeneration to create a comprehensive tool box of anatomical and functional outcomes. Herein, we present a Large Animal IVD Scoring Algorithm based on three scales: macroscopic (gross morphology, imaging, and biomechanics), microscopic (histological, biochemical, and biomolecular analyses), and clinical (neurologic state, mobility, and pain). The proposed algorithm encompasses a stepwise evaluation on all three scales, including spinal pain assessment, and relevant structural and functional components of IVD health and disease. This comprehensive tool box was designed for four commonly used preclinical large animal models (dog, pig, goat, and sheep) in order to facilitate standardization and applicability. Furthermore, it is intended to facilitate comparison across studies while discerning relevant differences between species within the context of outcomes with the Naomi N. Lee and Elias Salzer, contributed equally (shared first authorship); Julie B. Engiles and Marianna A. Tryfonidou contributed equally (shared last authorship)

Neck and low back pain are common among the adult human population and impose large social and economic burdens on health care and quality of life. Spine-related disorders are also significant health concerns for canine companions with etiopathogeneses, clinical presentations, and diagnostic and therapeutic options that are very similar to their human counterparts. Historically, induced and spontaneous pathology in laboratory rodents, dogs, sheep, goats, pigs, and nonhuman primates have been used for study of human spine disorders. While each of these can serve as useful preclinical models, they all have inherent limitations. Spontaneously occurring spine disorders in dogs provide highly translatable data that overcome many of the limitations of other models and have the added benefit of contributing to veterinary healthcare as well. For this scoping review, peer-reviewed manuscripts were selected from PubMed and Google Scholar searches using keywords: "intervertebral disc," "intervertebral disc degeneration," "biomarkers," "histopathology," "canine," and "mechanism." Additional keywords such as "injury," "induced model," and "nucleus degeneration" were used to further narrow inclusion. The objectives of this review were to (a) outline similarities in key features of spine disorders between dogs and humans; (b) describe relevant canine models; and (c) highlight the applicability of these models for advancing translational research and clinical application for mechanisms of disease, diagnosis, prognosis, prevention, and treatment, with a focus on intervertebral disc degeneration. Best current evidence suggests that dogs share important anatomical, physiological, histological, and molecular components of spinal disorders in humans, such that induced and spontaneous canine models can be very effective for translational research. Taken together, the peer-reviewed literature supports numerous advantages for use of canine models for study of disorders of the spine when the potential limitations and challenges are addressed.

The gut microbiota (GM) is the sum of hundreds of distinct microbial species that can equal or outnumber their host’ssomatic cells. The GM influences a multitude of physiologic and immunologic processes in the host, and changes in the GM have been shown to alter the phenotypes of animal models. Previous studies using rodents have also shown that the composition of the GM is affected by many factors, including diet, husbandry, housing, and the genetic background of the animals. However, limited information exists about factors that may modulate GM in other laboratory species, such as dogs. We sought to eliminate sporadic Giardia colonization of dogs using fenbendazole (FBZ), an antiprotozoal widely used in biomedical research dog colonies. Concerns that FBZ could have inadvertent effects on the canine GM led us to assess GM over the course of treatment. FBZ (50 mg/kg) was given orally to all dogs in 3 different facilities (n = 19 to 25) for 10 consecutive days. Fecal samples were obtained 2 d before the initiation of treatment, on the last day of treatment, and 2 wk after the completion of treatment. Targeted 16S rRNA gene sequencing was used to analyze fecal microbiota. All dogs were clinically normal throughout the sample collection period. Statistical analyses of data showed significant differences between dogs housed in the 3 different facilities, further emphasizing the effect of housing and husbandry factors on the GM. However,negligible differences were seen between time points, indicating that FBZ did not significantly alter the canine GM. Comparison of the GM of Giardia lamblia positive and negative dogs revealed no significant difference between the 2 groups. These findings suggest that FBZ can be used therapeutically in dogs with minimal impact on the GM. Furthermore, the presence ofG. lamblia in clinically normal animals may not be sufficient to influence the normal canine microbiota.

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