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Characterization of Oral Microbiota in Cats: Novel Insights on the Potential Role of Fungi in Feline Chronic Gingivostomatitis.

ABSTRACT: Previous studies have suggested the involvement of viral and bacterial components in the initiation and progression of feline chronic gingivostomatitis (FCGS), but the role of fungi remains entirely unknown. This pilot study aimed to investigate the bacteriome and mycobiome in feline oral health and disease. Physical exams, including oral health assessment, of privately owned, clinically healthy (CH) cats (n = 14) and cats affected by FCGS (n = 14) were performed. Using a sterile swab, oral tissue surfaces of CH and FCGS cats were sampled and submitted for 16S rRNA and ITS-2 next-generation DNA sequencing. A high number of fungal species (n = 186) was detected, with Malassezia restricta, Malassezia arunalokei, Cladosporium penidielloides/salinae, and Aspergillaceae sp. being significantly enriched in FCGS samples, and Saccharomyces cerevisiae in CH samples. The bacteriome was significantly distinct between groups, and significant inter-kingdom interactions were documented. Bergeyella zoohelcum was identified as a potential biomarker of a healthy feline oral microbiome. These data suggest that fungi might play a role in the etiology and pathogenesis of FCGS, and that oral health should not simply be regarded as the absence of microbial infections. Instead, it may be viewed as the biological interactions between bacterial and fungal populations that coexist to preserve a complex equilibrium in the microenvironment of the mouth. Additional investigations are needed to improve our understanding of the feline oral ecosystem and the potential interactions between viruses, bacteria, and fungi in FCGS.

SUBMITTER: Krumbeck JA

PROVIDER: S-EPMC8308807 | biostudies-literature |

REPOSITORIES: biostudies-literature

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feline chronic gingivostomatitis

Project description:feline chronic gingivostomatitis Raw sequence reads

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Transcriptomic analysis of feline chronic gingivostomatitis (FCGS)

Project description:The purpose of this study was to characterize the transcriptomic alterations accompanying the inflammation involved in feline chronic gingivostomatitis (FCGS). Towards this goal next-generation sequencing (NGS)-based gene expression profiling (RNA-Sequencing; RNA-Seq) was performed on matched pairs of FCGS diseased and healthy tissues obtained from three feline subjects.

2020-09-25 | GSE149881 | GEO

The Oral Microbiome across Oral Sites in Cats with Chronic Gingivostomatitis, Periodontal Disease, and Tooth Resorption Compared with Healthy Cats.

Project description:Feline chronic gingivostomatitis (FCGS) is a chronic mucosal and gingival inflammatory disease in which pathogenesis remains unclear. Interactions between the host inflammatory process, the host immune response, and the oral microbiome are implicated in this pathogenesis. To begin to understand this disease and the impact of the microbiome to host inflammatory disease states, we collected sterile noninvasive plaque biofilm samples from ten distinct sites within the oral cavity in cats with stomatitis (n = 12), healthy cats (n = 9), and cats with tooth resorption or periodontitis (n = 11). Analysis of full-length 16S rRNA gene sequences indicated that the microbiomes of cats with FCGS presented marked dysbiosis at multiple oral sites. Additionally, microbiome beta diversity varied with oral condition, indicating that stomatitis, periodontitis, and/or tooth resorption influence the microbiome differently. Lastly, we found that the microbiomes of swabs taken from the oral cavity were comparable to those taken from plaque using endodontic paper points, validating this as another sampling method. Collectively, our work furthers our understanding of the dysbiosis and composition of bacteria in the oral microbiome in FCGS, with hopes of contributing to the prevention, diagnosis, and treatment of this challenging condition in felines.

| S-EPMC10668797 | biostudies-literature

Feline chronic gingivostomatitis current concepts in clinical management.

