The feline skin microbiome: interrelationship between health and disease.

PRACTICAL RELEVANCE: As with other species, the skin microbiome of cats has been assessed over the past few years utilizing modern technologies. This has resulted in the identification of many more bacterial and fungal organisms compared with what had been recorded historically on the skin in various states of health and disease using culture-based studies. This information is expanding the knowledge of how microbial communities are impacted by various changes in the skin health of cats. More specifically, how these microbial communities change in the face of health and disease, and how various therapeutic interventions affect the cutaneous microbiome, lends a greater understanding of disease pathogenesis and provides a growing area of research for correcting dysbiosis and improving feline skin health. EVIDENCE BASE: Most studies on the feline skin microbiome thus far have been descriptive in nature. These provide a framework for the next level of investigations on how various states of health and disease impact the products produced by the cutaneous microbiome (ie, the cutaneous metabolome), as well as how targeted interventions may promote the restoration of balance. AIMS: This review aims to summarize what is currently known about the feline cutaneous microbiome and its clinical implications. The role of the skin microbiome in health and disease, the current state of research in this area and the potential for future studies to produce targeted interventions for cats are a particular focus.

An ancient haplotype containing antimicrobial peptide gene variants is associated with severe fungal skin disease in Persian cats.

Dermatophytosis, also known as ringworm, is a contagious fungal skin disease affecting humans and animals worldwide. Persian cats exhibit severe forms of the disease more commonly than other breeds of cat, including other long-haired breeds. Certain types of severe dermatophytosis in humans are reportedly caused by monogenic inborn errors of immunity. The goal of this study was to identify genetic variants in Persian cats contributing to the phenotype of severe dermatophytosis. Whole-genome sequencing of case and control Persian cats followed by a genome-wide association study identified a highly divergent, disease-associated haplotype on chromosome F1 containing the S100 family of genes. S100 calcium binding protein A9 (S100A9), which encodes a subunit of the antimicrobial heterodimer known as calprotectin, contained 13 nonsynonymous variants between cases and controls. Evolutionary analysis of S100A9 haplotypes comparing cases, controls, and wild felids suggested the divergent disease-associated haplotype was likely introgressed into the domestic cat lineage and maintained via balancing selection. We demonstrated marked upregulation of calprotectin expression in the feline epidermis during dermatophytosis, suggesting involvement in disease pathogenesis. Given this divergent allele has been maintained in domestic cat and wildcat populations, this haplotype may have beneficial effects against other pathogens. The pathogen specificity of this altered protein should be investigated before attempting to reduce the allele frequency in the Persian cat breed. Further work is needed to clarify if severe Persian dermatophytosis is a monogenic disease or if hidden disease-susceptibility loci remain to be discovered. Consideration should be given to engineering antimicrobial peptides such as calprotectin for topical treatment of dermatophytosis in humans and animals.

ABHD5 frameshift deletion in Golden Retrievers with ichthyosis.

Ichthyoses are hereditary skin disorders characterized by the formation of scales and defects in the outermost layer of the epidermis. In dogs, at least six different breed-specific ichthyoses including a relatively common PNPLA1-related autosomal recessive ichthyosis in Golden Retrievers are known. In this study, we investigated 14 Golden Retrievers with scales that were not homozygous for the mutant PNPLA1 allele suggesting a genetically distinct new form of ichthyosis. Histopathological examinations showed lamellar, orthokeratotic hyperkeratosis, and mildly hyperplastic epidermis that led to the diagnosis of a nonepidermolytic ichthyosis. Combined linkage and homozygosity mapping in 14 cases and 30 nonaffected family members delimited a critical interval of ∼12.7 Mb on chromosome 23. Whole-genome sequencing of an affected dog revealed a single protein-changing variant within this region that was not present in 795 control genomes. The identified variant is a 14 bp deletion in the ABHD5 gene (c.1006_1019del), leading to a frameshift and altering the last 14 codons p.(Asp336Serfs*6). The genotypes at this variant showed perfect cosegregation with the ichthyosis phenotype in a large family comprising 14 cases and 72 controls. ABHD5 encodes an acyltransferase required for lipid metabolism. In humans, variants in ABHD5 cause Chanarin-Dorfman syndrome, a neutral lipid storage disease with ichthyosis. Our data in dogs together with the knowledge on the effects of ABHD5 variants in humans strongly suggest ABHD5:c.1006_1019del as candidate causative genetic variant for a new canine form of ichthyosis, which we propose to designate as Golden Retriever ichthyosis type 2 (ICH2).

