Identifying potential connections between microbe-drug pairs play an important role in drug discovery and clinical treatment. Techniques like graph neural networks effectively derive accurate node representations from sparse topologies,however, they struggle with over-smoothing and over-compression, and their interpretability is relatively poor. Conversely, mathematical methods with low-rank approximations are interpretable but often get trapped in local optima. To address these issues, we propose a new prediction model named NNSFMDA, in which, the bounded nuclear norm minimization and the simplified transformer were combined to infer possible drug-microbe associations. In NNSFMDA, we first constructed a heterogeneous microbe-drug network by integrating multiple microbe and drug similarity metrics, according to which, we subsequently transformed the prediction problem to a matrix filling problem, and then, iteratively approximated the matrix by minimizing the number of bounded nuclear norm. Finally, based on the newly-filled matrix, we introduced a simplified transformer to estimate possible scores of microbe-drug pairs. Results showed that NNSFMDA could achieve reliable AUC value of 0.98, which outperformed existing state-of-the-art competitive methods. In the experimental section, ablation experiments and modular analyses further demonstrate the superiority of the model, and case studies of microbe-drug associations confirm the validity of the model. These tests have all highlighted the potential of the NNSFMDA to predict latent microbe-drug associations in the future.

Over the past 3 years, there has been a growing interest in clinical research regarding the potential involvement of intestinal flora in thyroid cancer (TC). This review delves into the intricate connection between intestinal flora and TC, focusing on the particular intestinal flora that is directly linked to the disease and identifying which may be able to predict potential microbial markers of TC. In order to shed light on the inflammatory pathways connected to the onset of TC, we investigated the impact of intestinal flora on immune modulation and the connection between chronic inflammation when investigating the role of intestinal flora in the pathogenesis of TC. Furthermore, the potential role of intestinal flora metabolites in the regulation of thyroid function was clarified by exploring the effects of short-chain fatty acids and lipopolysaccharide on thyroid hormone synthesis and metabolism. Based on these findings, we further explore the effects of probiotics, prebiotics, postbiotics, vitamins, and trace elements.

Bladder cancer (BC) remains a significant global health concern, with substantial sex and racial disparities in incidence, progression, and outcomes. BC is the sixth most common cancer among males and the seventeenth most common among females worldwide. Over 90% of BC cases are urothelial carcinoma (UC) with high degrees of pathological heterogeneity. Molecular subtyping of BC has also revealed distinct luminal, basal, and neuroendocrine subtypes, each with unique genetic and immune signatures. Emerging research uncovers the biasing effects of the sex hormones with androgens increasing BC risk through both tumor cell intrinsic and extrinsic mechanisms. The sex chromosomes, including both the X and Y chromosomes, also contribute to the sex differences in BC. The effect of sex chromosome is both independent from and synergistic with the effects of sex hormones. Loss of the Y chromosome is frequently observed in BC patients, while an extra copy of the X chromosome confers better protection against BC in females than in males. Advent of advanced technologies such as multiomics and artificial intelligence will likely further improve the understanding of sex differences in BC, which may ultimately lead to personalized preventative and treatment strategies depending on the biological sex of patients. This review delves into the impacts of biology of sex on BC, emphasizing the importance of further research into sex-specific biology to improve cancer prevention and care.

The intratumoral microbiota plays a critical role in lung cancer development, metastasis, and treatment response, offering valuable insights into the tumor microenvironment (TME) and revealing new therapeutic opportunities. Lung cancer remains the leading cause of cancer-related deaths worldwide, with the intratumoral microbiota exhibiting unique characteristics and functions within this disease. In this review, we summarized the origin of the intratumoral microbiota, its entry into the tumor, its detailed composition, functions, and its potential clinical applications in lung cancer. For the first time, we estimate the absolute abundance of different microbes in lung cancer, highlight the specific differences in microorganisms, and track their dynamic changes from health to disease. We also describe the overall landscape of intratumoral microbiota. Finally, we discuss the challenges and implications of this emerging field, offering insights for future research and therapeutic strategies.

