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PubMed2025

Animal farming and the oral microbiome in the Agricultural Health Study.

BACKGROUND: Raising farm animals imparts various exposures that may shape the human microbiome. The oral microbiome has been increasingly implicated in disease development. Animal farming has also been associated with certain chronic diseases such as cancer; however, underlying biological mechanisms are unclear. We investigated associations between raising farm animals and the oral microbiome in the Agricultural Health Study. METHODS: This analysis included 1,245 participants (865 farmers and 380 spouses) who provided oral wash specimens and information on types and numbers of specific animals raised on their farms within 2 years before sample collection. The oral microbiome was measured by sequencing the V4 region of the 16S ribosomal RNA gene. We evaluated associations of farm animal exposures with alpha and beta diversity metrics (within- and between-sample diversity, respectively), as well as presence and relative abundance of specific bacterial genera. All analyses adjusted for potential confounders (e.g., age, sex, smoking, alcohol consumption). RESULTS: Overall, 63 % of participants raised farm animals, most commonly cattle (46 %) and hogs (20 %). Those who raised a large number of hogs (≥2,000 vs. no hogs) had higher alpha diversity. Conversely, raising sheep/goats and raising larger numbers of poultry were associated with lower alpha diversity. Beta diversity was not significantly different between participants with and without any farm animals. Participants raising any farm animals had higher relative abundance of Porphyromonas and lower relative abundances of Prevotella and Ruminococcaceae UCG-014. Several genera were more likely to be absent with specific animal exposures (e.g., Capnocytophaga for cattle and sheep/goats; Corynebacterium, Dialister, Stomatobaculum, and Solobacterium for sheep/goats and poultry). CONCLUSIONS: This was the largest study of farm animal exposures and the human microbiome to date. Findings suggest that raising specific farm animals may influence the oral microbiome, supporting the need to further investigate the potential role of animal farming in disease etiology.

Microbiota↗

PubMed2025

A high-quality genomic catalog of the human oral microbiome broadens its phylogeny and clinical insights.

The oral microbiome is increasingly linked to human health. To further examine this microbial community, we present the human reference oral microbiome (HROM), with 72,641 high-quality genomes from 3,426 species, including 2,019 previously unidentified species, improving metagenomic sequence read classification over existing catalogs. Notably, HROM unveils 1,137 previously uncharacterized candidate phyla radiation (CPR) species, establishing Patescibacteria as the most prevalent phylum in the oral microbiota and distinct from environmental Patescibacteria. Additionally, an oral CPR subclade is associated with periodontitis, complementing Porphyromonas gingivalis in predicting disease. Finally, comparing HROM with reference genomes of the gut microbiome reveals taxonomic and functional divergence between these microbiomes. HROM contains 42 ectopic oral species, and their relative abundance in gut microbiota is predictive of intestinal, cardiovascular, and liver diseases. Thus, HROM offers an expanded view of the oral microbiome and highlights the clinical importance of further examining the links between oral microbes and systemic disorders.

Humans↗

PubMed2025

Metagenomic characterization of oral microbiome signatures to predict upper gastrointestinal and pancreaticobiliary cancers: a case-control study.

BACKGROUND: This study investigated the oral microbiome signatures associated with upper gastrointestinal (GI) and pancreaticobiliary cancers. METHODS: Saliva samples from cancer patients and age- and sex-matched healthy controls were analyzed using 16S rRNA-targeted sequencing, followed by comprehensive bioinformatics analysis. RESULTS: 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. CONCLUSIONS: 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.

Humans↗

PubMed2026

Lesion-specific oral microbiome signatures and predicted carcinogenic pathways in oral squamous cell carcinoma: a paired-site study in Pakistan.

