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Incidence and clinical presentation of oral mucositis during chemotherapy and correlation with antineoplastics. a Intraoral images of a patient affected by oral mucositis. b Mucositis incidence according to the WHO scale, which evaluates in a categorical scale of 0 to 4 objective signs and patient-reported symptoms, and to the OMAS scale, which is based solely on objective signs of erythema and ulceration. OMAS scores reported here could range from 0 to 45 and represent the aggregated scores from nine intra-oral sites evaluated. c, d The clinical progression of mucositis in mucositis-positive subjects (n = 32 for the WHO scale and n = 37 for OMAS). Graphs show individual data points with median and range. ** indicates a p value < 0.01 and *** indicates a p value < 0.001 when comparing each time point to baseline via Wilcoxon matched-pairs signed rank tests. e Incidence of mucositis in subjects taking 5-FU and those on doxorubicin. * indicates a p value of < 0.05 when comparing incidence via chi-square. f Correlations between chemotherapeutic total drug doses and mucositis severity. Data represent Spearman correlation coefficients with p values in parenthesis. Colored cells show correlations significant after adjustment for multiple comparisons via the FDR method. Only drugs given to at least 15% of subjects were included in the analysis
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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 respo...
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The Middle Eastern prevalence of sickle cell anemia, a genetic disorder that affects red blood cells, necessitates additional research. On a molecular level, we sought to identify and sort the oral microbiota of healthy individuals and those with sickle cell anemia. Furthermore, it is crucial to comprehend how changes in the genetic makeup of the o...
Citations
... Understanding the pathobiology of oral mucositis and creating innovative treatments to lessen its effects on patients with head and neck cancer are the main goals of research efforts. Patients' quality of life is greatly reduced by the severe morbidity linked to oral mucositis, which can even interfere with the delivery of cancer medicines that could save lives (Hong et al., 2019). Due to differences in study designs and diagnostic scoring standards, the worldwide prevalence of oral mucositis is still underreported despite its clinical importance. ...
Haematopoietic stem cell transplantation, chemotherapy, and radiation therapy are frequently linked to the crippling condition known as oral mucositis (OM). It can seriously impair quality of life and possibly interfere with cancer treatment plans. It manifests as painful ulceration, erythema, and oedema. Microbiota dysbiosis, oxidative stress, and inflammatory pathways are all intricate components of the pathophysiology of OM. Its severity is influenced by several risk factors, such as chemotherapy, radiation dosage, genetic predisposition, and oral hygiene. There is still no ideal gold-standard treatment for it, despite its high prevalence. Pharmacological interventions like cytoprotective agents, anti- inflammatory medications, growth factors, biological response modifiers, and antimicrobial agents are all part of the multimodal approach used in current management strategies. Low-level laser therapy (LLLT), cryotherapy, and dental hygiene practices are examples of non-pharmacological methods that have demonstrated promise in reducing symptoms and enhancing patient outcomes. Recent developments in OM pathophysiology and treatment approaches are compiled in this review, which highlights the importance of tailored, evidence-based treatment plans. To improve patient care and reduce OM-related morbidity, more research is necessary to create innovative, affordable, and widely recognized treatments.
... Periplanetasin-5 also showed anti-inflammatory activity by inhibiting the generation of NO, COX-2, and the pro-inflammatory cytokines TNF-α and IL-6 induced by lipopolysaccharide (Kim et al., 2020). The oral bacteriome was disrupted during chemotherapy and was independently and strongly associated with the severity of oral mucositis (Hong et al., 2019). The oral microbiota may aggravate cancer treatment-induced mucosal damage by promoting cell apoptosis and pro-inflammatory cytokine production (Stringer and Logan, 2015). ...
Objective
Chemotherapy-induced oral mucositis (CTOM) is a common side effect affecting 20%–40% of cancer patients receiving chemotherapy. Kangfuxin liquid (KFXL) has been used clinically to prevent and treat CTOM, but the evidence has not been systematically evaluated. This study aimed to evaluate the preventive and therapeutic effects of KFXL on CTOM.
Methods
Nine electronic databases were searched to identify KFXL-related randomized controlled trials (RCTs) for the prevention and treatment of CTOM from inception to September 2024. The primary outcomes were incidence rate, efficacy rate and cure rate, and the secondary outcomes was healing time.
