Epidemiological investigation of feline chronic gingivostomatitis and its relationship with oral microbiota in Xi'an, China.

Feline chronic gingivostomatitis (FCGS) is an ulcerative and/or proliferative disease that typically affects the palatoglossal folds. Because of its unknown pathogenesis and long disease course, it is difficult to treat and has a high recurrence rate. Most of the bacteria in the oral microbiota exist in the mouth symbiotically and maintain a dynamic balance, and when the balance is disrupted, they may cause disease. Disturbance of the oral microbiota may play an important role in the development of FCGS. In this study, the medical records of 3109 cats in three general pet hospitals in Xi 'an were collected. Sixty-one cats with FCGS were investigated via questionnaires, routine oral examinations and laboratory examinations. Oral microbiota samples were collected from 16 FCGS-affected cats, and microbial species were identified by 16S rDNA sequencing. The results showed that the incidence of FCGS had no significant correlation with age, sex or breed. However, the incidence of FCGS was associated with immunization, a history of homelessness and multicat rearing environments. The number of neutrophils and the serum amyloid A concentration were increased, and the percentage of cells positive for calicivirus antigen was high in all cases. All the cats had different degrees of dental calculus, and there were problems such as loss of alveolar bone or tooth resorption. Compared with those in healthy cats, the bacterial diversity and the abundance of anaerobic bacteria were significantly increased in cats with FCGS. Porphyromonas, Treponemas and Fusobacterium were abundant in the mouths of the affected cats and may be potential pathogens of FCGS. After tooth extraction, a shift could be seen in the composition of the oral microbiota in cats with FCGS. An isolated bacteria obtained from the mouths of the affected cats was homologous to P. gulae. Both the identified oral microbiota and the isolated strain of the cats with FCGS had high sensitivity to enrofloxacin and low sensitivity to metronidazole. This study provides support to current clinical criteria in diagnosing FCGS and proposes a more suitable antibiotic therapy.

Placebo-Controlled Trial of Daily Oral Cannabidiol as Adjunctive Treatment for Cats with Chronic Gingivostomatitis.

A placebo-controlled study evaluated the clinical efficacy and safety of a commercially available cannabidiol (CBD) oral formulation as an adjunctive treatment for pain management for feline chronic gingivostomatitis (FCGS). CBD was included in a multimodal treatment routinely performed on client-owned cats with FCGS that were submitted to dental extractions. Twenty-two cats were consecutively included in the study. The first group was treated using a fixed dosage of 4 mg per cat every 12 h for 15 consecutive days, and the second received a placebo of similar features. Treatments began 2 h before dental extractions. Pain and disease severity were assessed at days 0 and 15 using the Composite Oral Pain Scale (COPS-C/F) and the Stomatitis Disease Activity Index score (SDAI). Weight, vital and biochemistry parameters, and analgesic reinforcement needs were also registered at the same time points. In the treated cats, blood was collected after 4, 8, and 12 h to determine CBD serum concentrations using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS). After data analysis using mixed models, a significant improvement in the SDAI scores of cats medicated with CBD was found. The protocol is safe since severe adverse effects and biochemical changes were not observed during the treatment period. This study suggests that the cats benefited from this treatment.

Feline calicivirus and natural killer cells: A study of its relationship in chronic gingivostomatitis.

Background and Aims: Feline chronic gingivostomatitis (FCGS) is a frequent chronic inflammatory condition in the oral cavity with an etiopathogenesis not completely identified. This study aimed to contribute to the knowledge of FCGS by identifying the presence of feline calicivirus (FCV) antigens and natural killer (NK) cells and comparing them. Materials and Methods: Forty biopsies from the oral mucosa of cats diagnosed with chronic gingivostomatitis were subjected to immunohistochemical techniques to evaluate cells with FCV antigens and NK cells positive for CD56. Results: NK cells were identified in all samples, with an average of 725.3 ± 409.1 cells. Regarding FCV, it was identified in 18 out of 30 samples (60%), with a different number of cells with virus in between the analyzed cases. In all cases, the number of cells infected with FCV was lower than the number of NK cells present in the same samples, but there was no statistical association between them. Conclusion: This preliminary study shows that NK cells are present in gingivostomatitis lesions not exclusively caused by FCV-stimulus, as only 60% of all cases were positive for this virus, but other antigens should be considered in the etiology of FCGS.

Prevalence of feline chronic gingivostomatitis in feral cats and its risk factors.

