Pancreatic cancers have high mortality and rising incidence rates which may be related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and obesity rates. Recent data also suggest a role for the gut microbiome in the development of pancreatic cancer. Here, we review the experimental and observational evidence for the roles of the oral, gut and intratumoural microbiomes, impaired gut barrier function and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to pancreatic disease with a focus on pancreatic ductal adenocarcinoma (PDAC) initiation and progression. We also highlight some emerging gut microbiome editing techniques currently being investigated in the context of pancreatic disease. Notably, while the gut microbiome is significantly altered in PDAC and its precursor diseases, its utility as a diagnostic and prognostic tool is hindered by a lack of reproducibility and the potential for reverse causality in case-control cohorts. Future research should emphasise longitudinal and mechanistic studies as well as integrating lifestyle exposure and multi-omics data to unravel complex host-microbiome interactions. This will allow for deeper aetiologic and mechanistic insights that can inform treatments and guide public health recommendations.

Pancreatic cancer, marked by its high lethality and poor 5-year survival rate, requires a thorough understanding of its risk factors and etiological mechanisms. In this review, we collected the latest findings from Mendelian randomization (MR) studies to identify potential causal factors for pancreatic cancer.

The present analysis encompasses MR studies on the gut and oral microbiomes, non-malignant phenotypes, blood metabolites, immune cells, and chronic inflammation. Specific gut and oral microbiome species have been identified as potential causal factors for pancreatic cancer, some with protective effects, and others increasing the risk. The review also highlights causal associations between obesity, type 2 diabetes, and pancreatic cancer, as well as the impact of blood metabolites and immune cell phenotypes on disease risk. Additionally, it investigates the causal effects of inflammatory bowel disease, showing a significant risk increase associated with Crohn's disease.

These insights emphasize the need for interdisciplinary research and personalized medicine to enhance prevention and treatment strategies for pancreatic cancer.

Knowledge about the association between oral microbiome diversity within individuals and cardiovascular disease (CVD) and non-CVD mortality is scarce. Besides, variation by sex and racial and ethnic groups, and the potential mediators of these associations remain unclear. We aimed to investigate the associations of oral microbiome alpha diversity with all-cause, CVD, and non-CVD mortality, and the interaction effects of sex and racial and ethnic groups and potential mediators in the associations.

The National Health and Nutrition Examination Survey (NHANES) is a population-based observational study, conducted periodically in Mexican American, Other Hispanic, Non-Hispanic (NH) White, NH Black, and other racial/ethnic participants. We linked 2009-12 survey data of 8199 adults to the mortality data until 2019. By analyzing RNA gene sequences from oral rinse samples, microbiome alpha diversity within individuals was assessed using operational taxonomic unit (OTU) richness. Potential mediators included obesity, diabetes mellitus, dyslipidemia, hypertension, and periodontitis. Multivariable Cox proportional hazards regression and causal mediation analysis were used.

Baseline mean ± standard deviation (SD) age was 42.1 ± 15.1 years. Over a median follow-up of 9.1 years, 405 all-cause mortality occurred (CVD, 105; non-CVD, 300). Each 1-SD increment in OTU richness was inversely associated with all-cause mortality (hazard ratio [HR] 0.92, 95 % confidence interval [CI] 0.90-0.95), CVD mortality (HR, 0.92; 95 % CI, 0.90-0.95), and non-CVD mortality (HR, 0.92; 95 % CI, 0.90-0.95). With evidence of significant racial and ethnic groups-interaction (p <0.05), these associations were evident in Mexican American, NH White, and others racial/ethnic participants. None of the potential mediators significantly mediated the associations of OTU richness with all-cause, CVD, and non-CVD mortality.

Lower oral microbiome alpha diversity is associated with higher risk for all-cause, CVD, and non-CVD mortality, and the associations are varied by racial and ethnic groups.

