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).

Tooth loss not only impairs oral function but also affects gut health by altering the host microbiota. Understanding the oral-gut axis can provide insights into systemic health implications following tooth loss.

Using an animal model, we extracted the molars of C57 mice. Saliva and fecal samples were collected for 16S rRNA and metagenomic sequencing to analyze changes in the oral and gut microbiota. Pearson correlation analysis assessed the relationship between altered microbial communities.

The study found a significant reduction in oral microbiota diversity following tooth loss, with increased Proteobacteria and decreased Muribacter. Gut microbiota showed increased Firmicutes and decreased Bacteroidota. Correlations between oral and gut microbiota changes were observed, indicating a potential link between tooth loss and alterations in intestinal microbial balance.

In the mouse model, tooth loss disrupted the balance of the oral-gut microbiota, with potential implications for intestinal health. Although these findings are from a murine model, considering the existence of the oral-gut axis balance in the human body, it is reasonable to postulate that following tooth loss in humans, the health of the intestinal microecology may also warrant attention.

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.

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 aim of this study was to investigate the biomarkers of salivary and fecal microbiota in Colorectal cancer (CRC). Initially, the study scrutinized the microbial community composition disparities among groups. Utilizing Lasso analysis, it sifted through operational taxonomic units (OTUs) to pinpoint distinctive features. Subsequently, by intersecting feature OTUs across groups, it curated a set of core-shared OTUs and devised a corresponding network. Concluding with functional enrichment analysis, the research delved into the divergent biological functions of these microbial communities within the studied groups. Analysis revealed higher bacterial diversity in saliva compared to feces, with distinct differences at both phylum and genus levels. Feces primarily contained Firmicutes, while saliva was dominated by Bacteroidetes and Proteobacteria. Notably, Escherichia-Shigella and Fusobacterium in feces and Streptococcus in saliva showed increasing abundance from average to adenoma to colorectal cancer. Specific dominant flora was identified within and between groups, including CRC and adenomas across different stages. Seventeen core shared OTUs were identified, and networks of shared OTUs were constructed for each group. Functional enrichment analysis highlighted distinct microbial community functions among the groups. This study's findings on characteristic OTUs in saliva and fecal samples offer valuable insights for distinguishing between healthy individuals, adenoma patients, and those with colorectal cancer. This study identified distinctive OTUs in saliva and feces to distinguish between healthy individuals, adenoma patients, and those with CRC, offering a valuable diagnostic reference.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most important methods for treating a wide range of hematologic malignancies and bone marrow failure diseases. However, graft-versus-host disease (GVHD), a major complication associated with this method, can seriously affect the survival and quality of life of patients. Acute GVHD (aGVHD) occurs within 100 days after transplantation, and gastrointestinal aGVHD (GI-aGVHD) is one of the leading causes of nonrecurrent death after allo-HSCT. In recent years, fecal microbiota transplantation (FMT) has been attempted as an emerging treatment method for various diseases, including aGVHD after HSCT. Studies have shown encouraging preliminary clinical results after the application of FMT in aGVHD, particularly steroid-resistant aGVHD. Additionally, several studies have demonstrated that the gut microbiota plays an important immunomodulatory role in the pathogenesis of GVHD. Consensus guidelines recommend FMT as a secondary option for the treatment of aGVHD. This article aims to review FMT treatment for GI-aGVHD after allo-HSCT.

The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC are required. Recent studies have revealed an imbalance in the oral and gut microbiomes of patients with CRC, as well as impaired gut vascular barrier function. In the present study, the microbiomes of saliva, crevicular fluid, feces, and non-neoplastic and tumor intestinal tissue samples of 93 CRC patients and 30 healthy individuals without digestive disorders (non-CRC) were analyzed by 16S rRNA metabarcoding procedures. The data revealed that Parvimonas, Fusobacterium, and Bacteroides fragilis were significantly over-represented in stool samples of CRC patients, whereas Faecalibacterium and Blautia were significantly over-abundant in the non-CRC group. Moreover, the tumor samples were enriched in well-known periodontal anaerobes, including Fusobacterium, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella. Co-occurrence patterns of these oral microorganisms were observed in the subgingival pocket and in the tumor tissues of CRC patients, where they also correlated with other gut microbes, such as Hungatella. This study provides new evidence that oral pathobionts, normally located in subgingival pockets, can migrate to the colon and probably aggregate with aerobic bacteria, forming synergistic consortia. Furthermore, we suggest that the group composed of Fusobacterium, Parvimonas, Bacteroides, and Faecalibacterium could be used to design an excellent noninvasive fecal test for the early diagnosis of CRC. The combination of these four genera would significantly improve the reliability of a discriminatory test with respect to others that use a single species as a unique CRC biomarker.

