The oral-gut axis is believed to play a role in the pathogenesis of colorectal cancer (CRC). Previous studies have demonstrated the transmission of oral microbiota to the gut, disrupting gut microbial balance and creating a protumorigenic microenvironment conducive to CRC progression. Fusobacterium nucleatum is a putative periodontal pathogen recognized as a specific bacterium that promotes CRC development. However, the possible involvement of other periodontal pathogens in CRC is poorly understood. This study aimed to explore the effects of ingested periodontal pathogens on experimental CRC in mice and elucidate the underlying mechanisms.

In this study, experimental colitis-induced CRC mouse models were used. The mice were orally administered periodontal pathogens (Porphyromonas gingivalis and Prevotella intermedia) three times a week during the experimental period. The CRC severity between the P. gingivalis-treated and P. intermedia-treated groups was compared. Lumen-associated microbiota (LAM) and mucosa-associated microbiota (MAM) were analyzed in both mouse and human samples. In vitro studies were conducted using intestinal epithelial cells to explore the possible mechanisms by which the periodontal pathogens affect the CRC development.

The P. gingivalis-treated group exhibited significantly increased CRC severity compared to the other groups among azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse models. The LAM and MAM exhibited distinct bacterial compositions, and P. gingivalis was enriched more in MAM than in LAM. In vitro adhesion assays revealed that P. gingivalis had higher adhesive capacity to intestinal epithelial cells than P. intermedia and indicated the possible involvement of gingipains in such a capacity.

P. gingivalis is enriched in MAM, and its subsequent adhesion to intestinal epithelial cells is potentially involved in the progression of CRC.

Colon cancer (CC) is one of the most common cancers globally, which is associated with the gut microbiota intimately. In current research, exploring the complex interaction between microbiomes and CC is a hotspot. However, the information on microbiomes in most previous studies is based on fecal, which does not fully display the microbial environment of CC. Herein, we collected mucosal and tissue samples from both the tumor and normal regions of 19 CC patients and clarified the composition of mucosal microbiota by 16S rRNA and metagenomic sequencing. Additionally, RNA-Seq was also conducted to identify the different expression genes between tumor and normal tissue samples. We revealed significantly different microbial community structures and expression profiles to CC. Depending on correlation analysis, we demonstrated that 1,472 genes were significantly correlated with CC tumor microbiota. Our study reveals a significant enrichment of Campylobacter jejuni in the mucosa of CC, which correlates with bile secretion. Additionally, we observe a negative correlation between C. jejuni and immune cells CD4+ Tem and mast cells. Finally, we discovered that metabolic bacterial endosymbiont of Bathymodiolus sp., Bacillus wiedmannii, and Mycobacterium tuberculosis had a significant survival value for CC, which was ignored by previous research. Overall, our study expands the understanding of the complex interplay between microbiota and CC and provides new targets for the treatment of CC.

This study contributes to our understanding of the interaction between microbiota and colon cancer (CC). By examining mucosal and tissue samples rather than solely relying on fecal samples, we have uncovered previously unknown aspects of CC-associated microbiota. Our findings reveal distinct microbial community structures and gene expression profiles correlated with CC progression. Notably, the enrichment of Campylobacter jejuni in CC mucosa, linked to bile secretion, underscores potential mechanisms in CC pathogenesis. Additionally, observed correlations between microbial taxa and immune cell populations offer new avenues for immunotherapy research in CC. Importantly, this study introduces CC-associated microbiota with survival implications for CC, expanding therapeutic targets beyond conventional strategies. By elucidating these correlations, our study not only contributes to uncovering the potential role of gut microbiota in colon cancer but also establishes a foundation for mechanistic studies of gut microbiota in colon cancer, emphasizing the broader impact of microbiota research on cancer biology.

Activation of the epithelial-mesenchymal transition (EMT), a pivotal process in tumor metastasis and evasion, as well as the NLRP3 inflammasome, both promote colorectal cancer (CRC) progression. Recent studies have shown that Transmembrane protein 176B (TMEM176B) regulates NLRP3 and promotes CRC malignant phenotypes.

To investigate the role of TMEM176B in modulating NLRP3 inflammasome and its implications on EMT and tumor progression in CRC.

CRC in situ mouse and co-cultured cell models were established using CT26 cells, BALB/c mice, and primary cultured mouse natural killer (NK) cells. Short hairpin RNA knocked down TMEM176B and NLRP3 expression in CT26 cells. Fluorescence imaging, Terminal deoxynucleotidyl transferase dUTP nick end labeling assays, immunohistochemistry staining, flow cytometry, and molecular assays were used to investigate the effects of TMEM176B knockdown on the NLRP3 inflammasome in NK cells to assess tumor metastasis, apoptosis, and EMT indicators.

Silencing TMEM176B in CRC mice significantly reduced tumor metastasis, proliferation, and EMT, while activating apoptosis, NLRP3 inflammasome, and NK cell activity. Furthermore, silencing TMEM176B in co-cultured cell models inhibited cell migration and invasion, and promoted apoptosis. The interference of NLRP3 reversed these effects by modulating key proteins such as phosphorylated nuclear factor kappa B subunit 1 p65, matrix metallopeptidase 9, and transforming growth factor-β.

This study highlights the critical role of TMEM176B/NLRP3 in CRC progression and provides a basis for targeting this axis as a novel therapeutic approach to manage CRC progression and metastasis.

Colorectal cancer (CRC), with a rising prevalence, is the third most commonly diagnosed cancer and the third leading cause of cancer-related death. Studies have shown that a complex interplay between the development of CRC and alterations in the oral microbiome. Recent advancements in genomics and metagenomics have highlighted the significant roles of certain oral microbes, particularly Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum), in the progression of CRC. However, the detailed mechanisms by which the oral microbiota influence CRC development remain unclear. This review aims to elucidate the role of oral microbiota in CRC progression, evaluate their potential as biomarkers, and explore therapeutic strategies targeting these microbes. This review offers insights into the mechanisms underlying the interaction between oral microbiota and CRC, underscoring the potential of oral microbes as diagnostic and prognostic biomarkers, as well as therapeutic targets. Future research should focus on clarifying the exact pathways and developing innovative therapeutic strategies to enhance the diagnosis and treatment.