OBJECTIVES: This study investigated the prevalence of feline chronic gingivostomatitis in urban feral cats in South Korea and analysed its risk factors. METHODS: Three hundred and forty-five feral cats that visited the hospital for neutering using a trap-neuter-return approach were screened for feline chronic gingivostomatitis based on clinical criteria. In addition, we determined if body weight, sex and the presence of tongue lesions are risk factors for feline chronic gingivostomatitis. The difference in severity due to the presence or absence of risk factors, and the relationship between gross findings and histopathological lesions, were analysed by grading lesion severity. RESULTS: Feline chronic gingivostomatitis was diagnosed in 92 cats. Disease prevalence did not significantly differ with body weight and sex but was significantly related to tongue lesions. CONCLUSIONS AND RELEVANCE: The prevalence of feline chronic gingivostomatitis in urban feral cats in South Korea was 26.6%. It was significantly more prevalent in cats that had tongue lesions. Severity was also significantly associated with tongue lesions. Feline chronic gingivostomatitis may be associated with an infectious agent that causes tongue lesions.

Secretory Profile of Adipose-Tissue-Derived Mesenchymal Stem Cells from Cats with Calicivirus-Positive Severe Chronic Gingivostomatitis.

The feline calicivirus (FCV) causes infections in cats all over the world and seems to be related to a broad variety of clinical presentations, such as feline chronic gingivostomatitis (FCGS), a severe oral pathology in cats. Although its etiopathogeny is largely unknown, FCV infection is likely to be a main predisposing factor for developing this pathology. During recent years, new strategies for treating FCGS have been proposed, based on the use of mesenchymal stem cells (MSC) and their regenerative and immunomodulatory properties. The main mechanism of action of MSC seems to be paracrine, due to the secretion of many biomolecules with different biological functions (secretome). Currently, several pathologies in humans have been shown to be related to functional alterations of the patient's MSCs. However, the possible roles that altered MSCs might have in different diseases, including virus-mediated diseases, remain unknown. We have recently demonstrated that the exosomes produced by the adipose-tissue-derived MSCs (fAd-MSCs) from cats suffering from FCV-positive severe and refractory FCGS showed altered protein contents. Based on these findings, the goal of this work was to analyze the proteomic profile of the secretome produced by feline adipose-tissue-derived MSCs (fAd-MSCs) from FCV-positive patients with FCGS, in order to identify differences between them and to increase our knowledge of the etiopathogenesis of this disease. We used high-resolution mass spectrometry and functional enrichment analysis with Gene Ontology to compare the secretomes produced by the fAd-MSCs of healthy and calicivirus-positive FCGS cats. We found that the fAd-MSCs from cats with FCGS had an increased expression of pro-inflammatory cytokines and an altered proteomic profile compared to the secretome produced by cells from healthy cats. These findings help us gain insight on the roles of MSCs and their possible relation to FCGS, and may be useful for selecting specific biomarkers and for identifying new therapeutic targets.

Environmental risk factors for the development of oral squamous cell carcinoma in cats.

BACKGROUND: Risk factors for oral squamous cell carcinoma (OSCC) in cats are derived from a single study dated almost 20 years ago. The relationship between inflammation of oral tissues and OSCC is still unclear. OBJECTIVES: To investigate previously proposed and novel potential risk factors for OSCC development, including oral inflammatory diseases. ANIMALS: Hundred cats with OSCC, 70 cats with chronic gingivostomatitis (CGS), 63 cats with periodontal disease (PD), and 500 controls. METHODS: Prospective, observational case-control study. Cats with OSCC were compared with an age-matched control sample of client-owned cats and cats with CGS or PD. Owners of cats completed an anonymous questionnaire including demographic, environmental and lifestyle information. RESULTS: On multivariable logistic regression, covariates significantly associated with an increased risk of OSCC were rural environment (OR: 1.77; 95% CI: 1.03-3.04; P = .04), outdoor access (OR: 1.68; 95% CI: 1.07-2.63; P = .02), environmental tobacco smoke (OR: 1.77; 95% CI: 1.05-3; P = .03), and petfood containing chemical additives (OR: 1.98; 95% CI: 1.04-3.76; P = .04). Risk factors shared with CGS and PD were outdoor access and petfood containing chemical additives, respectively. A history of oral inflammation was reported in 35% of cats with OSCC but did not emerge as a risk factor. CONCLUSIONS AND CLINICAL IMPORTANCE: The study proposes novel potential risk factors for OSCC in cats. Although a history of inflammatory oral disease was not significantly more frequent compared with random age-matched controls, OSCC shared several risk factors with CGS and PD.