BACKGROUND: Oral squamous cell carcinoma accounts for over 90% of oral neoplasms. Despite therapeutic advances, the lack of reliable, non-invasive biomarkers and delayed diagnosis continues to impede effective clinical management. By combining paired lesion and non-lesion sampling with predictive metagenomics analysis, our study addresses this gap and advances the current understanding of microbiome‒tumor interactions. METHODS: We analyzed 92 buccal swab samples from 39 OSCC patients and 14 healthy controls using 16S rRNA gene (V3-V4) sequencing. Taxonomic profiling was conducted using QIIME2 and SILVA/eHOMD databases, functional pathways were predicted using PICRUSt2, and hub taxa were identified through co-abundance network analysis. RESULTS: Microbial community structure differed significantly across lesion, non-lesion, and healthy sites (PERMANOVA, p = 0.001). Lesions were enriched with Selenomonas infelix and Treponema vincentii, while healthy controls harbored Streptococcus oralis and Gemella haemolysans. Co-abundance network analysis revealed lesion-specific hub species, notably T. vincentii, strongly correlated with predicted activation of pyrimidine biosynthesis pathways (r = 0.69, q < 1E-6), suggesting predicted metabolic alterations in the tumor microenvironment. Non-lesion sites were also characterized by two hub species, Prevotella melaninogenica and Segatella oulorum. CONCLUSION: Our findings define a lesion-specific microbial signature of OSCC characterized by the depletion of health-associated taxa, enrichment of pro-inflammatory pathobionts, and predicted associations with metabolic pathways implicated in carcinogenesis. These alterations reflect a predicted functionally altered tumor microenvironment.

16S rRNA gene↗

PubMed2026

The Oral Microbiome of King Richard III of England.

OBJECTIVES: Metagenomic investigations of ancient dental calculus provide insights into oral health, disease, and diet. Here, we analyze the dental calculus metagenome of King Richard III of England (1452-1485). MATERIALS AND METHODS: Dental calculus DNA was extracted from three teeth of King Richard III and shotgun sequenced to a depth of nearly 400 million reads. The metagenomic data were taxonomically profiled and compared to new and previously published dental calculus metagenomes from England, Ireland, the Netherlands, and Germany spanning the Neolithic to the present. Sequencing data were de novo assembled, and metagenome-assembled genomes assigned to the genus Tannerella were investigated for phylogenetic relatedness and virulence. Putative dietary DNA was assessed for authenticity. RESULTS: The dental calculus of King Richard III was well-preserved and yielded an exceptionally high quantity of DNA. Oral microbiome species diversity fell within the range previously observed among other northern European populations, suggesting that a royal lifestyle and a rich diet did not substantially impact his oral microbiota. The reconstructed Tannerella genomes contained many virulence factors found today among oral Tannerella species. No putative dietary DNA could be authenticated. DISCUSSION: The dental calculus of King Richard III produced one of the richest ancient oral metagenomes published to date, yet the species diversity was indistinguishable from that of commoners living in northern Europe over the last 7000 years. Insufficient plant and animal DNA were recovered to investigate diet, suggesting that dental calculus may not be a sufficient source of dietary DNA even when exceptionally well-preserved.

Humans↗

PubMed2025

Mapping the oral microbiome opens links to periodontitis.

Many microbiome analysis techniques can only detect the microbes present in the reference genome database used. In this issue of Cell Host & Microbe, Cha et al. establish an improved genome database of the human oral microbiome, which they use to discover a connection between periodontitis and an enigmatic bacterial phylum.

Humans↗

PubMed2026

Challenges and future directions in AI-driven biomaterials for microbiome-associated oral infectious diseases: A systematic review.

