Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis.

BACKGROUND: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. RESULTS: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. CONCLUSIONS: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis

A systematic review of dental disease management in cancer patients

10.1007/s00520-017-3829-ySUPPORTIVE CARE IN CANCER261155-17

Prevention of post-operative bleeding in hemostatic compromised patients using native porcine collagen fleeces-retrospective study of a consecutive case series

Various anticoagulant therapy regimes bear the risk of postsurgical bleeding events after dental extractions. Local hemostyptic measures, e.g., collagen fleeces, are applied by surgeons to prevent such bleedings. No standard protocol in prevention of bleeding events has met general acceptance among surgeons yet. The purpose of this retrospective study was to determine if post-operative bleeding can be prevented by suturing native collagen fleeces into extraction wounds immediately after teeth removal, regardless what anticoagulant regime is performed. A total of 741 extraction units were removed from 200 consecutive in-ward patients with or without alternation of different anticoagulant therapy regimes. Anti-vitamin K agents were the most prescribed drugs (n = 104, 52 %), followed by Acetylsalicylate (ASS) (n = 78, 39 %). Nineteen (9.5 %) patients received a dual anti-platelet therapy. Out of 104 patients receiving an anti-vitamin K agent (phenprocoumon), 84 patients were bridged, 20 patients continued to their anticoagulant therapy without alterations. Following careful tooth extraction, extraction sockets were filled using a native type I and III porcine collagen sponge (Collacone, Botiss Biomaterials, Berlin), supported by single and mattress sutures for local hemostasis. Post-operative bleeding events were rated according to their clinical relevance. In the post-operative phase, 8 out of 200 consecutively treated patients experienced a post-operative bleeding event. All of them had been designated for a long-term anti-vitamin K therapy (p <= 0.05), and extractions were performed under a heparin bridging regime (n = 6) or an uninterrupted anti-vitamin K agent therapy (n = 2). No bleeding events occurred in patients with ASS 100 therapy or low-dose LMWH therapy (p <= 0.05), or in patients with dual anti-platelet therapy (0 out of 24). None of the bleeding events put patients' health at risk or required systemic intervention. Sufficiently performed local hemostyptic measures, like the application of collagen fleeces in combination with atraumatic surgery, bears a great potential for preventing heavy bleeding events in hemostatic compromised patients, regardless of their anticoagulant therapy

Oral hygiene and infective endocarditis: a case control study

Objective: To determine if oral hygiene is associated with infective endocarditis (IE) among those at moderate risk for IE. Study Design: This is a case control study of oral hygiene among hospitalized patients with IE (cases) and outpatients with heart valve disease but without IE (controls). The primary outcome was mean dental calculus index. Secondary outcomes included other measures of oral hygiene and periodontal disease (e.g., dental plaque, gingivitis) and categorization of blood culture bacterial species. Results: The 62 case participants had 53% greater mean dental calculus index than the 119 control participants (0.84, 0.55, respectively; difference = 0.29, 95% CI:0.11, 0.48; p=0.002) and 26% greater mean dental plaque index (0.88, 0.70, respectively; difference = 0.18, 95% CI: 0.01,0.36; p=0.043). Overall, cases reported fewer dentist and dental hygiene visits (p= 0.013) and fewer dental visits in the 12 weeks prior to enrollment than controls (p=0.007). Common oral bacteria were identified from blood cultures in 27 of 62 cases (44%). Conclusions: These data provide evidence to support and strengthen current AHA guidance that those at risk for IE can reduce potential sources of IE-related bacteremia by maintaining optimal oral health through regular professional dental care and oral hygiene procedures