Historically, broad-spectrum antibiotics have represented a major component of the therapeutic armamentarium used to treat common oral diseases associated with a bacterial etiology. The fact that these diseases are due to the accumulation of multispecies biofilms composed of ever-increasing numbers of resistant organisms has dramatically affected the efficacy of many of these drugs. Furthermore, it is now appreciated that repeated use of broad-spectrum antibiotics also affects the composition of the host commensal microbiota, which can have both local and systemic implications. In recognition of the limitations of classical antibiotics, alternative chemical, physical, and mechanical strategies are either in use or development. These include novel narrow-spectrum antimicrobials such as antitoxins, bacteriophages, and antibody-conjugated drugs that can target specific microbes while minimizing the emergence of resistant organisms and preserving eubiotic microbes. Other approaches, such as new broad-spectrum non-antibiotic strategies and probiotics, are aimed at disrupting or altering the composition of oral biofilms and their extracellular matrices to facilitate the elimination of overt pathogens by the host response and/or adjunctive antimicrobials. This critical review describes the use and limitations of broad- and narrow-spectrum strategies currently being used to treat common bacterially induced oral diseases as well as alternative methods in development.

Tongue diagnosis can assess the physiological functions and pathological conditions of colorectal cancer (CRC).

To investigate the characteristics of tongue images and the bacteria composition of tongue coating in patients with CRC.

A total of 59 CRC patients were enrolled and underwent tongue image analysis using a diagnostic instrument. Third-generation sequencing technique was used to determine tongue coating bacteria. The relationships among tongue images, tongue coating bacteria and clinical information (age, gender, and location) were further analyzed. Statistical analyses were performed to investigate the potential associations between tongue coating microbiota and two key variables (tongue images and age).

CRC patients typically present with four distinct tongue images, including yellow greasy coating, petechiae, white greasy coating, and red tongue with little coating. Notably, the microbiota composition of tongue coatings demonstrates a statistically significant correlation with both tongue diagnostic features and patient age compared to other clinical parameters. Alloprevotella rava may be primary contributors to the formation of yellow greasy coating, while Prevotella intermedia appears to be associated with the development of white greasy coating. Furthermore, Streptococcus parasanguinis might emerged as a potential biomarker for CRC patients under 62 years of age, whereas Prevotella sp. 000163055 appears to be a predominant species in the tongue coating microbiota of CRC patients over 62 years.

Overall, this study emphasizes the variations in the community structure and diversity of tongue coating bacteria in CRC patients through different tongue images. The findings provide novel insights that could enhance the predictive capacity of tongue diagnosis for clinical progression monitoring and contribute to the development of early intervention strategies in CRC management.

To determine bacterial blood translocation signatures and their association with the subgingival microbiota in individuals with and without periodontitis.

Cross-sectional study. DNA was extracted from blood and subgingival samples of individuals with periodontitis (n = 21) and control volunteers (n = 24). Subgingival microbiota was explored by 16 S rRNA gene sequencing. Detection frequency and loads of total bacteria, Porphyromonas gingivalis (Pg), Porphyromonas endodontalis (Pe) and Fusobacterium nucleatum (Fn) were determined in all samples using quantitative polymerase chain reaction (qPCR). The statistical analysis was performed using STATA 16.

Subgingival samples from individuals with periodontitis presented higher relative abundance of Prevotella intermedia, F. nucleatum subsp. vincentii, Treponema sp. HMT 237, Alloprevotella tannerae, Filifactor alocis, Pg, Treponema denticola and Pe, and higher loads of total bacteria, Pg, Pe and Fn, compared to the control group (p < 0.001). While Pg and Fn were not detected in blood, Pe was detected in 95% of individuals with periodontitis and 83% of the control ones (p = 0.205), with higher loads in blood samples from periodontitis (p = 0.034). No significant correlation was found between subgingival bacterial loads and blood loads of Pe in periodontitis and control groups (p > 0.05).

Individuals with periodontitis presented higher relative abundance and loads of periodontal bacteria in subgingival samples and higher Pe loads in blood samples, although further research is needed to understand the correlation between subgingival and blood bacterial loads.

The present study showed higher loads of Pe in the blood of individuals with periodontitis, suggesting potential extraoral dissemination and a linking mechanism with several systemic diseases.

Emerging evidence links oral-derived gut microbes to colorectal cancer (CRC) development, but CRC prognosis-related microbial alterations in oral remain underexplored. In a retrospective study of 312 CRC patients, we examined the oral microbiota using 16S rRNA gene full-length amplicon sequencing to identify prognostic microbial biomarkers for CRC. Neisseria oralis and Campylobacter gracilis increased CRC progression risk (HR = 2.63 with P = 0.007, HR = 2.27 with P = 0.001, respectively), while Treponema medium showed protective effects (HR = 0.41, P = 0.0002). A microbial risk score (MRS) incorporating these species effectively predicted CRC progression risk (C-index = 0.68, 95% CI = 0.61-0.76). When compared to a model constructed solely from clinical factors, including tumor stage, lymphatic metastasis, and perineural invasion, the predictive accuracy significantly improved with the addition of the MRS, resulting in a C-index rising to 0.77 (P = 2.33 × 10-5). Our findings suggest that oral microbiota biomarkers may contribute to personalized CRC monitoring strategies, their implementation in clinical surveillance necessitates confirmatory studies.

Although several studies have identified a distinct gut microbiota in individuals with acute ischemic stroke (AIS), there is a limited amount of research that has simultaneously investigated alterations in the oral and intestinal microbiota in AIS patients and their correlation with clinical prognosis. This was a prospective and observational single-center cohort study in which we included 160 AIS patients who were admitted within 24 h after a stroke event. We collected oral and rectal swab samples for analysis using 16S rRNA high-throughput sequencing. Our study revealed that patients with unfavorable outcomes after AIS showed early disruptions in their oral and intestinal microbiota. Rectal swabs showed increased levels of facultatively anaerobic bacteria in patients with a poor prognosis, while the oral cavity exhibited higher levels of anaerobic and opportunistic pathogenic bacteria. By employing machine learning analysis, we found that the microbiota composition at both rectal and oral sites could predict early and long-term outcomes. Moreover, patients with a poor prognosis displayed increased oral bacterial colonization in the rectal microbiota and altered interactions between the oral and gut microbiota. This study reveals distinct rectal and oral bacteria that could predict unfavorable outcomes for AIS patients. Monitoring the microbiota of various body sites during the early stages after admission may hold prognostic value and inform personalized treatment strategies. The presence of oral bacteria colonizing the intestines during the acute phase of stroke could serve as an early indication of poor outcomes for AIS patients.

