Burning Mouth Syndrome and the Oral Microbiome: Unveiling Potential Links

Background: Depression is a mental disorder characterized by a combination of somatic and cognitive disturbances, in which a predominantly sad or irritable mood significantly interferes with the patient's functioning. This condition can affect individuals of all ages and socioeconomic backgrounds. Currently, various studies are exploring a possible association between oral dysbiosis and depression-an increasingly relevant topic, as confirmation of such a relationship could position the oral microbiota as a potential etiological or diagnostic factor for depression, given its accessibility and ease of analysis. Aim: To present a qualitative synthesis of studies addressing how oral dysbiosis influences the onset of depression, as well as the importance of controlling this alteration of the oral microbiota to aid in the prevention of the disease. Materials and Methods: The PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) outline the procedures to be followed for conducting this systematic review. The article search was carried out on 22 May 2025, across the PubMed, Scopus, Scielo, and The Cochrane Library databases, using terms related to "depression" and "oral dysbiosis". Studies published within the last 10 years that addressed the potential association between oral dysbiosis, and depression were included. Furthermore, the quality of the studies was assessed using various tools depending on their design: the Newcastle-Ottawa Scale (NOS) was applied to case-control and cohort studies; the Joanna Briggs Institute (JBI) critical appraisal checklist was used for cross-sectional studies; and experimental studies were evaluated using SYRCLE's Risk of Bias Tool. Results: A total of eleven studies were included in this systematic review. The findings suggest the presence of alterations in the oral microbiota of patients with depression, particularly in terms of composition, structure, and diversity. A reduction in alpha diversity-an indicator of local microbial balance-was observed, along with an increase in beta diversity, indicating greater inter-individual variability, which may be associated with inflammatory processes or immunological dysfunctions. Some studies reported differing results, which may be attributable to methodological variability regarding study design, or the populations sampled. Conclusions: This systematic review suggests that the oral microbiome could be considered a diagnostic biomarker and therapeutic target for depression, as the analyzed studies demonstrate a significant association between oral microbiome dysbiosis and this mental disorder. However, the methodological heterogeneity among the studies highlights the need for further research to confirm this potential relationship.

Dry mouth symptoms in patients with primary Sjögren's syndrome (pSS) may be associated with oral microbiome dysbiosis, which plays a critical role in the pathogenesis of pSS and potentially contributes to disease progression. This study systematically reviews and meta-analyzes the latest research on the relationship between the oral microbiome and pSS to identify potential diagnostic biomarkers. A systematic search was conducted across nine international databases (PubMed, Cochrane Library, Embase, Web of Science, Scopus, VIP, CNKI, Wanfang, and SinoMed) up to October 1, 2024, using a combination of Medical Subject Headings (MeSH) and free-text terms: "oral microbiome" OR "oral flora" AND "Sjögren's Syndrome" OR "pSS." Only studies analyzing the oral microbiota of pSS patients were included. A random-effects meta-analysis was performed for quantitative synthesis. And use a funnel chart to assess the publication bias of the included articles. The conclusions are tempered by the moderate risk of bias in some included studies, substantial heterogeneity (partly attributed to methodological), and the limited number of studies for certain subgroup analyses, which may affect the precision of the pooled estimates. A total of 833 studies were identified, 21 of which were included, with 16S rRNA sequencing being the most commonly used technique. QIIME (Quantitative Insights Into Microbial Ecology) is a mainstream bioinformatics analysis tool. Of the 21 studies (1094 participants) included, 19 provided data on α diversity. Overall, declines in the α diversity index were common in pSS (Chao1: SMD = -0.79, [95% CI = -1.381, -0.21], p＜0.001; Shannon index: SMD = -0.16, [95%CI = -0.53, -0.21], p=0.400; Simpson index: SMD = -0.14, [95% CI = -0.79, -1.06]), p=0.770. Ten of these studies provided data on β diversity, suggesting a clear difference between the pSS group and the healthy control group. Firmicutes (mainly including Streptococcus spp., Velon spp., etc.) showed a significant enrichment trend in pSS patients, and the relative relative abundance of Proteobacteria (Haemophilus), Actinomycetes and Spiromycetes decreased in pSS patients. pSS patients demonstrate reduced oral microbiome diversity compared to HCs（Healthy controls）. Enrichment of Veillonella, Streptococcus, and Prevotella may correlate with pSS pathogenesis, whereas Haemophilus parainfluenzae might serve as a protective taxon. Oral dysbiosis appears to be a distinctive feature of pSS compared to systemic lupus erythematosus (SLE). Further mechanistic studies are needed to explore causal relationships and therapeutic targets.

