Microbiome In Cancer Research Articles

A Perspective on Lung Cancer and Lung Microbiome: Insight on Immunity.

Although the carcinogenic potential of microbes has long been recognized, their significance may have been underestimated. Currently, the connection between microbiota and cancer is under extensive research. The lung microbiota may serve as a proxy for the state of lung health based on its crucial role in preserving lung hemostasis. This review tried to outline the state of our understanding of the contribution of lung microbiome and lung cancer. A literature search was performed using PubMed, Google Scholar, and Scopus databases for recent research focusing on the development and possible pathogenesis of lung microbiome and lung cancer. Early research on lung cancer indicated that dysbiosis significantly impacted the development and spread of the tumor. As a result of these findings, the study of the lung microbiota as a possible therapeutic target and diagnostic marker has accelerated. Early-stage disease diagnostic biomarkers could be represented as microbiota profiles. Additionally, the microbiome is involved in anticancer therapy. There are limited studies on lung microbiota, and most microbiome studies commonly concentrate on the gut microbiota. A proper understanding of lung microbiota can have several potential therapeutic approaches. Therefore, more studies in this field may initiate remarkable advancements in microbiome-dependent treatment. Convincing data from studies on both humans and animals indicates that the microbiota might play a role in cancer initiation, influenced by internal and environmental factors of the host. Notably, the lung harbors its microbiome, as do lung cancers. In general view, it seems microbiome diversity in lung cancer patients is reduced. Meanwhile, some genera were increased in lung cancer patients in comparison with a noncancerous population (such as Streptococcus genus), and some of them were decreased (Granulicatella adiacens, G. adiacens). Furthermore, research on the microbiome-carcinogenesis relationship is still in its infancy, and much remains to be fully understood.

Comprehensive analysis of the interaction microbiome and prostate cancer: an initial exploration from multi-cohort metagenome and GWAS studies

IntroductionProstate cancer is one of the most common cancers in the United States with a high mortality rate. In recent years, the traditional opinion about prostate microbiome was challenged. Although there still are some arguments, an escalating number of researchers are shifting their focus toward the microbiome within the prostate tumor environment.MethodsWe mined the data of the microbiome extracted from the metagenome, and it offers a broader taxonomic coverage and accurate functional profiling. We used Kraken2, a mapping tool, to mine the gut microbiota of prostate cancer patients. A two-sample Mendelian Randomization was conducted to reflect the association between gut microbiome and cancer.ResultsIn the study, we found the consistency of the special intratumor microbiome of both non-metastatic tumors and metastatic tumors. And we dig the gut microbiome in patients with different treatments. We found that some microbiotas may be associated with prostate cancer progression and a special microbiome in metastatic prostate cancer may exist. The anti-androgen therapy can significantly change both the intratumor and gut microbiome.ConclusionWith the progression and metastasis of prostate cancer, some intratumor microbiome changes. And anti-androgen influences both the intratumor and gut microbiome. Our discovery may help researchers further understand the progression, metastasis, and resistance of prostate cancer from the perspective of microbiome level.

A Connection Between the Gut Microbiome and Epigenetic Modification in Age-Related Cancer: A Narrative Review.

As individuals age, physiological changes influence the composition and function of the gut microbiome, significantly impacting the onset and progression of various illnesses, including cancer. Notably, the gut microbiome affects epigenetic modifications such as DNA methylation and histone alterations. Furthermore, it contributes to the age-related decline in immune system efficiency, increasing susceptibility to infections and cancers. This dual role of the gut microbiome-both a protective factor and a risk factor-is a key aspect of its importance in maintaining long-term health, making it a significant topic of discussion in this review. Moreover, a challenge faced by the elderly is the concurrent use of multiple medications. Polypharmacy can interact with the gut microbiome, potentially altering its efficacy, leading to adverse drug reactions, and affecting vital microbiome diversity. The effects of these interactions on cancer therapies and the overall health of elderly patients are becoming increasingly important. Understanding the complex relationship between aging, the gut microbiome, cancer, and polypharmacy is crucial for developing more effective therapeutic strategies and improving patient outcomes. Here, we discuss recent advances in understanding age-related physiological changes in the microbiome and their significance in cancer development and therapy. Specifically, we will explor how epigenetic changes acquired during aging, along with ongoing prescriptions of multiple medications and the decline of immune function, contribute to the intricate relationship between aging and cancer.