Menopause is characterized by the cessation of menstruation and a decline in reproductive function, which is an intrinsic component of the aging process. However, it has been a frequently overlooked field of women's health. The oral and gut microbiota, constituting the largest ecosystem within the human body, are important for maintaining human health and notably contribute to the healthy aging of menopausal women. Therefore, a comprehensive review elucidating the impact of the gut and oral microbiota on menopause for healthy aging is of paramount importance. This paper presents the current understanding of the microbiome during menopause, with a particular focus on alterations in the oral and gut microbiota. Our study elucidates the complex interplay between the microbiome and sex hormone levels, explores microbial crosstalk dynamics, and investigates the associations between the microbiome and diseases linked to menopause. Additionally, this review explores the potential of microbiome-targeting therapies for managing menopause-related diseases. Given that menopause can last for approximately 30 years, gaining insights into how the microbiome and menopause interact could pave the way for innovative interventions, which may result in symptomatic relief from menopause and an increase in quality of life in women.

Individual genes from microbiomes can drive host-level phenotypes. To help identify such candidate genes, several recent tools estimate microbial gene copy numbers directly from metagenomes. These tools rely on alignments to pangenomes, which, in turn, are derived from the set of all individual genomes from one species. While large-scale metagenomic assembly efforts have made pangenome estimates more complete, mixed communities can also introduce contamination into assemblies, and it is unknown how robust pangenome-based metagenomic analyses are to these errors. To gain insight into this problem, we re-analyzed a case-control study of the gut microbiome in cirrhosis, focusing on commensal Clostridia previously implicated in this disease. We tested for differentially prevalent genes in the Lachnospiraceae and then investigated which were likely to be contaminants using sequence similarity searches. Out of 86 differentially prevalent genes, we found that 33 (38%) were probably contaminants originating in taxa such as Veillonella and Haemophilus, unrelated genera that were independently correlated with disease status. Our results demonstrate that even small amounts of contamination in metagenome assemblies, below typical quality thresholds, can threaten to overwhelm gene-level metagenomic analyses. However, we also show that such contaminants can be accurately identified using a method based on gene-to-species correlation. After removing these contaminants, we observe that several flagellar motility gene clusters in the Lachnospira eligens pangenome are associated with cirrhosis status. We have integrated our analyses into an analysis and visualization pipeline, PanSweep, that can automatically identify cases where pangenome contamination may bias the results of gene-resolved analyses.IMPORTANCEMetagenome-assembled genomes, or MAGs, can be constructed without pure cultures of microbes. Large-scale efforts to build MAGs have yielded more complete pangenomes (i.e., sets of all genes found in one species). Pangenomes allow us to measure strain variation in gene content, which can strongly affect phenotype. However, because MAGs come from mixed communities, they can contaminate pangenomes with unrelated DNA; how much this impacts downstream analyses has not been studied. Using a metagenomic study of gut microbes in cirrhosis as our test case, we investigate how contamination affects analyses of microbial gene content. Surprisingly, even small, typical amounts of MAG contamination (<5%) result in disproportionately high levels of false positive associations (38%). Fortunately, we show that most contaminants can be automatically flagged and provide a simple method for doing so. Furthermore, applying this method reveals a new association between cirrhosis and gut microbial motility.

Oral diseases affect approximately 3.5 billion people worldwide, disproportionately burdening populations in developing countries. Chronic diarrhea and constipation, as common intestinal disorders, may interact bidirectionally with oral health, though their population-level associations remain unexamined.

We analyzed data from the National Health and Nutrition Examination Surveys (NHANES) 2005-2008, selecting participants based on inclusion criteria. Chronic diarrhea and constipation were defined based on the bowel health questionnaire. Oral health indicators (teeth condition and oral pain frequency) were derived from the oral health questionnaire. Covariates selected by Lasso regression were analyzed through adjusted logistic regression to examine associations between bowel habits and oral health. Restricted cubic splines (RCS), subgroup stratification, and sensitivity analyses were also used.

A total of 7512 participants aged ≥ 20 with complete information were included. Multivariable logistic regression revealed a significant association between chronic constipation and poor teeth condition (OR:1.45, 95% CI: 1.05-2.01, P = 0.029). A U-shaped dose-response relationship was observed between stool frequency and poor teeth condition (nonlinear P-value = 0.002) using RCS analysis, with both abnormally low and high bowel frequencies correlating with increased oral health risks. No significant association was identified between oral pain frequency and abnormal bowel habits after full covariate adjustment. Stratified analyses indicated that daily dietary fiber intake ≥ 25 g was associated with reduced risks of poor teeth condition (chronic diarrhea OR: 0.40, 95% CI: 0.12-0.98; chronic constipation OR: 0.44, 95% CI: 0.13-1.09), whereas higher income (PIR > 3.5) correlated with elevated risks (chronic diarrhea OR: 2.38, 95% CI: 1.35-3.98; chronic constipation OR: 2.18, 95% CI: 1.22-3.70). Sensitivity analyses supported the stability of associations between abnormal bowel habits and poor teeth condition.

Both chronic constipation and diarrhea were associated with higher risk of poor teeth condition. In the general population and subgroup analyses, individuals with stool frequency around 8-10 times per week demonstrated the lowest risk of poor teeth condition. Stratified analysis indicates that dietary fiber intake and PIR might modify the observed relationship between abnormal bowel habits and teeth condition.

Porphyromonas gingivalis encodes three CRP/FNR superfamily proteins: HcpR, PgRsp, and CrpPg, with CrpPg similar to cAMP-sensing proteins but not classified into known families. This study investigates the role of CrpPg in regulating the expression of factors essential for P. gingivalis virulence in A7436 and ATCC 33277 strains.

The role of CrpPg protein in P. gingivalis was determined using the ΔcrpPg mutant strains to characterize their phenotype and to assess the impact of crpPg inactivation on gene expression using RNA-seq and RT-qPCR. Additionally, the CrpPg protein was purified and characterized.

