Intratumoral microbiota are increasingly recognized for their impact on gastric cancer, with growing evidence highlighting their complexity and significance. This review synthesizes current knowledge on the origins, heterogeneity, detection, and mechanistic roles of intratumoral microbiota in gastric carcinogenesis. In gastric cancer, intratumoral microbiota can originate from mucosal disruption and may migrate from normal adjacent tissues or be influenced by the TME. It exhibits spatial and functional heterogeneity within gastric cancer. Despite challenges in the detection of intratumoral microbiota, advances in deep sequencing and spatial omics have enhanced our understanding of microbial diversity and functionality. Mechanistically, intratumoral microbiota influence gastric cancer development through genetic and epigenetic alterations, signaling pathway modulation, metabolic reprogramming, and regulation of chronic inflammation and immune responses. These insights underscore the microbiota's dual function in both promoting and hindering tumor advancement. Therapeutically, the microbiota's impact on chemotherapy resistance and immune modulation presents opportunities for novel interventions. Integrating microbiome analysis into cancer research and leveraging microbial therapies may enable more effective, personalized treatment strategies. Future research should further elucidate the intricate microbe-tumor interactions to advance clinical applications and improve outcomes for gastric cancer patients.

Findings from previous gastric cancer microbiome studies have been conflicting, potentially due to patient and/or tumor heterogeneity. The intratumoral gastric cancer microbiome and its relationship with clinicopathological variables have not yet been characterized in detail. We hypothesized that variation in gastric cancer microbial abundance, alpha diversity, and composition is related to clinicopathological characteristics.

Metagenomic analysis of 529 GC samples was performed, including whole exome sequencing data from The Cancer Genome Atlas (TCGA) and whole genome sequencing data from the 100,000 Genomes Project. Microbial abundance, alpha diversity, and composition were compared across patient age, sex, tumor location, geographic origin, pathological depth of invasion, pathological lymph node status, histological phenotype, microsatellite instability status, and TCGA molecular subtype.

Gastric cancer microbiomes resembled previous results, with Prevotella, Selenomonas, Stomatobaculum, Streptococcus, Lactobacillus, and Lachnospiraceae commonly seen across both cohorts. Within the TCGA cohort, microbial abundance and alpha diversity were greater in gastric cancers with microsatellite instability, lower pathological depth of invasion, intestinal-type histology, and those originating from Asia. Microsatellite instability status was associated with microbiome composition in both cohorts. Sex and pathological depth of invasion were associated with microbiome composition in the TCGA cohort.

The intratumoral gastric cancer microbiome appears to differ according to clinicopathological factors. Certain clinicopathological factors associated with favourable outcomes in gastric cancer were observed to be associated with greater microbial abundance and diversity. This highlights the need for further work to understand the underlying biological mechanisms behind the observed microbiome differences and their potential clinical and therapeutic impact.

The demonstration that Helicobacter pylori is a pathogenic bacterium with marked carcinogenic potential has paved the way for new preventive approaches for gastric cancer. Although decades of research have uncovered complex interactions of H. pylori with epithelial cells, current insights have refined our view on H. pylori-associated carcinogenesis. Specifically, the cell-type-specific effects on gastric stem and progenitor cells deep in gastric glands provide a new view on the ability of the bacteria to colonize long-term, manipulate host responses and promote gastric pathology. Furthermore, new, large-scale epidemiological data have shed light on factors that determine why only a subset of carriers progress to gastric cancer. Currently, technological advances have brought yet another revelation: H. pylori is far from the only microorganism able to colonize the stomach. Instead, the stomach is colonized by a diverse gastric microbiota, and there is emerging evidence for the occurrence and pathological effect of dysbiosis resulting from an aberrant interplay between H. pylori and the gastric mucosa. With the weight of this evidence mounting, here we consider how the lessons learned from H. pylori research inform and synergize with this emerging field to bring a more comprehensive understanding of the role of microbes in gastric carcinogenesis.