Oral biofilm-induced antimicrobial resistance is the core pathogenic mechanism of microbiome-associated oral infectious diseases (dental caries, periodontitis, peri-implantitis, and endodontic infection). Traditional therapies and biomaterials are limited by poor biofilm penetration, drug resistance induction, single functionality, and inadequate adaptation to dynamic oral microenvironmental changes (e.g., pH fluctuations, salivary rinsing, masticatory stimulation). Artificial intelligence (AI) has transformed the field by integrating materials science, microbiology, and stomatology data. Via machine learning, deep learning, and multi-physics simulation, AI optimizes biomaterial physicochemical properties, decodes microenvironmental signals, constructs precise sensing-response loops, and supports the full chain of material design, performance prediction, and action simulation, advancing treatment from empirical intervention to precision regulation. This systematic review retrieved literature from PubMed, Embase, and Web of Science (January 2016-January 2026) using keywords across three dimensions: AI, biomaterials, and oral microbiome. Following inclusion/exclusion criteria, 99 articles were included. It elaborates on five core mechanisms of AI-driven oral biomaterials (precise oral microbiome analysis, targeted material design/optimization, performance prediction/simulation, targeted delivery/intervention, effect evaluation/dynamic regulation), analyzes their applications in microbiome-targeted biomaterial research and development (R&D) and clinical practice for the four major oral infectious diseases, addresses technical bottlenecks (insufficient targeting specificity and precision of biomaterials, poor stability and durability in complex oral microenvironments, inadequate biofilm disruption capacity, and clinical translation obstacles), and proposes future directions (multimodal design to enhance targeting specificity, structural and component optimization to improve stability/durability, development of multi-mechanism synergistic biofilm disruption strategies, strengthening translational research for clinical application, and deep integration of AI in the full chain of biomaterial R&D). This work provides comprehensive theoretical and practical support for the R&D, optimization, and clinical translation of AI-driven microbiome-targeted oral biomaterials.

Humans↗

PubMed2026

Dental wastewater reveals a hidden reservoir of oral bacteriophage diversity.

Bacteriophages (phages) are being explored as alternatives or complements to antibiotics because of their ability to selectively kill bacterial pathogens. However, phages that infect many oral bacteria remain undiscovered. Here, we discovered that dental wastewater harbors previously underexplored phage diversity. Viral particles concentrated from dental wastewater displayed diverse morphologies, including abundant filamentous phage-like particles. Deep long-read metagenomic sequencing of concentrated viral particles generated 7.4 billion bases of sequence data and yielded 255 medium- to high-quality viral operational taxonomic units (vOTUs), including 46 predicted complete genomes. Comparison with large phage databases revealed that 63 of these 255 vOTUs had no detectable match, indicating that extensive sequencing of dental wastewater substantially expands the number of potential bacteriophages associated with the human oral microbiome. Host prediction linked many vOTUs to oral-associated bacterial taxa, including species with few or no previously reported phages, such as Porphyromonas gingivalis, Tannerella forsythia, and Candidatus Saccharibacteria. Functional annotation identified diverse genes associated with antiphage defense systems within a subset of vOTUs, suggesting that oral phages may contribute to the movement of genes encoding bacterial immune functions within the oral microbiome. Together, these findings expand the known oral phageome and show that dental wastewater contains a largely untapped diversity of phages.IMPORTANCEThe human oral cavity contains a diverse microbial community, but the bacteriophages (phages) that infect many oral bacteria remain poorly characterized. This gap limits our understanding of how phages shape oral microbial communities. Here, we show that dental wastewater is an underexplored source of oral phage diversity. Deep long-read metagenomic sequencing revealed 255 medium- to high-quality phage operational taxonomic units, many of which are not present in existing oral phage databases. These genomes include predicted phages of periodontal disease-associated bacteria and other oral taxa with few or no known phages. Dental wastewater therefore expands the known human oral phageome and reveals candidate phages linked to bacteria associated with oral health and disease.

Bacteriophages↗

PubMed2026

Causal Relationships Between Oral Microbiota and Inflammatory Skin Diseases.