Occurrence of Antimicrobial Resistance Genes in the Oral Cavity of Cats with Chronic Gingivostomatitis.

Feline chronic gingivostomatitis (FCGS) is a severe immune-mediated inflammatory disease with concurrent oral dysbiosis (bacterial and fungal). Broad-spectrum antibiotics are used empirically in FCGS. Still, neither the occurrence of antimicrobial-resistant (AMR) bacteria nor potential patterns of co-occurrence between AMR genes and fungi have been documented in FCGS. This study explored the differential occurrence of AMR genes and the co-occurrence of AMR genes with oral fungal species. Briefly, 14 clinically healthy (CH) cats and 14 cats with FCGS were included. Using a sterile swab, oral tissue surfaces were sampled and submitted for 16S rRNA and ITS-2 next-generation DNA sequencing. Microbial DNA was analyzed using a proprietary curated database targeting AMR genes found in bacterial pathogens. The co-occurrence of AMR genes and fungi was tested using point biserial correlation. A total of 21 and 23 different AMR genes were detected in CH and FCGS cats, respectively. A comparison of AMR-gene frequencies between groups revealed statistically significant differences in the occurrence of genes conferring resistance to aminoglycosides (ant4Ib), beta-lactam (mecA), and macrolides (mphD and mphC). Two AMR genes (mecA and mphD) showed statistically significant co-occurrence with Malassezia restricta. In conclusion, resistance to clinically relevant antibiotics, such as beta-lactams and macrolides, is a significant cause for concern in the context of both feline and human medicine.

A Case Series Analysis of Dental Extractions' Outcome in Cats with Chronic Gingivostomatitis Carrying Retroviral Disease.

This study aims to evaluate and compare the clinical outcome after dental extractions of cats with FCGS infected with feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV). A retrospective case series included cats with diagnosis of FCGS, availability of detailed clinical records, full-mouth dental radiographs, and retroviral disease test results. Effectiveness of surgical treatment (EOT) was registered. Three groups were defined: control, FIV and FeLV. In this study, 111 cats were included: 60 controls, 29 FIV- and 22 FeLV-positive cats. When compared with control cases, FeLV-positive cats had significantly less proliferative stomatitis lesions, and they tended to have more lingual ulcers. Concurrently, FeLV-positive cats had significantly less tooth resorptive lesions. No other significant differences in FCGS clinical signs were found between groups. FeLV-positive cats had a significantly worse outcome after dental extractions compared to the other groups. In fact, FeLV-positive cats had 7.5 times more chances of having no improvement after dental extractions. This study concludes that the response to dental extractions in FeLV-positive cats is significantly worse, when comparing to cats that do not carry retroviral disease. Therefore, it is important to acknowledge the effect of FeLV status on the prognosis of these cats.

Altered Proteomic Profile of Adipose Tissue-Derived Mesenchymal Stem Cell Exosomes from Cats with Severe Chronic Gingivostomatitis.

Feline chronic gingivostomatitis (FCGS) is a pathology with a complicated therapeutic approach and with a prevalence between 0.7 and 12%. Although the etiology of the disease is diverse, feline calicivirus infection is known to be a predisposing factor. To date, the available treatment helps in controlling the disease, but cannot always provide a cure, which leads to a high percentage of refractory animals. Mesenchymal stem cells (MSCs) play a pivotal role in the homeostasis and reparation of different tissues and have the ability to modulate the immune system responses. This ability is, in part, due to the capacity of exosomes to play a part in intercellular cell communication. However, the precise role of MSC-derived exosomes and their alterations in immunocompromised pathologies remains unknown, especially in veterinary patients. The goal of this work was to analyze the proteomic profile of feline adipose tissue-derived MSCs (fAd-MSCs) from calicivirus-positive FCGS patients, and to detect possible modifications of the exosomal cargo, to gain better knowledge of the disease's etiopathogenesis. Using high-resolution mass spectrometry and functional enrichment analysis with Gene Ontology, exosomes isolated from the fAd-MSCs of five healthy cats and five calicivirus-positive FCGS patients, were pooled and compared. The results showed that the fAd-MSCs from cats suffering from FCGS not only had a higher exosome production, but also their exosomes showed significant alterations in their proteomic profile. Eight proteins were exclusively found in the exosomes from the FCGS group, and five proteins could only be found in the exosomes from the healthy cats. When comparing the exosomal cargo between the two groups, significant upregulation of 17 and downregulation of 13 proteins were detected in the FCGS group compared to the control group. These findings shed light on new perspectives on the roles of MSCs and their relation to this disease, which may help in identifying new therapeutic targets and selecting specific biomarkers.