The most common diseases in humans are oral infections. Although modern research is mainly concerned with the role of the gut microbiota in systemic diseases, there are also reports indicating that oral infections, and especially periodontal infection, are one of the risk factors for atherosclerotic cardiovascular disease (CVD).The composition of the oral biofilm is a community of several hundred species of bacteria, fungi, spirochetes, viruses and protozoa. It varies depending on the state of health and disease. Pathogenic bacteria in the oral cavity can cause systemic disease by entering the bloodstream or by triggering immune responses at the cellular level. The discovery of the role of the oral microbiome in CVD is leading to new methods of prevention and their treatment. In this review, we discuss the various mechanisms by which oral dysbiosis may contribute to the pathogenesis of CVD as well as available options for their prevention and treatment. Oral dysbiosis, or the imbalance of bacteria in the oral cavity, has been linked to an increased risk of CVD. Several mechanisms have been proposed to explain how oral dysbiosis may contribute to CVD, including: The production of inflammatory molecules by oral bacteria. The activation of the immune system, which can lead to inflammation throughout the body. The entry of oral bacteria into the bloodstream, where they can travel to other organs and tissues. There are a number of things that can be done to prevent oral dysbiosis and reduce the risk of CVD, including: Good oral hygiene, such as brushing and flossing twice a day. Regular dental checkups and cleanings. Avoiding tobacco use. Eating a healthy diet. Conclusions. The evidence is growing that oral dysbiosis is a risk factor for CVD. Further research is needed to better understand the mechanisms involved and to develop effective interventions for prevention and treatment. The following are some other important points: The role of oral dysbiosis in CVD is likely to be complex and involve multiple factors. The effects of oral dysbiosis on CVD may vary depending on the individual's overall health status and other risk factors. More research is needed to determine the optimal methods for preventing and treating oral dysbiosis in order to reduce the risk of CVD.

Oral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host disease.

It is well known that pregnancy is under the constant influence of hormonal, metabolic and immunological factors and this may impact the oral microbiota toward pregnancy gingivitis. However, it is still not clear how the oral microbial dysbiosis can modulate oral diseases as oral microbiome during pregnancy is very poorly characterized. In addition, the recent revelation that placental microbiome is akin to oral microbiome further potentiates the importance of oral dysbiosis in adverse pregnancy outcomes. Hence, leveraging on the 16S rRNA gene sequencing technology, we present a snapshot of the variations in the oral microbial composition with the progression of pregnancy and in the postpartum period and its association with pregnancy gingivitis. Despite the stability of oral microbial diversity during pregnancy and postpartum period, we observed that the microbiome makes a pathogenic shift during pregnancy and reverts back to a healthy microbiome during the postpartum period. Co-occurrence network analysis provided a mechanistic explanation of the pathogenicity of the microbiome during pregnancy and predicted taxa at hubs of interaction. Targeting the taxa which form the ecological guilds in the underlying microbiome would help to modulate the microbial pathogenicity during pregnancy, thereby alleviating risk for oral diseases and adverse pregnancy outcomes. Our study has also uncovered the possibility of novel species in subgingival plaque and saliva as the key players in the causation of pregnancy gingivitis. The keystone species hold the potential to open up avenues for designing microbiome modulation strategies to improve host health during pregnancy.

Microbial signatures of areca nut chewing: Bridging the gap between oral dysbiosis and submucous fibrosis.

Background: The oral microbiome may play an important role in colorectal carcinogenesis. However, few studies have investigated the association between oral microbiome and the development of colorectal cancer (CRC). We aimed to investigate whether oral health-colorectal tumor association has an underlying microbial basis, in the quest for novel non-invasive biomarkers for CRC.Methods: We collected oral swab samples from 161 patients with CRC, 34 patients with colorectal adenoma (CRA), and 58 healthy volunteers. The oral microbiota was assessed using 16S rRNA sequencing. We characterized oral microbiome, identified microbial markers, constructed and validated colorectal tumor (CRA and CRC) classifier.Results: Oral microbial composition and diversity were significantly different among the three groups, and the CRA group had the highest diversity. Analysis of the functional potential of oral microbiota demonstrated that the pathway involving cell motility was overrepresented in the CRA and CRC groups relative to that in the healthy controls. Moreover, a random forest model was constructed based on oral microbial markers, which could distinguish the colorectal tumor groups from the healthy controls and achieve a powerful classification potential in the discovery and validation cohorts.Conclusion: This study suggests a potential association between oral microbiome dysbiosis and colorectal cancer. Oral microbiota-based biomarkers may be helpful in predicting the risks for the development of CRA and CRC.