The pancreas, previously considered a sterile organ, has recently been shown to harbor its own microbiota that may influence tumor biology and patient outcomes. Despite increasing interest in the impact of the microbiome on cancer, the relationship between pancreatic tissue and oral microbiomes in pancreatic ductal adenocarcinoma (PDAC) remains limited. In this study, the oral and pancreas tissue microbiomes of patients with PDAC were compared to patients with other periampullary cancers (DC/AC) and a healthy control group using 16S rRNA gene sequence analysis. The results showed a significant reduction in microbial diversity in the saliva of cancer patients compared to healthy controls, while the PDAC patients exhibited a distinct microbial profile in their pancreatic tissues, consisting predominantly of Firmicutes, Proteobacteria, and Actinobacter, after filtering the microbiome of the indoor environment. Notably, the presence of oral bacteria such as Anoxybacillus, Clostridium, and Bacillus in pancreatic tissues suggests potential translocation from the oral cavity. This study emphasizes the importance of understanding the role of body fluid and tissue microbiota in pancreatic cancer, proposing that oral dysbiosis may contribute to disease progression. Moreover, the results suggest that the microbiome of the indoor environment in which samples are collected and analyzed is also important in microbiota analysis studies.

The process of wound healing consists of multiple phases, and any disruptions in these phases can lead to the wound becoming chronic and impose heavy financial and psychological costs on the patient and a huge economic burden on the country's healthcare system. Various treatments such as drugs, matrix and scaffolds, blood products, cell therapy, and a combination of these treatments are used for wound healing. The use of mesenchymal stem cells (MSCs) is one of these methods that have produced appropriate responses in the healing of patients' wounds. MSCs by secreting growth factors, cytokines, chemokines, and RNAs elicit changes in cell proliferation, migration, growth, signaling, immunomodulation, and wound re-epithelialization process, and as a result, accelerate wound closure and wound healing. These cells can be isolated from different body sources with different cell characteristics and used directly on the wound site or by injection. In addition, MSCs-derived exosomes have attracted growing attention due to circumventing concerns relating to the direct use of MSCs. To increase the performance of MSCs, they can be used together with other compounds such as platelets, matrices, or scaffolds. This study examined the functions of MSCs in wound healing, as well as the vesicles they secrete, cellular and molecular mechanisms, and combined treatments with MSCs for wound healing.

The convergence of organoid technology and artificial intelligence (AI) is poised to revolutionise oral healthcare. Organoids - three-dimensional structures derived from human tissues - offer invaluable insights into the complex biology of diseases, allowing researchers to effectively study disease mechanisms and test therapeutic interventions in environments that closely mimic in vivo conditions. In this review, we first present the historical development of organoids and delve into the current types of oral organoids, focusing on their use in disease models, regeneration and microbiome intervention. We then compare single-source and multi-lineage oral organoids and assess the latest progress in bioprinted, vascularised and neural-integrated organoids. In the next part of the review, we highlight significant advancements in AI, emphasising how AI algorithms may potentially promote organoid development for early disease detection and diagnosis, personalised treatment, disease prediction and drug screening. However, our main finding is the identification of remaining challenges, such as data integration and the critical need for rigorous validation of AI algorithms to ensure their clinical reliability. Our main viewpoint is that current AI-enabled oral organoids are still limited in applications but, as we look to the future, we offer insights into the potential transformation of AI-integrated oral organoids in oral disease diagnosis, oral microbial interactions and drug discoveries. By synthesising these components, this review aims to provide a comprehensive perspective on the current state and future implications of AI-enabled oral organoids, emphasising their role in advancing oral healthcare and improving patient outcomes.