INTRODUCTION AND AIMS: The oral microbiome has been increasingly linked to systemic inflammation and immune dysregulation, but whether specific oral bacteria causally contribute to inflammatory skin diseases remains unclear due to confounding and reverse causation. This study aimed to assess the causal effects of 43 oral microbiota taxa on the risk of five inflammatory skin diseases using a Mendelian randomization (MR) approach. METHODS: We performed a two-sample MR analysis using genetic instruments for oral microbiota derived from publicly available genome-wide association studies and outcome data from the FinnGen consortium. Causal effects of oral taxa on systemic lupus erythematosus, vitiligo, pemphigus, localized scleroderma, and dermatitis herpetiformis were estimated. The inverse-variance weighted method served as the primary analysis, complemented by sensitivity analyses to evaluate horizontal pleiotropy, heterogeneity, and reverse causality. RESULTS: MR analyses identified several putative causal associations between oral microbiota and inflammatory skin diseases. Genus Granulicatella and an unknown Streptococcus species (ASV0009) showed causal effects on systemic lupus erythematosus. Family Lachnospiraceae_[XIV] and an unknown Rothia species (ASV0016) were associated with vitiligo. Five oral microbiota taxa demonstrated causal associations with pemphigus. Actinomyces species micronuciformis was linked to localized scleroderma. Order Fusobacteriales and an unknown Neisseria species (ASV0004) were associated with dermatitis herpetiformis. No significant heterogeneity or horizontal pleiotropy was detected in sensitivity analyses. CONCLUSION: This MR study provides genetic evidence supporting a causal role of specific oral bacteria in the development of several inflammatory skin diseases, highlighting the oral microbiome as a potential contributor to cutaneous autoimmunity and inflammation. CLINICAL RELEVANCE: Our findings highlight the putative role of the oral microbiome as a plausible candidate for mechanistic and clinical investigations into the prevention or adjunctive management of selected inflammatory skin diseases. However, oral hygiene improvement, targeted antimicrobials, and other microbiota-directed interventions were not directly tested in this MR study and remain hypothetical strategies requiring validation in experimental and clinical studies.

Humans↗

PubMed2026

Longitudinal development of infant oral ecosystem: salivary metabolomic, bacteriome, and virome dynamics in early infancy.

This prospective cohort study investigated the longitudinal development of the salivary bacteriome, virome, and metabolome during early infancy. We assessed the associations between oral bacteria, viruses, and metabolites from 10 mother-infant dyads, with oral samples collected at 1 and 2 years of age. Forty saliva and plaque samples underwent untargeted metabolomic analysis, and infant saliva samples underwent metagenomic sequencing. Maternal salivary and plaque metabolomic profiles remained largely stable, whereas infant profiles were clearly separated from maternal profiles and changed with age. Notably, infant dental plaque metabolism underwent more substantial changes from year 1 to year 2 than saliva, with age-dependent metabolite shifts mainly involving energy, amino acid, nucleotide, and lipid metabolic pathways. Our findings also revealed significant developmental shifts in salivary bacteriome, virome, and functional pathway profiles during early childhood. The most abundant oral bacteria in early life, comprising over 75% of total abundance, included Veillonella, Streptococcus, Rothia, Prevotella, Neisseria, and Actinomyces species. While human viruses like Roseolovirus were detected, bacteriophages constituted the majority of the virome. Comparing infants at year 1 and year 2, we identified differentially abundant bacteria, viruses, metabolic functional pathways, and specific metabolites. We observed associations between bacteria and viruses, noting that these cross-kingdom relationships attenuated as infants grew. The study results underscore the complex and dynamic development of the oral microbiome, virome, and metabolome during early childhood.IMPORTANCEThe human oral cavity undergoes substantial microbial and metabolic development during early childhood, yet the temporal changes in the infant oral ecosystem remain incompletely understood. In this study, we longitudinally profiled the salivary metabolome, bacteriome, and virome of infants at 1 and 2 years of age. We demonstrated that the infant oral metabolome undergoes substantial developmental shifts, particularly in pathways related to energy, amino acid, and lipid metabolism; whereas maternal metabolic profiles remained stable over the same period. Furthermore, our results revealed the dynamic assembly of infant salivary virome and bacteriome and their associations with the functional pathways and metabolites. These findings provide new insights into the complex and dynamic development of the oral microbiome, virome, and metabolome in early infancy.

bacteriome↗

PubMed2026

Causal relationships between oral-gut microbiome and bone neoplasm-related phenotypes: Insights from bidirectional Mendelian randomization.