Revisiting the cancer microbiome using PRISM.

Recent controversy around the cancer microbiome highlights the need for improved microbial analysis methods for human genomics data. We developed PRISM, a computational approach for precise microorganism identification and decontamination from low-biomass sequencing data. PRISM removes spurious signals and achieves excellent performance when benchmarked on a curated dataset of 62,006 known true- and false-positive taxa. We then use PRISM to detect microbes in 8 cancer types from the CPTAC and TCGA datasets. We identify rich microbiomes in gastrointestinal tract tumors in CPTAC and identify bacteria in a subset of pancreatic tumors that are associated with altered glycoproteomes, more extensive smoking histories, and higher tumor recurrence risk. We find relatively sparse microbes in other cancer types and in TCGA, which we demonstrate may reflect differing sequencing parameters. Overall, PRISM does not replace gold-standard controls, but it enables higher-confidence analyses and reveals tumor-associated microorganisms with potential molecular and clinical significance.

Unveiling the Intratumor Microbiome in Liver Cancer: Current Insights and Prospective Applications.

The role of the gut microbiome in the development and progression of liver cancer has long been recognized. However, the presence of microbes in tumors that were previously considered sterile has only recently been discovered. The intratumor microbiome in liver cancer likely originates from various sources, including the gut, hematogenous spread from other mucosal locations, adjacent non-cancerous tissues, and co-metastasis with the tumor cells. As a newly discovered component of the tumor microenvironment, it regulates host immune responses, promotes chronic inflammation, modulates metabolic pathways, and exerts other influences in liver cancer. These unique features offer potential new biomarkers for liver cancer prognosis and treatment response. Exploring the complex interactions between intratumor microbiome and the host to modulate or target the intratumor microbiome may provide new avenues for liver cancer treatment. This article provides a comprehensive review of our current understanding regarding the potential origins of the intratumor microbiome in liver cancer, its unique characteristics, and the underlying mechanisms by which it affects liver cancer. Furthermore, we discuss the promising clinical implications and potential challenges that remain before this knowledge can be fully integrated into clinical practice.

Evaluation of multidrug resistance in the Gram-negative microbiome of cancer patients and the adverse effects of their metabolites on albino rats and epithelial or fibroblasts cell lines

BackgroundCancer is a significant global health issue due to its high incidence and mortality rates. In recent years, the relationship between the human microbiota and cancer has garnered attention across various medical fields. This includes research into the microbial communities that influence cancer development, tumor-associated microorganisms, and the interactions between the microbiome and tumor, collectively referred to as the oncobiome.MethodsThe negative effects of secondary metabolites extracted from selected multidrug-resistant Gram-negative bacteria within the cancer microbiota were evaluated. These effects included carcinogenicity, mutagenicity, hepatotoxicity, nephrotoxicity, and sperm deformities observed in albino rats after one month of oral ingestion of these microbial extracts.ResultsOur findings in the present investigation revealed that among the bacterial community derived from the microbiota, Gram-negative bacteria accounted for 74.87% the total microbiota (146 out of 195) and their spectrum including Escherichia sp. (n = 36, 24.66%) followed by Acinetobacter sp. (n = 34, 23.29%), Stenotrophomonas sp. (n = 29, 19.86%), Pseudomonas sp. (n = 26, 17.81%) and Serratia sp. (n = 21, 14.38%), as the most prevalent pathogens. All isolates derived from the cancer microbiome exhibited multidrug resistance to a large number of conventional therapies. Out of them Serratia sp. Esraa 1, Stenotrophomonas sp. Esraa 2, Acinetobacter sp. Esraa 3, Escherichia sp. Esraa 4 and Pseudomonas sp. Esraa 5 strains showed multidrug resistant profile against all antibiotic classes under study including penicillins, cephalosporins, carbapenems, fluoroquinolones, β-lactamase inhibitors combinations, folate synthesis pathway inhibitors, phosphonic, aminoglycosides, polymyxins, tetracyclines, macrolides, and chloramphenicol antibiotics. The adverse effects of oral ingestion of their metabolites were evaluated in albino rats. They induced pronounced carcinogenesis along with severe raise in the inflammatory cytokines, hepatotoxicity, nephrotoxicity, mutagenicity along with sperm deformities in treated animals. Moreover, all metabolites showed marked cytotoxicity against human normal cell lines; human mammary epithelial (MCF10A), human lung fibroblasts (WI38) and human dermal fibroblasts (HDFs).ConclusionThese bacterial strains isolated from the cancer microbiome may play significant roles in inducing cancer, inflammation, mutagenesis, hepatotoxicity, nephrotoxicity, and sperm abnormalities, along with histopathological changes in the treated animal groups by orally administrated metabolites in compared to the untreated group.Graphical