Key findings in the ΔcrpPg mutant strain include up-regulated mfa1-5 and rgpA genes and down-regulated trxA, soxR, and ustA genes. While crpPg inactivation does not affect growth in liquid culture media, it impairs biofilm formation and enhances adhesion to and invasion of gingival keratinocytes. CrpPg binds directly to its own and mfa promoters without interacting with cyclic nucleotides or di-nucleotides. Its three-dimensional structure, resembling E. coli Crp in complex with cAMP and DNA, suggests that CrpPg functions as a global regulator independently of cAMP binding. The highest crpPg expression in the early exponential growth phase declines as cell density and metabolic conditions change over time, suggesting a regulatory function depending on the CrpPg protein amount.

By controlling the shift from planktonic to biofilm lifestyle, CrpPg may play a role in pathogenicity. Regulating the expression of virulence factors required for host cell invasion and intracellular replication, CrpPg may help P. gingivalis evade immune responses.

Alcohol use is associated with cognitive impairment and dysregulated inflammation. Oral nitrate may benefit cognitive impairment in aging through altering the oral microbiota. Similarly, the beneficial effects of nitrate on alcohol-induced cognitive decline and the roles of the oral microbiota merit investigation. Here we found that nitrate supplementation effectively mitigated cognitive impairment induced by chronic alcohol exposure in mice, reducing both systemic and neuroinflammation. Furthermore, nitrate restored the dysbiosis of the oral microbiota caused by alcohol consumption. Notably, removing the oral microbiota led to a subsequent loss of the beneficial effects of nitrate. Oral microbiota from donor alcohol use disordered humans who had been taking the nitrate intervention were transplanted into germ-free mice which then showed increased cognitive function and reduced neuroinflammation. Finally, we examined 63 alcohol drinkers with varying levels of cognitive impairment and found that lower concentrations of nitrate metabolism-related bacteria were associated with higher cognitive impairment and lower nitrate levels in plasma. These findings highlight the protective role of nitrate against alcohol-induced cognition impairment and neuroinflammation and suggest that the oral microbiota associated with nitrate metabolism and brain function may form part of a "microbiota-mouth-brain axis".

Artemisia annua. L, as a valuable Chinese medicine, has been applied for millennia in China. Its major active ingredient, artemisinin, has demonstrated diverse pharmacological properties, including anti-inflammatory, antioxidant, and anti-diabetic effects. Recent studies suggest that artesunate (ART), an artemisinin derivative, exhibits promising therapeutic effects on diabetic complications. Nevertheless, the role and underlying mechanisms of ART in the treatment of diabetic xerostomia (DX) remain unclear.

This study aimed to elucidate the effects of ART on DX in a type 2 diabetes mellitus (T2DM) rat model, primarily from the perspective of oral microbiota and salivary gland (SG) metabolism, and to further explore potential mechanisms involved.

Various assessments including blood levels, insulin resistance (IR), saliva flow rate, as well as histological analyses through hematoxylin and eosin and Masson staining were performed to verify the reliability of DX model and protective effects of ART on the DX. Untargeted metabolomics and 16S rDNA sequencing were employed to respectively evaluate effects of ART on metabolite changes in SG and oral microbiota in the DX rats. Network pharmacology was employed to predict key pathways and targets with critical roles in ART's therapeutic effect on DX. Additionally, molecular docking and molecular dynamics (MD) simulations were utilized to evaluate interactions between ART and the identified key pathway targets. Surface plasmon resonance (SPR) experiment was performed to verify our computational predictions. Finally, molecular biology experiments were conducted to further validate the identified key pathway targets.

ART treatment ameliorated the hyperglycemia, IR and hyposalivation, and ameliorated pathological changes and oxidative stress of SGs in the DX rats. Besides, 16S rDNA sequencing suggested that ART alleviated the perturbation of oral microbiota (such as Veillonella, Lactobacillus, Clostridium sensu stricto 1, Escherichia-Shigella, and Dubosiella). Untargeted metabolomics revealed that steroid hormone biosynthesis, taurine and hypotaurine metabolism of SGs in the DX rats were partially corrected by ART treatment. Correlation analysis demonstrated an obvious association between the oral microbiota species and SG metabolites. Network pharmacology analysis identified NF-κB pathway as a critical pathway of ART in treating DX. Meanwhile, molecular docking and MD simulation suggested stable binding of ART to NF-κB/NLRP3 pathway targets, particularly NLRP3. Furthermore, SPR confirmed a stable binding of ART to NLRP3, a key target in the NF-κB/NLRP3 pathway. Oxidative stress indicators involved in NF-κB pathway, including MDA and SOD levels, were significantly reduced after ART intervention. Western blotting and qRT-PCR experiments further revealed that ART inhibited increase of NF-κB/NLRP3 pathway related targets expression, including NF-κB, NLRP3, Caspase1, IL-1β, IL-18, TNF-α, and IL-6 in the SGs of DX rats.

ART exerted beneficial therapeutic effects on DX by modulating oral microbiota dysbiosis and restoring SG's metabolic profiles, and inhibiting activation of NF-κB/NLRP3 pathway, suggesting its potential novel application in DX treatment.

Inflammatory bowel disease (IBD) flares can lead to excessive morbidity and mortality. This study aimed to determine whether oral dysbiosis/periodontal disease (PD) is common in IBD and is associated with disease activity in IBD.

This single-center, prospective, cross-sectional, proof-of-concept, and observational study assessed the frequency of periodontal inflammatory disease and interrogated oral and stool microbiota using 16S rRNA gene amplicon sequencing of active-IBD (aIBD), inactive-IBD (iIBD), and healthy controls (HC). Questionnaires assessed diet, alcohol usage, oral hygiene behavior, and disease activity. A subset of participants underwent comprehensive dental examinations to evaluate PD.

Periodontal disease was severer in aIBD subjects than in HC, as aIBD had poorer quality diets (lower Mediterranean diet scores) than iIBD and HC. Significant differences in microbial community structure were observed in unstimulated saliva, stimulated saliva, gingiva, and stool samples, primarily between aIBD and HC. Saliva from aIBD had higher relative abundances of putative oral pathobionts from the genera Streptococcus, Granulicatella, Rothia, and Actinomyces relative to HC, despite similar oral hygiene behaviors between groups.

Our study suggests that patients with aIBD have severer periodontal disorders and higher relative abundances of putative 'pro-inflammatory' microbiota in their oral cavity, despite normal oral hygiene behaviors. Our data are consistent with the potential presence of an oral-gut inflammatory axis that could trigger IBD flare-ups in at-risk patients. Routine dental health assessments in all IBD patients should be encouraged as part of the health maintenance of IBD and as a potential strategy to decrease the risk of IBD flares.