Project description:Practical relevanceFeline chronic gingivostomatitis (FCGS) is a debilitating disease for cats and a challenge for veterinarians and cat caregivers alike. Recent literature indicates that the disease is immune-mediated in nature and likely associated with a chronic viral infection in patients with higher alpha diversity of their subgingival microbiome. The immune-mediated nature of FCGS includes both local as well as systemic effects, and the transcriptomic analysis of affected patients supports these findings.Treatment optionsLocalized therapy in the form of surgical extraction of all, or nearly all, teeth continues to be the mainstay of treatment. For cats that do not respond to surgical management, medical management, in the form of immunosuppressive or immunomodulatory therapy, remains an option. Analgesia is of fundamental importance. Immunomodulation utilizing mesenchymal stromal cell therapy provides an alternative treatment avenue for refractory patients and likely targets the chronic viral infection present in this disease. The potential for treatment stratification and use of novel systemic treatment options may be revealed as the molecular pathways involved in this disease are better described.AimsThis review outlines current and emerging concepts linking available science pertaining to FCGS and clinical management of the disease.Evidence baseThe article draws on the best evidence base at this juncture and is also driven by the authors' collective experience of working on the disease for over a decade.

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

Project description: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.

| S-EPMC10487179 | biostudies-literature

Histological, Immunological, and Genetic Analysis of Feline Chronic Gingivostomatitis.

Project description:Feline chronic gingivostomatitis (FCGS) is an immune-mediated inflammatory condition affecting the oral mucosa that results in substantial pain and suffering. The goal of this study was to complete an in-depth immunohistochemistry analysis of affected FCGS mucosa, to perform and compare immune cell phenotypes in the blood of FCGS and healthy controls cats, and to determine a transcriptomic profile of the affected and normal oral mucosa of FCGS cats. We hypothesized that cats with FCGS would have circulating activated CD8+ T cells and that tissues would be infiltrated with activated B and T cells with a highly proinflammatory transcriptome. We found that oral mucosal tissues from cats with FCGS have high tissue infiltration of B cells and that T cells include both CD4+ and CD8+ lymphocytes. Cells positive for CD25 (IL2 receptor, indicative of lymphocyte activation) and FOXP3 (indicative of regulatory T cells) were scattered throughout the mucosa. Compared to healthy individuals, cats with FCGS had high circulating CD8+ effector memory cells with a concurrent decrease in central memory cells and evidence of circulating activated CD8+ T cells (CD25+, CD62L-). Gene expression in the affected tissues was enriched for genes associated with T-cell signaling, cell adhesion molecules, leukocyte migration, inflammatory signaling pathways, extracellular matrix-receptor interactions, cytokine-cytokine receptor interactions, and natural killer cell-mediated cytotoxicity, among others. These data are essential to understand disease pathogenesis, to inform mechanism of action studies for future and current therapies, and to help select prognostic biomarkers and potency assays for stem cell treatment of FCGS.

| S-EPMC7283503 | biostudies-literature

A pilot study to evaluate the serum Alpha-1 acid glycoprotein response in cats suffering from feline chronic gingivostomatitis.

Project description:BackgroundFeline chronic gingivostomatitis (FCGS) is a multifactorial immune-mediated disease that can lead to chronic pain, anorexia, and weight loss and has substantial health and welfare effects. Currently, the recommended treatment includes dental extractions to decrease the inflammatory stimulation associated with dental plaque. However, complete remission is observed in less than half of the cases, and the majority need comprehensive medical management. This study aimed to evaluate the serum levels of the acute phase protein alpha-1 acid glycoprotein (AGP) in cats with FCGS and to examine whether dental extractions contribute to a significant decrease in the systemic inflammatory response at two postoperative time points.ResultsAGP serum concentrations in the cats with FCGS were significantly higher at all time points than that in the control groups and were significantly correlated with the global caudal stomatitis score at day 0 but not at day 30 or 60. A significant improvement of some clinical scores, such as perceived comfort and global caudal stomatitis, was observed 60 days after the dental extraction. However, the levels of AGP did not significantly change over time.ConclusionsCats with FCGS were more likely to have a systemic inflammatory response compared with age- and dental disease-matched controls. Dental extractions, in most cases, did not contribute to a significant decrease of AGP both at 30 and 60 days. Therefore, this study reinforces the need to pursue comprehensive medical management after dental extractions to attenuate the systemic inflammatory response as a result of this disease.

| S-EPMC7558631 | biostudies-literature

Cytokine mRNA expression in lesions in cats with chronic gingivostomatitis.