Obesity, dietary interventions and microbiome alterations in the development and progression of prostate cancer.

The role of the microbiome in prostate cancer is an emerging subject of research interest. Certain lifestyle factors, such as obesity and diet, can also impact the microbiome, which has been implicated in many diseases, such as heart disease and diabetes. However, this link has yet to be explored in detail in the context of prostate cancer. The purpose of this review is to explore the cross-talk between obesity, dietary interventions, and microbiome alterations in the development and progression of prostate cancer. Many possible mechanisms exist linking obesity and dietary interventions to microbiome alterations and prostate cancer. The gut microbiome produces metabolites that could play a role in prostate cancer oncogenesis, including short-chain fatty acids, cholesterol derivatives, and folic acid. The microbiome also plays a pivotal role in the prostate tumor microenvironment (TME), contributing to inflammation, local tissue hypoxia, and epithelial-mesenchymal transition. A bidirectional relationship exists between obesity and the microbiome, and certain diets can enact changes to the microbiome, its associated metabolites, and prostate cancer outcomes. Cross-talk exists between obesity, dietary interventions, and the role of the microbiome in the development and progression of prostate cancer. To further our understanding, future human studies in prostate cancer should investigate microbiome changes and incorporate an assessment of microbiome-derived metabolites and cellular/immune changes in the TME.

Promising new drugs and therapeutic approaches for treatment of ovarian cancer—targeting the hallmarks of cancer

Abstract Ovarian cancer remains the most lethal gynecological malignancy. Despite the approval of promising targeted therapy such as bevacizumab and PARP inhibitors, 5-year survival has not improved significantly. Thus, there is an urgent need for new therapeutics. New advancements in therapeutic strategies target the pivotal hallmarks of cancer. This review is giving an updated overview of innovative and upcoming therapies for the treatment of ovarian cancer that focuses specific on the hallmarks of cancer. The hallmarks of cancer constitute a broad concept to reenact complexity of malignancies and furthermore identify possible targets for new treatment strategies. For this purpose, we analyzed approvals and current clinical phase III studies (registered at ClinicalTrials.gov (National Library of Medicine, National Institutes of Health; U.S. Department of Health and Human Services, 2024)) for new drugs on the basis of their mechanisms of action and identified new target approaches. A broad spectrum of new promising drugs is currently under investigation in clinical phase III studies targeting mainly the hallmarks “self-sufficiency in growth signals,” “genomic instability,” and “angiogenesis.” The benefit of immune checkpoint inhibitors in ovarian cancer has been demonstrated for the first time. Besides, targeting the tumor microenvironment is of growing interest. Replicative immortality, energy metabolism, tumor promoting inflammation, and the microbiome of ovarian cancer are still barely targeted by drugs. Nevertheless, precision medicine, which focuses on specific disease characteristics, is becoming increasingly important in cancer treatment. Graphical Abstract

Microbial signatures in head and neck squamous cell carcinoma: an in silico study.