Early detection of specific oral bacterial species would enable timely treatment and prevention of certain oral diseases. In this work, we investigated the sensitivity and specificity of functionalized gold nanoparticles for plasmonic sensing of oral bacteria. This approach is based on the aggregation of positively charged gold nanoparticles on the negatively charged bacteria surface and the corresponding localized surface plasmon resonance (LSPR) shift. Gold nanoparticles were synthesized in different sizes, shapes and functionalization. A biosensor array was developed consisting of spherical- and anisotropic-shaped (1-hexadecyl) trimethylammonium bromide (CTAB) and spherical mercaptoethylamine (MEA) gold nanoparticles. It was used to detect four oral bacterial species (Aggregatibacter actinomycetemcomitans, Actinomyces naeslundii, Porphyromonas gingivalis and Streptococcus oralis). The plasmonic response was measured and analysed using RGB and UV-vis absorbance values. Both methods successfully detected the individual bacterial species based on their unique responses to the biosensor array. We present an in-depth study relating the bacteria zeta potential and AuNP aggregation to plasmonic response. The sensitivity depends on multiple parameters, such as bacterial species and concentration as well as gold nanoparticle shape, concentration and functionalization.

Epidemiological studies have spotlighted the intricate relationship between individual oral bacteria and tumor occurrence. Porphyromonas gingivalis and Fusobacteria nucleatum, which are known periodontal pathogens, have emerged as extensively studied participants with potential pathogenic abilities in carcinogenesis. However, the complex dynamics arising from interactions between these two pathogens were less addressed. This narrative review aims to summarize the current knowledge on the prevalence and mechanism implications of P. gingivalis and F. nucleatum in the carcinogenesis of oral squamous cell carcinoma (OSCC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). In particular, it explores the clinical and experimental evidence on the interplay between P. gingivalis and F. nucleatum in affecting oral and gastrointestinal carcinogenesis. P. gingivalis and F. nucleatum, which are recognized as keystone or bridging bacteria, were identified in multiple clinical studies simultaneously. The prevalence of both bacteria species correlated with cancer development progression, emphasizing the potential impact of the collaboration. Regrettably, there was insufficient experimental evidence to demonstrate the synergistic function. We further propose a hypothesis to elucidate the underlying mechanisms, offering a promising avenue for future research in this dynamic and evolving field.

The human microbiota is widely recognized as providing crucial health benefits to its host, specifically by modulating immune homeostasis. Microbial imbalance, known as dysbiosis, is linked to several conditions in the body. The oral cavity and gut host the two largest microbial communities playing a major role in microbial-associated diseases. While the oral-gut axis has been previously explored, our review uniquely highlights the significance of incorporating the circulatory system into this axis. The interaction between immune cells, inflammatory factors, circulating bacteria, and microbial metabolites influences the homeostasis of both the oral and gut microbiota in a bidirectional manner. In this comprehensive review, we aim to describe the bacterial components of the oral-gut-circulatory axis in both health and disease, with a specific focus on colon cancer.

Gastric cancer is one of the leading causes of death worldwide, and resections are performed to cure the disease. We have previously reported the changes in the gastric microbiota after gastric cancer resection, which may be associated with the oral microbiota; however, the changes in the oral microbiota remain uncharacterized. This study aimed to characterize the changes in the salivary microbiota caused by gastric cancer resection and to evaluate their association with the gastric fluid microbiota. Saliva and gastric fluid samples were collected from 63 patients who underwent gastrectomy before and after surgery, and a 16S rRNA metagenomic analysis was performed to compare the microbiota composition. The number of bacterial species in the salivary microbiota decreased, and the bacterial composition changed after the resection of gastric cancer. In addition, we identified several bacterial genera that varied significantly in the salivary microbiota, some of which also showed similar changes in the gastric fluid microbiota. These findings indicate that changes in the gastric environment affect the oral microbiota, emphasizing the close association between the oral and gastric fluid microbiota. Our study signifies the importance of focusing on the oral microbiota in the perioperative period of gastrectomy in patients with gastric cancer.