23 Background: The oral microbiome may play an important role in colorectal carcinogenesis. However, few studies have investigated the association between oral microbiome and the development of colorectal cancer (CRC). We aimed to investigate whether oral health–colorectal tumor association has an underlying microbial basis, in the quest for novel non-invasive biomarkers for CRC. Methods: We collected oral swab samples from 161 patients with CRC, 34 patients with colorectal adenoma (CRA), and 58 healthy volunteers. The oral microbiota was assessed using 16S rRNA sequencing. The oral microbiome was characterized, microbial markers were identified, and colorectal tumor (CRA and CRC) classifiers were constructed and validated. Results: Oral microbial composition and diversity were significantly different among the three groups; the CRA group had the highest diversity. Analysis of the functional potential of oral microbiota demonstrated that the pathway involving cell motility was overrepresented in the CRA and CRC groups relative to that in the healthy controls. Moreover, a random forest model was constructed based on oral microbial markers, which could distinguish the colorectal tumor groups from the healthy controls and achieve a powerful classification potential in the discovery and validation cohorts. Conclusions: This study suggests a potential association between oral microbiome dysbiosis and colorectal cancer. Oral microbiota-based biomarkers may be helpful in predicting the risk of developing CRA and CRC.

Oral microbiota dysbiosis alters chronic restraint stress-induced depression-like behaviors by modulating host metabolism

Human oral cavity harbors a complex ecosystem of numerous microorganisms, including bacteria, fungi, viruses, and bacteriophages, referred to as the oral microbiota (Peng et al., 2022) . In a healthy state, the oral microbiota is composed of commensals. The mutual commensal oral microbiota plays a crucial role in promoting not only oral, but also systemic health (Han et al., 2022) . However, in a diseased state, host-microbial networks lead to dysbiosis. The influence of oral microbiota dysbiosis can extend beyond the oral cavity, and some systemic conditions are also associated with the oral microbiota (Peng et al., 2022) . A mechanistic understanding for such associations may arise from the ability of many oral microorganisms to alter the inflammatory microenvironment and to interfere with host signaling pathways that control cell viability, proliferation and differentiation. Furthermore, there is likely to be an alteration in oral microbial composition or bacterial pathogenicity in systemic pathologic conditions (Graves et al., 2019) . Therefore, there may be a bidirectional relationship between the oral microbiota and systemic diseases. The abundance of oral microbiota specifically associated with systemic diseases appears to be a clinical biomarker to some extent, although further exploration is still necessary. If this clinical phenomenon is confirmed, early prediction of systemic diseases using microbial detection might be a crucial breakthrough. In the present research topic, we aim to assemble original research articles and reviews discussing recent advancements in understanding the association between oral microbiota dysbiosis and the development of systemic conditions.

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in burning mouth syndrome patients with normocytosis

Human microbiomes are microbial populations that form a symbiotic relationship with humans. There are up to 1000 species on the surface of human skin and mucosal system, among which gut microbiota attracts the most interest. As the beginning of the digestive tract, oral cavity is also an important microbial habitat in the human body which is the first line of defense against pathogens entering the body. Many studies have revealed that oral microbial dysbiosis could not only contribute to oral diseases but also whole-body systemic diseases and health status. Oral microorganisms can enter the gastrointestinal tract with saliva and food, or enter the blood circulation through mouth breakage, thus causing systemic inflammation and aging-related diseases including some causal links to Alzheimer’s disease. A series of changes take place in oral microbial composition during development, with different age stages marked by different dominant microbial species. Despite a lack of comprehensive studies on aging oral microbiota, through systemic inflammation, oral pathogenic microbes are likely to contribute inflammatory aging. As inflammaging is a key signature and one of the causes for accelerated aging, improving the structure of oral microbiome may be not only a new strategy for disease prevention and treatment, but also for aging intervention.