The human microbiome plays a crucial role in modulating health and disease susceptibility through a complex network of interactions with the host. When the delicate balance of this microbial ecosystem is disrupted, it often correlates with the onset of systemic diseases. An over-abundance of pathogenic microorganisms within the microbiome has been implicated as a driving factor in the development of disease conditions such as diabetes, obesity, and chronic infections. It has been observed that microbiome dysbiosis perturbs metabolic, inflammatory, and immunological pathways, potentially facilitating carcinogenesis. Furthermore, the metabolites associated with microbial dysbiosis exert multifaceted effects, including metabolic interference, host DNA damage, and tumor promotion, further underscoring the microbiome's significance in several of the cancers. This new exploration of microbiome involvement in carcinogenesis needs additional patient sample analysis, which could provide new insights into cancer diagnosis and treatment. However, treating these diseases using drugs, traditional methods, etc. has resulted in multi-drug resistance, and this has eventually made the situation worrisome. This review highlights the importance of nanotechnology, which may tackle these pathogenic conditions simultaneously by targeting common receptors present in bacteria and cancer. Herein, we have explained how nanotechnology may come to the forefront for these treatments. It explores the potential of non-antibiotic disinfectants, i.e., nanoparticles (NPs) with dual targeting capabilities against microbes and cancer cells, using mechanisms such as ROS generation and DNA damage while minimizing the chances of drug resistance.

Microbiome analysis has become a crucial tool for basic and translational research due to its potential for translation into clinical practice. However, there is ongoing controversy regarding the comparability of different bioinformatic analysis platforms and a lack of recognized standards, which might have an impact on the translational potential of results. This study investigates how the performance of different microbiome analysis platforms impacts the final results of mucosal microbiome signatures. Across five independent research groups, we compared three distinct and frequently used microbiome analysis bioinformatic packages (DADA2, MOTHUR, and QIIME2) on the same subset of fastQ files. The source data set encompassed 16S rRNA gene raw sequencing data (V1-V2) from gastric biopsy samples of clinically well-defined gastric cancer (GC) patients (n = 40; with and without Helicobacter pylori [H. pylori] infection) and controls (n = 39, with and without H. pylori infection). Independent of the applied protocol, H. pylori status, microbial diversity and relative bacterial abundance were reproducible across all platforms, although differences in performance were detected. Furthermore, alignment of the filtered sequences to the old and new taxonomic databases (i.e., Ribosomal Database Project, Greengenes, and SILVA) had only a limited impact on the taxonomic assignment and thus on global analytical outcomes. Taken together, our results clearly demonstrate that different microbiome analysis approaches from independent expert groups generate comparable results when applied to the same data set. This is crucial for interpreting respective studies and underscores the broader applicability of microbiome analysis in clinical research, provided that robust pipelines are utilized and thoroughly documented to ensure reproducibility.IMPORTANCEMicrobiome analysis is one of the most important tools for basic and translational research due to its potential for translation into clinical practice. However, there is an ongoing controversy about the comparability of different bioinformatic analysis platforms and a lack of recognized standards. In this study, we investigate how the performance of different microbiome analysis platforms affects the final results of mucosal microbiome signatures. Five independent research groups used three different and commonly used bioinformatics packages for microbiome analysis on the same data set and compared the results. This data set included microbiome sequencing data from gastric biopsy samples of GC patients. Regardless of the protocol used, Helicobacter pylori status, microbial diversity, and relative bacterial abundance were reproducible across all platforms. The results show that different microbiome analysis approaches provide comparable results. This is crucial for the interpretation of corresponding studies and underlines the broader applicability of microbiome analysis.

Gastric cancer (GC) is a malignant tumour with high morbidity and mortality worldwide, and there is an urgent need for early diagnosis and precision treatment. In recent years, the role of microbiota in the occurrence and development of GC has drawn extensive attention. Particularly, the in-depth study of GC-related microbiota by 16S rRNA sequencing technology has offered valuable tools and new perspectives for exploring the microbial characteristics of GC patients. This review systematically summarises the microbial diversity and composition of GC and non-GC samples based on 16S rRNA data, outlines the progress in identifying GC-related microbial biomarkers, explores the potential mechanisms by which diagnostic microbial biomarkers influence the development of GC, and reflects on the limitations of present studies. By integrating the current evidence, this review intends to offer a new theoretical foundation and further direction for the clinical translation of microbiota research in the diagnosis and treatment of GC.