Gut microbiota plays an important role in colorectal cancer (CRC) pathogenesis through microbes and their metabolites, while oral pathogens are the major components of CRC-associated microbes. Multiple studies have identified gut and fecal microbiome-derived biomarkers for precursors lesions of CRC detection. However, few studies have used salivary samples to predict colorectal polyps. Therefore, in order to find new noninvasive colorectal polyp biomarkers, we searched into the differences in fecal and salivary microbiota between patients with colorectal polyps and healthy controls.

In this case-control study, we collected salivary and fecal samples from 33 patients with colorectal polyps (CP) and 22 healthy controls (HC) between May 2021 and November 2022. All samples were sequenced using full-length 16S rRNA sequencing and compared with the Nucleotide Sequence Database. The salivary and fecal microbiota signature of colorectal polyps was established by alpha and beta diversity, Linear discriminant analysis Effect Size (LEfSe) and random forest model analysis. In addition, the possibility of microbiota in identifying colorectal polyps was assessed by Receiver Operating Characteristic Curve (ROC).

In comparison to the HC group, the CP group's microbial diversity increased in saliva and decreased in feces (p < 0.05), but there was no significantly difference in microbiota richness (p > 0.05). The principal coordinate analysis revealed significant differences in β-diversity of salivary and fecal microbiota between the CP and HC groups. Moreover, LEfSe analysis at the species level identified Porphyromonas gingivalis, Fusobacterium nucleatum, Leptotrichia wadei, Prevotella intermedia, and Megasphaera micronuciformis as the major contributors to the salivary microbiota, and Ruminococcus gnavus, Bacteroides ovatus, Parabacteroides distasonis, Citrobacter freundii, and Clostridium symbiosum to the fecal microbiota of patients with polyps. Salivary and fecal bacterial biomarkers showed Area Under ROC Curve of 0.8167 and 0.8051, respectively, which determined the potential of diagnostic markers in distinguishing patients with colorectal polyps from controls, and it increased to 0.8217 when salivary and fecal biomarkers were combined.

The composition and diversity of the salivary and fecal microbiota were significantly different in colorectal polyp patients compared to healthy controls, with an increased abundance of harmful bacteria and a decreased abundance of beneficial bacteria. A promising non-invasive tool for the detection of colorectal polyps can be provided by potential biomarkers based on the microbiota of the saliva and feces.

Periodontitis is a prevalent inflammatory oral disease associated with an increased risk of colorectal cancer. Experimental animal models are critical tools to investigate the effects and mechanisms of periodontitis on colorectal cancer. Several murine periodontitis models have been used in research, including oral gavage, periodontal pathogen injection, and ligature models. The role of experimental periodontitis caused by silk ligation in colorectal cancer remains unclear. In this study, we used an experimental periodontitis model on a colitis-associated colorectal cancer model and a spontaneous model, respectively. We observed the promotion of colorectal cancer in ligature-induced periodontitis mice compared to those control mice in 2 different models, as assessed by tumor number, tumor size, and tumor load. Since bacterial dysbiosis is an important feature of periodontitis, we next analyzed the oral and gut microbiomes using 16S ribosomal RNA gene sequencing. We found that the experimental periodontitis model reshaped the microbial community in the oral cavity and gut. In addition, we found a higher extent of programmed death 1 (PD-1)-positive CD8⁺ T-cell infiltration in tumor samples of the periodontitis group than in controls by immunofluorescence staining. Regarding the potential molecular mechanism, we transplanted the fecal microbiota of the periodontitis patient into mice and observed a tumor-promoting effect in the periodontitis group, assessed by tumor volume and tumor weight, together with a low level of INF-γ⁺ CD8⁺ T-cell infiltration in subcutaneous tumor mice. Taken together, we show that ligature-induced periodontitis model promotes colorectal cancer by microbiota remodeling and suppression of the immune response.

