Periodontitis is widely acknowledged as the most prevalent type of oral inflammation, arising from the dynamic interplay between oral pathogens and the host's immune responses. It is also recognized as a contributing factor to various systemic diseases. Dysbiosis of the oral microbiota can significantly alter the composition and diversity of the gut microbiota. Researchers have delved into the links between periodontitis and systemic diseases through the "oral-gut" axis. However, whether the associations between periodontitis and the gut microbiota are simply correlative or driven by causative mechanistic interactions remains uncertain. This review investigates how dysbiosis of the gut microbiota impacts periodontitis, drawing on existing preclinical and clinical data. This study highlights potential mechanisms of this interaction, including alterations in subgingival microbiota, oral mucosal barrier function, neutrophil activity, and abnormal T-cell recycling, and offers new perspectives for managing periodontitis, especially in cases linked to systemic diseases.

As the opposite ends of the orodigestive tract, the oral cavity and the intestine share anatomical, microbial, and immunological ties that have bidirectional health implications. A growing body of evidence suggests an interconnection between oral pathologies and inflammatory bowel disease [IBD], implying a shift from the traditional concept of independent diseases to a complex, reciprocal cycle. This review outlines the evidence supporting an 'oral-gut' axis, marked by a higher prevalence of periodontitis and other oral conditions in IBD patients and vice versa. We present an in-depth examination of the interconnection between oral pathologies and IBD, highlighting the shared microbiological and immunological pathways, and proposing a 'multi-hit' hypothesis in the pathogenesis of periodontitis-mediated intestinal inflammation. Furthermore, the review underscores the critical need for a collaborative approach between dentists and gastroenterologists to provide holistic oral-systemic healthcare.

Over the past two decades, the importance of the microbiota in health and disease has become evident. Pathological changes to the oral bacterial microbiota, such as those occurring during periodontal disease, are associated with multiple inflammatory conditions, including inflammatory bowel disease. However, the degree to which this association is a consequence of elevated oral inflammation or because oral bacteria can directly drive inflammation at distal sites remains under debate. In this Perspective, we propose that in inflammatory bowel disease, oral disease-associated bacteria translocate to the intestine and directly exacerbate disease. We propose a multistage model that involves pathological changes to the microbial and immune compartments of both the oral cavity and intestine. The evidence to support this hypothesis is critically evaluated and the relevance to other diseases in which oral bacteria have been implicated (including colorectal cancer and liver disease) are discussed.

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

In modern medicine, the oral cavity has often been viewed as a passive conduit to the upper airways and gastrointestinal tract; however, its connection to the rest of the body has been increasingly explored over the last 40 years. For several diseases, the periodontium and gingiva are at the center of this oral-systemic link. Over 50 systemic conditions have been specifically associated with gingival and periodontal inflammation, including inflammatory bowel diseases (IBD), which have recently been elevated from simple "associations" to elegant, mechanistic investigations. IBD and periodontitis have been reported to impact each other's progression via a bidirectional relationship whereby chronic oral or intestinal inflammation can impact the other; however, the precise mechanisms for how this occurs remain unclear. Classically, the etiology of gingival inflammation (gingivitis) is oral microbial dysbiosis in the subgingival crevice that can lead to destructive periodontal disease (periodontitis); however, the current understanding of gingival involvement in IBD is that it may represent a separate disease entity from classical gingivitis, arising from mechanisms related to systemic inflammatory activation of niche-resident immune cells. Synthesizing available evidence, we hypothesize that once established, IBD can be driven by microbiomial and inflammatory changes originating specifically from the gingival niche through saliva, thereby worsening IBD outcomes and thus perpetuating a vicious cycle. In this review, we introduce the concept of the "gum-gut axis" as a framework for examining this reciprocal relationship between the periodontium and the gastrointestinal tract. To support and explore this gum-gut axis, we 1) provide a narrative review of historical studies reporting gingival and periodontal manifestations in IBD, 2) describe the current understanding and advances for the gum-gut axis, and 3) underscore the importance of collaborative treatment and research plans between oral and GI practitioners to benefit this patient population.

Crohn's disease (CD) is a granulomatous inflammatory bowel disease (IBD) that can affect any part of the gastrointestinal tract, but its etiology is still unclear. CD patients usually have extraintestinal manifestations including oral manifestations, and this can also occasionally appear in children. Oral manifestations, including aphthous stomatitis, typically develop on the mucocutaneous tissue. As pediatric CD is not common, there have been no reports concerning alveolar bone resorption for these kinds of patients. An 11-year-old Chinese girl was referred to our hospital because of reoccurring painful oral ulcers, with a 2.5-year history of CD and recurrent oral ulcers. Clinical examinations revealed intestinal lesions, oral ulcers, and alveolar bone loss. CD and its related periodontitis were diagnosed. After comprehensive therapy, including periodontal scaling and anti-inflammatory treatment, the oral ulcers gradually healed. One year later, follow-up visit showed the anterior alveolar bone to be stable and new alveolar bone regenerating around the mandibular anterior teeth at some sites. It is rare for CD children to have periodontitis, especially with severe alveolar bone loss. This case suggests that when treating periodontitis in children, the possibility of systemic disease, such as CD, should be considered and attended to. Early diagnosis and symptomatic treatment and care are crucial.