Bacterial cell surface components such as lipoteichoic acids (LTAs) play critical roles in host-microbe interactions and alter host responses based on their chemical structures. Mitis group streptococci have commensal and pathogenic interactions with the human host and produce Type IV LTAs that are slightly different in chemical structures between species. To reveal the molecular bases for the intricate interactions between MGS and human hosts, a detailed understanding of the structure and biosynthetic process of MGS LTAs is needed. In this study, we used genomic and lipidomic techniques to elucidate the biosynthetic processes of Type IV LTA and its associated glycolipid anchors, monohexosyl-diacylglycerol and dihexosyl-diacyglycerol, in the infectious endocarditis isolate Streptococcus sp. strain 1643. Through establishing a murine sepsis model, we validated the essentiality of these glycolipids in the full virulence of S. mitis. Additionally, we found that these glycolipids play an important role in protecting the bacteria from antimicrobials. Overall, results obtained through this study both confirm and dispute aspects of the existing model of glycolipids biosynthesis, provide insights into the fundamental roles of bacterial glycolipids, as well as suggest the potential of targeting glycolipids for developing antimicrobial therapeutics.

Pancreatic ductal adenocarcinoma (PDAC) has high mortality and rising incidence rates. Recent data indicate that the gut microbiome and associated metabolites may play a role in the development of PDAC. To complement and inform observational studies, we investigated associations of genetically predicted abundances of individual gut bacteria and genetically predicted circulating concentrations of microbiome-associated metabolites with PDAC using Mendelian randomisation (MR). Gut microbiome-associated metabolites were identified through a comprehensive search of Pubmed, Exposome Explorer and Human Metabolome Database. Single Nucleotide Polymorphisms (SNPs) associated by Genome-Wide Association Studies (GWAS) with circulating levels of 109 of these metabolites were collated from Pubmed and the GWAS catalogue. SNPs for 119 taxonomically defined gut genera were selected from a meta-analysis performed by the MiBioGen consortium. Two-sample MR was conducted using GWAS summary statistics from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), including a total of 8,769 cases and 7,055 controls. Inverse variance-weighted MR analyses were performed along with sensitivity analyses to assess potential violations of MR assumptions. Nominally significant associations were noted for genetically predicted circulating concentrations of mannitol (odds ratio per standard deviation [ORSD] = 0.97; 95% confidence interval [CI]: 0.95-0.99, p = 0.006), methionine (ORSD= 0.97; 95%CI: 0.94-1.00, p = 0.031), stearic acid (ORSD= 0.93; 95%CI: 0.87-0.99, p = 0.027), carnitine = (ORSD=1.01; 95% CI: 1.00-1.03, p = 0.027), hippuric acid (ORSD= 1.02; 95%CI: 1.00-1.04, p = 0.038) and 3-methylhistidine (ORSD= 1.05; 95%CI: 1.01-1.10, p = 0.02). Two gut microbiome genera were associated with reduced PDAC risk; Clostridium sensu stricto 1 (OR: 0.88; 95%CI: 0.78-0.99, p = 0.027) and Romboutsia (OR: 0.87; 95%CI: 0.80-0.96, p = 0.004). These results, though based only on genetically predicted gut microbiome characteristics and circulating bacteria-related metabolite concentrations, provide evidence for causal associations with pancreatic carcinogenesis.

Individuals with pancreatic-related health conditions usually show lower diversity and different composition of bacterial and viral species between the gut and oral microbiomes compared to healthy individuals. We performed a thorough microbiome analysis, using deep shotgun sequencing of stool and saliva samples obtained from patients with chronic pancreatitis (CP), pancreatic ductal adenocarcinoma (PDAC), and healthy controls (HCs).We observed similar microbiota composition at the species level in both the gut and oral samples in PDAC patients compared to HCs, among which the most distinctive finding was that the abundance of oral-originated Fusobacterium nucleatum species did not differ between the oral and the gut samples. Moreover, comparing PDAC patients with HCs, Klebsiella oxytoca was significantly more abundant in the stool samples of PDAC patients, while Streptococcus spp. showed higher abundance in both the oral and stool samples of PDAC patients. Finally, the most important finding was the distinctive gut phage-bacterial interactome pattern among PDAC patients. CrAssphages, particularly Blohavirus, showed mutual exclusion with K. oxytoca species, while Burzaovirus showed co-occurrence with Enterobacteriaceae spp., which have been shown to be capable of inducing DNA damage in human pancreatic cells ex vivo. The interactome findings warrant further mechanistic studies, as our findings may provide new insights into developing microbiota-based diagnostic and therapeutic methods for pancreatic diseases.