The human oral and gut microbiota are the 4 largest microbial communities in the body and play crucial roles in maintaining homeostasis and influencing disease. Observational studies have suggested links between these microbiota and bone neoplasm-related phenotypes, but establishing causality has been challenging due to confounding factors and reverse causality. We conducted a bidirectional, 2-sample Mendelian randomization (MR) study to investigate evidence consistent with a potential causal association between the saliva and gut microbiota and various bone neoplasm-related phenotypes. Genetic instruments for saliva and gut microbiota were sourced from large genome-wide association studies. Inverse variance weighted was the primary MR method, supplemented by 4 other MR techniques. Sensitivity analyses, including MR-Egger regression, were performed to assess pleiotropy and heterogeneity. In the forward MR analysis, Veillonella parvula from the saliva microbiota was associated with a decreased risk of bone and connective tissue neoplasms (β: -0.236, 95% CI: [-0.275, -0.197], P = 8.20E-33). MR analyses identified genetically predicted associations between several microbial taxa and bone neoplasm-related phenotypes. Reverse MR analyses showed that genetic liability to bone neoplasm-related phenotypes was associated with variation in the composition of the oral (e.g., Order Bacteroidales, Rothia mucilaginosa) and gut microbiota (e.g., Class Methanobacteria, Genus Eubacterium oxidoreducens group). Sensitivity analyses confirmed the robustness of these findings, as no statistical evidence of substantial heterogeneity or directional horizontal pleiotropy was detected. This study provides genetic evidence supporting a bidirectional causal relationship between specific saliva and gut microbiota and bone neoplasm-related phenotypes. Our findings identify several microbial taxa as potential candidates for future biomarker development and therapeutic investigation in bone neoplasm-related phenotypes. However, these genetically informed associations require further mechanistic, experimental, and prospective clinical validation before clinical application.

Humans↗

PubMed2025

Oral Lachnoanaerobaculum Levels and Survival in Patients With Head and Neck Cancer.

IMPORTANCE: The oral microbiome plays a critical role in cancer treatment responses, yet its influence on outcomes in patients with head and neck squamous cell carcinoma (HNSCC) undergoing (chemo)radiotherapy remains poorly understood. Identifying specific microbiome signatures associated with treatment effectiveness could provide novel prognostic biomarkers and therapeutic targets. OBJECTIVE: To investigate the association between salivary Lachnoanaerobaculum spp abundance and treatment outcomes in patients with HNSCC undergoing (chemo)radiotherapy and to explore potential mechanisms. DESIGN, SETTING, AND PARTICIPANTS: This prognostic study analyzed saliva samples from patients with HNSCC who were enrolled in 2 independent prospective biomarker studies (SALIVA and ZissTrans) and underwent definitive (chemo)radiotherapy. Oral microbiome composition was assessed using 16S rRNA gene sequencing. Tumor-infiltrating lymphocytes (TILs) were evaluated via immunohistochemistry in patients with available data. Findings were further assessed using data from The Cancer Microbiome Atlas and The Cancer Genome Atlas. Sample collection occurred from 2008 to 2011 (SALIVA) and from 2017 to 2022 (ZissTrans), and the data for this study were analyzed from July to December 2024. EXPOSURE: Definitive (chemo)radiotherapy. MAIN OUTCOMES AND MEASURES: The primary outcome was locoregional recurrence-free survival (LRFS) and a secondary outcome was overall survival (OS). Additional secondary analyses evaluated the association between Lachnoanaerobaculum spp levels and TIL levels, and the incidence of severe radiation-induced oral mucositis. RESULTS: The analysis included 92 patients with HNSCC (mean [SD] age, 61.1 [7.9] years; 15 female [16.3%] 77 male [83.7%] individuals) and found that higher Lachnoanaerobaculum spp abundance was associated with substantially improved LRFS (median, 69 vs 11 months; hazard ratio [HR], 0.50; 95% CI, 0.29-0.86) and OS (median, 75 vs 27 months; HR, 0.54; 95% CI, 0.30-0.98). This finding was confirmed by multivariable Cox regression (LRFS: HR, 0.50; 95% CI, 0.25-1.00; OS: HR, 0.37; 95% CI, 0.16-0.85). TILs were evaluated in 76 patients (82.2%) and showed that increased Lachnoanaerobaculum spp levels were associated with higher CD4-positive and CD8-positive TIL counts. Lachnoanaerobaculum spp abundance showed no meaningful association with severe radiation-induced oral mucositis. Data from The Cancer Microbiome Atlas (n = 157) indicated that higher intratumoral Lachnoanaerobaculum spp levels were associated with improved OS (HR, 0.62; 95% CI, 0.39-0.98). Transcriptomic analyses in The Cancer Genome Atlas cohort further supported an immune-stimulated tumor microenvironment in Lachnoanaerobaculum-high tumors. CONCLUSIONS AND RELEVANCE: This prognostic study found that higher salivary Lachnoanaerobaculum spp abundance was associated with improved tumor control and survival in patients with HNSCC undergoing (chemo)radiotherapy. These findings support further investigation into microbiome-targeted interventions to improve HNSCC treatment effectiveness.