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally, both in terms of diagnoses and cancer-related mortality. Increasing evidence suggests that an imbalance in intestinal flora can contribute to the progression of CRC, and fecal microbiota may serve as potential biomarkers for its screening and diagnosis. Notably, Porphyromonas gingivalis has been identified in the malignant tissues and feces of CRC patients, establishing it as a significant biomarker for early screening, diagnosis, and prognostic assessment of CRC. Current methods for detecting P. gingivalis face numerous challenges, including high costs, complex procedures, and lengthy implementation times. Therefore, developing rapid, highly specific, and sensitive detection methods for P. gingivalis is of great importance. In this study, we utilized the whole-bacterium systematic evolution of ligands by exponential enrichment method to identify highly specific and high-affinity aptamers targeting P. gingivalis through 15 selection cycles. Subsequently, we developed an aptasensor driven by MoS2 nanoflowers, which integrates strand displacement amplification and CRISPR/Cas12a double amplification for sensitive detection of P. gingivalis, achieving a limit of detection of 10 CFU/mL. Using this aptasensor, we evaluated the abundance of P. gingivalis in clinical fecal samples and observed significantly higher levels in the feces of CRC patients compared to healthy individuals, corroborating the results obtained from quantitative polymerase chain reaction. In summary, we developed a highly specific and sensitive aptasensor for the first time, representing a promising new approach for the identification of P. gingivalis, with significant potential for CRC screening and diagnosis.

The association between the oral pathogen Porphyromonas gingivalis (PG) and the gut microbiota in colorectal cancer (CRC) patients has been explored with inconsistent results. This study aims to systematically assess this potential association.

A systematic review was conducted across three databases (Pubmed, Embase and Web of Science) from inception up to January 2023 and updated until November 2024. Inclusion criteria were observational studies examining PG in the microbiota of adults with CRC compared to healthy controls. Exclusion criteria were studies without control group of healthy individuals, other designs or without full-text access. Two reviewers independently selected and extracted data following a pre-registered protocol. Disagreements were resolved by consensus or with a third reviewer. Risk of bias (RoB) was assessed using the Newcastle-Ottawa Scale (NOS). Results were summarized with a flow diagram, tables, and narrative descriptions. Meta-analysis was not feasible, so Fisher's method for combining p-values and the sign test were used as alternative integration methods.

Finally, 18 studies, with 23 analysis units were included, providing a total sample of 4,373 participants (48.0% cases and 52.0%controls), 38.2% men and 61.8% women, with a similar distribution among cases and controls. The mean (SD) age of cases was 63.3 (4.382) years old and 57.0 (7.753) years for controls. Most of the studies analyzed the presence of PG in feces (70.0%) collected before colonoscopy (55.0%) and were classified with good quality (70.0%) in the RoB assessment. Results suggested an effect (Fisher's test, p = .000006) with some evidence towards a positive association of PG in CRC patients compared to healthy controls (Sign test, p = .039).

Results of the systematic review suggest that PG is associated with the microbiota of CRC patients. Lack of information to calculate the effect size prevented the performance of a meta-analysis. Future research should aim for standardized protocols and statistical approaches.

No funding was received for this work.

The research protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 2023 (registration number: CRD42023399382).

Colorectal cancer (CRC), the second leading cause of cancer-related deaths worldwide, is intricately linked to the dysregulation of the gut microbiota. Manipulating the gut microbiota has emerged as a novel strategy for the prevention and treatment of CRC. Natural products, a pivotal source in new drug discovery, have shown promise in recent research as regulators of the gut microbiota, offering potential applications in the prevention and treatment of CRC. In this work, commencing with a focus on the gut microbiota, we first elucidate the latest research on the intricate relationship between the gut microbiota and CRC. Additionally, we explore the impact of the gut microbiota on immunotherapy and chemotherapy treatments for CRC. Subsequently, we review the latest research findings on the regulation of the gut microbiota for CRC prevention through various mechanisms by natural products. These mechanisms include promoting the growth of beneficial bacteria, eradicating harmful bacteria, and enhancing the synthesis of beneficial metabolites. Furthermore, we summarize the advancements in research on natural products that alleviate chemotherapy toxicity and enhance the efficacy of immunotherapy by modulating the gut microbiota. Ultimately, we aspire to leverage advancements in nanomedicine and multiomics technologies to gain a deeper understanding of the mechanisms by which natural products regulate the gut microbiota. This work leverages gut microbiota as a focal point, aiming to offer new perspectives for developing novel natural products for colorectal cancer prevention and treatment.

Recent advancements have revealed the presence of a microbiome within tumor tissues, underscoring the crucial role of the tumor microbiome in the tumor ecosystem. This review delves into the characteristics of the intratumoral microbiome, underscoring its dual role in modulating immune responses and its potential to both suppress and promote tumor growth. We examine state-of-the-art techniques for detecting and analyzing intratumoral bacteria, with a particular focus on their interactions with the immune system and the resulting implications for cancer prognosis and treatment. By elucidating the intricate crosstalk between the intratumoral microbiome and the host immune system, we aim to uncover novel therapeutic strategies that enhance the efficacy of cancer treatments. Additionally, this review addresses the existing challenges and future prospects within this burgeoning field, advocating for the integration of microbiome research into comprehensive cancer therapy frameworks.