The increase in metagenome-assembled genomes (MAGs) has advanced our understanding of the functional characterization and taxonomic assignment within the human microbiome. However, MAGs, as population consensus genomes, often aggregate heterogeneity among species and strains, thereby obfuscating the precise relationships between microbial hosts and mobile genetic elements (MGEs). In contrast, single amplified genomes (SAGs) derived via single-cell genome sequencing can capture individual genomic content, including MGEs.

We introduce the first substantial SAG dataset (bbsag20) from the human oral and gut microbiome, comprising 17,202 SAGs above medium-quality without co-assembly. This collection unveils a diversity of bacterial lineages across 312 oral and 647 gut species, demonstrating different taxonomic compositions from MAGs. Moreover, the SAGs showed cellular-level evidence of the translocation of oral bacteria to the gut. We also identified broad-host-range MGEs harboring antibiotic resistance genes (ARGs), which were not detected in the MAGs.

The difference in taxonomic composition between SAGs and MAGs indicates that combining both methods would be effective in expanding the genome catalog. By connecting mobilomes and resistomes in individual samples, SAGs could meticulously chart a dynamic network of ARGs on MGEs, pinpointing potential ARG reservoirs and their spreading patterns in the microbial community. Video Abstract.

The review aimed to investigate the diversity of oral microbiota and its influencing factors, as well as the association of oral microbiota with oral health and the possible effects of dysbiosis and oral disorder. The oral cavity harbors a substantial microbial burden, which is particularly notable compared to other organs within the human body. In usual situations, the microbiota exists in a state of equilibrium; however, when this balance is disturbed, a multitude of complications arise. Dental caries, a prevalent issue in the oral cavity, is primarily caused by the colonization and activity of bacteria, particularly streptococci. Furthermore, this environment also houses other pathogenic bacteria that are associated with the onset of gingival, periapical, and periodontal diseases, as well as oral cancer. Various strategies have been employed to prevent, control, and treat these disorders. Recently, techniques utilizing microbiota, like probiotics, microbiota transplantation, and the replacement of oral pathogens, have caught the eye. This extensive examination seeks to offer a general view of the oral microbiota and their metabolites concerning oral health and disease, and also the resilience of the microbiota, and the techniques used for the prevention, control, and treatment of disorders in this specific area.

The incidence of pancreatic cancer is rising. At present, pancreatic cancer is the third most common cancer-causing death in Germany, but it is expected to become the second in 2030 and finally the leading cause of cancer death in 2050. Pancreatic ductal adenocarcinoma (PC) is generally diagnosed at advanced stages, and 5-year-survival has remained poor. Early detection of sporadic PC at stage IA, however, can yield a 5-year-survival rate of about 80%. Early detection initiatives aim at identifying persons at high risk. People with new-onset diabetes at age 50 or older have attracted much interest. Novel strategies regarding how to detect sporadic PC at an early stage are being discussed.

This comprehensive review explores the complexities surrounding pancreatic head cancer, a highly fatal and challenging-to-treat illness with a survival rate of less than five years. Despite being a major contributor to cancer-related deaths, pancreatic head malignancy often eludes early detection due to its posterior location and high metastatic potential. The review delves into the associated symptoms, including gastric outlet obstruction and obstructive jaundice, highlighting the impact on the patient's eligibility for surgery. Examining recent advancements, the article discusses fast-track surgery recovery programs and emerging immunotherapeutic approaches, acknowledging the unique challenges posed by the immunosuppressive environment of pancreatic head cancer. Additionally, the review elucidates the intricate relationship between pancreatic cancer and glucose levels, emphasizing the role of islets of Langerhans in insulin production. The pathogenesis section explores lifestyle and genetic factors contributing to pancreatic head carcinoma, shedding light on risk factors such as smoking, obesity, diabetes, and hereditary predispositions. The extensive analysis of pancreatic cancer diagnosis methods encompasses imaging techniques, biopsies, and biomarkers, emphasizing the challenges posed by late-stage diagnoses. Addressing treatment modalities, the review emphasizes the significance of surgery, chemotherapy, radiotherapy, and targeted therapy. The intricate details of neoadjuvant, immunotherapy, and microbial therapy provide a comprehensive understanding of evolving treatment strategies. The review concludes by highlighting promising areas of research, including oncolytic viral therapy and gene editing technology, aiming to enhance the limited treatment options for this devastating disease.