Cytokine expression in feline allergic dermatitis and feline asthma.

BACKGROUND: The pathogenesis of feline allergic dermatitis (FAD) is unclear, with several differences from allergic dermatitis in dogs and humans. HYPOTHESIS/OBJECTIVES: To survey cytokine expression levels in healthy cats and cats affected with allergic dermatitis or asthma. ANIMALS: Formalin-fixed, paraffin-embedded skin biopsies from 22 cats with allergic dermatitis and 21 cats without allergic dermatitis were used for cutaneous assays. Serum was obtained from 17 healthy cats, 18 cats with allergic dermatitis, and 18 cats with a presumptive diagnosis of asthma. METHODS AND MATERIALS: Cutaneous mRNA expression was evaluated with quantitative PCR [interleukin (IL)-31 and IL-31 Receptor A] and RNA in situ hybridisation (ISH) [IL-5, IL-31, IL-31RA, IL-33 and Oncostatin M receptor (OSMR)-ß]. IL-31 protein concentrations were evaluated in serum with an enzyme-linked immunosorbent assay. Serum levels of 19 additional cytokines were evaluated using a Luminex panel. RESULTS: IL-31, IL-31RA, IL-5 and IL-33 mRNA expression were either expressed in low quantities or undetectable in most samples. By contrast, OSMR-ß expression was significantly higher in the skin of allergic versus healthy cats (P < 0.0001). Although serum IL-31 was detected in a larger number of cats with allergic dermatitis than healthy cats, and concentrations appeared to be higher in cats with allergies, this difference was not statistically significant. Cats affected by asthma also exhibited insignificantly higher concentrations of IL-31 in the serum. CONCLUSIONS AND CLINICAL RELEVANCE: Our results suggest that feline allergic diseases may exhibit different pathomechanisms from allergic diseases affecting other species. These findings are useful in guiding further therapeutic development toward targets that may have a role in the pathogenesis of feline allergic skin disease.

Characterization of the cutaneous mycobiota in Persian cats with severe dermatophytosis.

BACKGROUND: Persian cats are predisposed to chronic and severe dermatophytosis. Alterations to the cutaneous microbiota are one potential contributor to this predisposition. OBJECTIVES: To characterise the cutaneous and environmental fungal microbiota of Persian cats with chronic, severe dermatophytosis, and to compare the fungal microbiota of cats with and without dermatophytosis. ANIMALS: Thirty-six client-owned cats, including 26 Persian cats and 10 domestic long hair (DLH) cats. METHODS AND MATERIALS: Skin and home environment swabs were collected from Persian cats with severe, chronic dermatophytosis as well as groups of healthy control cats (Persian and DLH). Sequencing of the internal transcribed spacer 1 (ITS1) region was performed in addition to ITS1 quantitative PCR and fungal culture. RESULTS: Next-generation sequencing (NGS) targeting the fungal ITS region detected Microsporum sp. DNA from all Persian cats diagnosed with dermatophytosis and from environmental samples of their homes. A significant difference in community structure was identified between cases and controls, largely resulting from the Microsporum spp. DNA in samples from affected cats. Persian cats with dermatophytosis do not exhibit decreased fungal diversity. NGS failed to identify dermatophyte DNA on two culture-positive asymptomatic Persian controls and identified Trichophyton rubrum DNA from a culture-negative asymptomatic Persian control. CONCLUSIONS: Aside from M. canis, our results indicate that an underlying fungal dysbiosis is not likely to play a role in development of dermatophytosis in Persian cats. Other explanations for predisposition to this disease, such as a primary immunodeficiency, ineffective grooming or unique features of Persian cat hair should be investigated.

Characterization of staphylococcal communities on healthy and allergic feline skin.