Porphyromonas gingivalis (P. gingivalis) is a gram-negative bacterium and the main causative agent of periodontitis, a disease closely associated with the development of periodontal disease. The progression of periodontitis, a chronic infectious disease, is intricately linked to the inflammatory immune response. Inflammatory cytokines act on periodontal tissues via immunomodulation, resulting in the destruction of the periodontal tissue. Recent studies have established connections between periodontitis and various systemic diseases, including cardiovascular diseases, tumors, and neurodegenerative diseases. Neurodegenerative diseases are neurological disorders caused by immune system dysfunction, including Alzheimer's and Parkinson's diseases. One of the main characteristics of neurodegenerative diseases is an impaired inflammatory response, which mediates neuroinflammation through microglial activation. Some studies have shown an association between periodontitis and neurodegenerative diseases, with P. gingivalis as the primary culprit. P. gingivalis can cross the blood-brain barrier (BBB) or mediate neuroinflammation and injury through a variety of pathways, including the gut-brain axis, thereby affecting neuronal growth and survival and participating in the onset and progression of neurodegenerative diseases. However, comprehensive and systematic summaries of studies on the infectious origin of neurodegenerative diseases are lacking. This article reviews and summarizes the relationship between P. gingivalis and neurodegenerative diseases and its possible regulatory mechanisms. This review offers new perspectives into the understanding of neurodegenerative disease development and highlights innovative approaches for investigating and developing tailored medications for treating neurodegenerative conditions, particularly from the viewpoint of their association with P. gingivalis.

Tongue diagnosis, a cornerstone of Traditional Chinese Medicine (TCM), relies significantly on the assessment of tongue coating, which is used to evaluate Zang-fu organ functions, qi and blood dynamics, and the influence of pathogenic factors. This diagnostic method is integral to disease diagnosis and treatment in TCM. Recent research suggests a strong correlation between the characteristics of tongue coating and its microbial composition. These microbial variations may influence the formation and changes in tongue coating and are potentially linked to the progression of specific diseases. However, comprehensive research on the association between tongue coating, its microorganisms, and colorectal cancer (CRC) is limited. Notably, the quantitative aspects of tongue diagnosis and the microbial diversity in tongue coatings across different stages of colorectal cancer (from healthy individuals to colorectal adenoma (CRA) and CRC patients) are yet to be fully elucidated. By studying the cross-population characteristics of tongue image and tongue coating microorganisms during the evolution of colorectal cancer, the differences of tongue image characteristics and tongue coating microorganisms among different populations were further evaluated, providing references for early screening, diagnosis and treatment of colorectal cancer.

The tongue image features of the subjects were collected by DS01-B tongue surface information collection system, mainly including tongue quality and tongue coating, and the tongue image was quantitatively analyzed by color space Lab value. The microbial characteristics of tongue coating were detected by high-throughput sequencing (16SrRNA amplicon sequencing). All subjects came from the patients in the Sixth Affiliated Hospital of Sun Yat-sen University and recruited volunteers (divided into health group, CRA group and CRC group), and obtained the ethical approval of the Sixth Affiliated Hospital of Sun Yat-sen University (ethical batch number: 2021ZSLYEC-328).

A total of 377 subjects were recruited in this study, including 56 healthy subjects, 65 colorectal adenomas and 256 colorectal cancer patients. The results showed that: in terms of texture of fur, the "thick fur" was a significant statistical difference (p < 0.05) in the 3 groups. In addition, there was also a statistical difference in "greasy fur" and "peeled fur" among the 3 groups (p < 0.05). Lab quantitative analysis of tongue color and fur color: The results showed that the L value of tongue color in healthy group was significantly different from that in CRA group and CRC group (p < 0.01), but there was no significant difference between CRA group and CRC group (p > 0.05). Tongue coating microorganisms, there was no significant difference in the richness and diversity of the three groups of subjects (p > 0.05). There were 296 species in the three groups, accounting for 44.65%, and the species in colorectal cancer population was the most, reaching 502. From the differences in community composition among the three groups, it was found that there were certain differences in bacterial community composition between healthy people, CRA and CRC, and the differences became more and more obvious with the development of the disease.

This study revealed the specific cross-population tongue image characteristics and the specificity of tongue coating microorganisms in the evolution of CRC, providing new research ideas for early screening, early diagnosis, mechanism exploration, prevention and treatment of colorectal cancer.

Gout poses a significant health threat. The use of Lactobacillus from the gut microbiota is one potential remedy. However, the intricate molecular mechanisms governing the impact of Lactobacillus on gout remain largely uncharted. In this study, a strain of Limosilactobacillus reuteri RE225 was separated from the gut of mice and colitis was treated with polypeptide intervention.

Limosilactobacillus reuteri RE225 reduced foot tumefaction markedly in mice with gout and extended the pain threshold time in their feet. It also improved the health of gut microbiota. Intervention with L. reuteri RE225 also suppressed the TLR4/MyD88/NF-κB and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways in the mice, reduced the levels of pro-inflammatory cytokines - interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) - and increased the level of the anti-inflammatory cytokine interleukin 10 (IL-10), thereby mitigating inflammation.

This study provides a theoretical basis for the comprehensive development of Limosilactobacillus reuteri and new ideas for the non-pharmacological treatment of gout. © 2024 Society of Chemical Industry.

The correlation between periodontitis and colorectal cancer (CRC) has drawn widespread attention. However, how periodontitis affects CRC progression remains unclear.

C57BL/6 mice were used to establish experimental periodontitis and CRC model. Histological alterations of periodontium and colon were observed by hematoxylin and eosin staining. Micro-computed tomography (micro-CT) was applied to evaluate alveolar bone loss (ABL). Tumor growth was detected by immunofluorescence. Gut bacteria were analyzed using 16S rRNA sequencing. Gas chromatography-mass spectrometry (GC-MS) was performed to observe the alterations of gut microbial metabolites. The detection of associated pathways was carried out using quantitative real-time PCR (qRT-PCR).

Experimental periodontitis significantly induced increases in tumor number in mice with CRC. Double immunofluorescence for Ki67 and β-catenin, as well as Cyclin D1 and β-catenin, indicated that experimental periodontitis observably promoted tumor growth. 16S rRNA sequencing and untargeted metabolomics analysis displayed that experimental periodontitis altered gut microbial community and metabolite profiles in CRC mice. Notably, we found that experimental periodontitis dramatically increased the level of three oncometabolites (serotonin, adenosine, and spermine) in mice with CRC.

Alterations of gut microbial community and metabolites might be relevant in experimental periodontitis deteriorating CRC.