The human microbiome, found throughout various body parts, plays a crucial role in health dynamics and disease development. Recent research has highlighted microbiome disparities between patients with different diseases and healthy individuals, suggesting the microbiome's potential in recognizing health states. Traditionally, microbiome-based status classification relies on pre-trained machine learning (ML) models. However, most ML methods overlook microbial relationships, limiting model performance.

To address this gap, we propose PM-CNN (Phylogenetic Multi-path Convolutional Neural Network), a novel phylogeny-based neural network model for multi-status classification and disease detection using microbiome data. PM-CNN organizes microbes based on their phylogenetic relationships and extracts features using a multi-path convolutional neural network. An ensemble learning method then fuses these features to make accurate classification decisions. We applied PM-CNN to human microbiome data for status and disease detection, demonstrating its significant superiority over existing ML models. These results provide a robust foundation for microbiome-based state recognition and disease prediction in future research and applications.

PM-CNN software is available at https://github.com/qdu-bioinfo/PM_CNN.

The oral microbiome potentially wields significant influence in the development of cancer. Within the human oral cavity, an impressive diversity of more than 700 bacterial species resides, making it the second most varied microbiome in the body. This finely balanced oral microbiome ecosystem is vital for sustaining oral health. However, disruptions in this equilibrium, often brought about by dietary habits and inadequate oral hygiene, can result in various oral ailments like periodontitis, cavities, gingivitis, and even oral cancer. There is compelling evidence that the oral microbiome is linked to several types of cancer, including oral, pancreatic, colorectal, lung, gastric, and head and neck cancers. This review discussed the critical connections between cancer and members of the human oral microbiota. Extensive searches were conducted across the Web of Science, Scopus, and PubMed databases to provide an up-to-date overview of our understanding of the oral microbiota's role in various human cancers. By understanding the possible microbial origins of carcinogenesis, healthcare professionals can diagnose neoplastic diseases earlier and design treatments accordingly.

The incidence of pancreatic cancer is increasing worldwide. The most common form is represented by pancreatic ductal adenocarcinoma (PDAC) which has been shown to be linked to chronic inflammation. Notably, the gut microbiota has emerged as a critical player in regulating immune responses and inflammation. Indeed, intestinal dysbiosis, characterized by an imbalance in the gut microbiota composition, can contribute to the initiation of chronic inflammation. Sterile chronic inflammation can occur, probably activated by the translocation of bacterial components, such as lipopolysaccharide (LPS), the major component of Gram-negative microbiota, with the consequent induction of innate mucosal immunity, through the activation of Toll-like receptors (TLRs). Furthermore, the interaction between LPS and TLRs could enhance cancer progression. Recent research has shed light on the pivotal role of nutrition, as a modifiable risk factor, in PDAC immunological processes, particularly focusing on the immuno-modulatory effects of the gut microbiota. Different dietary regimens, fiber intake, immunonutrients, and antioxidants have the potential to either exacerbate or mitigate chronic inflammation, thereby influencing the pathogenesis and natural history of PDAC. These dietary components may affect the gut microbiota composition and, consequently, the level of inflammation, either promoting or protecting against PDAC. In this review of reviews, we discuss the modulatory role of nutrition and the gut microbiota in PDAC's immunological processes to explore a translational therapeutic approach that could improve the survival and quality of life of these patients.