Project description:Semiquantitative reverse transcription-PCR assays were developed to measure feline interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, and IL-12 (p35 & p40); gamma interferon (IFN-gamma); and glyceraldehyde-3-phosphate dehydrogenase mRNA concentrations in biopsies of feline oral mucosa. Biopsies were collected from 30 cats with chronic gingivostomatitis (diseased) prior to each cat receiving one of four treatments. In 23 cases replicate biopsies were collected 3 months after treatment commenced. Biopsies were also analyzed from 11 cats without clinical disease (nondiseased). Expression of IL-2, IL-10, IL-12 (p35 and p40), and IFN-gamma was detected in most nondiseased biopsies, while IL-6 was detected in a minority, and IL-4 and IL-5 were both undetectable. Compared to nondiseased cats, the diseased population showed a significant increase in the relative mRNA expression of IL-2, IL-4, IL-6, IL-10, IL-12 (p35 and p40), and IFN-gamma. In contrast, IL-5 mRNA expression was unchanged and was only detected in one case. No significant relationship was demonstrable between the change in relative expression of specific cytokine mRNA and the change in clinical severity of the local mucosal lesions over the treatment period. The results demonstrate that the normal feline oral mucosa is biased towards a predominantly (Th) type 1 profile of cytokine expression and that during the development of lesions seen in feline chronic gingivostomatitis there is a shift in the cytokine profile from a type 1 to a mixed type 1 and type 2 response.

| S-EPMC95710 | biostudies-literature

Transcriptomic signatures of feline chronic gingivostomatitis are influenced by upregulated IL6.

Project description:Feline chronic gingivostomatitis (FCGS) is a relatively common and debilitating disease characterized by bilateral inflammation and ulceration of the caudal oral mucosa, alveolar and buccal mucosa, and varying degrees of periodontal disease. The etiopathogenesis of FCGS remains unresolved. In this study, we performed bulk RNA-seq molecular profiling of affected tissues derived from a cohort of client-owned cats with FCGS compared to tissues from unaffected animals, to identify candidate genes and pathways that can help guide future exploration of novel clinical solutions. We complemented transcriptomic findings with immunohistochemistry and in situ hybridization assays to better understand the biological significance of the results and performed RNA-seq validation of biologically relevant differentially expressed genes using qPCR assays to demonstrate technical reproducibility. Transcriptomic profiles of oral mucosal tissues in cats with FCGS are enriched with immune- and inflammation-related genes and pathways that appear to be largely influenced by IL6, and include NFKB, JAK/STAT, IL-17 and IFN type I and II signaling, offering new opportunities to develop novel clinical applications based on a more rational understanding of the disease.

| S-EPMC10439118 | biostudies-literature

Transcriptomic signatures of feline chronic gingivostomatitis are influenced by upregulated IL6

Project description:Feline chronic gingivostomatitis (FCGS) is a relatively common and debilitating disease characterized by bilateral inflammation and ulceration of the caudal oral mucosa, alveolar and buccal mucosa, and varying degrees of periodontal disease. The etiopathogenesis of FCGS remains unresolved. In this study, we performed bulk RNA-seq molecular profiling of affected tissues derived from a cohort of client-owned cats with FCGS compared to tissues from unaffected animals, to identify candidate genes and pathways that can help guide future exploration of novel clinical solutions. We complemented transcriptomic findings with immunohistochemistry and in situ hybridization assays to better understand the biological significance of the results and performed RNA-seq validation of selected differentially expressed genes using qPCR assays to demonstrate technical reproducibility. Transcriptomic profiles of oral mucosal tissues in cats with FCGS are enriched with immune- and inflammation-related genes and pathways that appear to be largely influenced by IL6, and include NFKB, JAK/STAT, IL-17 and IFN type I and II signaling, offering new opportunities to develop novel clinical applications based on a more rational understanding of the disease.

2023-05-24 | GSE230491 | GEO

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