The innate immune response, particularly the reaction of polymorphonuclear neutrophils (PMNs), is crucial in shaping the outcomes of chronic inflammation, fibrosis, or osseointegration following biomaterial implantation. Peri-implantitis or peri-implant mucositis, inflammatory conditions linked to dental implants, pose a significant threat to implant success. We developed a single-cell analysis approach using a murine model to assess the immune response to implant materials, offering a practical screening tool for potential dental implants.

We performed bioinformatics analysis and established a peri-implant inflammation model by inserting two titanium implants into the maxillary region, to examine the immune response.

Bioinformatics analysis revealed that titanium implants triggered a host immune response, primarily mediated by PMNs. In the in vivo experiments, we observed a rapid PMN-mediated response, with increased infiltration around the implants and on the implant surface by day 3. Remarkably, PMN attachment to the implants persisted for 7 days, resembling the immune profiles seen in human implant-mediated inflammation.

Our findings indicate that persistent attachment of the short-living PMNs to titanium implants can serve as an indicator or traits of peri-implant inflammation. Therefore, analyzing gingival tissue at the single-cell level could be a useful tool for evaluating the biocompatibility of candidate dental implants.

There is growing evidence suggesting a strong association between members of the oral microbiota and various types of cancer, including oral cancer, colorectal cancer, esophageal squamous cell carcinoma, and pancreatic cancer. Periodontal diseases closely associated with pathogenic bacteria in the oral cavity have been shown to be correlated with the occurrence and development of cancers. Among the periodontal disease-associated bacteria in the oral cavity, two prominent oral pathogens, Porphyromonas gingivalis and Fusobacterium nucleatum, have been found to promote tumor cell proliferation, invasion, and migration, as well as to inhibit immune cell function, thereby facilitating tumor progression. The presence of other oral pathogenic bacteria, such as Treponema denticola, Tannerella forsythia, Parvimonas micra, and Aggregatibacter actinomycetemcomitans, has also been found to be associated with cancer worsening. Oral commensal bacteria play a crucial role in maintaining the normal oral homeostasis. However, the relationship between oral commensal bacteria and the occurrence and development of cancers remains controversial. Some studies suggest an increase in oral commensal bacteria during tumor development, while others suggest an association of certain commensal bacteria with lower tumor risk. The microbiota can significantly alter responses and toxicity to various forms of cancer treatment through interactions with the human body, thereby influencing disease progression. In this chapter, we provide a concise overview of current understanding of the role of the oral microbiota in cancer.

The discoveries of the oncomicrobiome (intratumoral microbiome) and oncomicrobiota (intratumoral microbiota) represent significant advances in tumor research and have rapidly become of key interest to the field. Within tumors, microorganisms such as bacteria, fungi, viruses, and archaea form the oncomicrobiota and are primarily found within tumor cells, immunocytes, and the intercellular matrix. The oncomicrobiome exhibits marked heterogeneity and is associated with tumor initiation, progression, metastasis, and treatment response. Interactions between the oncomicrobiome and the immune system can modulate host antitumor immunity, influencing the efficacy of immunotherapies. Oncomicrobiome research also faces numerous challenges, including overcoming methodological issues such as low target abundance, susceptibility to contamination, and biases in sample handling and analysis methods across different studies. Furthermore, studies of the oncomicrobiome may be confounded by baseline differences in microbiomes among populations driven by both environmental and genetic factors. Most studies to date have revealed associations between the oncomicrobiome and tumors, but very few have established mechanistic links between the two. This review introduces the relevant concepts, detection methods, sources, and characteristics of the oncomicrobiome. We then describe the composition of the oncomicrobiome in common tumors and its role in shaping the tumor microenvironment. We also discuss the current problems and challenges to be overcome in this rapidly progressing field.

The bidirectional associations between periodontitis and inflammatory bowel disease (IBD) with temporal directionality remain inconclusive. This study aims to evaluate the bidirectional associations between periodontitis and IBD through a systematic review and meta-analysis. Five databases (PubMed, Embase, Web of Science, Scopus and Cochrane Library) were systematically searched from inception to 27 February 2024. Two independent reviewers performed a review of the retrieved studies. Longitudinal studies, including cohort and nested case-control studies, were considered eligible for the study design. The pooled risk ratio (RR) and hazard ratio (HR) derived from the meta-analysis were used to assess whether periodontitis (or IBD) was a risk factor for IBD (or periodontitis). Trial sequential analysis (TSA) was performed to evaluate the reliability of the results. Four studies (n = 10 270 912) on the risk of IBD in patients with periodontitis and two (n = 33 420) on the risk of periodontitis in patients with IBD were included. The result suggested that periodontitis did not increase the risk of IBD (pooled RR = 1.04, 95% confidence interval [CI]: 0.99-1.09; p = .164; I-squared statistic [I2] = 27%). For subtypes of IBD, periodontitis was associated with the occurrence of ulcerative colitis (UC) (pooled RR = 1.12, 95% CI: 1.04-1.21; p = .003; I2 = 38%), but not with Crohn's disease (CD) (pooled RR = 0.98, 95% CI: 0.92-1.04; p = .475; I2 = 0%). Specifically, the risk of UC was higher among men (pooled HR = 1.11, 95% CI: 1.01-1.22; p = .025; I2 = 0%) and smokers (pooled HR = 1.23, 95% CI: 1.07-1.42; p = .004; I2 = 0%) with periodontitis than their counterparts without periodontitis. Patients with IBD may have a higher risk of developing periodontitis (pooled HR = 1.37, 95% CI: 1.26-1.49; p < .001; I2 = 18%); however, whether IBD subtypes increased the occurrence of periodontitis remained uncertain. The TSA results confirmed the reliability of the primary findings. Based on limited longitudinal evidence, patients with periodontitis do not exhibit an increased risk of developing IBD overall, but they are at increased risk of UC (not CD). On the contrary, patients with IBD have a higher risk of developing periodontitis over time. More high-quality longitudinal studies are needed to determine the effect of specific subtypes of IBD on periodontitis.