Feline oral cavity lesions diagnosed by histopathology: a 6-year retrospective study in Portugal.

OBJECTIVES: The aim of this study was to analyse the frequency of oral cavity lesions in cats, their anatomical location and histological diagnosis, and the effect of life stage, breed and sex on different diagnoses. METHODS: For this purpose, a retrospective study comprising 297 feline oral cavity lesions was performed over a 6-year period between 2010 and 2015. Histopathological records from the DNAtech Pathology Laboratory (Lisbon, Portugal) were analysed. RESULTS: The incidence of oral disease was higher in male cats (n = 173; 58.4%), mature adults (ranging from 7 to 10 years old [n = 88; 33.0%]) and in the European Shorthair breed (n = 206; 73.6%). The gingiva was the site where oral lesions were most commonly found, with 128 samples (43.1%). Incisional biopsies were used to obtain the majority of samples (n = 256; 86.2%), while excisional biopsies and punch biopsies were performed in 36 (12.1%) and five (1.7%) cases, respectively. Inflammatory and neoplastic lesions accounted for 187 (63%) and 110 (37%) of the studied cases, respectively. Malignancies were found in >80% of neoplastic cases. Feline chronic gingivostomatitis was the most common histological diagnosis (n = 116; 39.1%), followed by squamous cell carcinoma (n = 49; 16.5%) and eosinophilic granuloma complex (n = 33; 11.1%). CONCLUSIONS AND RELEVANCE: The present work, involving a large series of samples of feline oral cavity lesions, from numerous geographically scattered practices and all examined at a reference veterinary pathology laboratory, adds important new understanding of the epidemiology of feline oral disease.

Inter- and intra-observer reliability of quantitative sensory testing performed with the SMall animal ALGOmeter (SMALGO) to evaluate pain associated with feline gingivostomatitis.

OBJECTIVES: The aim of this study was to evaluate the inter- and intra-observer reliability of quantitative sensory testing performed with the SMall animal ALGOmeter (SMALGO) in healthy cats and in cats with chronic gingivostomatitis (CGS), and to evaluate the SMALGO as a tool to detect and quantify pain in cats with CGS. METHODS: Thirty cats from a private shelter were included and assigned to one of two groups: group C (healthy cats; n = 15) or group CGS (cats with CGS; n = 15). In all cats the mechanical thresholds were measured with the SMALGO, with the sensor tip applied to the superior lip above the canine root, by two independent investigators (A, experienced; B, unexperienced), on two different occasions (day 1 and day 2) with a 24 h interval. A CGS scale was used in the diseased cats to assess the severity of the condition. For the reliability analysis, intra-class correlation coefficients (ICCs) were calculated. Other statistical tests used were Pearson correlation coefficient and a paired t-test. RESULTS: The inter- and intra-observer levels of agreement were fair (ICC = 0.50) and good, respectively (ICC = 0.73 for investigator A; ICC = 0.60 for investigator B). However, the thresholds measured in healthy cats (169 ± 59 g) did not differ from those obtained from diseased cats (156 ± 82 g; P = 0.35). There was no correlation between the scores of the CGS scale and the thresholds measured in diseased cats (Pearson correlation coefficient = 0.047; P = 0.87). CONCLUSIONS AND RELEVANCE: Quantitative sensory testing performed with the SMALGO in cats is repeatable and reliable, regardless of the expertise of the investigator. However, the findings of this study suggest that the mechanical thresholds measured with the SMALGO may not be a valuable indicator of pain in cats with CGS.

Mesenchymal stem cells therapy in companion animals: useful for immune-mediated diseases?

Mesenchymal stem cells are multipotent cells, with capacity for self-renewal and differentiation into tissues of mesodermal origin. These cells are possible therapeutic agents for autoimmune disorders, since they present remarkable immunomodulatory ability.The increase of immune-mediated diseases in veterinary medicine has led to a growing interest in the research of these disorders and their medical treatment. Conventional immunomodulatory drug therapy such as glucocorticoids or other novel therapies such as cyclosporine or monoclonal antibodies are associated with numerous side effects that limit its long-term use, leading to the need for developing new therapeutic strategies that can be more effective and safe.The aim of this review is to provide a critical overview about the therapeutic potential of these cells in the treatment of some autoimmune disorders (canine atopic dermatitis, feline chronic gingivostomatitis, inflammatory bowel disease and feline asthma) compared with their conventional treatment.Mesenchymal stem cell-based therapy in autoimmune diseases has been showing that this approach can ameliorate clinical signs or even cause remission in most animals, with the exception of canine atopic dermatitis in which little to no improvement was observed.Although mesenchymal stem cells present a promising future in the treatment of most of these disorders, the variability in the outcomes of some clinical trials has led to the current controversy among authors regarding their efficacy. Mesenchymal stem cell-based therapy is currently requiring a deeper and detailed analysis that allows its standardization and better adaptation to the intended therapeutic results, in order to overcome current limitations in future trials.