Cirrhosis complications are often triggered by bacterial infections with multidrug-resistant organisms. Alterations in the gut and oral microbiome in decompensated cirrhosis (DC) influence clinical outcomes. We interrogated: (i) gut and oral microbiome community structures, (ii) virulence factors (VFs) and antimicrobial resistance genes (ARGs) and (iii) oral-gut microbial overlap in patients with differing cirrhosis severity.

Fifteen healthy controls (HCs), as well as 26 patients with stable cirrhosis (SC), 46 with DC, 14 with acute-on-chronic liver failure (ACLF) and 14 with severe infection without cirrhosis participated. Metagenomic sequencing was undertaken on paired saliva and faecal samples. 'Salivatypes' and 'enterotypes' based on genera clustering were assessed against cirrhosis severity and clinical parameters. VFs and ARGs were evaluated in oral and gut niches, and distinct resistotypes identified.

Salivatypes and enterotypes revealed a greater proportion of pathobionts with concomitant reduction in autochthonous genera with increasing cirrhosis severity and hyperammonaemia. Increasing overlap between oral and gut microbiome communities was observed in DC and ACLF vs. SC and HCs, independent of antimicrobial, beta-blocker and gastric acid-suppressing therapies. Two distinct gut microbiome clusters harboured genes encoding for the PTS (phosphoenolpyruvate:sugar phosphotransferase system) and other VFs in DC and ACLF. Substantial ARGs (oral: 1,218 and gut: 672) were detected (575 common to both sites). The cirrhosis resistome was distinct, with three oral and four gut resistotypes identified, respectively.

The degree of oral-gut microbial community overlap, frequency of VFs and ARGs all increase significantly with cirrhosis severity, with progressive dominance of pathobionts and loss of commensals. Despite similar antimicrobial exposure, patients with DC and ACLF have reduced microbial richness compared to patients with severe infection without cirrhosis, supporting the additive pathobiological effect of cirrhosis.

This research underscores the crucial role of microbiome alterations in the progression of cirrhosis in an era of escalating multidrug resistant infections, highlighting the association and potential impact of increased oral-gut microbial overlap, virulence factors, and antimicrobial resistance genes on clinical outcomes. These findings are particularly significant for patients with decompensated cirrhosis and acute-on-chronic liver failure, as they reveal the intricate relationship between microbiome alterations and cirrhosis complications. This is relevant in the context of multidrug-resistant organisms and reduced oral-gut microbial diversity that exacerbate cirrhosis severity, drive hepatic decompensation and complicate treatment. For practical applications, these insights could guide the development of targeted microbiome-based therapeutics and personalised antimicrobial regimens for patients with cirrhosis to mitigate infectious complications and improve clinical outcomes.

The oral and gastrointestinal (GI) tract microbiota in humans is susceptible to geographical influences and represents vital factors impacting healthy aging. The northeastern region of China, characterized by distinct dietary and climatic conditions, significantly influences the human microbiome composition. However, the microbial structure of the entire long-lived population in this area has not been evaluated. This study recruited a cohort of 142 individuals aged 55-102 residing in Northeast China, and their oral and gut microbiota were evaluated using full-length 16S rRNA gene amplicon sequencing. The results indicate that the oral and GI tract microbiota of long-lived individuals showed reduced microbial taxonomic richness and evenness compared to sub-longevity individuals. With aging, the core species experience a gradual decline in abundance, while subordinate species show an increase. The long-lived population exhibited a heightened ability to enrich beneficial bacteria including Akkermansia, Alistipes, Parabacteroides, and Eubacterium coprostanoligenes in the GI tract, which are associated with host metabolism and have the potential to act as probiotics, reducing the risks of unhealthy aging in the northeast population. Bifidobacterium sp. and Lactobacillus salivarius have been found to coexist in both the oral cavity and the GI tract of long-lived individuals. We hypothesize that beneficial bacterial taxa from the oral cavity colonize the GI tract more extensively in long-lived individuals compared to those with a shorter lifespan. These findings pave the way for identifying probiotic strains that can promote healthy aging in Northeast China.

As humans, we host personal microbiomes intricately connected to our biology and health. Far from being isolated entities, our microbiomes are dynamically shaped by microbial exchange with the surroundings, in lifelong microbiome acquisition and transmission processes. In this Review, we explore recent studies on how our microbiomes are transmitted, beginning at birth and during interactions with other humans and the environment. We also describe the key methodological aspects of transmission inference, based on the uniqueness of the building blocks of the microbiome - single microbial strains. A better understanding of human microbiome transmission will have implications for studies of microbial host regulation, of microbiome-associated diseases, and for effective microbiome-targeting strategies. Besides exchanging strains with other humans, there is also preliminary evidence we acquire microorganisms from animals and food, and thus a complete understanding of microbiome acquisition and transmission can only be attained by adopting a One Health perspective.

Subacute rumen acidosis (SARA) is a common metabolic disorder in ruminants that disrupts the rumen microbiome and animal health, but diagnosis is challenging due to subtle symptoms and invasive testing requirements. This study explores the potential of the buccal (oral) microbiome as a diagnostic indicator for SARA, hypothesizing an interaction with the rumen microbiome.

The study involved 47 dairy goats, including 11 on a control diet and 36 on high-concentrate diets with increasing rumen-degradable starch. Animals were grouped based on dietary exposure and ruminal pH: Control, Low-RDS Tolerance/SARA (LRDST/LRDSS), and High-RDS Tolerance/SARA (HRDST/HRDSS). Transcriptomics of rumen epithelium showed heightened inflammatory pathway gene expression in SARA-susceptible goats compared to controls and tolerant groups. Alpha diversity of ruminal bacteria showed lower Shannon diversity in HRDSS goats compared to HRDST whereas buccal bacteria displayed significantly lower Chao1 diversity in LRDSS goats compared to HRDST. Beta diversity analyses revealed distinct patterns between SARA-affected goats and healthy controls in both ruminal and buccal microbiomes. Prevotellaceae_UCG-003 emerged as a candidate biomarker, with reduced abundance in SARA-susceptible goats in both rumen and buccal samples. Machine learning classifiers achieved high accuracy in distinguishing SARA-susceptible goats using this genus (rumen AUC = 0.807; buccal AUC = 0.779). Source tracking analysis illustrated diminished cross-population of bacteria from the buccal to rumen (2.86% to 0.25%) and vice versa (8.59% to 1.17%), signifying compromised microbial interchange in SARA-affected goats. A microbiota transplant experiment verified SARA microbiota's ability to induce pH decline, escalate inflammation-related gene expression (MAPK10, IL17B, FOSB, SPP1), disrupt microbial transfer, and reduce Prevotellaceae_UCG-003 in recipients.