The oral cavity harbors a plethora of bacterial species. Dysbiosis of oral and gut microbiota is associated with several oral and systemic pathologies, such as cancer, obesity, diabetes, atherosclerosis and gastrointestinal diseases. Imbalance in the oral-gut microbial axis has been associated with head and neck squamous cell carcinoma (HNSCC). This study aims to analyze the bacterial profile of HNSCC across various taxonomic units, investigate molecular patterns associated with prevalent bacterial phylum in HNSCC, and compare the bacterial profile in HNSCC and gastrointestinal (GI) carcinoma using computational analysis. The microbe-host transcriptomic, proteomic, and epigenetic analyses of HNSCC and GI carcinomas were performed using The Cancer Microbiome Atlas (TCMA) database. The differential expression of the host's mRNA transcripts and proteins associated with tumor microbiome were analyzed using The University of Alabama at Birmingham Cancer data analysis (UALCAN) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) websites. A decrease in Actinobacteria and an enrichment of Flavobacteria at the class level, Neisseriales, Pasteurellales, and Campylobacterales at the order level, Pasteurellaceae, Flavobacteriaceae, Campylobacteraceae, and Peptoniphilaceae at the family level, and Hemophilus, Porphyromonas, and Leptotrichia at the genus level were observed in HNSCC compared to the normal mucosa. RICTOR protein, mRNA transcripts (HIST1H2BB, SCARNA11, TBC1D21 gene), and hsa-miR-200a-5p miRNA were significantly correlated with prevalent bacterial species in HNSCC. A major increase in Actinobacteria, Fusobacteria, and Spirochaetes was observed in HNSCC compared to GI carcinoma. The oral-gut microbial dysbiosis, as reflected by the differential abundance of bacterial species in oral and GI carcinomas, suggests the implication of tumor microbiome and their genomic interactions with the host in carcinogenesis.

Modeling cancer–microbiome interactions in vitro: A guide to co‐culture platforms

AbstractThe biology of cancer is characterized by an intricate interplay of cells originating not only from the tumor mass, but also its surrounding environment. Different microbial species have been suggested to be enriched in tumors and the impacts of these on tumor phenotypes is subject to intensive investigation. For these efforts, model systems that accurately reflect human–microbe interactions are rapidly gaining importance. Here we present a guide for selecting a suitable in vitro co‐culture platform used to model different cancer–microbiome interactions. Our discussion spans a variety of in vitro models, including 2D cultures, tumor spheroids, organoids, and organ‐on‐a‐chip platforms, where we delineate their respective advantages, limitations, and applicability in cancer microbiome research. Particular focus is placed on methodologies that facilitate the exposure of cancer cells to microbes, such as organoid microinjections and co‐culture on microfluidic devices. We highlight studies offering critical insights into possible cancer–microbe interactions and underscore the importance of in vitro models in those discoveries. We anticipate the integration of more complex microbial communities and the inclusion of immune cells into co‐culture systems to more accurately simulate the tumor microenvironment. The advent of ever more sophisticated co‐culture models will aid in unraveling the mechanisms of cancer‐microbiome interplay and contribute to exploiting their potential in novel diagnostic and therapeutic strategies.

Colonization of stenotrophomonas and its associated microbiome between paired primary colorectal cancers and their lung metastatic tumors (experimental studies).

The role of gut microbiome in colorectal cancer (CRC) lung metastases is still unclear. Herein, we collected primary colorectal tumors, matched lung metastasis, and adjacent normal colon from seven patients for 16S rRNA sequencing to evaluate microbiome signature in distant site metastasis and analyze prognosis. Fecal samples from 19 non-metastases CRC patients and 11 CRC lung metastases patients were analyzed for validation. Our efforts led to a discovery of comprehensive microbiome in CRC lung metastatic tumors, characterized by a decreased microbial diversity and an increase bacterial interaction between gram-negative bacteria Stenotrophomonas and Brevundimonas . The primary-metastatic tumor pairs harbored highly similar microbial composition in both genus and species level, especially the high level of Stenotrophomonas maltophilia . Correspondingly, the S. maltophilia levels were positively associated with poor prognosis and cancer progression. Our work highlights the great potential of S. maltophilia and its associated microbiome as biomarkers in pathogenesis and prognosis of CRC lung metastases.