As a complicated and heterogeneous condition, breast cancer (BC) has posed a tremendous public health challenge across the world. Recent studies have uncovered the crucial effect of human microbiota on various perspectives of health and disease, which include cancer. The oral-gut microbiome axis, particularly, have been implicated in the occurrence and development of colorectal cancer through their intricate interactions with host immune system and modulation of systemic inflammation. However, the research concerning the impact of oral-gut microbiome axis on BC remains scarce. This study focused on comprehensively reviewing and summarizing the latest ideas about the potential bidirectional relation of the gut with oral microbiota in BC, emphasizing their potential impact on tumorigenesis, treatment response, and overall patient outcomes. This review can reveal the prospect of tumor microecology and propose a novel viewpoint that the oral-gut microbiome axis can be a breakthrough point in future BC studies.

Porphyromonas gingivalis is a gram-negative anaerobic bacterium linked to periodontal disease. Remarkably, P. gingivalis thrives in an inflamed environment rich in activated neutrophils. Toll-like receptor 2 (TLR2) recognition is required for P. gingivalis to evade innate immune killing; however, the mechanisms through which P. gingivalis uncouples host inflammation from bactericidal activity are only partially known. Since integrin activation and alternative signaling are implicated in P. gingivalis TLR2-mediated immune escape, we explored the role of CD47, a widely expressed integrin-associated protein known to suppress phagocytosis and implicated as an interacting partner with other innate immune receptors. We found that CD47 associates with TLR2, and blocking CD47 leads to decreased intracellular P. gingivalis survival in macrophages in a manner dependent on the bacterial major fimbria. In vivo, CD47 knock-out mice cleared P. gingivalis more efficiently than wild-type mice. Next, we found increased expression and secretion of the CD47 ligand thrombospondin-1 (TSP-1) following P. gingivalis infection. Secreted TSP-1 broadly protected P. gingivalis and other periodontitis-associated bacterial species from neutrophil bactericidal activity. Therefore, CD47-TLR2 cosignaling in response to P. gingivalis induces TSP-1 that in turn suppresses neutrophil activity, an effect that can explain how species such as P. gingivalis survive in an inflamed environment and cause dysbiosis.

Fusobacterium nucleatum (Fn) has been extensively studied for its connection to colorectal cancer (CRC) and its potential role in chemotherapy resistance. Studies indicate that Fn is commonly found in CRC tissues and is associated with unfavorable prognosis and treatment failure. It has been shown that Fn promotes chemoresistance by affecting autophagy, a cellular process that helps cells survive under stressful conditions. Additionally, Fn targets specific signaling pathways that activate particular microRNAs and modulate the response to chemotherapy. Understanding the current molecular mechanisms and investigating the importance of Fn-inducing chemoresistance could provide valuable insights for developing novel therapies. This review surveys the role of Fn in tumor proliferation, metastasis, and chemoresistance in CRC, focusing on its effects on the tumor microenvironment, gene expression, and resistance to conventional chemotherapy drugs. It also discusses the therapeutic implications of targeting Fn in CRC treatment and highlights the need for further research.

Porphyromonas gingivalis (P. gingivalis), the main pathogen responsible for periodontitis, is linked to systemic disorders via the oral-gut axis. Short-chain fatty acids (SCFAs) are vital for gut health, but their role in P. gingivalis-induced gut disorders remains unclear. This study utilized metabolomics and 16 S rRNA sequencing to explore gut microbiota and SCFAs levels in P. gingivalis-induced periodontitis mouse models. Significant changes were observed in gut, including a reduction in SCFAs-producing bacteria, such as Lactobacillus, Ligilactobacillus, Allobucalum, and a notable decrease in Firmicutes and Actinobacteriota. The intestinal permeability tests and histological analyses revealed that periodontitis led to epithelial inflammation, reduced mucin secretion, and compromised gut barrier integrity. In vitro experiments with Caco-2 cells co-cultured with P. gingivalis showed that the bacterium disrupted cellular junctions by impairing autophagy, specifically through the ATG5-LC3 pathway, leading to decreased expression of tight junction proteins and reduced SCFA absorption. Remarkably, rapamycin treatment both in vitro and in vivo restored gut barrier function by enhancing autophagy, increasing tight junction protein expression, and promoting SCFAs absorption via MCT1 and SMCT1, alongside GPR43/GPR109a pathway activation. These findings reveal autophagy's novel role in regulating SCFAs metabolism in P. gingivalis-induced gut dysbiosis, offering insights for preventing and treating periodontitis-related systemic diseases.

Emerging studies have disclosed the pivotal role of cancer-associated microbiota in supporting cancer development, progression and dissemination, with the in-depth comprehending of tumor microenvironment. In particular, certain invasive bacteria that hide in various cells within the tumor tissues can render assistance to tumor growth and invasion through intricate mechanisms implicated in multiple branches of cancer biology. Thus, tumor-resident intracellular microbes are anticipated as next-generation targets for oncotherapy. This review is intended to delve into these internalized bacteria-driven cancer-promoting mechanisms and explore diversified antimicrobial therapeutic strategies to counteract the detrimental impact caused by these intruders, thereby improving therapeutic benefit of antineoplastic therapy.

Mounting evidence suggests a significant role of the gut microbiota in the development and progression of colorectal cancer (CRC). In particular, an over-representation of oral pathogens has been linked to CRC. The aim of this study was to further investigate the faecal microbial landscape of CRC patients, with a focus on the oral pathogens Parvimonas micra and Fusobacterium nucleatum.

In this study, 16S rRNA sequencing was conducted using faecal samples from CRC patients (n = 275) and controls without pathological findings (n = 95).

We discovered a significant difference in microbial composition depending on tumour location and microsatellite instability (MSI) status, with P. micra, F. nucleatum, and Peptostreptococcus stomatis found to be more abundant in patients with MSI tumours. Moreover, P. micra and F. nucleatum were associated with a cluster of CRC-related bacteria including Bacteroides fragilis as well as with other oral pathogens such as P. stomatis and various Porphyromonas species. This cluster was distinctly different in the control group, suggesting its potential linkage with CRC.