The gut microbiome influences the host immune system, cancer development and progression, as well as the response to immunotherapy during cancer treatment. Here, we analyse the composition of the gut bacteriome in metastatic Non-Small Cell Lung Cancer (NSCLC) patients receiving Pembrolizumab immunotherapy within a prospective maintenance trial through opportunistic sampling during treatment.

The gut microbiome profiles of NSCLC patients were obtained from stool samples collected during Pembrolizumab treatment and analysed with 16S rRNA metagenomics sequencing. Patient profiles were compared to a group of healthy individuals of matching ethnic group, age, sex, BMI and comorbidities.

A significant decrease in the treated patients was observed in two prominent bacterial families of the phylum Firmicutes, Lachnospiraceae and Ruminoccocaceae, which comprised 31.6% and 21.8% of the bacteriome in the healthy group but only 10.9% and 14.2% in the treated patient group, respectively. Species within the Lachnospiraceae and Ruminococcaceae families are known to break down undigested carbohydrates generating short chain fatty acids (SCFA), such as butyrate, acetate and propionate as their major fermentation end-products, which have been implicated in modifying host immune responses. In addition, a significant increase of the Bacteroidacaeae family (Bacteroidetes phylum) was observed from 10.7% in the healthy group to 23.3% in the treated patient group. Moreover, and in agreement with previous studies, a decrease in the Firmicutes to Bacteroidetes ratio in the metastatic NSCLC Pembrolizumab-treated patients was observed.

The observed differences indicate dysbiosis and a compromised intestinal health status in the metastatic NSCLC Pembrolizumab-treated patients. This data could inform future studies of immunotherapy treatment responses and modulation of the gut microbiome to minimise dysbiosis prior or concurrent to treatment.

SWIPE Trial (NCT02705820).

Cancer metastasis is the leading cause of death in patients. In recent years, there has been a growing recognition of the role of tumor-associated microflora in tumor metastasis. The connection between oral and gut microflora and the tumor microenvironment has also been extensively studied. The migration of oral and gut microflora is closely associated with tumor development. Although there is awareness regarding the significant impact of microbial communities on human health, the focus on their relationship with host organisms, particularly those related to tumor-associated microflora, remains inadequate. As an integral part of the body, the host microflora is crucial for regulating the cancer risk and preventing tumor recurrence. The oral-gut axis plays an indispensable role in human immunity, and many types of cancers, such as colorectal, pancreatic, and breast, are significantly influenced by their internal microbial communities. However, further exploration into the mechanisms underlying the role of the intratumoral microflora in cancer is necessary to achieve a comprehensive understanding. We have summarized and analyzed related articles in PubMed. This article reviews the impact of the oral-gut axis on the human immune system, explores the relationship between the translocation of the oral and intestinal flora and the tumor microenvironment, analyzes the specific mechanisms involved in the translocation of the oral and intestinal microflora during the evolution and progression of tumors, and elaborates on the correlations between the occurrence and development of tumors and the changes in the microflora. Finally, a summary of these abovementioned points is provided.

Streptococcus vasculosus is a common oral and intestinal symbiotic bacteria, but it can transform into a pathogen under certain conditions, affecting the host's immune response. Studies have shown that Streptococcus vasculosus may promote tumor growth and metastasis by activating host inflammatory responses. This study simulated the environment of Streptococcus vascularis infection through in vitro cell culture experiment, and observed the influence of streptococcus vascularis at different time points and different concentrations on cancer cells. The expression and activity of GSDME, cleaved caspase-3 and NLRP3 proteins were detected by Western blot, immunofluorescence and flow cytometry. By constructing gene knockout and overexpression cell models, the role of these protein molecules in promoting cancer progression of Streptococcus vascularis was further verified. It was found that GSDME activation is a key step in Pyroptosis occurrence, and cleaved caspase-3 plays an important role in GSDME cleavage activation. The activation of NLRP3 inflammatome is closely related to the inflammatory response induced by Streptococcus vasculosus, and thus affects the tumor microenvironment.