Beneficial microbiome and diet interplay in early-onset colorectal cancer.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Although the risk of developing CRC increases with age, approximately 10% of newly diagnosed cases occur in individuals under the age of 50. Significant changes in dietary habits in young adults since industrialization create a favorable microenvironment for colorectal carcinogenesis. We aim here to shed light on the complex interplay between diet and gut microbiome in the pathogenesis and prevention of early-onset CRC (EO-CRC). We provide an overview of dietary risk factors associated with EO-CRC and contrast them with the general trends for CRC. We delve into gut bacteria, fungi, and phages with potential benefits against CRC and discuss the underlying molecular mechanisms. Furthermore, based on recent findings from human studies, we offer insights into how dietary modifications could potentially enhance gut microbiome composition to mitigate CRC risk. All together, we outline the current research landscape in this area and propose directions for future investigations that could pave the way for novel preventive and therapeutic strategies.

Lung Microbiome in Lung Cancer: A Systematic Review.

To identify the predominant bacterial taxa at the phylum and genus levels in bronchopulmonary cancer using samples collected through bronchoalveolar lavage and to determine a potential proportional pattern that could contribute to the diagnosis of bronchopulmonary cancer. A systematic review of English articles using MEDLINE, Embase, and Web of Science. Search terms included lung microbiome, lung cancer, and bronchoalveolar lavage. Studies that investigated the lung microbiome in bronchopulmonary cancer with samples collected via bronchoalveolar lavage. Independent extraction of articles using predefined data fields, including study quality indicators. Nine studies met the inclusion criteria, focusing on those that utilized a percentage expression of the microbiome at the phylum or genus level. There was noted heterogeneity between studies, both in terms of phylum and genus, with a relatively constant percentage of the Firmicutes phylum and the genera Streptococcus and Veillonella being mentioned. Significant differences were also observed regarding the inclusion criteria for study participants, the method of sample collection, and data processing. To date, there is no consistent percentage pattern at the phylum or genus level in bronchopulmonary cancer, with the predominance of a phylum or genus varying across different patient cohorts, resulting in non-overlapping outcomes.

A Mixed Effect Similarity Matrix Regression Model (SMRmix) for Integrating Multiple Microbiome Datasets at Community Level.

Recent studies have highlighted the importance of human microbiota in our health and diseases. However, in many areas of research, individual microbiome studies often offer inconsistent results due to the limited sample sizes and the heterogeneity in study populations and experimental procedures. This inconsistency underscores the necessity for integrative analysis of multiple microbiome datasets. Despite the critical need, statistical methods that incorporate multiple microbiome datasets and account for the study heterogeneity are not available in the literature. In this paper, we develop a mixed effect similarity matrix regression (SMRmix) approach for identifying community level microbiome shifts between outcomes. SMRmix has a close connection with the microbiome kernel association test, one of the most popular approaches for such a task but is only applicable when we have a single study. SMRmix enables researchers to consolidate findings from diverse microbiome studies. Via extensive simulations, we show that SMRmix has well-controlled type I error and higher power than some potential competitors. We applied the SMRmix to two real-world datasets. The first, from the HIV-reanalysis consortium, integrated data from 17 studies on gut dysbiosis in HIV. Our analysis confirmed consistent associations between the gut microbiome and HIV infection as well as MSM (men who have sex with men) status, demonstrating greater power than competing methods. The second dataset involved 11 studies on the gut microbiome in colorectal cancer; analysis with SMRmix confirmed significant dysbiosis in affected individuals compared to healthy controls. The development of SMRmix enables the integration of multiple studies and effectively managing study heterogeneity, and provides a powerful tool for uncovering consistent associations between diseases and community-level microbiome data.

Metagenomic characterization of the tracheobronchial microbiome in lung cancer

Metagenomic characterization of the tracheobronchial microbiome in lung cancer

From microbes to medicine: harnessing the power of the microbiome in esophageal cancer.