Our results suggest a similar distribution of several CRC-associated bacteria within CRC patients, underscoring the importance of considering the concomitant presence of bacterial species in studies investigating the mechanisms of CRC development and progression.

The emergence of 16S rRNA and metagenomic sequencing has gradually revealed the close relationship between dysbiosis and colorectal cancer (CRC). Recent studies have confirmed that intestinal dysbiosis plays various roles in the occurrence, development, and therapeutic response of CRC. Perturbation of host immunity is one of the key mechanisms involved. The intestinal microbiota, or specific bacteria and their metabolites, can modulate the progression of CRC through pathogen recognition receptor signaling or via the recruitment, polarization, and activation of both innate and adaptive immune cells to reshape the protumor/antitumor microenvironment. Therefore, the administration of gut bacteria to enhance immune homeostasis represents a new strategy for the treatment of CRC. In this review, we cover recent studies that illuminate the role of gut bacteria in the progression and treatment of CRC through orchestrating the immune response, which potentially offers insights for subsequent transformative research.

Increasing evidence suggests a significant association between periodontal disease and the occurrence of various cancers. The carcinogenic potential of several periodontal pathogens has been substantiated in vitro and in vivo. This review provides a comprehensive overview of the diverse mechanisms employed by different periodontal pathogens in the development of cancer. These mechanisms induce chronic inflammation, inhibit the host's immune system, activate cell invasion and proliferation, possess anti-apoptotic activity, and produce carcinogenic substances. Elucidating these mechanisms might provide new insights for developing novel approaches for tumor prevention, therapeutic purposes, and survival improvement.

Colorectal cancer (CRC) is one of the most prevalent and lethal malignant tumors globally, posing significant health risks and societal burdens. Recently, advancements in next-generation sequencing technology have identified CRC intratumoral microbiota, thereby opening up novel avenues for further research. This review synthesizes the current advancements in CRC intratumoral microbiota and their impact on CRC progression and discusses the disparities in the relative abundance and community composition of CRC intratumoral microbiota across various colorectal tumors based on their anatomical location and molecular subtypes, as well as the tumor stages, and spatial tumor distribution. Intratumoral microbiota predominantly influence CRC development by modulating colonic epithelial cells, tumor cells, and the tumor microenvironment. Mechanistically, they can cause DNA damage, apoptosis and epithelial-mesenchymal transition. The effects of different intratumoral microbiota on CRC have been shown to be two-fold. In the future, to address the limitations of existing studies, it is important to develop comprehensive experimental protocols and suitable in vitro models for elucidating more mechanisms of intratumoral microbiota on CRC, which will facilitate the clinical application of microbe-related therapeutic strategies in CRC and potentially other tumors.

Most patients diagnosed with oral squamous cell carcinoma (OSCC) present with locally advanced stages, which are typically associated with poor outcomes. Although immunotherapy offers potential improvements in patient survival, its efficacy is hampered by low response rates. The microbiome is widely involved in tumor immunity and may play a role in immunotherapy. This study aimed to investigate the potential association between the oral (salivary) microbiome and immunotherapy response in patients with OSCC. Salivary metagenome sequencing was performed on 47 patients with OSCC undergoing neoadjuvant immunotherapy (NAIT) in a clinical trial (NCT04649476). Patients were divided into responders and nonresponders based on their pathological responses. The results showed that the species richness of the salivary microbiome was lower in the nonresponders before NAIT than in the responders. Differential analysis revealed that nonresponders exhibited a lower relative abundance of 34 bacterial species and a higher relative abundance of 4 bacterial species. Notably, low levels of Eubacterium infirmum, Actinobaculum, and Selenomas (EAS) in the saliva may be associated with the nonresponse of patients with OSCC to NAIT. A nomogram based on EAS was developed and validated to determine the efficacy of NAIT. The area under the curve for the training cohort was 0.81 (95% confidence interval, 0.66 to 0.81). Quantitative polymerase chain reaction confirmed that low levels of salivary EAS effectively identified nonresponders to NAIT. Furthermore, the low abundance of salivary EAS was closely correlated with a low density of intratumoral CD4+, CD14+, CD68+, and FOXP3+ cells. Metabolic functional annotation revealed numerous biosynthetic processes associated with EAS that were more active in responders. In summary, this study provides valuable data resources for the salivary microbiome and reveals that nonresponders have different salivary microbiome profiles than responders do before NAIT. Low salivary EAS levels can serve as potential biomarkers for distinguishing nonresponders from responders.

Colorectal cancer (CRC) continues to be a significant contributor to global morbidity and mortality. Emerging evidence indicates that disturbances in gut microbial composition, the formation of reactive oxygen species (ROS), and the resulting inflammation can lead to DNA damage, driving the pathogenesis and progression of CRC. Notably, bacterial metabolites can either protect against or contribute to oxidative stress by modulating the activity of antioxidant enzymes and influencing signaling pathways that govern ROS-induced inflammation. Additionally, microbiota byproducts, when supplemented through probiotics, can affect tumor microenvironments to enhance treatment efficacy and selectively mediate the ROS-induced destruction of CRC cells. This review aims to discuss the mechanisms by which taxonomical shifts in gut microbiota and related metabolites such as short-chain fatty acids, secondary bile acids, and trimethylamine-N-oxide influence ROS concentrations to safeguard or promote the onset of inflammation-mediated CRC. Additionally, we focus on the role of probiotic species in modulating ROS-mediated signaling pathways that influence both oxidative status and inflammation, such as Nrf2-Keap1, NF-κB, and NLRP3 to mitigate carcinogenesis. Overall, a deeper understanding of the role of gut microbiota on oxidative stress may aid in delaying or preventing the onset of CRC and offer new avenues for adjunct, CRC-specific therapeutic interventions such as cancer immunotherapy.