Intracellular microbes are actively present in various tumor types in low biomass and play a major role in metastasis. Eliminating intracellular microbes on a cellular level with precision remains a challenge. To address this issue, we designed a screening pipeline to characterize intracellular microbes and their interaction with host cells. We used host and microbial in vitro lab-based constant and reproducible model, host as (mammalian cancer HeLa), and microbial strain as (Escherichia coli 25922). To study the pharmacological impact on intracellular bacterial load, we used antibiotics (ampicillin, roxithromycin, and ciprofloxacin) and chemotherapy drugs (doxorubicin and cisplatin) as external stimuli for both host and microbes. We found that increasing pharmacological stress does not increase microbial load inside the host cells. Eliminations of intracellular bacteria was done by using permutation orthogonal arrays (POA), whereby we acquired optimal drug combination in particular sequence of drugs, which reduced 90%-95% of the intracellular microbial load. Proteomic analysis revealed that upon invasion of Escherichia coli 25922, HeLa cells enriched ATP production pathways to activate intermediate filaments, which should be investigated closely via in vivo models.

Head and neck squamous cell carcinoma (HNSCC) remains among the most aggressive malignancies with limited treatment options, especially in recurrent and metastatic cases. Despite advances in surgery, radiotherapy, chemotherapy, and immune checkpoint inhibitors, survival rates remain suboptimal due to tumor heterogeneity, immune evasion, and treatment resistance. In recent years, Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized hematologic cancer treatment by genetically modifying T cells to target tumor-specific antigens like CD19, CD70, BCMA, EGFR, and HER2, leading to high remission rates. Its success is attributed to precise antigen recognition, sustained immune response, and long-term immunological memory, though challenges like cytokine release syndrome and antigen loss remain. Notably, its translation to solid tumors, including HNSCC, faces significant challenges, such as tumor microenvironment (TME)-induced immunosuppression, antigen heterogeneity, and limited CAR T-cell infiltration. To address these barriers, several tumor-associated antigens (TAAs), including EGFR, HER2 (ErbB2), B7-H3, CD44v6, CD70, CD98, and MUC1, have been identified as potential CAR T-cell targets in HNSCC. Moreover, innovative approaches, such as dual-targeted CAR T-cells, armored CARs, and CRISPR-engineered modifications, aim to enhance efficacy and overcome resistance. Notably, combination therapies integrating CAR T-cells with immune checkpoint inhibitors (e.g., PD-1/CTLA-4 blockade) and TGF-β-resistant CAR T designs are being explored to improve therapeutic outcomes. This review aimed to elucidate the current landscape of CAR T-cell therapy in HNSCC, by exploring its mechanisms, targeted antigens, challenges, emerging strategies, and future therapeutic potential.

The gut microbiota is a diverse ecosystem that significantly impacts human health and disease. This article focuses on how the gut microbiota interacts with inflammatory bowel diseases and colorectal tumors, especially through immune regulation. The gut microbiota plays a role in immune system development and regulation, while the body's immune status can also affect the composition of the microbiota. These microorganisms exert pathogenic effects or correct disease states in gastrointestinal diseases through the actions of toxins and secretions, inhibition of immune responses, DNA damage, regulation of gene expression, and protein synthesis. The microbiota and its metabolites are essential in the development and progression of inflammatory bowel diseases and colorectal tumors. The complexity and bidirectionality of this connection with tumors and inflammation might render it a new therapeutic target. Hence, we explore therapeutic strategies for the gut microbiota, highlighting the potential of probiotics and fecal microbiota transplantation to restore or adjust the microbial community. Additionally, we address the challenges and future research directions in this area concerning inflammatory bowel diseases and colorectal tumors.

Gut microbiota play a critical role in mediating the bidirectional association between cancer and depression. Emerging evidence indicates that adjusting the dietary component intake can significantly alter gut microbiota composition, thereby influencing the host's metabolism and immune function. Changes in gut microbiota and their metabolites may represent key factors in preventing cancer-depression comorbidity.

English publications were searched in databases including the Web of Science, Scopus, and PubMed using a series of keywords: "cancer", "depression", "gut microbiota", "dietary components", and related terms, individually or in combination. The search focused on preclinical and clinical studies describing the regulatory effects of dietary component interventions.