Results
Twenty-one trials involving 1825 patients were included in this review. The results of our meta-analysis showed that, compared with basic oral care (BOC), KFXL significantly reduced the incidence rate of CTOM and severe CTOM (RR = 0.54, p < 0.00001; RR = 0.23, p < 0.00001, respectively), improved the efficacy rate of CTOM and severe CTOM (RR = 1.23, p = 0.0003; RR = 1.99, p = 0.05, respectively), improved the cure rate of CTOM (RR = 2.06, p = 0.0004),and accelerated the healing process (MD = −2.48, p < 0.00001). However, KFXL and other drugs have the same efficacy rate in treating CTOM and severe CTOM (RR = 1.00, p = 0.99; RR = 1.00, p = 1.00, respectively), and the same cure rate in CTOM (RR = 0.91, p = 0.39), and the same healing time (MD = −0.01, p = 1.00).
Conclusion
The results suggest that KFXL may provide more benefit in the prevention and treatment for CTOM compared to BOC. Although KFXL may be a promising drug for the prevention and treatment of CTOM, the evidence is insufficient to prove its superiority over other guideline-recommended treatment.
Systematic Review Registration
https://www.crd.york.ac.uk/PROSPERO/view/CRD42024585859, ID: CRD42024585859.
... We evaluated the antibacterial activity of ENs/Gel, ORI/Gel, ORI+ENs/Gel, and ORI/ENs/Gel against two prevalent wound bacteria (S. aureus and E. coli) against the blank group. 6,44 It can be seen that bacteria in the control group grew well and the bacterial count has reached 90%. Figure 3A and C indicate that after 3 h and 6 h of direct contact with bacteria, the growth of S. aureus was significantly reduced in ENs/Gel, ORI/Gel, ORI+ENs/Gel, and ORI/ENs/Gel groups, while the antibacterial effect on E. coli was slight in the ENs/Gel group and higher in the ORI/Gel, ORI+ENs/Gel, and ORI/ENs/ Gel groups. The inhibition of the proliferation of both bacteria in all groups had a time effect; prolonging the incubation time enhanced the inhibition effect. ...
Background
Oral mucositis (OM) is a common acute side effect among patients undergoing chemotherapy and/or radiotherapy, with complex pathogenesis and limited current treatment efficacy. Rabdosia rubescens, a traditional Chinese herb, contains oridonin (ORI) with antibacterial and anti - inflammatory properties. However, ORI’s poor solubility and low bioavailability hamper its clinical use. Medicinal plant - derived exosome - like nanovesicles (ENs) are emerging as a promising drug delivery system for wound repair. This study aimed to develop a novel therapeutic approach.
Methods
We fabricated internally-externally homologous drug-loaded exosome-like nanovesicles (ORI/ENs) derived from Rabdosia rubescens and encapsulated them in a semi-interpenetrating network hydrogel system (ORI/ENs/Gel) to repair chemoradiotherapy-induced OM. The morphology, biocompatibility, and antibacterial properties were evaluated. Moreover, the proliferative and migratory capacity were measured using L929 cells. In addition, the pro-healing effects and the underlying molecular mechanisms of ORI/ENs/Gel were assessed in vivo.
Results
ENs were extracted and purified from Rabdosia rubescens by sequential ultra-centrifugations. The encapsulation efficiency (EE) and loading capacity (LC) of ORI in ORI/ENs were 76.4 ± 3.2% and 9.21 ± 0.45%, respectively, suggesting that ENs had a high loading efficiency for homologous drug ORI. The evaluation of toxicity and antibacterial effects has been proven that ORI/ENs has biocompatibility and antibacterial properties. In vivo, ORI/ENs/Gel promoted collagen deposition, targeted NLRP3 to reduce inflammation, and accelerated OM wound healing.
Conclusion
The hydrogel composite incorporating internally-externally homologous drug-loaded ENs offers the potential to provide targeted therapy, improve bioavailability, and promote efficient healing of the OM.
... Among the keystone drivers in CTOM development and severity are direct epithelial cytotoxicity, leading to apoptosis and atrophy, followed by dysfunction of the epithelial barrier with endotoxin and bacterial translocation through tight mucosal junctions, subsequent innate immune activation and up-regulation of the inflammatory reaction 6 . The host-microbe interactions and dynamic changes in resident microbial composition (bacteria and fungi) during development of oral CTOM has also been recognized [8][9][10][11][12][13][14][15] . The development of appropriate anti-microbial therapy is difficult 16 , hence the need to better understand the role of the oral microbiota in the development of CTOM. ...