Esophageal cancer (EC) is a malignancy with a high incidence and poor prognosis, significantly influenced by dysbiosis in the esophageal, oral, and gut microbiota. This review provides an overview of the roles of microbiota dysbiosis in EC pathogenesis, emphasizing their impact on tumor progression, drug efficacy, biomarker discovery, and therapeutic interventions. Lifestyle factors like smoking, alcohol consumption, and betel nut use are major contributors to dysbiosis and EC development. Recent studies utilizing advanced sequencing have revealed complex interactions between microbiota dysbiosis and EC, with oral pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promoting inflammation and suppressing immune responses, thereby driving carcinogenesis. Altered esophageal microbiota, characterized by reduced beneficial bacteria and increased pathogenic species, further exacerbate local inflammation and tumor growth. Gut microbiota dysbiosis also affects systemic immunity, influencing chemotherapy and immunotherapy efficacy, with certain bacteria enhancing or inhibiting treatment responses. Microbiota composition shows potential as a non-invasive biomarker for early detection, prognosis, and personalized therapy. Novel therapeutic strategies targeting the microbiota-such as probiotics, dietary modifications, and fecal microbiota transplantation-offer promising avenues to restore balance and improve treatment efficacy, potentially enhancing patient outcomes. Integrating microbiome-focused strategies into current therapeutic frameworks could improve EC management, reduce adverse effects, and enhance patient survival. These findings highlight the need for further research into microbiota-tumor interactions and microbial interventions to transform EC treatment and prevention, particularly in cases of late-stage diagnosis and poor treatment response.

The Intersection of the Oral Microbiome and Salivary Metabolites in Head and Neck Cancer: From Diagnosis to Treatment.

Head and neck cancers (HNCs) are the seventh most common cancer worldwide, accounting for 4-5% of all malignancies. Salivary metabolites, which serve as key metabolic intermediates and cell-signalling molecules, are emerging as potential diagnostic biomarkers for HNC. While current research has largely concentrated on these metabolites as biomarkers, a critical gap remains in understanding their fluctuations before and after treatment, as well as their involvement in oral side effects. Recent studies emphasise the role of the oral microbiome and its metabolic activity in cancer progression and treatment efficacy by bacterial metabolites and virulence factors. Oral bacteria, such as P. gingivalis and F. nucleatum, contribute to a pro-inflammatory environment that promotes tumour growth. Additionally, F. nucleatum enhances its virulence through flagellar assembly and iron transport mechanisms, facilitating tumour invasion and survival. Moreover, alterations in the oral microbiome can influence chemotherapy efficacy and toxicity through the microbiota-host irinotecan axis, highlighting the complex interplay between microbial communities and therapeutic outcomes. Salivary metabolite profiles are influenced by factors such as gender, methods, and patient habits like smoking-a major risk factor for HNC. Radiotherapy (RT), a key treatment for HNC, often causes side effects such as xerostomia, oral mucositis, and swallowing difficulties which impact survivors' quality of life. Intensity-modulated radiotherapy (IMRT) aims to improve treatment outcomes and minimise side effects but can still lead to significant salivary gland dysfunction and associated complications. This review underscores the microbial and host interactions affecting salivary metabolites and their implications for cancer treatment and patient outcomes.

Existence and distribution of the microbiome in tumour tissues of children with hepatoblastoma

Cancer microbiota have recently been demonstrated in several cancer types. The microbiome enhances inflammation in the cancer microenvironment and affects the disease pathology by regulating tumourigenesis, cancer progression, and chemotherapy resistance. Hepatoblastoma (HB), the most common childhood malignant tumour, is a malignant embryonic tumour. However, the pathogenesis and molecular basis of HB remain poorly understood. In this study, to explore the existence and distribution of the microbiome in tumour tissues and adjacent non-tumour tissues of children with HB, we mainly performed 16S rDNA sequencing, and the results showed that the diversity and abundance of the microbiome in children with HB were significantly different between HB tumours and adjacent non-tumour tissues (p < 0.01). At the phylum level, the dominant microbiome in the tumour tissues were Proteobacteria, Bacteroidetes, and Firmicutes. At the genus level, Ruminococcus was more abundant in HB tumours than in the adjacent non-tumour tissues. Simultaneously, the abundances of Bacteroides, Parabacteroides, Lachnospiracea-NK4A136, and Alistipes in HB tumours were lower than those in the adjacent non-tumour tissues. In addition, Romboutsia strongly correlated with alpha-fetoprotein, an important indicator of HB. Sphingomonas was abundant in primary HB tumours, whereas Oscillibacter and Pandoraea were abundant in metastatic HB tumours. However, whether these bacteria are associated with HB needs further evaluation. Therefore, we identified the microbiome that correlated with the occurrence and development of HB. Ruminococcus and Romboutsia were identified as potential bacterial markers of HB tumours. To conclude, we found that HB also contains cancer microbiome, and it is necessary to shed light on the microbiome characteristics of HB in the future.