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

The role of microbiota in human health and disease is becoming increasingly clear as a result of modern microbiome studies in recent decades. The gastrointestinal tract is the major habitat for microbiota in the human body. This microbiota comprises several trillion microorganisms, which is equivalent to almost ten times the total number of cells of the human host. Helicobacter pylori is a known pathogen that colonizes the gastric mucosa of almost half of the world population. H. pylori is associated with several gastric diseases, including gastric cancer (GC) development. However, the impact of the gastric microbiota in the colonization, chronic infection, and pathogenesis is still not fully understood. Several studies have documented qualitative and quantitative changes in the microbiota's composition in the presence or absence of this pathogen. Among the diverse microflora in the stomach, the Firmicutes represent the most notable. Bacteria such as Prevotella sp., Clostridium sp., Lactobacillus sp., and Veillonella sp. were frequently found in the healthy human stomach. In contrast, H.pylori is very dominant during chronic gastritis, increasing the proportion of Proteobacteria in the total microbiota to almost 80%, with decreasing relative proportions of Firmicutes. Likewise, H. pylori and Streptococcus are the most abundant bacteria during peptic ulcer disease. While the development of H. pylori-associated intestinal metaplasia is accompanied by an increase in Bacteroides, the stomachs of GC patients are dominated by Firmicutes such as Lactobacillus and Veillonella, constituting up to 40% of the total microbiota, and by Bacteroidetes such as Prevotella, whereas the numbers of H. pylori are decreasing. This review focuses on some of the consequences of changes in the gastric microbiota and the function of probiotics to modulate H. pylori infection and dysbiosis in general.

The gut microbiota plays a crucial role in modulating anticancer immunity, significantly impacting the effectiveness of various cancer therapies, including immunotherapy, chemotherapy, and radiotherapy. Its impact on the development of cancer is complex; certain bacteria, like Fusobacterium nucleatum and Bacteroides fragilis, can stimulate the growth of tumors by causing immunological evasion and inflammation, while advantageous strains, like Faecalibaculum rodentium, have the ability to suppress tumors by modifying immune responses. Cytokine activity and immune system regulation are intimately related. Cytokines including TGF-β, IL-6, and IL-10 promote tumor development by inhibiting efficient immune surveillance. The gut microbiome exhibits a delicate balance between pro- and anti-tumorigenic factors, as evidenced by the enhancement of anti-tumor immunity by cytokines such as IL-12 and IFN-γ. Improved immunotherapy responses are linked to a diverse microbiota, which is correlated with higher tumor infiltration and cytotoxic T-cell activation. Because microbial metabolites, especially short-chain fatty acids, affect cytokine expression and immune cell activation inside the tumor microenvironment, this link highlights the need to maintain microbial balance for optimal treatment effects. Additionally, through stimulating T-cell activation, bacteria like Lactobacillus rhamnosus and Bifidobacterium bifidum increase cytokine production and improve the efficacy of immune checkpoint inhibitors (ICIs). An option for overcoming ICI resistance is fecal microbiota transplantation (FMT), since research suggests that it improves melanoma outcomes by increasing CD8+ T-cell activation. This complex interaction provides an opportunity for novel cancer therapies by highlighting the possibility of microbiome modification as a therapeutic approach in personalized oncology approaches.

Gastric cancer (GC) is one of the most common malignancies and a prominent cause of cancer mortality worldwide. A distinctive characteristic of GC is its intimate association with commensal microbial community. Although Helicobacter pylori is widely recognised as an inciting factor of the onset of gastric carcinogenesis, increasing evidence has indicated the substantial involvement of microbes that reside in the gastric mucosa during disease progression. In particular, dysregulation in gastric microbiota could play pivotal roles throughout the whole carcinogenic processes, from the development of precancerous lesions to gastric malignancy. Here, current understanding of the gastric microbiota in GC development is summarised. Potential translational and clinical implications of using gastric microbes for GC diagnosis, prognosis and therapeutics are also evaluated, with further discussion on conceptual haziness and limitations at present. Finally, we highlight that modulating microbes is a novel and promising frontier for the prevention and management of GC, which necessitates future in-depth investigations.

Fusobacterium nucleatum (F. nucleatum) is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation, such as periodontitis and gingivitis. In the last 10 years, F. nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression, metastasis and poor disease outcome. While the role of F. nucleatum in colon carcinogenesis has been intensively studied, its role in gastric carcinogenesis is still poorly understood. Although Helicobacter pylori infection has historically been recognized as the strongest risk factor for the development of gastric cancer (GC), with recent advances in DNA sequencing technology, other members of the gastric microbial community, and F. nucleatum in particular, have received increasing attention. In this review, we summarize the existing knowledge on the involvement of F. nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F. nucleatum in GC.