Cancer therapy-induced oral mucositis is a frequent major oncological problem, secondary to cytotoxicity of chemo-radiation treatment. Oral mucositis commonly occurs 7–10 days after initiation of therapy; it is a dose-limiting side effect causing significant pain, eating difficulty, need for parenteral nutrition and a rise of infections. The pathobiology derives from complex interactions between the epithelial component, inflammation, and the oral microbiome. Our longitudinal study analysed the dynamics of the oral microbiome (bacteria and fungi) in nineteen patients undergoing chemo-radiation therapy for oral and oropharyngeal squamous cell carcinoma as compared to healthy volunteers. The microbiome was characterized in multiple oral sample types using rRNA and ITS sequence amplicons and followed the treatment regimens. Microbial taxonomic diversity and relative abundance may be correlated with disease state, type of treatment and responses. Identification of microbial-host interactions could lead to further therapeutic interventions of mucositis to re-establish normal flora and promote patients’ health. Data presented here could enhance, complement and diversify other studies that link microbiomes to oral disease, prophylactics, treatments, and outcome.
... 2 It is noteworthy that in India, there is a likelihood of one in nine individuals developing cancer during their lifetime. 2 Chemotherapy is one of the most widely used treatments for cancer patients 3,4 and is usually prescribed for patients with non-localized cancer cells; it also has the potential to metastasize or spread to various parts of the body. 5,6 Mucositis is a common complication of cancer treatment that typically manifests four-five days following the initiation of chemotherapeutic drugs and is characterized by the identification of erythematic regions inside the oral cavity. ...
Background The most prevalent, widely recognized, and challenging side effect experienced by cancer patients undergoing chemotherapy is mucositis, which results in considerable morbidity and has the potential to impede the treatment regimen and augment therapeutic costs. Therefore, a comparison between the two experimental interventions in the present study was performed to represent the effectiveness of different treatments or preventative measures. Aim To evaluate the efficacy of oral cryotherapy compared to normal saline mouthwash in reducing alkylating drug-induced mucositis among cancer patients. Methods A Randomized controlled clinical trial-parallel group design was conducted in a tertiary care hospital in the oncology ward of Bhubaneswar, with a total number of 74 participants (of which 37 were administered cryotherapy and 37 were administered normal saline mouthwash) using the WHO mucositis assessment scale. Results Association of mucositis assessment grading with groups was performed on day 1st, 7 th day, 14 th day and 21 st day followed by intervention. The review on 21 st day revealed that 70.3% of the cryotherapy group had grade 0 mucositis, which is a big jump from 48.6% on day 14. In contrast, in the normal saline group, the corresponding increase was only 18.9% to 27.0% only. Conclusion There is clear evidence that on day 21, the improvement in mucositis grade was much higher in the cryotherapy group than in the normal saline group, as there was a significant association between mucositis grade and group (p<0.001) on day 21. CTRI Trial Registration No CTRI/2023/04/051450 Date of CTRI Trial Registration No.: 10/04/2023
... Exposure to cytotoxic cancer treatments induces direct injury to oral mucosal tissue, triggering subsequent innate immune inflammatory responses. Potential factors contributing to oral microbiota dysbiosis encompass the direct antimicrobial effects of cancer therapies or pathological alterations within the oral cavity, such as mucosal barrier disruption and immune activation [65]. Changes in microbiota composition transform microbial communities into entities that expedite disease progression, potentially fostering aberrant innate immune signals within the oral mucosa during the development of RIOM/ CIOM [15]. ...
Radiotherapy- or chemotherapy-induced oral mucositis (RIOM/CIOM) presents significant challenges in cancer treatment, severely impacting patients’ quality of life (QoL) and therapeutic outcomes. Despite advancements, existing prevention and treatment measures have notable limitations. RIOM/CIOM involves a multifaceted interplay of inflammatory cascades orchestrated by the innate immune response. Furthermore, dysbiosis of oral and intestinal microbiota, triggered by anticancer therapy, exacerbates mucosal damage through intricate interactions with the innate immune system. This review provides an update on pivotal signaling pathways governing the initiation and progression of RIOM/CIOM. It also elucidates the intricate relationship between microbiota dysbiosis and dysregulation of oral mucosal immune homeostasis. Moreover, potential interventions targeting these pathogenic mechanisms are summarized, offering valuable insights for further exploration of RIOM/CIOM’s complex pathophysiology and the development of more effective interventions.