Burning mouth syndrome (BMS) is a chronic nociplastic pain condition of unknown etiology, predominantly affecting women and highly comorbid with depression and anxiety. This narrative review proposes a comprehensive model integrating the significant role of the oral and intestinal microbiomes in BMS pathology. We explore how microbial dysbiosis compromises barrier functions, leading to systemic and neuroinflammation, and subsequently modulates key brain networks involved in pain processing and emotional regulation. Evidence suggests that dysbiosis within the oral microbiome (e.g., increased Streptococcus, Rothia, Bergeyella, Granulicatella, Neisseria) and/or the intestinal microbiome contributes to BMS pathology. This dysbiosis can compromise oral and intestinal barrier functions, leading to the systemic dissemination of bacterial components and inflammatory mediators. These factors induce neuroinflammation, which directly influences and dysregulates key brain networks such as the default mode network and salience network, crucial for pain processing and emotional regulation. The vagus nerve serves as a critical bidirectional communication pathway within this axis. Preliminary studies indicate potential therapeutic benefits of probiotics (e.g., Lactobacillus reuteri in BMS), but large-scale evidence is still emerging. The pathology of BMS, intertwined with depression and anxiety, can be significantly influenced by the oral and intestinal microbiomes. Dysbiosis contributes to chronic systemic and neuroinflammation, driving maladaptive changes in brain networks and neurotransmitter systems. While promising, the field is nascent, requiring further causal studies, detailed mechanistic insights, and robust clinical trials to establish the full therapeutic potential of microbiome-targeted interventions.

This systematic review explores the relationship between the oral microbiome in edentulous patients and cardiovascular diseases (CVD). A search was conducted across databases PubMed, Scopus, Web of Science, Embase, and gray literature sources. The review followed PRISMA and AMSTAR guidelines. After removing duplicates, the articles were evaluated by titles and abstracts, and 21 were selected for full-text review, with 9 ultimately included in the final analysis. Oral dysbiosis, linked to systemic conditions like obesity, diabetes, and CVD, is common in inflammatory oral diseases such as periodontitis and denture stomatitis, disrupting original oral microbiota. This imbalance may lead to transient bacteremia and systemic inflammation, contributing to CVD development. Tooth loss reduces salivary microbiome diversity, and denture use in CVD patients is linked to decreased life expectancy compared to dentate individuals. The findings suggest tooth loss, denture use, and oral microbiota dysbiosis are unconventional risk factors for CVD progression.

BackgroundDespite advances in our understanding of the critical role of the microbiota in stroke patients, the oral microbiome has rarely been reported to be associated with stroke-associated pneumonia (SAP). We sought to profile the oral microbial composition of SAP patients and to determine whether microbiome temporal instability and special taxa are associated with pneumonia progression and functional outcomes.MethodsThis is a prospective, observational, single-center cohort study that examined patients with acute ischemic stroke (AIS) who were admitted within 24 h of experiencing a stroke event. The patients were divided into three groups based on the occurrence of pneumonia and the use of mechanical ventilation: nonpneumonia group, SAP group, and ventilator-associated pneumonia (VAP) group. We collected oral swabs at different time points post-admission and analyzed the microbiota using 16 S rRNA high-throughput sequencing. The microbiota was then compared among the three groups.ResultsIn total, 104 nonpneumonia, 50 SAP and 10 VAP patients were included in the analysis. We found that SAP and VAP patients exhibited significant dynamic differences in the diversity and composition of the oral microbiota and that the magnitude of this dysbiosis and instability increased during hospitalization. Then, by controlling the potential effect of all latent confounding variables, we assessed the changes associated with pneumonia after stroke and explored patients with a lower abundance of Streptococcus were more likely to suffer from SAP. The logistic regression analysis revealed that an increase in specific taxa in the phylum Actinobacteriota was linked to a higher risk of poor outcomes. A model for SAP patients based on oral microbiota could accurately predict 30-day clinical outcomes after stroke onset.ConclusionsWe concluded that specific oral microbiota signatures could be used to predict illness development and clinical outcomes in SAP patients. We proposed the potential of the oral microbiota as a non-invasive diagnostic biomarker in the clinical management of SAP patients.Clinical Trial registrationNCT04688138. Registered 29/12/2020, https://clinicaltrials.gov/ct2/show/NCT04688138.