Gastric cancer is one of the most common malignant tumors worldwide and has a high mortality rate. However, tests for the early screening and diagnosis of gastric cancer are limited and invasive. Certain oral microorganisms are over-expressed in gastric cancer, but there is heterogeneity among different studies. Notably, each oral ecological niche harbors specific microorganisms. Among them, tongue coating, saliva, and dental plaque are important and unique ecological niches in the oral cavity. The colonization environment in different oral niches may be a source of heterogeneity. In this paper, we systematically discuss the latest developments in the field of the oral microbiota and gastric cancer and elucidate the enrichment of microorganisms in the oral ecological niches of the tongue coatings, saliva, and dental plaque in gastric cancer patients. The various potential mechanisms by which the oral microbiota induces gastric cancer (activation of an excessive inflammatory response; promotion of proliferation, migration, invasion, and metastasis; and secretion of carcinogens, leading to imbalance in gastric microbial communities) are explored. In this paper, we also highlight the applications of the rapeutics targeting the oral microbiota in gastric cancer and suggests future research directions related to the relationship between the oral microbiota and gastric cancer.

As the opposite ends of the orodigestive tract, the oral cavity and the intestine share anatomical, microbial, and immunological ties that have bidirectional health implications. A growing body of evidence suggests an interconnection between oral pathologies and inflammatory bowel disease [IBD], implying a shift from the traditional concept of independent diseases to a complex, reciprocal cycle. This review outlines the evidence supporting an 'oral-gut' axis, marked by a higher prevalence of periodontitis and other oral conditions in IBD patients and vice versa. We present an in-depth examination of the interconnection between oral pathologies and IBD, highlighting the shared microbiological and immunological pathways, and proposing a 'multi-hit' hypothesis in the pathogenesis of periodontitis-mediated intestinal inflammation. Furthermore, the review underscores the critical need for a collaborative approach between dentists and gastroenterologists to provide holistic oral-systemic healthcare.

Asthma is a prevalent pulmonary disease that affects more than 300 million people worldwide and imposes a substantial economic burden. While medication can effectively control symptoms in some patients, severe asthma attacks, driven by airway inflammation induced by environmental and infectious exposures, continue to be a major cause of asthma-related mortality. Heterogeneous phenotypes of asthma include type 2 (T2) and non-T2 asthma. Non-T2 asthma is often observed in patients with severe and/or steroid-resistant asthma. This review covers the molecular mechanisms, clinical phenotypes, causes and promising treatments of non-T2 severe asthma. Specifically, we discuss the signalling pathways for non-T2 asthma including the activation of inflammasomes, interferon responses and interleukin-17 pathways, and their contributions to the subtypes, progression and severity of non-T2 asthma. Understanding the molecular mechanisms and genetic determinants underlying non-T2 asthma could form the basis for precision medicine in severe asthma treatment.

The role of the microbiome in cancer and its crosstalk with the tumor microenvironment (TME) has been extensively studied and characterized. An emerging field in the cancer microbiome research is the concept of the intratumoral microbiome, which refers to the microbiome residing within the tumor. This microbiome primarily originates from the local microbiome of the tumor-bearing tissue or from translocating microbiome from distant sites, such as the gut. Despite the increasing number of studies on intratumoral microbiome, it remains unclear whether it is a driver or a bystander of oncogenesis and tumor progression. This review aims to elucidate the intricate role of the intratumoral microbiome in tumor development by exploring its effects on reshaping the multileveled ecosystem in which tumors thrive, the TME. To dissect the complexity and the multitude of layers within the TME, we distinguish six specialized tumor microenvironments, namely, the immune, metabolic, hypoxic, acidic, mechanical and innervated microenvironments. Accordingly, we attempt to decipher the effects of the intratumoral microbiome on each specialized microenvironment and ultimately decode its tumor-promoting or tumor-suppressive impact. Additionally, we portray the intratumoral microbiome as an orchestrator in the tumor milieu, fine-tuning the responses in distinct, specialized microenvironments and remodeling the TME in a multileveled and multifaceted manner.

Dental calculus severely affects the oral health of humans and animal pets. Calculus deposition affects the gingival appearance and causes inflammation. Failure to remove dental calculus from the dentition results in oral diseases such as periodontitis. Apart from adversely affecting oral health, some systemic diseases are closely related to dental calculus deposition. Hence, identifying the mechanisms of dental calculus formation helps protect oral and systemic health. A plethora of biological and physicochemical factors contribute to the physiological equilibrium in the oral cavity. Bacteria are an important part of the equation. Calculus formation commences when the bacterial equilibrium is broken. Bacteria accumulate locally and form biofilms on the tooth surface. The bacteria promote increases in local calcium and phosphorus concentrations, which triggers biomineralization and the development of dental calculus. Current treatments only help to relieve the symptoms caused by calculus deposition. These symptoms are prone to relapse if calculus removal is not under control. There is a need for a treatment regime that combines short-term and long-term goals in addressing calculus formation. The present review introduces the mechanisms of dental calculus formation, influencing factors, and the relationship between dental calculus and several systemic diseases. This is followed by the presentation of a conceptual solution for improving existing treatment strategies and minimizing recurrence.

We investigates the effects of 16-week high-intensity interval training and moderate-intensity continuous training on the composition of the oral microbiota. To the best of our knowledge, at the time of writing this paper no other scholars had described the oral metagenomic changes associated with prescribed exercise in older adults.

Forty-three participants aged 60-74 years were randomized 1:1:1 to a control group, high-intensity interval training or moderate-intensity continuous training twice weekly for 16 weeks. Saliva samples were sequenced at baseline, week 8 and week 16 of intervention.

High-intensity interval training produced significant differences over time in Richness and a clear trend to decreased Simpson and Shannon diversity indices. In contrast, Simpson and Shannon indices showed an upward trend over time with moderate-intensity continuous training, which also decreased Firmicutes and increased Bacteroidetes levels. Significant differences in the abundance of pathogenic species were also observed after the participants completed the exercise interventions of either type.

Both types of exercise promoted subtle changes in the oral microbiota, confirming the modulatory effect of high-intensity interval training and moderate-intensity continuous training on the oral microbiome. Clinical trial registration NCT05220670.