... Antibiotics and cancer-related immunosuppression upset the delicate balance between commensal bacteria and the host in individuals with malignant tumors, leading to dysbiosis and worsening chemotherapy-induced oral mucositis (Dasari and Tchounwou, 2014;Wilson et al., 2014). Research has shown that chemotherapy patients have a significantly lower α-diversity of salivary microbiota, which is characterized by an enrichment of inflammation-associated Gram-negative taxa (like Fusobacterium and Prevotella) and a depletion of commensal taxa (like Streptococcus and Actinomyces) that are strongly correlated with the severity of mucositis (Ye et al., 2013;Hong et al., 2019). ...
... Additionally, high doses of 5-fluorouracil and docetaxel have been shown to exacerbate dysbiosis in a dose-dependent manner (Hong et al., 2019). Modulating the microbiota, through approaches such as probiotics and microbiota-regulating agents, is considered an effective strategy for alleviating chemotherapy-associated mucositis, highlighting its potential in clinical diagnostics and therapeutics. ...
The advancement of high-throughput sequencing technology in recent decades has led to a greater understanding of the components of the oral microbiota, providing a solid foundation for extensive research in this field. The oral microbiota plays an important role in an individual’s overall health. It has been shown to be significantly correlated with chronic human diseases, including diabetes, rheumatoid arthritis, cardiovascular disease, periodontal disease, and Alzheimer’s disease. Furthermore, tumor occurrence and development are closely related to the oral microbiome. Specific bacteria, such as Fusobacterium nucleatum (F. nucleatum), Porphyromonas gingivalis (P. gingivalis), Streptococcus, Streptomyces, Prevotella, and Fibrophagy gingivalis, play critical roles in cancer development. The oral microbiota has various oncogenic mechanisms, including bacterial inflammation, immunological suppression, tumor growth mediated by bacterial toxins, antiapoptotic activity, and carcinogenic effects. This paper reviews the role of the oral microbiota in the occurrence and progression of cancer and systematically elucidates the molecular mechanisms by which dysbiosis influences tumorigenesis and tumor progression. This information can provide a theoretical basis for exploring cancer treatment strategies and offer new insights for cancer prevention.
... Thus, the development of effective treatments requires additional research to identify the origin of FCGS but will also likely necessitate an approach that considers individual variations that affect response to treatment. In individualized treatment approaches, which integrates personalized treatment plans, understanding the microbiomes associated with disease state and treatment response will be imperative as the importance of the oral microbiome in regulating host health is becoming increasingly apparent [2,8,[13][14][15][16][17]. Disruptions to this delicate equilibrium, whether due to dietary changes, stress, antibiotics, or other factors, can lead to a dysbiotic community [18,19]. This microbial imbalance can trigger an inflammatory response characterized by increased levels of proinflammatory cytokines and infiltration of immune cells [20,21]. ...
The cat oral microbiome plays an important role in maintaining host health, yet little is known about how to apply microbial data in a clinical setting. One such use of microbiome signatures is in cases of feline chronic gingivostomatitis (FCGS), a severe debilitating complex disease of the oral cavity. FCGS-afflicted cats have limited treatment options, and individual patient responses to treatment are needed. In this work, we used deep sequencing of total RNA of the oral microbiome to chronicle microbial changes that accompanied an FCGS-afflicted cat’s change from treatment-non-responsive to treatment-responsive within a 17-month span. The oral microbiome composition of the two treatment-non-responsive time points differed from that of the treatment-responsive point, with notable shifts in the abundance of Myscoplasmopsis, Aspergillus, and Capnocytophaga species. Intriguingly, the presence of the fungal groups Aspergillus and Candida primarily differentiated the two non-responsive microbiomes. Associated with responder status were multiple Capnocytophaga species, including Capnocytophaga sp. H2931, Capnocytophaga gingivalis, and Capnocytophaga canimorsus. The observation that the oral microbiome shifts in tandem by response to treatment in FCGS suggests a potential use for microbiome evaluations in a clinical setting. This work contributes to developing improved molecular diagnostics for enhanced efficacy of individualized treatment plans to improve oral disease.