Our findings highlight SARA's dual impact on ruminal and buccal microbiota, exacerbating epithelial inflammation gene expression. Shifts in the buccal microbiome, specifically reductions in Prevotellaceae_UCG-003, mirror ruminal changes and can be influenced by inter-compartmental bacterial transmission, thereby offering a non-invasive diagnostic approach for SARA.

The aim of this study was to investigate the effects of diet, oral hygiene, visits to the dentist, and body mass index (BMI) on the risk of dental decay.

240 patients aged 18-50 were included in the study. Participants completed a questionnaire that included demographic information and oral hygiene habits. They were also required to submit dietary analysis forms, which asked about the foods and amounts consumed at breakfast, lunch, dinner, and during two snacks. Intraoral and radiographic examinations of the patients were performed, and the values for DMFT, plaque index, dental calculus index, and oral hygiene index (OHI-S) were recorded. Statistical analysis, including Chi-square tests, independent samples t-tests, and one-way ANOVA, was conducted on the data (p < 0.05).

The oral hygiene index(OHI-S) was determined to be good in 58.3% of the study participants and poor in 10%. No statistical difference was found between BMI and DMFT index (p > 0,005). When the relationship between food consumption frequencies and DMFT was evaluated, it was determined that there was no statistically significant relationship between bread, rice, milk, legumes, and DMFT values (p > 0,005), but there was a statistically significant relationship between fruit, vegetables, yoghurt, cheese, meat/chicken/fish, eggs, honey, sugar, glutens, acidic drinks, tae/coffee consumption and DMFT indices (p < 0,005 ).

The types of food consumed by patients and the frequency of consumption affect the risk of caries.

The association between periodontitis and gastrointestinal tract (GIT) cancer has undergone extensive investigation. However, there is ongoing controversy regarding the impact of periodontitis on the incidence and mortality rates among GIT cancer patients. This study aims to clarify the relationship between periodontitis and the risk as well as mortality rates of GIT cancer.

The data utilized in this study were obtained from the National Health and Nutrition Examination Survey (NHANES) database for the years 2009-2014, which included a total of 10,706 participants from the United States. The incidence and mortality rates of GIT cancer were analyzed in relation to periodontitis. To ensure the reliability of the results, additional adjustments for covariates and stratification analyses were conducted.

In the multivariate logistic regression analysis, various variables such as age, sex, race, BMI, income, education, smoking, alcohol consumption, hypertension, hyperlipidemia, and diabetes mellitus were adjusted for. The analysis revealed no positive association between periodontitis and an increased risk of total cancer or GIT cancer including colorectal cancer. However, periodontitis was found to be significantly associated with higher mortality rates among participants for all-cause (HR: 1.58; 95% CI: 1.26-2.00; P < 0.001), GIT cancer (HR: 1.65; 95% CI: 1.24-2.20; P < 0.001), and colorectal cancer (HR: 1.65; 95% CI: 1.24-2.19; P < 0.001) individually.

The study demonstrates that periodontitis is not associated with an increased risk of incidence for total cancer, or GIT cancer including colorectal cancer. However, it is significantly associated with a higher risk of mortality for all-cause, GIT cancer, and colorectal cancer among participants in the NHANES study.

Schizophrenia (SZ) is a chronic, severe mental disorder that presents significant challenges to diagnosis and effective treatment. Emerging evidence suggests that gut microbiota may play a role in the disease's pathogenesis. However, fewer studies have directly investigated the potential links between oral microbiota and SZ.

This study aimed to explore the relationship between salivary microbiota dysbiosis and SZ, examining microbial and metabolic alterations that may contribute to SZ pathophysiology.

Salivary samples from 30 hospitalized patients diagnosed with SZ and 10 healthy controls were collected. The microbial and metabolic profiles were analyzed using 16S rRNA gene sequencing and metabolomic profiling. Clinical parameters, including oral health status, were also evaluated to minimize variability in sampling.

Patients with SZ exhibited significantly poorer oral health compared to healthy controls, with more missing teeth and worse periodontal status. Microbiota sequencing revealed notable alterations in the overall structure and composition of the salivary microbiome in SZ patients, characterized by increased abundance of specific genera such as Neisseria and Porphyromonas. Metabolomic analysis indicated significant differences between the SZ and control groups, with upregulation of key metabolic pathways, including "β-alanine metabolism" and "vitamin digestion and absorption". Correlations between microbial dysbiosis and elevated levels of certain metabolites, such as L-methionine sulfoxide (L-MetO) and tyramine, were observed, suggesting links to oxidative stress.

The study highlights the presence of significant dysbiosis and metabolic dysfunction in the salivary microbiota of SZ patients, suggesting that alterations in the oral microbiome may contribute to SZ pathogenesis. These results provide new insights into potential diagnostic biomarkers and therapeutic targets for SZ. Further studies with larger sample sizes are required to validate these findings.

The gut microbiota plays a critical role in the occurrence and development of IBS-D, however, IBS-D-associated tongue coating microbiome dysbiosis has not yet been clearly defined. To address this, we analyzed the structure and composition of the tongue coating microbiome in 23 IBS-D patients and 12 healthy controls using 16S rRNA high-throughput sequencing analysis. The 16S rRNA sequencing results revealed that the overall observed OTUs of tongue coating microbiome in IBS-D patients exhibited a significant decrease compared with the healthy controls. Alpha diversity analysis showed that the diversity and community richness were significantly reduced in IBS-D patients, and PCoA revealed a distinct clustering of tongue coating microbiome between the IBS-D patients and healthy controls. Microbial comparisons at the genus level showed that the abundance of Veillonella, Prevotella in IBS-D patients was higher than those in healthy controls, while Streptococcus, Haemophilus, Granulicatella, and Rothia were significantly reduced compared with the healthy volunteers. Functional analysis results showed significant differences in 88 functional metabolic pathways between the IBS-D patients and the healthy controls, including fatty acid biosynthesis. These findings identified the structure, composition, functionality of tongue coating microbiome in IBS-D patients, and hold promise the potential for therapeutic targets during IBS-D management.