Multidimensional analysis of the impact of Gemmatimonas, Rhodothermus, and Sutterella on drug and treatment response in colorectal cancer.

Colorectal cancer is the third most prevalent cancer across the globe. Despite a diversity of treatment methods, the recurrence and mortality rates of the disease remain high. Recent studies have revealed a close association of the gut microbiota with the occurrence, development, treatment response, and prognosis of colorectal cancer. This study aims to integrate transcriptome and microbiome data to identify colorectal cancer subtypes associated with different gut microbiota and evaluate their roles in patient survival prognosis, tumor microenvironment (TME), and drug treatment response. An integrated analysis of microbiome data was conducted on samples of colorectal cancer from public databases. Based on this, two tumor subtypes (C1 and C2) closely associated with patient survival prognosis were identified and a risk score model was constructed. The survival status, clinical parameters, immune scores, and other features were analyzed in-depth, and the sensitivity of various potential drugs was examined. A thorough examination of microbiome information obtained from colorectal cancer patients led to the identification of two primary tumor clusters (C1 and C2), exhibiting notable variations in survival outcomes. Patients with the C1 subtype were closely associated with better prognosis, while those with the C2 subtype had higher gut microbial richness and poorer survival prognosis. A predictive model utilizing the microbiome data was developed to accurately forecast the survival outcome of patients with colorectal cancer. The TME scores provided a biological basis for risk assessment in high-risk (similar to the C2 subtype) patient cohorts. Evaluation of the sensitivity of different subtypes to various potential drugs, indicated the critical importance of personalized treatment. Further analysis showed good potential of the developed risk-scoring model in predicting immune checkpoint functions and treatment response of patients, which may be crucial in guiding the selection of immunotherapy strategies for patients with colorectal cancer. This study, through a comprehensive analysis of colorectal cancer microbiome, immune microenvironment, and drug sensitivity, enhances the current understanding of the multidimensional interactions of colorectal cancer and provides important clinical indications for improving future treatment strategies. The findings offer a new perspective on improving treatment response and long-term prognosis of patients with CRC through the regulation of microbiota or the utilization of biomarkers provided by it.

Immune-reactive tumor organoids system to determine the effects of microbial metabolites on cancer immunity and immunotherapies

Immunotherapies are a revolutionary approach to treating cancer by utilizing the body’s immune system to target and combat cancer cells. This approach offers promising alternatives to traditional chemotherapies. Its potential to induce long-lasting remissions and specificity for cancer cells, which minimizes side effects, makes it a cutting-edge treatment with tremendous potential. With the increase of the clinical usage of immunotherapy, evidence emerges of the microbiome’s impact on both tumor growth and response to immunotherapy. The proposed involvement of the microbiome can change treatment efficacy by altering drug metabolism and reshaping the immune system response. Understanding the specific interactions between tumor cells, immune cells, and the microbiome is a critical step in the advancement of immunotherapy. To study the complex interaction between cancer immunity and the microbiome, various preclinical in vivo and in vitro models have been developed. We have recently described the use of an ex vivo preclinical model for anti-cancer treatment outcome prediction –tumor tissue equivalents (organoids). Specifically, immune-reactive tumor organoids are proposed as a novel tool for understanding how the microbiome influences cancer immunity and immunotherapy. More importantly, this platform can utilize patient samples to dissect patient-specific elements regulating cancer immune response and microbiome influence. This review presents the rationale for using the immune-reactive tumor organoids model to study the interactions between the microbiome and cancer immunotherapy. It will discuss available components of the model and analyze their interplay, summarize relevant experimental data, and assess their validity. Additionally, it explores the potential of immune-reactive organoids for personalized treatment approaches. Understanding the microbiome’s role in immunotherapy outcomes will lead to transformative cancer treatment via a simple change of diet or other microbiome manipulations. Ongoing research on microbiome-cancer interactions utilizing the described model systems will lead to innovative treatment strategies and improved patient outcomes.