The term "periodontal disease" refers to a group of chronic inflammatory illnesses caused by specific microorganisms from subgingival biofilm, that affect the tooth-supporting tissues. Recent research has also shown that periodontal infection plays a role in aggravating systemic disease states at distal sites, reinforcing the significance of the oral cavity for general health. Additionally, it has been suggested that gastroenterological malignancies may be promoted by hematogenous, enteral or lymphatic translocation of periopathogens. In the past 25 years, the global burden of pancreatic cancer (PC) has more than doubled, making it one of the major causes of cancer-related mortality. Periodontitis has been linked to at least 50% increased risk of PC and it could be considered a risk factor for this malignancy. A recent study performed on 59000 African American women with a follow up of 21 years showed that participants who had poor dental health had higher chances of PC. The findings, according to researchers, might be related to the inflammation that some oral bacteria trigger. Regarding the mortality of PC, periodontitis considerably raises the chance of dying from PC. Microbiome alterations in the gut, oral cavity and pancreatic tissues of PC patients occur when compared to healthy flora, demonstrating a link between PC and microecology. Inflammation may also contribute to PC development, although the underlying pathway is not yet known. The function of the microbiome in PC risk has drawn more focus over the last decade. Future risk of PC has been linked to the oral microbiome, specifically increased levels of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans and decreased relative abundance of Leptotrichia and Fusobacteria, suggesting that it may have an impact on the inflammatory condition by expanding, altering, and regulating the commensal microbiome. Patients who received periodontal treatment had significantly decreased incidence rate ratios for PC. By analyzing patterns in the microbiome composition throughout PC development and establishing strategies to enhance the cancer-associated microbial system, we can increase the efficacy of therapy and eventually find an application for the microbial system. The development of immunogenomics and gut micro-genomics in the life sciences will result in a significant advancement in our understanding of how microbial systems and immunotherapy interact, and it may also have intriguing therapeutic implications for extending the lifetime of PC patients.

Human body is colonized by a florid microbial community of bacteria, archaea, fungi, protists, helminths, and viruses, known as microbiota, which co-evolves with the host and influences its health through all stages of its life. It is well known that oral microorganisms form highly structurally and functionally organized multi-species biofilms and establish a network of complex mutual inter-species interactions having a primary function in synergy, signaling, or antagonism. This ecological model allows the microorganisms to increase their resistance to antimicrobial agents and settle a balanced microbes-host symbiotic relationship that ensures oral and global health status in humans. The host-associated microbiome is an important factor in human health and disease. Therefore, to develop novel diagnostic, therapeutic, and preventive strategies, microbiome's functions and the reciprocal interactions every microbiome entertains with other microbial communities in the human body are being investigated. This review provides an analysis of the literature about the close connection between the two largest microbial communities in humans: the oral and the gut microbiomes. Furthermore, it focuses on how the alteration of their microbial and functional characteristics can lead to and reciprocally influence the onset of both oral and intestinal microbiome-associated illness, along with the potential role of probiotics in ameliorating inflammation and microbial dysbiosis.

In recent decades, the comprehensive cancer treatments including surgery, chemotherapy, and radiotherapy have improved the overall survival rate and quality of life of many cancer patients. However, we are still facing many difficult problems in the cancer treatment, such as unpredictable side effects, high recurrence rate, and poor curative effect. Therefore, the better intervention strategies are needed in this field. In recent years, the role and importance of microbiota in a variety of diseases were focused on as a hot research topic, and the role of some intracellular bacteria of cancer cells in carcinogenesis has recently been discovered. The impact of bacteria on cancer is not limited to their contribution to tumorigenesis, but the overall susceptibility of bacteria to subsequent tumor progression, the development of concurrent infections, and the response to anti-cancer therapy have also been found to be affected. Concerns about the contribution of bacteria in the anti-cancer response have inspired researchers to develop bacteria-based anti-cancer treatments. In this paper, we reviewed the main roles of bacteria in the occurrence and development of tumors, and summarized the mechanism of bacteria in the occurrence, development, and clinical anti-tumor treatment of tumors, providing new insights for the in-depth study of the role of bacteria in tumor diagnosis and treatment. This review aims to provide a new perspective for the development of new technologies based on bacteria to enhance anti-tumor immunotherapy.