Humans↗

PubMed2026

A host-encoded prophage targets a Candidate Phyla Radiation bacterium and shapes episymbiotic interactions.

The Patescibacteriota, also known as the Candidate Phyla Radiation (CPR), represent a large lineage of ultrasmall bacteria with highly reduced genomes and obligate dependence on bacterial hosts. Although genomic analyses have revealed CRISPR-Cas and restriction-modification systems in many CPR genomes, no cognate bacteriophages (phages) have been isolated, leaving CPR-phage interactions unexplored. Nanosynbacter lyticus TM7x, the first cultivated CPR bacterium, grows episymbiotically on its host, Schaalia odontolytica XH001, in the human oral microbiome. Here, we identify Xhp1, an inducible prophage of XH001 that is preferentially activated during episymbiosis with TM7x. Released Xhp1 particles infect prophage-free XH001 via distinct strategies determined by host growth mode, establishing lysogeny under planktonic conditions but driving lytic infection during surface-associated growth. Xhp1 also binds efficiently to TM7x and exhibits limited infection under the conditions tested, indicating direct phage-CPR interactions. Importantly, TM7x modulates Xhp1 availability in a spatially dependent manner. In planktonic culture, free-floating TM7x reduces lysogenic conversion of XH001ΔXhp1, consistent with TM7x acting as a phage sink that lowers effective phage concentration. In contrast, during surface-associated growth, TM7x increases XH001ΔXhp1 susceptibility to lytic infection, likely by locally concentrating phage particles within a constrained niche. These results demonstrate that CPR bacteria can regulate viral encounter rates through spatial organization. In spatially structured environments such as oral biofilms, such modulation may shape infection dynamics and community structure. Together, this work characterizes the first CPR-targeting phage and reveals a an important role for phages in CPR-host bacteria interactions.

Prophages↗

PubMed2025

Integrative oral and gut microbiome profiling highlights microbial correlates of complications in type 1 diabetes: a cross-sectional analysis.

BACKGROUND/OBJECTIVE: Chronic vascular complications are the primary threat in long-standing type 1 diabetes (T1D) patients. We examined the associations between oral-gut microbiome dysbiosis and these complications, offering novel insights into therapeutic strategies and underlying mechanisms. METHODS: This cross-sectional study enrolled 75 T1D participants (disease duration ≥ 10 years) and 43 healthy controls who underwent comprehensive clinical assessment, including blood glucose, lipid profile, and complication-related examinations. Fecal and oral rinse samples were collected for shotgun metagenomic sequencing. T1D participants were stratified by the presence of microvascular (retinopathy, nephropathy, or neuropathy) or macrovascular complications separately. Microbial differences across groups were assessed. RESULTS: Significant differences in oral and gut microbiota compositions were observed between T1D participants with and without complications (both microvascular and macrovascular). A core set of 26 gut and 8 oral microbial species was specifically associated with vascular complications. Butyrate-producing gut bacteria (Blautia wexlerae, Anaerobutyricum hallii, Roseburia inulinivorans, A. soehngenii) and specific oral Neisseria species were enriched in T1D without complications individuals, suggesting protective effects against complications. Mediation analysis indicated associations consistent with partial mediation between certain microbial species and the relationships of glycemic control or insulin resistance (HbA1c, glucose risk index, estimated glucose disposal rate) with complication risk. Moreover, potential oral-gut microbiome interconnections were implicated in complication development. Finally, classification models integrating both oral and gut microbial features significantly outperformed models based on either site alone in distinguishing T1D patients with complications. CONCLUSIONS: Distinct oral and gut microbiome features are associated with chronic vascular complications in T1D. These findings highlight the potential of microbiome-targeted strategies for understanding and preventing T1D-related complications.