The metabolites and microbiota in tongue coating display distinct characteristics in certain digestive disorders, yet their relationship with colorectal cancer (CRC) remains unexplored. Here, we employed liquid chromatography coupled with tandem mass spectrometry to analyze the lipid composition of tongue coating using a nontargeted approach in 30 individuals with colorectal adenomas (CRA), 32 with CRC, and 30 healthy controls (HC). We identified 21 tongue coating lipids that effectively distinguished CRC from HC (AUC = 0.89), and 9 lipids that differentiated CRC from CRA (AUC = 0.9). Furthermore, we observed significant alterations in the tongue coating lipid composition in the CRC group compared to HC/CRA groups. As the adenoma-cancer sequence progressed, there was an increase in long-chain unsaturated triglycerides (TG) levels and a decrease in phosphatidylethanolamine plasmalogen (PE-P) levels. Furthermore, we noted a positive correlation between N-acyl ornithine (NAOrn), sphingomyelin (SM), and ceramide phosphoethanolamine (PE-Cer), potentially produced by members of the Bacteroidetes phylum. The levels of inflammatory lipid metabolite 12-HETE showed a decreasing trend with colorectal tumor progression, indicating the potential involvement of tongue coating microbiota and tumor immune regulation in early CRC development. Our findings highlight the potential utility of tongue coating lipid analysis as a noninvasive tool for CRC diagnosis.

Tea tree (Melaleuca alternifolia) oil (TTO) is an antimicrobial agent, and hence, its use in fabricating nanoparticles (NP) may be useful in providing more efficacious antimicrobial agents. The current research aimed to test the antimicrobial efficacy of TTO and its TTO-Metal-NPs against oral microbes: Porphyromonas gingivalis, Enterococcus faecalis, and Streptococcus mutans. The antimicrobial activity of TTO and zinc (Zn) and iron (Fe) nanoparticles (NPs) and the combined effects of antimicrobial agents were investigated using agar well diffusion assays. Fourier-transform infrared spectroscopy (FT-IR) was used to identify the phyto-constituents of TTO. Field emission scanning electron microscopy (FE-SEM), dynamic light scatter (DLS), and zeta potential were utilized to analyze the biogenic nanoparticles' morphology, size, and potential. The antimicrobial mode of action was determined by assessing the morphological changes under scanning electron microscopy (SEM). The TTO extracts converted Zn and Fe ions to NPs, having an average size of 97.50 (ZnNPs) and 102.4 nm (FeNPs). All tested agents had significant antibacterial efficacy against the tested oral microbes. However, the TTO extract was more efficacious than the NPs. Combination treatment of TTO with antibiotics resulted in partial additive effects against P. gingivalis and partial antagonistic effects against E. faecalis, S. mutans, and common mouthwashes (Oral B and chlorhexidine). TTO and NP-treated bacteria underwent morphological changes on treatment. M. alternifolia phytochemicals could be useful for further research and development of antimicrobial NPs. The current study highlights the variance in activity observed for different types of bacteria and antagonistic effects seen with common mouthwashes, which represent a threat to therapeutic efficacy and heighten the risk of clinical microbial resistance.

Worldwide, more than 125 million people are infected with Shigella each year and develop shigellosis. In our previous study, we provided evidence that Shigella sonnei infection triggers activation of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome in macrophages. NLRP3 inflammasome is responsible for regulating the release of the proinflammatory cytokines interleukin (IL)-1β and IL-18 through the protease caspase-1. Researchers and biotech companies have shown great interest in developing inhibitors of the NLRP3 inflammasome, recognizing it as a promising therapeutic target for several diseases. The leaves of Cinnamomum osmophloeum kaneh, an indigenous tree species in Taiwan, are rich in cinnamaldehyde (CA), a compound present in significant amounts. Our aim is to investigate how CA affects the activation of the NLRP3 inflammasome in S. sonnei-infected macrophages.

Macrophages were infected with S. sonnei, with or without CA. ELISA and Western blotting were employed to detect protein expression or phosphorylation levels. Flow cytometry was utilized to assess H2O2 production and mitochondrial damage. Fluorescent microscopy was used to detect cathepsin B activity and mitochondrial ROS production. Additionally, colony-forming units were employed to measure macrophage phagocytosis and bactericidal activity.

CA inhibited the NLRP3 inflammasome in S. sonnei-infected macrophages by suppressing caspase-1 activation and reducing IL-1β and IL-18 expression. CA also inhibited pyroptosis by decreasing caspase-11 and Gasdermin D activation. Mechanistically, CA reduced lysosomal damage and enhanced autophagy, while leaving mitochondrial damage, mitogen-activated protein kinase phosphorylation, and NF-κB activation unaffected. Furthermore, CA significantly boosted phagocytosis and the bactericidal activity of macrophages against S. sonnei, while reducing secretion of IL-6 and tumour necrosis factor following infection.

CA shows promise as a nutraceutical for mitigating S. sonnei infection by diminishing inflammation and enhancing phagocytosis and the bactericidal activity of macrophages against S. sonnei.

The interaction between bacteria and the host plays a vital role in the initiation and progression of systemic diseases, including gastrointestinal and oral diseases, due to the secretion of various virulence factors from these pathogens. GroEL, a potent virulence factor secreted by multiple oral pathogenic bacteria, is implicated in the damage of gingival epithelium, periodontal ligament, alveolar bone and other peripheral tissues. However, the underlying biomechanism is still largely unknown. In the present study, we verify that GroEL can trigger the activation of NLRP3 inflammasome and its downstream effector molecules, IL-1β and IL-18, in human periodontal ligament stem cells (hPDLSCs) and resultantly induce high activation of gelatinases (MMP-2 and MMP-9) to promote the degradation of extracellular matrix (ECM). GroEL-mediated activation of the NLRP3 inflammasome requires the participation of Toll-like receptors (TLR2 and TLR4). High upregulation of TLR2 and TLR4 induces the enhancement of NF-κB (p-p65) signaling and promotes its nuclear accumulation, thus activating the NLRP3 inflammasome. These results are verified in a rat model with direct injection of GroEL. Collectively, this study provides insight into the role of virulence factors in bacteria-induced host immune response and may also provide a new clue for the prevention of periodontitis.