Alcohol-related liver disease (ALD) is one of the leading causes of liver-related death worldwide. However, roles of oral microbiota in regulating the progression of ALD remain unknown. Here, we fed mice with control or ethanol diet to establish chronic-plus-binge ALD model. 16S ribosomal DNA sequencing was performed on oral and cecum samples. We demonstrated that alcohol drinking influenced bacterial richness, microbial structure, and composition in oral samples of ethanol-fed mice compared with control mice. Alcohol consumption also remodeled relationships among oral microbes and altered functions of oral microbiota. Furthermore, oral microbiota, such as Streptococcus, Helicobacter, Alloprevotella, and Psychrobacter were closely associated with ALD parameters. Finally, we observed Sutterellaceae_uncultured, Dyella, and Gemmatimonas possibly translocated along with oral-gut axis and positively correlated with the severity of ALD. Altogether, alcohol consumption reprogramed composition and functions of oral microbiota to promote ALD progression, suggesting that oral microbes might become a new target for ALD therapy.

A growing number of studies demonstrate the oral bacterial shift in cancer patients and the enrichment of oral bacteria in distant tumours. During the oncological treatment, opportunistic oral bacteria correlate with oral toxicities. This review focused on the most recent studies to identify which genera are the most mentioned and deserved further investigation.

This review evaluated bacterial changes in patients with head and neck, colorectal, lung and breast cancer. Greater composition of disease-related genera (e.g., Fusobacterium , Porphyromonas , Lactobacillus , Streptococcus , and Parvimonas ) are present in the oral cavity of these groups of patients. The tumour specimen characterisation of head and neck, pancreatic and colorectal cancer also describes the presence of oral taxa. No evidence indicates that commensal oral bacteria have protective roles in distant tumours. Regardless, oral care is critical to prevent the growth of oral pathogens and reduce infection foci.

Recent evidence suggests that oral microbiota is a potential biomarker for oncological clinical outcomes and oral toxicities. Currently, the literature presents a remarkable methodological variety - from the sample collection site to the preference of the data analysis tools. For the oral microbiome to achieve the stage of being used as a clinical tool in the oncological context, more studies are necessary.

Pancreatic cancer is one of the most lethal human malignancies, in part because it is often diagnosed at late stages when surgery and systemic therapies are either unfeasible or ineffective. Therefore, diagnosing pancreatic cancer in earlier stages is important for effective treatment. However, because the signs and symptoms may be nonspecific and not apparent until the disease is at a late stage, the timely diagnoses of pancreatic cancer can be difficult to achieve. Recent studies have shown that selective screening and increased usage of biomarkers could improve the early diagnosis of pancreatic cancer. In this review, we discuss recent advancements in the early detection of pancreatic ductal carcinoma and precancerous lesions. These include innovations in imaging modalities, the diagnostic utility of various biomarkers, biopsy techniques, and population-based surveillance approaches. Additionally, we discuss how machine learning methods are being applied to develop integrated methods of identifying individuals at high risk of developing pancreatic disease. In the future, the overall survival of pancreatic cancer patients could be improved by the development and adoption of these new methods and techniques.

Oral dysbiosis has long been associated with pancreatic ductal adenocarcinoma (PDAC). In this work, we explore the relationship between the oral and tumor microbiomes of patients diagnosed with PDAC. Salivary and tumor microbiomes were analyzed using a variety of sequencing methods, resulting in a high prevalence and relative abundance of oral bacteria, particularly Veillonella and Streptococcus, within tumor tissue. The most prevalent and abundant taxon found within both saliva and tumor tissue samples, Veillonella atypica, was cultured from patient saliva, sequenced and annotated, identifying genes that potentially contribute to tumorigenesis. High sequence similarity was observed between sequences recovered from patient matched saliva and tumor tissue, indicating that the taxa found in PDAC tumors may derive from the mouth. These findings may have clinical implications in the care and treatment of patients diagnosed with PDAC.

Over the past decade, a plethora of studies have delved into the oral microbiome. Our objective was to evaluate the trends in oral microbiome research employing a quantitative approach.