Gastric cancer is a remarkably heterogeneous tumor. Despite some advances in the diagnosis and treatment of gastric cancer in recent years, the precise treatment and curative outcomes remain unsatisfactory. Poor prognosis continues to pose a major challenge in gastric cancer. Therefore, it is imperative to identify effective targets to improve the treatment and prognosis of gastric cancer patients. It should be noted that glycosylation, a novel form of posttranslational modification, is a process capable of regulating protein function and influencing cellular activities. Currently, numerous studies have shown that glycosylation plays vital roles in the occurrence and progression of gastric cancer. As crucial enzymes that regulate glycan synthesis in glycosylation processes, glycosyltransferases are potential targets for treating GC. Hence, investigating the regulation of glycosyltransferases and the expression of associated proteins in gastric cancer cells is highly important. In this review, the related glycosyltransferases and their related signaling pathways in gastric cancer, as well as the existing inhibitors of glycosyltransferases, provide more possibilities for targeted therapies for gastric cancer.

Gastric cancer (GC) treatment regimens are still unsatisfactory. Recently, Urolithin A (UroA) has gained tremendous momentum due to its anti-tumor properties. However, the therapeutic effect and underlying mechanisms of UroA in GC are unclear. We explored the effects and related mechanisms of UroA on GC both in vivo and in vitro. A Cell Counting Kit-8 was used to determine the influence of UroA on the proliferation of GC cell lines. The Autophagy inhibitor 3-methyladenine (3MA) was employed to clarify the role of autophagy in the anti-tumor effect of UroA. Simultaneously, we detected the core-component proteins involved in autophagy and its downstream pathways. Subsequently, the in vivo anti-tumor effect of UroA was determined using a xenograft mouse model. Western blotting was used to detect the core protein components of the anti-tumor pathways, and 16S rDNA sequencing was used to detect the effect of UroA on the gut microbiota. We found that UroA suppressed tumor progression. The use of 3MA undermined the majority of the inhibitory effect of UroA on tumor cell proliferation, further confirming the importance of autophagy in the anti-tumor effect of UroA. Invigorating of autophagy activated the downstream Hippo pathway, thereby inhibiting the Warburg effect and promoting cell apoptosis. In addition, UroA modulated the composition of the gut microbiota, as indicated by the increase of probiotics and the decrease of pathogenic bacteria. Our research revealed new anti-tumor mechanisms of UroA, which may be a promising candidate for GC treatment.

Anastomotic leakage (AL) is a potentially life-threatening complication following colorectal cancer (CRC) resection. In this study, we aimed to unravel longitudinal changes in microbial structure before, during, and after surgery and to determine if microbial alterations may be predictive for risk assessment between sufficient anastomotic healing (AS) and AL prior surgery. We analysed the microbiota of 134 colon mucosal biopsies with 16S rRNA V1-V2 gene sequencing. Samples were collected from three location sites before, during, and after surgery, and patients received antibiotics after the initial collection and during surgery. The microbial structure showed dynamic surgery-related changes at different time points. Overall bacterial diversity and the abundance of some genera such as Faecalibacterium or Alistipes decreased over time, while the genera Enterococcus and Escherichia_Shigella increased. The distribution of taxa between AS and AL revealed significant differences in the abundance of genera such as Prevotella, Faecalibacterium and Phocaeicola. In addition to Phocaeicola, Ruminococcus2 and Blautia showed significant differences in abundance between preoperative sample types. ROC analysis of the predictive value of these genera for AL revealed an AUC of 0.802 (p = 0.0013). In summary, microbial composition was associated with postoperative outcomes, and the abundance of certain genera may be predictive of postoperative complications.

The morbidity and mortality of gastrointestinal (GI) malignancies are among the highest in the world, posing a serious threat to human health. Because of the insidious onset of the cancer, it is difficult for patients to be diagnosed at an early stage, and it rapidly progresses to an advanced stage, resulting in poor treatment and prognosis. Fusobacterium nucleatum (F. nucleatum) is a gram-negative, spore-free anaerobic bacterium that primarily colonizes the oral cavity and is implicated in the development of colorectal, esophageal, gastric, and pancreatic cancers via various intricate mechanisms. Recent development in novel research suggests that F. nucleatum may function as a biomarker in GI malignancies. Detecting the abundance of F. nucleatum in stool, saliva, and serum samples of patients may aid in the diagnosis, risk assessment, and prognosis monitoring of GI malignancies. This editorial systematically describes the biological roles and mechanisms of F. nucleatum in GI malignancies focusing on the application of F. nucleatum as a biomarker in the diagnosis and prognosis of GI malignancies to promote the clinical translation of F. nucleatum and GI tumors-related research.