... Essa bactéria foi a segunda mais prevalente em ambiente hospitalar [16]. A literatura destaca que P. aeruginosa e S. aureus estavam presentes em lesões de orofaringe e língua, respectivamente [9,19,21,[28][29][30]. ...
O paciente oncológico pode apresentar comprometimento da imunidade em virtude da doença e/ou dos efeitos colaterais do tratamento, sendo a cavidade bucal uma potencial porta de entrada de microrganismos, os quais poderiam estar alojados nas escovas dentais. Objetivo: Realizar um estudo microbiológico das escovas de dente de crianças internadas para tratamento oncológico e comparar duas formas de descontaminação. Material e métodos: Foram avaliadas 20 escovas após dez dias de uso. Realizou-se a incubação da escova dental em caldo brain heart infusion (BHI), em estufa a 37ºC durante 24 horas, e depois a inoculação em placas de ágar sangue, MacConkey e Sabouraud. Após identificação da microbiota utilizaram-se gluconato de clorexidina 0,12% e hipoclorito de sódio 2,5% para descontaminação. Resultados: No momento da coleta 95% das escovas estavam úmidas, 55% apresentavam restos de dentifrício e 45% com restos de alimentos. Houve crescimento bacteriano acima de 300 unidades formadoras de colônia (UFC). Em três escovas foram encontradas bactérias hospitalares: P. aeruginosa e S. aureus. A maior parte das escovas foi descontaminada com hipoclorito de sódio 2,5% e clorexidina 0,12%, entretanto a escova que apresentou crescimento concomitante de P. aeruginosa e S. aureus não foi descontaminada pelas substâncias químicas usadas. Conclusão: Houve contaminação por S. aureus e P. aeruginosa, e somente P. aeruginosa foi eliminada com os dois agentes testados. Sugerem-se mais estudos sobre a microbiologia e descontaminação das escovas dentais utilizadas em ambiente hospitalar.
... In this single-center study of 115 adult alloHCT recipients, pre-conditioning antibiotic exposure was associated with a statistically non-significant increased risk for moderate-to-severe OM 5 , suggesting a role for the baseline oral microbiota in OM pathogenesis. This finding was consistent with contemporaneous observations in patients with head and neck cancer receiving radiotherapy [20][21][22] and those with solid tumors receiving 5-fluorouracil or doxorubicin-based chemotherapy 23 . Only a few studies to date have evaluated the relationship between the oral microbiota and OM after alloHCT [13][14][15][16] . ...
... Once the association between O. asaccharolyticum and OM has been confirmed in an independent cohort, mechanistic studies in animal models and/or proteomic/ metabolomic analysis of saliva may reveal the pathogenetic pathways involved. The strongest mechanistic evidence for a role played by the oral microbiota in mediating OM severity in the setting of cytotoxic damage comes from a study of patients receiving 5-fluorouracil or doxorubicinbased chemotherapy for solid tumors 23 . OM-associated microbiota shifts were independent of antibiotic exposure (consistent with the resilience of the oral microbiota to systemic antibiotics 38 ) and antimicrobial activity of specific antineoplastic drugs. ...
The success of allogeneic hematopoietic cell transplantation (alloHCT) in curing hematologic disorders is limited by its short- and long-term toxicities. One such toxicity is oral mucositis (OM), causing pain, speech/swallowing difficulty, and prolonged hospitalization. Although conditioning chemoradiotherapy is the direct cause of OM, potential host-intrinsic mediators of mucosal injury remain elusive. We hypothesized that the oral microbiota may influence OM severity. We used a validated comprehensive scoring system based on specialized Oral Medicine examinations to longitudinally quantify OM severity in alloHCT recipients. High-throughput multi-site profiling of the oral microbiota was performed in parallel. We identify a sex-dependent commensal bacterium, Oribacterium asaccharolyticum, whose presence in saliva before transplantation is associated with more severe OM 14 days after transplantation. The sex predilection of this species correlated with higher uric acid levels in men. Our findings represent the first sex-dependent microbiota-mediated pathway in OM pathogenesis and introduce novel targets for preventative interventions.