Periodontitis is an immuno-inflammatory disease of the soft tissues surrounding the teeth. Periodontitis is linked to many communicable and non-communicable diseases such as diabetes, cardiovascular disease, rheumatoid arthritis, and cancers. The oral-systemic link between periodontal disease and systemic diseases is attributed to the spread of inflammation, microbial products and microbes to distant organ systems. Oral bacteria reach the gut via swallowed saliva, whereby they induce gut dysbiosis and gastrointestinal dysfunctions. Some periodontal pathogens like Porphyromonas. gingivalis, Klebsiella, Helicobacter. Pylori, Streptococcus, Veillonella, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus, Haemophilus, Aggregatibacter actinomycetomcommitans and Streptococcus mutans can withstand the unfavorable acidic, survive in the gut and result in gut dysbiosis. Gut dysbiosis increases gut inflammation, and induce dysplastic changes that lead to gut dysfunction. Various studies have linked oral bacteria, and oral-gut axis to various GIT disorders like inflammatory bowel disease, liver diseases, hepatocellular and pancreatic ductal carcinoma, ulcerative colitis, and Crohn's disease. Although the correlation between periodontitis and GIT disorders is well established, the intricate molecular mechanisms by which oral microflora induce these changes have not been discussed extensively. This review comprehensively discusses the intricate and unique molecular and immunological mechanisms by which periodontal pathogens can induce gut dysbiosis and dysfunction.

In recent years, juicing has often been promoted as a convenient way to increase fruit and vegetable intake, with juice-only diets marketed for digestive cleansing and overall health improvement. However, juicing removes most insoluble fiber, which may diminish the health benefits of whole fruits and vegetables. Lower fiber intake can alter the microbiota, affecting metabolism, immunity, and mental health, though little is known about juicing's specific effects on the microbiota. This study addresses this gap by exploring how juicing impacts gut and oral microbiome composition in an intervention study.

Fourteen participants followed one of three diets-exclusive juice, juice plus food, or plant-based food-for three days. Microbiota samples (stool, saliva, and inner cheek swabs) were collected at baseline, after a pre-intervention elimination diet, immediately after juice intervention, and 14 days after intervention. Moreover, 16S rRNA gene amplicon sequencing was used to analyze microbiota taxonomic composition.

The saliva microbiome differed significantly in response to the elimination diet (unweighted UniFrac: F = 1.72, R = 0.06, p < 0.005; weighted UniFrac: F = 7.62, R = 0.23, p-value = 0.0025) with a significant reduction in Firmicutes (p = 0.004) and a significant increase in Proteobacteria (p = 0.005). The juice intervention diets were also associated with changes in the saliva and cheek microbiota, particularly in the relative abundances of pro-inflammatory bacterial families, potentially due to the high sugar and low fiber intake of the juice-related products. Although no significant shifts in overall gut microbiota composition were observed, with either the elimination diet or the juice intervention diets, bacterial taxa associated with gut permeability, inflammation, and cognitive decline increased in relative abundance.

These findings suggest that short-term juice consumption may negatively affect the microbiota.

More and more evidences show that the imbalance of intestinal flora homeostasis can contribute to the progression of colorectal cancer (CRC). Solobacterium moorei (S. moorei), an anaerobic Gram-positive bacillus, was found to be enriched in fecal samples from CRC patients. However, the signaling regulatory mechanism of S. moorei promoting CRC progression remain unknown. Three CRC mouse models (ApcMin/+ mice, AOM/DSS-treated mice and subcutaneous colorectal xenograft mice) and two cell lines (DLD-1 and HT-29) were used to investigate the biological functions and molecular mechanisms of S. moorei on tumor progression of CRC in vivo and in vitro. S. moorei abundance increased in fecal samples and tumor tissues, and was significantly positively correlated with tumor staging of CRC. S. moorei promoted tumor progression in various CRC mouse models and it selectively adhered to cancer cells in comparison to colonic mucosal epithelial cells, enhancing CRC cell proliferation and inhibiting cell apoptosis. Mechanistically, S. moorei cellwall protein Cna B-type domain-containing protein binds to integrin α2/β1 on CRC cells, leading to the activation of PI3K-AKT-mTOR-C-myc pathway via phospho-FAK, thereby promoted tumor cell growth and progression. Blockade of integrin α2/β1 abolished S. moorei-mediated oncogenic response in vitro and in vivo. In summary, this study demonstrated that S. moorei promoted tumor progression via the integrin α2/β1-PI3K-AKT-mTOR-C-myc signaling pathway, which is a novel specific pathogen-mediated mechanism that might be a new potential target for CRC prevention, diagnosis, and treatment.

Recent research provides new insights into the early establishment of the infant gut microbiome, emphasizing the influence of breastfeeding on the development of gastrointestinal microbiomes. In our study, we longitudinally examined the taxonomic and functional dynamics of the oral and gastrointestinal tract (GIT) microbiomes of healthy infants (n = 30) in their first year, focusing on the often-over-looked aspects, the development of archaeal and anaerobic microbiomes. Breastfed (BF) infants exhibit a more defined transitional phase in their oral microbiome compared to non-breastfed (NBF) infants, marked by a decrease in Streptococcus and the emergence of anaerobic genera such as Granulicatella. This phase, characterized by increased alpha-diversity and significant changes in beta-diversity, occurs earlier in NBF infants (months 1-3) than in BF infants (months 4-6), suggesting that breastfeeding supports later, more defined microbiome maturation. We demonstrated the presence of archaea in the infant oral cavity and GIT microbiome from early infancy, with Methanobrevibacter being the predominant genus. Still, transient patterns show that no stable archaeome is formed. The GIT microbiome exhibited gradual development, with BF infants showing increased diversity and complexity between the third and eighth months, marked by anaerobic microbial networks. NBF infants showed complex microbial co-occurrence patterns from the start. These strong differences between BF and NBF infants' GIT microbiomes are less pronounced on functional levels than on taxonomic levels. Overall, the infant microbiome differentiates and stabilizes over the first year, with breastfeeding playing a crucial role in shaping anaerobic microbial networks and overall microbiome maturation.