Recently, research on the human microbiome, especially concerning the bacteria within the digestive system, has substantially advanced. This exploration has unveiled a complex interplay between microbiota and health, particularly in the context of disease. Evidence suggests that the gut microbiome plays vital roles in digestion, immunity and the synthesis of vitamins and neurotransmitters, highlighting its significance in maintaining overall health. Conversely, disruptions in these microbial communities, termed dysbiosis, have been linked to the pathogenesis of various diseases, including digestive system cancers. These bacteria can influence cancer progression through mechanisms such as DNA damage, modulation of the tumour microenvironment, and effects on the host's immune response. Changes in the composition and function within the tumours can also impact inflammation, immune response and cancer therapy effectiveness. These findings offer promising avenues for the clinical application of intratumoral bacteria for digestive system cancer treatment, including the potential use of microbial markers for early cancer detection, prognostication and the development of microbiome-targeted therapies to enhance treatment outcomes. This review aims to provide a comprehensive overview of the pivotal roles played by gut microbiome bacteria in the development of digestive system cancers. Additionally, we delve into the specific contributions of intratumoral bacteria to digestive system cancer development, elucidating potential mechanisms and clinical implications. Ultimately, this review underscores the intricate interplay between intratumoral bacteria and digestive system cancers, underscoring the pivotal role of microbiome research in transforming diagnostic, prognostic and therapeutic paradigms for digestive system cancers.

Gastric cancer (GC) is one of the most common cancers worldwide. Most patients are diagnosed at the progressive stage of the disease, and current anticancer drug advancements are still lacking. Therefore, it is crucial to find relevant biomarkers with the accurate prediction of prognoses and good predictive accuracy to select appropriate patients with GC. Recent advances in molecular profiling technologies, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, have enabled the approach of GC biology at multiple levels of omics interaction networks. Systemic biological analyses, such as computational inference of "big data" and advanced bioinformatic approaches, are emerging to identify the key molecular biomarkers of GC, which would benefit targeted therapies. This review summarizes the current status of how bioinformatics analysis contributes to biomarker discovery for prognosis and prediction of therapeutic efficacy in GC based on a search of the medical literature. We highlight emerging individual multi-omics datasets, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics, for validating putative markers. Finally, we discuss the current challenges and future perspectives to integrate multi-omics analysis for improving biomarker implementation. The practical integration of bioinformatics analysis and multi-omics datasets under complementary computational analysis is having a great impact on the search for predictive and prognostic biomarkers and may lead to an important revolution in treatment.

High-throughput sequencing has ushered in a paradigm shift in gastric microbiota, breaking the stereotype that the stomach is hostile to microorganisms beyond H. pylori. Recent attention directed toward the composition and functionality of this 'community' has shed light on its potential relevance in cancer. The microbial composition in the stomach of health displays host specificity which changes throughout a person's lifespan and is subject to both external and internal factors. Distinctive alterations in gastric microbiome signature are discernible at different stages of gastric precancerous lesions and malignancy. The robust microbes that dominate in gastric malignant tissue are intricately implicated in gastric cancer susceptibility, carcinogenesis, and the modulation of immunosurveillance and immune escape. These revelations offer fresh avenues for utilizing gastric microbiota as predictive biomarkers in clinical settings. Furthermore, inter-individual microbiota variations partially account for differential responses to cancer immunotherapy. In this review, we summarize current literature on the influence of the gastric microbiota on gastric carcinogenesis, anti-tumor immunity and immunotherapy, providing insights into potential clinical applications.

Numerous studies have cast light on the relationship between the gastric microbiota and gastric carcinogenesis. In this study, we conducted a bibliometric analysis of the relevant literature in the field of gastric cancer and the gastric microbiota and clarified its research status, hotspots, and development trends.

Publications were retrieved from the Web of Science Core Collection on 18 July 2023. CiteSpace 6.2.R4, VOSviewer 1.6.19.0, and Biblioshiny were used for the co-occurrence and cooperation analyses of countries, institutions, authors, references, and keywords. A keyword cluster analysis and an emergence analysis were performed, and relevant knowledge maps were drawn.