BACKGROUND: Various Staphylococcus species have been demonstrated to play important roles on the skin, including causing disease and protecting the host from pathogens. Although culture-based studies have isolated various Staphylococcus spp. from feline skin, very little is known regarding the species-level communities on the host. HYPOTHESIS/OBJECTIVES: To describe the species-level staphylococcal communities inhabiting the skin of healthy cats and cats with allergic dermatitis. ANIMALS: Skin swabs from the ear canal and groin of 11 healthy and 10 allergic (nonlesional) cats were obtained. METHODS AND MATERIALS: DNA was extracted from the skin swabs and used for next-generation sequencing targeting the V1-3 region of the 16S rRNA gene. Following a standard microbiota analysis of the sequencing data, species-level assignment for the staphylococcal sequences were obtained using a staphylococci-specific database. RESULTS: Staphylococcus spp. had similar relative abundance in healthy and allergic samples. The most abundant staphylococcal species were S. epidermidis in healthy samples, and S. felis and S. capitis in allergic samples. The composition of staphylococcal communities, as well as relative abundance of Staphylococcus spp., was variable between body sites and individual cats sampled. CONCLUSIONS AND CLINICAL RELEVANCE: These results demonstrate that diverse staphylococcal communities inhabit the skin of healthy and allergic cats, and provide a starting point for further research into the importance of Staphylococcus spp. in feline allergic skin disease.

A case report of total skin photon radiation therapy for cutaneous epitheliotropic lymphoma in a dog.

BACKGROUND: Total skin electron beam radiation therapy (TSEBT) is an effective treatment for primary diffuse cutaneous lymphomas in humans. While several techniques exist, they all require significant commitment of staff time and resources. In veterinary medicine, canine-specific techniques and strategies have been adapted and delivered but deemed not "realistically" clinically implementable given the time commitment of over 2.5 h plus per fraction or have been relegated to palliative intent. Leveraging these technologies of helical tomotherapy and 3D printing, we developed and clinically implemented a radiotherapeutic treatment strategy for the management of medically refractory diffuse cutaneous lymphoma in the dog. CASE PRESENTATION: A 13.5-year-old female spayed Bichon Frise presented to the Oncology service at Texas A&M University, College of Veterinary Medicine due to the progression of diffuse cutaneous epitheliotropic lymphoma (CEL) that had failed medical management. Twenty-seven gray were delivered to the patient with a treatment time requirement under 40 min including real time monitoring of anesthesia during setup and treatment. A partial response was noticeable after four fractions and the tumor completely regressed progressively over the entire treated area by the end of therapy. A grade 1 lethargy, fatigue, weight loss, and oral mucositis and grade 2 alopecia, nail/claw changes, pruritus, scaling, anorexia, and diarrhea were noted during treatment. Additionally, a grade 3 thrombocytopenia developed after fraction eight requiring a treatment interruption of 6 weeks and prescription modification prior to treatment continuation and completion. From the beginning of total skin photon radiation therapy (TSPT) treatment until the time of the patient was euthanized unrelated to cutaneous epitheliotropic lymphoma (123 days), only one new lesion on the head was identified and confirmed by histopathology within the treated fields. CONCLUSIONS: The proposed technique is an acceptable alternative to TSEBT that is actually clinically implementable within a palliative or definitive setting and clinical constraints, however further testing and refinement is needed to reduce hematological complications and to confirm and expand on preliminary findings.

The feline cutaneous and oral microbiota are influenced by breed and environment.

Previous research revealed the feline skin bacterial microbiota to be site-specific and the fungal microbiota to be individual-specific. The effect of other factors, such as genotype and environment, have not yet been studied in cats, but have been shown to be potentially important in shaping the cutaneous microbiota of other animals. Therefore, the objectives of this study were to evaluate the effect of these factors on the bacterial and fungal microbiota of feline skin and oral cavity. The influence of genotype was assessed through the analysis of different cat breeds, and the influence of environment through comparison of indoor and outdoor cats. DNA was extracted from skin and oral swabs, and bacterial and fungal next-generation sequencing were performed. Analysis of the skin microbiota of different cat breeds revealed significant differences in alpha diversity, with Sphynx and Bengal cats having the most diverse communities. Many taxa were found to be differentially abundant between cat breeds, including Veillonellaceae and Malassezia spp. Outdoor environment exposure had considerable influence on beta diversity, especially in the oral cavity, and resulted in numerous differentially abundant taxa. Our findings indicate that the oral bacterial microbiota and both fungal and bacterial microbiota of feline skin are influenced by breed, and to a lesser degree, environment.