The first year of life is a crucial period for establishing a healthy human microbiome. Our study analyses the role of archaea and obligate anaerobes in the development of the human oral and gut microbiome, with a specific focus on the impact of breastfeeding in this process. Our findings demonstrated that the oral and gut microbiomes of breastfed infants undergo distinct phases of increased dynamics within the first year of life. In contrast, the microbiomes of non-breastfed infants are more mature from the first month, leading to a steadier development without distinct transitional phases in the first year. Additionally, we found that archaeal signatures are present in infants under 1 year of age, but they do not form a stable archaeome. In contrast to this, we could track specific bacterial strains transitioning from oral to gut or persisting in the gut over time.

The intricate ecosystem of the gut microbiome exhibits sex-specific differences, influencing the susceptibility to cardiovascular diseases (CVD). Imbalance within the gut microbiome compromises the gut barrier, activates inflammatory pathways, and alters the production of metabolites, all of which initiate chronic diseases including CVD. In particular, the interplay between lifestyle choices, hormonal changes, and metabolic byproducts uniquely affects sex-specific gut microbiomes, potentially shaping the risk profiles for hypertension and CVD differently in men and women. Understanding the gut microbiome's role in CVD risk offers informative reasoning behind the importance of developing tailored preventative strategies based on sex-specific differences in CVD risk. Furthermore, insight into the differential impact of social determinants and biological factors on CVD susceptibility emphasizes the necessity for more nuanced approaches. This review also outlines specific dietary interventions that may enhance gut microbiome health, offering a glimpse into potential therapeutic avenues for reducing CVD risk that require greater awareness. Imbalance in natural gut microbiomes may explain etiologies of chronic diseases; we advocate for future application to alter the gut microbiome as possible treatment of the aforementioned diseases. This review mentions the idea of altering the gut microbiome through interventions such as fecal microbiota transplantation (FMT), a major application of microbiome-based therapy that is first-line for Clostridium difficile infections and patient-specific probiotics highlights more innovative approaches to hypertension and CVD prevention. Through increased analysis of gut microbiota compositions along with patient-centric probiotics and microbiome transfers, this review advocates for future preventative strategies for hypertension.

The term "gut microbiota" primarily refers to the ecological community of various microorganisms in the gut, which constitutes the largest microbial community in the human body. Although adequate bowel preparation can improve the results of colonoscopy, it may interfere with the gut microbiota. Bowel preparation for colonoscopy can lead to transient changes in the gut microbiota, potentially affecting an individual's health, especially in vulnerable populations, such as patients with inflammatory bowel disease. However, measures such as oral probiotics may ameliorate these adverse effects. We focused on the bowel preparation-induced changes in the gut microbiota and host health status, hypothesized the factors influencing these changes, and attempted to identify measures that may reduce dysbiosis, thereby providing more information for individualized bowel preparation for colonoscopy in the future.

The oral-gut microbiota axis plays a crucial role in cardiometabolic health. This review explores the interactions between these microbiomes through enteric, hematogenous, and immune pathways, resulting in disruptions in microbial balance and metabolic processes. These disruptions contribute to systemic inflammation, metabolic disorders, and endothelial dysfunction, which are closely associated with cardiometabolic diseases. Understanding these interactions provides insights for innovative therapeutic strategies to prevent and manage cardiometabolic diseases.

This study investigated the oral microbiome signatures associated with upper gastrointestinal (GI) and pancreaticobiliary cancers.

Saliva samples from cancer patients and age- and sex-matched healthy controls were analyzed using 16S rRNA-targeted sequencing, followed by comprehensive bioinformatics analysis.

Significant dissimilarities in microbial composition were observed between cancer patients and controls across esophageal cancer (EC), gastric cancer (GC), biliary tract cancer (BC), and pancreatic cancer (PC) groups (R2 = 0.067, = 0.075, = 0.068, and = 0.044; p = 0.001, = 0.001, = 0.002, and = 0.004, respectively). Additionally, the oral microbiome composition significantly differed by the four cancer sites (p = 0.001 for EC vs. GC, EC vs. BC, EC vs. PC, GC vs. BC, and GC vs. PC; p = 0.013 for BC vs. PC). We built oral metagenomic classifiers to predict cancer and selected specific microbial taxa with diagnostic properties. For EC, the classifier differentiated cancer patients and controls with good accuracy (area under the curve [AUC] = 0.791) and included three genera: Akkermansia, Escherichia-Shigella, and Subdoligranulum. For GC, the classifier exhibited high discriminative power (AUC = 0.961); it included five genera (Escherichia-Shigella, Gemella, Holdemanella, Actinomyces, and Stomatobaculum) and three species (Eubacterium sp. oral clone EI074, Ruminococcus sp. Marseille-P328, and Leptotrichia wadei F0279). However, microbial taxa with diagnostic features for BC and PC were not identified.

These findings suggested that the oral microbiome composition may serve as an indicator of tumorigenesis in upper GI and pancreaticobiliary cancers. The development of oral metagenomic classifiers for EC and GC demonstrates the potential value of microbial biomarkers in cancer screening.

Metagenomic studies have revealed the critical roles of complex microbial interactions, including horizontal gene transfer (HGT) and functional redundancy (FR), in shaping the gut microbiome's functional capacity and resilience. However, the lack of comprehensive data integration and systematic analysis approaches has limited the in-depth exploration of HGT and FR dynamics across large-scale gut microbiome datasets. To address this gap, we present GutMetaNet (https://gutmetanet.deepomics.org/), a first-of-its-kind database integrating extensive human gut microbiome data with comprehensive HGT and FR analyses. GutMetaNet contains 21 567 human gut metagenome samples with whole-genome shotgun sequencing data related to various health conditions. Through systematic analysis, we have characterized the taxonomic profiles and FR profiles, and identified 14 636 HGT events using a shared reference genome database across the collected samples. These HGT events have been curated into 8049 clusters, which are annotated with categorized mobile genetic elements, including transposons, prophages, integrative mobilizable elements, genomic islands, integrative conjugative elements and group II introns. Additionally, GutMetaNet incorporates automated analyses and visualizations for the HGT events and FR, serving as an efficient platform for in-depth exploration of the interactions among gut microbiome taxa and their implications for human health.