Inflammatory bowel disease (IBD), comprised Crohn's disease and ulcerative colitis, is a mucosal immune response that affects gastroenterological tract. The association between IBD and periodontitis was inconclusive. In this study, we aimed to investigate the association between IBD and periodontitis by using a register-based dataset.

The dataset conducting in this retrospective cohort study was obtained from the National Health Insurance Research database (NHIRD) in Taiwan. For IBD group, conditionally selected control subjects were matched in 1:4 ratio from general population. The risk of periodontitis among IBD group comparing with non-IBD group was calculated by multivariable Cox proportional hazards model.

In IBD cohort, 27 IBD patients (7 Crohn's disease and 20 ulcerative colitis) with catastrophic illness registry were identified. 108 controls were selected as non-IBD cohort. The median follow-up period was 3.00 years in the IBD group and 3.15 years in the non-IBD group. The cumulative incidence of IBD was 4.32 per 100,000 persons. After adjusting for several confounding factors, IBD group had higher risk for developing periodontitis than non-IBD group (adjusted HR: 1.82; 95% CI: 1.09-3.03). To further stratification with subtype, Crohn's disease group had significantly higher risk of periodontitis (adjusted HR: 3.95; 95% CI: 1.59-9.82).

Taken together, this retrospective cohort study showed that patients with IBD increase risk of having periodontitis comparing with non-IBD group, especially in Crohn's disease subgroup.

Chlorhexidine (CHX) and Tetracycline (TET) are the two antimicrobial agents used in the management of periodontal infections, due to their antimicrobial potency and substantivity. The benefits and limitations of an antimicrobial agent can only be assessed by determining their relative toxicity to microbes and host cells.

(1) To detect the effects of CHX and TET on neutrophil viability and functions in vitro. (2) To compare the effects of CHX and TET on crevicular blood neutrophils.

Crevicular blood was collected using 5-μl pipette, stored in EDTA-containing vacutainers and sent for evaluation of Cell Viability- Neutrophils would be mixed with 0.25 volume of 0.4% trypan blue in Hank's balanced salt solution (HBSS) and counted to assess the viability. Chemotaxis- Evaluated under agarose slides, a total of 100 μl crevicular blood Neutrophils-0.2% BSA or HBSS-0.2% containing concentration of CHX and TET. Oxidative Metabolism- would be assessed using nitro blue tetrazolium. In all experiments, three concentrations of TET (0.1%, 0.05%, 0.025%) and CHX (0.01%, 0.005%, 0.0025%) respectively were used. N-Formyl methionyl leucyl phenylalanine (1 μm) in the presence of 2 μg/ml cytochalasin B will be used as the activating agent. Neutrophils would be treated with CHX and TET similarly to that for chemotaxis.

TET comparatively has less deleterious effects on neutrophil functions as compared with that of CHX with statistically significant results for all parameters tested.

From this study, it is inferred that CHX and TET do cause certain changes in neutrophil functions.

Crohn's disease (CD) was reported to have oral manifestations. However, data on periodontal parameters and oral microbiology in CD are rare. Recent studies showed associations of variants in the caspase recruitment domain (CARD)15 gene with CD that are involved in the immune response toward bacterial products. Our aim is to investigate the periodontal status and prevalence of periodontal pathogens in patients with CD under consideration of the CARD15 polymorphism.

Oral soft tissue alterations and periodontal parameters of 147 patients with CD were assessed. Subgingival plaque samples were analyzed for the periodontal pathogens Aggregatibacter actinomycetemcomitans (Aa; previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf; previously T. forsythensis), Prevotella intermedia (Pi), and Campylobacter rectus (Cr ) using dot-blot hybridization. CARD15 genotyping was performed with the a polymerase chain reaction (PCR) based assay.

A total of 36.7% of patients had oral manifestations predominated by gingival swellings (27.2%) and hyperplastic lesions of the buccal mucosa (20.4%). The mean probing depth and mean clinical attachment level were 3.6 and 3.8 mm, respectively. A total of 57.8% of the patients had a Community Periodontal Index of Treatment Needs (CPITN) score 3, and 31.3% of had a CPITN score 4. The prevalence of Aa, Pg, Pi, Tf, and Cr was 76.9%, 62.6%, 79.6%, 64.6%, and 94.6%, respectively. Pi was significantly less frequent in carriers of CARD15 mutations compared to the wild type (69.7% versus 87.7%; P = 0.008). All other pathogens and clinical periodontal parameters did not differ significantly as to the CARD15 polymorphism.