Humans↗

PubMed2024

Shotgun metagenomic analysis of saliva microbiome suggests Mogibacterium as a factor associated with chronic bacterial osteomyelitis.

Osteomyelitis of the jaw is a severe inflammatory disorder that affects bones, and it is categorized into two main types: chronic bacterial and nonbacterial osteomyelitis. Although previous studies have investigated the association between these diseases and the oral microbiome, the specific taxa associated with each disease remain unknown. In this study, we conducted shotgun metagenome sequencing (≥10 Gb from ≥66,395,670 reads per sample) of bulk DNA extracted from saliva obtained from patients with chronic bacterial osteomyelitis (N = 5) and chronic nonbacterial osteomyelitis (N = 10). We then compared the taxonomic composition of the metagenome in terms of both taxonomic and sequence abundances with that of healthy controls (N = 5). Taxonomic profiling revealed a statistically significant increase in both the taxonomic and sequence abundance of Mogibacterium in cases of chronic bacterial osteomyelitis; however, such enrichment was not observed in chronic nonbacterial osteomyelitis. We also compared a previously reported core saliva microbiome (59 genera) with our data and found that out of the 74 genera detected in this study, 47 (including Mogibacterium) were not included in the previous meta-analysis. Additionally, we analyzed a core-genome tree of Mogibacterium from chronic bacterial osteomyelitis and healthy control samples along with a reference complete genome and found that Mogibacterium from both groups was indistinguishable at the core-genome and pan-genome levels. Although limited by the small sample size, our study provides novel evidence of a significant increase in Mogibacterium abundance in the chronic bacterial osteomyelitis group. Moreover, our study presents a comparative analysis of the taxonomic and sequence abundances of all genera detected using deep salivary shotgun metagenome data. The distinct enrichment of Mogibacterium suggests its potential as a marker to distinguish between patients with chronic nonbacterial osteomyelitis and chronic bacterial osteomyelitis, particularly at the early stages when differences are unclear.

Humans↗

PubMed2026

Association Between cnm-Positive Streptococci and Cerebral Small Vessel Disease: Insights From Oral Health and Microbiome Status.

INTRODUCTION AND AIMS: Cerebral small vessel disease (CSVD) is associated with various severe neurological outcomes; while oral cnm-positive streptococci are suggested to be involved in cerebrovascular lesions, the specific associative features between these bacteria and CSVD have not yet been systematically investigated. This study aims to investigate the prevalence of cnm-positive streptococci in patients with CSVD and explore the correlation between infection and CSVD severity. By integrating oral health indices and microbiome sequencing, we evaluate the oral hygiene status and microbial dysbiosis characteristics of cnm-positive streptococci carriers. Furthermore, cnm-positive streptococci derived from CSVD patients will be isolated, identified, and subjected to whole-genome sequencing to provide a foundation for future research. METHODS: To explore cnm-positive streptococci prevalence and its association with CSVD, we conducted a case-control study comparing their oral detection rates between healthy controls and CSVD patients. We also performed 16S rRNA gene high-throughput sequencing of oral plaque microbiota and assessed oral health, including the simplified oral hygiene index (OHI-S), the decayed, missing, and filled teeth (DMFT) index, oral hygiene practices, gingival status, and saliva scores. RESULTS: cnm-positive streptococci were more prevalent in CSVD patients, correlating with higher OHI-S and microbial dysbiosis. Multivariable regression models (adjusted for demographic/vascular risk factors) linked cnm positivity to periventricular hyperintensities (PVH), deep white matter hyperintensities (DWMH), Fazekas score, and total CSVD burden (not cerebral microbleeds (CMBs)/lacunes). CONCLUSION: Oral cnm-positive streptococci are independently associated with CSVD phenotypes, particularly those characterized by white matter injury. These findings presents a potential oral-cerebrovascular interaction and imply that managing specific virulent oral strains may be a noteworthy consideration in future clinical research.