Emerging evidence indicates that oral microbes are closely related to gastric microbes and gastric lesions, including gastric atrophy, intestinal metaplasia and gastric cancer (GC). Helicobacter pylori is a key pathogen involved in GC. However, the increasing prevalence of H. pylori-negative GC and gastric dysbiosis in GC patients emphasize the potential role of other microbial factors. In this review, we discussed the current evidence about the relationship between the oral-gastric microbial axis and oral and gastric health. Epidemiologic evidence indicates that poor oral hygiene is related to greater GC risk. Multiple oral-associated microbes are enriched in the stomach of GC patients. Once colonizing the stomach, oral-associated microbes Streptococcus anginosus and Prevotella melaninogenica, are involved in gastric inflammation or carcinogenesis. Microbial metabolites such as lactate, nitrite, and acetaldehyde promote malignant transformation. The stomach, as a checkpoint of microbial transmission in the digestive tract, is of great importance since the link between oral microbes and intestinal diseases has been emphasized. Still, new technologies and standardized metrics are necessary to identify potential pathogenetic microbes for GC and the core microbiota, interactions, richness, colonization, location and effect (CIRCLE). In the future, oral microbes could be candidates for noninvasive indicators to predict gastric diseases.

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.

In the last decades, groundbreaking research on the human microbiome has changed our reductionist conception of the etiology and pathogenesis of several chronic diseases. As a result, we have come to appreciate the significance of a balanced microbiome in maintaining human health. In this context, the upper and lower gastrointestinal tracts (GITs) comprise the most abundant and diverse microbiotas of the human body. In addition to its diversity, functional redundancy, and temporal stability, a healthy GIT microbiome is characterized by its body site specificity. In fact, current evidence has indicated that the translocation of oral species to the gut environment through the oral-gut axis is increased in an array of illnesses, including chronic inflammatory and metabolic diseases, neurological disorders, and cancer. Oral pathogens have also been shown to promote gut dysbiosis and systemic inflammation in animal models. Yet, some level of overlapping between oral and gut microbiomes may occur without disruption of these microbial communities and loss of site specificity. The uniqueness of each host-microbiome entity may hinder our ability to define a "universal" normal GIT microbiome. Despite that, this chapter summarizes the predominant health-related taxa along the human GIT, as well as their role in the physiology and immunity of the digestive system. Some mechanisms that may lead to disturbances and relevant shifts in the oral and gut microbiomes of major inflammatory chronic diseases are also pointed out. Lastly, oral-fecal microbial signatures are presented as potential biomarkers for several oral and systemic disorders. The recognition of such symbiotic/dysbiotic microbial profiles may provide insights into the development of more accurate early diagnosis and therapeutic ecological approaches to restore the balance of the GIT microbiome.

The small intestinal microbiota has a crucial role in gastrointestinal health, affecting digestion, immune function, bile acid homeostasis and nutrient metabolism. The challenges of accessibility at this site mean that our knowledge of the small intestinal microbiota is less developed than of the colonic or faecal microbiota. Here, we summarize the features and fluctuations of the microbiota along the small intestinal tract, focusing on humans, and discuss physicochemical factors and assessment methods, including the technical challenges of investigating the low microbial biomass of the proximal small bowel. We highlight the essential protective mechanisms of the small intestine, including motility, the paracellular barrier and mucus, and secretory immunity, to show their roles in limiting excessive exposure of host tissues to microbial metabolites. We address current knowledge gaps, particularly the variability among individuals, the effects of dysbiosis of the small intestinal microbiota on health and how different taxa in small intestinal microbiota could compensate for each other functionally.

The balance between health and disease is intrinsically linked to the interactions between microbial communities and the host. This complex environment of antagonism and synergy involves both prokaryotic and eukaryotic cells, whose collaborative metabolic pathways and immunomodulatory elements influence system homeostasis. As with the gut and other niches, the oral microbiome has the capacity to affect distal host sites. The ability to manipulate this environment holds the potential to impact local and systemic disease.With the increasing threat of antimicrobial resistance, novel approaches to reduce the burden of disease are essential. The use of probiotics and prebiotics is one such strategy. Probiotics introduce non-pathogenic bacteria into the environment to compete with pathogens for nutrients and attachment sites, or to produce metabolites that counteract disease aetiologies. Prebiotic compounds enhance the growth of health-associated organisms, offering additional benefits, whilst a conjunctive approach with probiotics potentially holds even greater promise. Though widely studied in the gastrointestinal context, their potential for treating oral diseases, such as dental caries and periodontitis, is less understood. Additionally, the use of microbial transplantations has demonstrated efficacy in other areas, reducing systemic inflammation and recolonising with commensal bacteria. Here we evaluate their use in the oral context and their modulatory impact on overall health.In this chapter, we discuss how pro- and prebiotic strategies seek to modulate both the oral and gut environments to promote oral health and prevent disease. We assess novel approaches for utilising health-associated microorganisms to combat oral disorders, either administered locally in the mouth or imparting influence through immune modulation via the oral-gut axis. By examining available clinical trial data, we aim to further understand the intricacies involved in this discipline. Furthermore, we consider the challenges facing the research community, including optimal candidate organism/compound selection and colonisation retention, as well as considerations for future research.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that leads to joint inflammation, progressive tissue damage and significant disability, severely impacting patients' quality of life. While the exact mechanisms underlying RA remain elusive, growing evidence suggests a strong link between intestinal microbiota dysbiosis and the disease's development and progression. Differences in microbial composition between healthy individuals and RA patients point to the role of gut microbiota in modulating immune responses and promoting inflammation. Therapies targeting microbiota restoration have demonstrated promise in improving treatment efficacy, enhancing patient outcomes and slowing disease progression. However, the complex interplay between gut microbiota and autoimmune pathways in RA requires further investigation to establish causative relationships and mechanisms. Here, we review the current understanding of the gut microbiota's role in RA pathogenesis and its potential as a therapeutic target.

The human body hosts trillions of microorganisms throughout many diverse habitats with different physico-chemical characteristics. Among them, the oral cavity and the gut harbour some of the most dense and diverse microbial communities. Although these two sites are physiologically distinct, they are directly connected and can influence each other in several ways. For example, oral microorganisms can reach and colonize the gastrointestinal tract, particularly in the context of gut dysbiosis. However, the mechanisms of colonization and the role that the oral microbiome plays in causing or exacerbating diseases in other organs have not yet been fully elucidated. Here, we describe recent advances in our understanding of how the oral and intestinal microbiota interplay in relation to their impact on human health and disease.