The number of published papers in this field totaled 215 and showed an increasing trend. The analysis of funding suggested that the input in this field is increasing steadily. China had the highest number of publications, while the United States had the highest betweenness centrality. Baylor College of Medicine published the most articles cumulatively. Both Ferreira RM and Cooker OO had the highest citation frequency. The journal Helicobacter showed the most interest in this field, while Gut provided a substantial research foundation. A total of 280 keywords were obtained using CiteSpace, which were primarily focused on the eradication and pathogenic mechanisms of Helicobacter pylori, as well as the application of the gastric microbiota in the evaluation and treatment of gastric cancer. The burst analysis suggested that in the future, research may focus on the application of gastric microorganisms, particularly Fusobacterium nucleatum, in the diagnosis and treatment of gastric cancer, along with their pathogenic mechanisms.

Current studies have been tracking the eradication of Helicobacter pylori and its pathogenic mechanisms, as well as changes in the gastric microbiota during gastric carcinogenesis. Future research may focus on the clinical application and pathogenesis of stomach microorganisms through bacteria such as Fusobacterium nucleatum.

Gastric cancer (GC) continues to pose a significant global threat in terms of cancer-related fatalities. Despite notable advancements in medical research and therapies, further investigation is warranted to elucidate its underlying etiology and risk factors. Recent times have witnessed an escalated emphasis on comprehending the role of the microbiota in cancer development.

This review briefly delves into recent developments in microbiome-related research pertaining to gastric cancer.

According to studies, the microbiota can influence GC growth by inciting inflammation, disrupting immunological processes, and generating harmful microbial metabolites. Furthermore, there is ongoing research into how the microbiome can impact a patient's response to chemotherapy and immunotherapy.

The utilization of the microbiome for detecting, preventing, and managing stomach cancer remains an active area of exploration.

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.

Next-generation sequencing technologies have started a new era of respiratory tract research in recent years. Alterations in the respiratory microbiome between healthy and malignant conditions have been revealed. However, the composition of the microbiome varies among studies, even in similar medical conditions. Also, there is a lack of complete knowledge about lung-gut microbiome interactions in lung cancer patients. The aim of this study was to explore the lung-gut axis in non-small-cell lung cancer (NSCLC) patients and the associations between lung-gut axis microbiota and clinical parameters (CRP, NLR, LPS, CD8, and PD-L1). Lung tissue and fecal samples were used for bacterial 16S rRNA sequencing. The results revealed, for the first time, that the bacterial richness in lung tumor tissue gradually decreased with an increase in the level of PD-L1 expression (p < 0.05). An analysis of β-diversity indicated a significant positive correlation between the genera Romboutsia and Alistipes in both the lung tumor biopsies and stool samples from NSCLC patients (p < 0.05). Survival analysis showed that NSCLC patients with higher bacterial richness in their stool samples had prolonged overall survival (HR: 2.06, 95% CI: 1.025-4.17, p = 0.0426).

Introduction. Multiple reports have attempted to describe the tumour microbiota in head and neck cancer (HNSC).Gap statement. However, these have failed to produce a consistent microbiota signature, which may undermine understanding the importance of bacterial-mediated effects in HNSC.Aim. The aim of this study is to consolidate these datasets and identify a consensus microbiota signature in HNSC.Methodology. We analysed 12 published HNSC 16S rRNA microbial datasets collected from cancer, cancer-adjacent and non-cancer tissues to generate a consensus microbiota signature. These signatures were then validated using The Cancer Microbiome Atlas (TCMA) database and correlated with the tumour microenvironment phenotypes and patient's clinical outcome.Results. We identified a consensus microbial signature at the genus level to differentiate between HNSC sample types, with cancer and cancer-adjacent tissues sharing more similarity than non-cancer tissues. Univariate analysis on 16S rRNA datasets identified significant differences in the abundance of 34 bacterial genera among the tissue types. Paired cancer and cancer-adjacent tissue analyses in 16S rRNA and TCMA datasets identified increased abundance in Fusobacterium in cancer tissues and decreased abundance of Atopobium, Rothia and Actinomyces in cancer-adjacent tissues. Furthermore, these bacteria were associated with different tumour microenvironment phenotypes. Notably, high Fusobacterium signature was associated with high neutrophil (r=0.37, P<0.0001), angiogenesis (r=0.38, P<0.0001) and granulocyte signatures (r=0.38, P<0.0001) and better overall patient survival [continuous: HR 0.8482, 95 % confidence interval (CI) 0.7758-0.9273, P=0.0003].Conclusion. Our meta-analysis demonstrates a consensus microbiota signature for HNSC, highlighting its potential importance in this disease.