Our findings suggest that patients with CD have an increased prevalence and moderate severity of periodontitis. The colonization of periodontal pathogens, in particular Cr, might be of particular value for the periodontal manifestation of CD. Although a modulating impact on periodontal microbiota can be supposed, our data do not support the role of CARD15 in oral symptoms and periodontal lesions in patients with CD.

Previous reports suggest a higher incidence of dental caries in patients with inflammatory bowel disease (IBD) and similarities in the immunopathogenesis of IBD and periodontitis. This study assessed the prevalence of periodontal disease and caries in patients with IBD.

In the present case-control study, 62 patients seeking treatment of IBD and 59 matched healthy controls of a dental practice were clinically examined. Oral soft-tissue alterations, the decayed, missing and filled tooth surface (DMF-S) index, dentine caries, plaque index (PI), bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment loss (CAL) were evaluated in each patient and in the controls.

Patients with IBD showed a significantly higher number of oral manifestations compared with controls. The DMF-S index showed no significant differences, but there was a significantly higher number of subjects with dentine caries in patients with IBD. The mean PPD in patients with IBD was 2.08 versus 2.23 mm in controls (p=0.014). Compared with controls, patients with IBD had more sites with CAL of at least 4 mm (81% versus 64% in controls, p=0.07) and 5 mm (63% versus 46%, p=0.07), respectively.

The results of this case-control study demonstrate a higher frequency of dentine caries in patients with IBD but the periodontal findings showed no distinct differences between cases and controls.

Previous reports have demonstrated that oral mucosa and periodontal lesions occur in patients suffering from inflammatory bowel disease (Crohn's disease [CD] and ulcerative colitis [UC]). It is unknown whether periodontal disease is an occasional or regular finding in these patients. The purpose of this study was to assess the prevalence and severity of periodontal disease in patients with inflammatory bowel disease (IBD). The periodontal status of 107 consecutive patients seeking treatment for inflammatory bowel disease was assessed. Examination of the mid- and mesiobuccal aspects of one quadrant on one jaw and the contralateral quadrant of the opposite jaw revealed the 93.5% of the CD patients and 95.1% of UC patients had at least one site with probing attachment loss of 2 mm or greater, and a mean probing attachment loss 1.4 +/- 0.9 mm and 1.5 +/- 1.0 mm, respectively. We found that 28.3% of CD patients and 29.5% of UC patients possessed at least 1 site with a pocket probing depth of 4 mm or greater; the mean pocket probing depth in these patients was 2.4 +/- 0.2 mm and 2.3 +/- 0.2 mm, respectively. Compared with the assessment of Oral Health of United States Adults, IBD patients revealed a 11.9% higher prevalence (P less than or equal to 0.01) but 0.6 mm lower severity (P less than or equal to 0.01) of periodontal disease. The magnitudes of these differences suggest no clinical implications for the management of periodontal disease in IBD subjects.

Polymorphonuclear neutrophils (PMN's) constitute the primary host resistance factor against infection. They are prominent cells in both the gingival tissue and gingival sulcus in most forms of periodontal disease. Although defective PMN function has been implicated in the pathogenesis of localized juvenile periodontitis (LJP) and rapidly progressive periodontitis (RPP), this may not necessarily be the case in adult periodontitis (AP). A number of studies have failed to detect PMN dysfunction in AP. However, it may be that in this form of chronic inflammatory periodontal disease (CIPD) the defects in peripheral blood PMN function are subtle and the methods used may lack the necessary sensitivity. Chemiluminescence (CL) is the light energy produced by the PMN during its interaction with bacteria or other particles and has been demonstrated to correlate well with antibacterial integrity. Measurement of CL produced by phagocytically challenged PMN's may provide a very sensitive assay of the functional ability of these cells, and, hence, may be useful in assessing PMN activity in CIPD. Recent studies using PMN's obtained from periodontal diseased patients challenged with the periodontopathic organism Fusobacterium nucleatum have revealed an elevated CL response compared to non-diseased controls. These results are reviewed and areas for future research discussed.

This review presents evidence for lysosomal enzymes being at least partly responsible for the tissue destruction seen in periodontal disease. However, many other inflammatory and immunologic mechanisms have been identified that can contribute to tissue destruction (Nisengard 1977). The relationship of PMN to the periodontal tissues is equivalent to the proverbial double-edged sword. The localized tissue destruction that may be due to the extracellular release of PMN enzymes in individuals with normal cell function must be weighed against the role of PMN in containment of gingival bacteria and their products. The consequences of qualitative and/or quantitative abnormalities of neutrophils are far more undesirable for the periodontium. It therefore seems logical to propose that the role of polymorphonuclear leukocytes in the gingival tissues is primarily a defensive one. The presence of neutrophils in the gingival crevice has been shown to reflect the inflammatory condition of the tissues. Due to their availability, it may prove beneficial to use gingival crevicular PMN activity as a reliable clinical index of disease activity. The development of appropriate tests to measure PMN may eventually lead to better diagnostic criteria, including the definition of active versus inactive disease.