We extracted clinical studies on the oral microbiome published between 2013 and 2022 from the Web of Science database, yielding 3024 articles. The assembled literature was visually scrutinized using VOSviewer 1.6.18, Citespace 6.1.6, Pajek, Scimago Graphica, and other specialized software to assess authors, institutions, countries, journals, co-cited literature, keywords, genes, and diseases.

Our analysis identified a total of 3024 articles. The volume and rate of annual publications steadily increased, with research interest in the oral microbiome progressively intensifying. The United States, China, and the UK contributed the highest number of publications. Growth rates of publications varied among countries over time. The Forsyth Institute emerged as the most collaborative institution, boasting the highest number of relevant papers (135) and securing the top rank, followed by Sichuan University and Harvard University. Paster Bruce J, Zhou Xuedong, and He Xuesong were pioneers in the field of oral microbiome research. This analysis demonstrates that the homeostatic balance of the oral microbiome, advanced microbial sequencing technology, connections with gut microbiota, and tumorigenesis, including oral cancer, have become emerging topics in the oral microbiome field.

This study delineated a comprehensive landscape of hotspots and frontiers in oral microbiome research, thus facilitating the identification of interdisciplinary advancements. We sincerely hope that our bibliometric analysis will enable researchers to leverage the oral microbiome to ultimately improve human oral health.

The oral microbiome is an emerging field that has been a topic of discussion since the development of next generation sequencing and the implementation of the human microbiome project. This article reviews the current literature surrounding the oral microbiome, briefly highlighting most recent methods of microbiome characterization including cutting edge omics, databases for the microbiome, and areas with current gaps in knowledge. This article also describes reports on microorganisms contained in the oral microbiome which include viruses, archaea, fungi, and bacteria, and provides an in-depth analysis of their significant roles in tissue homeostasis. Finally, we detail key bacteria involved in oral disease, including oral cancer, and the current research surrounding their role in stimulation of inflammatory cytokines, the role of gingival crevicular fluid in periodontal disease, the creation of a network of interactions between microorganisms, the influence of the planktonic microbiome and cospecies biofilms, and the implications of antibiotic resistance. This paper provides a comprehensive literature analysis while also identifying gaps in knowledge to enable future studies to be conducted.

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.

The oral microbiome plays a major role in shaping oral health/disease state; thus, a main challenge for dental practitioners is to preserve or restore a balanced oral microbiome. Nonetheless, when pathogenic microorganisms install in the oral cavity and are incorporated into the oral biofilm, oral infections, such as gingivitis, dental caries, periodontitis, and peri-implantitis, can arise. Several prophylactic and treatment approaches are available nowadays, but most of them have been antibiotic-based. Given the actual context of antimicrobial resistance (AMR), antibiotic stewardship in dentistry would be a beneficial approach to optimize and avoid inappropriate or even unnecessary antibiotic use, representing a step towards precision medicine. Furthermore, the development of new effective treatment options to replace the need for antibiotics is being pursued, including the application of photodynamic therapy and the use of probiotics. In this review, we highlight the advances undergoing towards a better understanding of the oral microbiome and oral resistome. We also provide an updated overview of how dentists are adapting to better manage the treatment of oral infections given the problem of AMR.

The microbiota impact on human diseases is well-known, and a growing body of literature is providing evidence about the complex interplay between microbiota-immune system-human physiology/pathology, including cancers. Together with the defined risk factors (e.g., smoke habits, diet, diabetes, and obesity), the oral, gut, biliary, and intrapancreatic microbiota contribute to pancreatic cancer development through different pathways including the interaction with the immune system. Unfortunately, a great majority of the pancreatic cancer patients received a diagnosis in advanced stages not amenable to be radically treated and potentially cured. Given the poor pancreatic cancer prognosis, complete knowledge of these complicated relationships could help researchers better understand the disease pathogenesis and thus provide early potential non-invasive biomarkers, new therapeutic targets, and tools for risk stratification that might result in greater therapeutic possibilities and eventually in a better and longer patient survival.