The tumor microbiome, a relatively new research field, affects tumor progression through several mechanisms. The Cancer Microbiome Atlas (TCMA) database was recently published. In the present study, we used TCMA and The Cancer Genome Atlas and examined microbiome profiling in head and neck squamous cell carcinoma (HNSCC), the role of the intratumoral microbiota in the prognosis of HNSCC patients, and differentially expressed genes in tumor cells in relation to specific bacterial infections. We investigated 18 microbes at the genus level that differed between solid normal tissue (n = 22) and primary tumors (n = 154). The tissue microbiome profiles of Actinomyces, Fusobacterium, and Rothia at the genus level differed between the solid normal tissue and primary tumors of HNSCC patients. When the prognosis of groups with rates over and under the median for each microbe at the genus level was examined, rates for Leptotrichia which were over the median correlated with significantly higher overall survival rates. We then extracted 35 differentially expressed genes between the over- and under-the-median-for-Leptotrichia groups based on the criteria of >1.5 fold and p < 0.05 in the Mann-Whitney U-test. A pathway analysis showed that these Leptotrichia-related genes were associated with the pathways of Alzheimer disease, neurodegeneration-multiple diseases, prion disease, MAPK signaling, and PI3K-Akt signaling, while protein-protein interaction analysis revealed that these genes formed a dense network. In conclusion, probiotics and specific antimicrobial therapy targeting Leptotrichia may have an impact on the prognosis of HNSCC.

Diet is one of the most important factors contributing to the multistep process of carcinogenesis. The clinical relevance of exogenous food-derived xeno-microRNAs (miRNAs) in human diseases is poorly understood. In this study, we aimed to evaluate the potential clinical relevance of the xeno-miRNA miR-168 in the gastric mucosa along the preneoplastic conditions and gastric carcinogenesis.

For a systematic analysis, we included stomach tissues from patients with different pathologies, including normal mucosa (N), chronic non-atrophic (CNAG) and atrophic gastritis (CAG) and intestinal metaplasia (IM) (n = 72), matched non-tumorous (NT) and tumorous (T) gastric cancer (GC) tissues (n = 81), matched colorectal cancer (CRC) tissues (n = 40), and colon mucosa and faeces from controls and IBD patients.

miR-168 was reproducibly detectable in all samples studied, with the highest levels in the proximal upper GI and in non-tumorous compared to tumorous tissues in both GC and CRC. There was no difference related to H. pylori positivity or inflammation grade, while higher miR-168 levels were observed in patients with moderate or severe AG/IM or OLGIM3/4. Survival analysis showed only a small, non-significant trend towards worse overall survival for patients with the highest to lowest miR-168 levels, while no differences were related to Lauren's classification.

Food-derived xeno miRNAs are reproducibly detectable in the gastric and colonic mucosa. Although the clinically relevant function remains to be elucidated, higher levels of miR-168 in patients with moderate and severe IM merit further investigation.

Gastric cancer remains an important global health burden. Helicobacter pylori is the major etiological factor in gastric cancer, infecting the stomach of almost half of the population worldwide. Recent progress in microbiome research offered a new perspective on the complexity of the microbial communities of the stomach. Still, the role of the microbiome of the stomach beyond H. pylori in gastric carcinogenesis is not well understood and requires deeper investigation. The gastric bacterial communities of gastric cancer patients are distinct from those of patients without cancer, but the microbial alterations that occur along the process of gastric carcinogenesis, and the mechanisms through which microorganisms influence cancer progression still need to be clarified. Except for Epstein-Barr virus, the potential significance of the virome and of the mycobiome in gastric cancer have received less attention. This chapter updates the current knowledge regarding the gastric microbiome, including bacteria, viruses, and fungi, within the context of H. pylori-mediated carcinogenesis. It also reviews the possible roles of the local gastric microbiota, as well as the microbial communities of the oral and gut ecosystems, as biomarkers for gastric cancer detection. Finally, it discusses future perspectives and acknowledges limitations in the area of microbiome research in the gastric cancer setting, to which further research efforts should be directed. These will be fundamental not only to increase our current understanding of host-microbial interactions but also to facilitate translation of the findings into innovative preventive, diagnostic, and therapeutic strategies to decrease the global burden of gastric cancer.