Humans↗

PubMed2026

Metax enables accurate cross-domain taxonomic profiling of metagenomes.

Taxonomic profiling is fundamental to microbiome research, yet achieving high species-level accuracy remains challenging for complex communities that span bacteria, viruses, eukaryotes, and archaea, and these limitations are exacerbated in low-biomass, host-dominated samples. We introduce Metax, a cross-domain taxonomic profiler that integrates coverage-based probabilistic modeling with an expectation-maximization framework to distinguish true microbial signals from artifacts. Across >600 samples from host-associated, environmental, wastewater, and low-biomass clinical settings, including benchmarks with limited reference representation, Metax improved profiling accuracy, achieving on average 55% higher F1 scores and 45% lower Bray-Curtis dissimilarity than other methods. Moreover, this broad evaluation demonstrated that Metax resolved bacterial and viral signatures of peri-implantitis in oral microbiomes and revealed signals suggestive of reagent-borne contaminants and reference misassemblies in plasma-cell-free DNA. By leveraging genome-wide coverage evidence, Metax enables robust cross-domain profiling across diverse sample types and sequencing depths, including settings where reference databases are highly incomplete.

abundance estimation↗

PubMed2026

Cross-kingdom dynamics of the subgingival bacteriome and mycobiome: A pilot study on the effects of a novel HA-H₂O₂-Glycine formulation to treat periodontitis.

OBJECTIVES: Traditional periodontal therapy primarily focuses on bacterial biofilm control; however, recent evidence also suggests a critical role for the oral mycobiome. This study evaluated the clinical and ecological impact of a novel mouthwash formulation containing hyaluronic acid (HA), hydrogen peroxide (H2O2), and glycine on periodontal patients METHODS: This prospective, randomized split-mouth trial included 13 adult participants with periodontitis treated with HA-H2O2-glycine formula (BMG0703A) used twice a day for seven days. Subgingival plaque samples were collected from periodontal pocket and healthy control sites at baseline (T0) and one-week post-treatment (T1). Microbial and fungal communities were characterized using Next-Generation Sequencing (NGS) of the 16S rRNA and ITS2 regions. Linear Mixed Models (LMM) and Spearman correlation were used to assess taxonomic shifts and cross-kingdom relationships. RESULTS: Sequencing revealed a promising ecological shift: the bacteriome shifted from anaerobic dominance (Olsenella, Peptostreptococcus) toward a health-associated aerobic profile, with Rothia near-doubling (11.91% to 22.68%). The mycobiome underwent a "normalization" effect: Candida abundance decreased significantly (22.8% to 9.1%), while fungal Shannon diversity in pockets returned to healthy-site levels. Inter-kingdom analysis identified antagonistic relationships between expanding commensal bacteria and opportunistic fungi, suggesting that the intervention may help re-establish a protective bacterial niche. CONCLUSIONS: The HA-H2O2-glycine formulation seems to facilitate a rapid, cross-kingdom modulation of the subgingival niche. By reducing anaerobic pathogens and normalizing the mycobiome it appear to induce short-term changes, suggesting potential as adjunctive strategy in periodontal management. CLINICAL SIGNIFICANCE: The present work underlines the possible cross-Kingdom effects of a novel compound.

Humans↗