Feline chronic gingivostomatitis is more prevalent in shared households and its risk correlates with the number of cohabiting cats.

OBJECTIVES: The aim of this study was to determine whether feline chronic gingivostomatitis (FCGS) is more prevalent in shared vs single-cat households, whether the number of cohabiting cats or outdoor access represent risk factors for FCGS and whether the number of cohabiting cats is a useful prognostic indicator for standard surgical treatment. METHODS: Cats diagnosed with FCGS (study group) in the past 5 years at a referral institution were identified. The number of cohabiting cats, outdoor access, number of other cohabiting cats diagnosed with FCGS, ⩾6 month surgical outcome, when applicable, and historical signs of upper respiratory disease among any of the cohabiting cats, as well as patient demographic information, were recorded. Data were collected from medical records and by means of a telephone interview with the owners. The same information was collected from a group of cats of similar demographic characteristics diagnosed with periodontal disease but free of FCGS (control group). RESULTS: Seventy-six cats were included, of which 36 (47%) had FCGS and 40 (53%) served as controls. Bivariate analysis showed that cats with FCGS were significantly more likely to come from shared households, and had significantly more total cats per household compared with controls. Multivariate analysis also showed that cats in shared households had a significantly increased odds of FCGS compared with those from single-cat households. Historical signs of upper respiratory disease and outdoor access among cats within the same household were not associated with FCGS. The number of cohabiting cats was not associated with surgical outcome. CONCLUSIONS AND RELEVANCE: Cats with FCGS are more likely to live in shared households. The risk of FCGS correlates with the number of cohabiting cats. The epidemiological features of FCGS may support an infectious etiology. The number of cohabiting cats within a household is not a useful prognostic indicator for standard surgical treatment of FCGS.

Feline chronic gingivostomatitis with calicivirus infection: case report / Gengivostomatite crônica felina com infecção por calicivírus: relato de caso

Feline chronic gingivostomatitis (FCGS) is an oral inflammatory condition that frequently affects felines. Its etiology is not well defined, but several viral agents are thought to be involved. Several therapeutic protocols have been described, yet treatment response is often variable, and the therapeutic success is transient with an unpredictable duration. Therefore, the therapeutic strategy needs to be tailored for each patient. This work relates a case characterized by viral involvement in its etiopathogenesis providing an alternative to the most widely-used methods that so often frustrate both veterinary doctors and pet owners.(AU)

A gengivostomatite crônica felina (FCGS) é uma condição inflamatória oral que frequentemente afeta felinos. A sua etiologia não está bem definida, mas acredita-se que vários agentes virais possam estar envolvidos. Muitos protocolos terapêuticos têm sido descritos, no entanto, a resposta ao tratamento é frequentemente variável e o sucesso terapêutico é transitório com uma duração imprevisível. Portanto, a estratégia terapêutica precisa ser adaptada para cada paciente. O presente trabalho propõe a caracterização do envolvimento viral na etiopatogenia da doença como uma alternativa aos métodos mais amplamente utilizados, que muitas vezes frustram médicos veterinários e os donos de animais de estimação.(AU)

Therapeutic Management of Feline Chronic Gingivostomatitis: A Systematic Review of the Literature.

Feline chronic gingivostomatitis (FCGS) is a disease characterized by protracted and potentially debilitating oral inflammation in cats, the etiology of which is currently unknown. The purpose of this review is to apply an evidence-based medicine approach to systematically review and critically evaluate the scientific literature reporting the outcome of medical and surgical management of FCGS. Those articles meeting inclusion criteria were reviewed and assigned an "Experimental Design Grade" (EDG) and an "Evidence Grade" (EG) in order to score relative strength of study design and produced data. Studies were evaluated and compared, especially highlighting the treatments, the outcomes, and the therapeutic success rates. This review found a lack of consistency between articles' data, rendering direct comparison of results unreliable. The field of FCGS research, and ultimately patient care, would benefit from standardizing studies by adopting use of a consistent semi-quantitative scoring system and extending follow-up duration. Future researchers should commit to large prospective studies that compare existing treatments and demonstrate the promise of new treatments.