This narrative review summarizes the associations among gut microbiota, cancer, and depression, and synthesizes current evidence on the modulatory effects and mechanisms of specific dietary component interventions, including dietary patterns, probiotics, prebiotics, and diet-derived phytochemicals, on gut microbiota. On the one hand, these interventions inhibit abnormal proliferation signals in the tumor microenvironment and enhance anticancer immune responses; on the other hand, they modulate neurotransmitter homeostasis, suppress neuroinflammation, and improve mood behaviors through the gut-brain axis interactions mediated by microbial metabolites.

The complex associations among cancer, depression, and gut microbiota require further clarification. Modulating gut microbiota composition through dietary components represents a novel therapeutic strategy for improving cancer-depression comorbidity. Regulated gut microbiota enhance immune homeostasis and intestinal barrier function, while their metabolites bidirectionally modulate one another via systemic circulation and the gut-brain axis, thereby improving both the tumor microenvironment and depressive-like behaviors in cancer patients while reducing the adverse effects of cancer.

Lung cancer is a significant health concern that poses a considerable threat to human health and quality of life. In order to enhance the prognosis of patients with lung cancer, we conducted a combined analysis of 16S rDNA gene sequencing of alveolar lavage fluid and LC-MS metabolomics research, with the objective of identifying biomarkers in patients with early-stage lung cancer presenting as SPN. A comparison of the benign nodule group and the early-stage lung cancer patients revealed that the phylum-level Bacteroidetes and the genus-level Chryseobacterium and Delftia were more abundant in the latter group. Additionally, the Fusobacteriales might serve as a predictive marker for the diagnosis of early-stage lung cancer. In the context of metabolomics, the early-stage lung cancer was found to be characterised by elevated levels of specific metabolites, including Alternariol, dTMP, Oxymatrine, Gedunin, PC 36:4. Conversely, reductions in other metabolites, such as LPC O-24:0, PC 18:2_18:3, PC 19:2_19:2, Cholecalciferol and T-2 Triol, were also observed. Correlation analyses demonstrated that alveolar lavage microorganisms were closely associated with differential metabolites. Specifically, reductions in Cholecalciferol were associated with a variety of high-abundance flora and involved in vitamin digestion and absorption pathways. Furthermore, reductions in cholecalciferol may serve as a robust predictor of early-stage lung cancer. These findings provide new predictive biomarkers for early-stage lung cancer manifested by SPN, which is clinically important and requires further study of the potential mechanisms of action and function of the targets.

While growing evidence highlights the role of gut microbiota and inflammatory proteins in cancer, with cancer-related inflammation now considered the seventh hallmark of cancer, the direct causal relationships between specific microbiota, cancer, and the potential mediating effects of inflammatory proteins have not been fully established.

We employed Mendelian randomization (MR) to assess the causal relationships between gut microbiota, inflammatory proteins, and eighteen distinct cancers using data from extensive genome-wide association studies (GWAS). The primary statistical method utilized was inverse variance weighting (IVW). We also investigated whether inflammatory proteins could mediate the effects of gut microbiota on cancer development.

Our findings revealed 42 positive and 49 inverse causal impacts of gut microbiota on cancer risk (P < 0.05). Additionally, we identified 32 positive and 28 inverse causal relationships between inflammatory proteins and cancer risk. Moreover, genus Collinsella decreased the risk of lung cancer by decreasing levels of T-cell surface glycoprotein CD5 (mediating effect = 16.667%), while genus Ruminococcaceae UCG005 increased the risk of mesothelioma by increasing levels of CCL4 (mediating effect = 5.134%).

Our study provides evidence for a causal association between gut microbiota, inflammatory proteins, and eighteen different cancer types. Notably, the T-cell surface glycoprotein CD5 and CCL4 were identified as mediators linking the genus Collinsella with lung cancer and the genus Ruminococcaceae UCG005 with mesothelioma, respectively.

Cancer, uncontrolled cell growth due to the loss of cell cycle regulation, is often found to be associated with viral infections and, as recent studies show, with bacterial infections as well. Emerging reports also suggest a strong link between fungi and cancer. The crucial virulence trait of fungi, the switch from yeast (Y) to hyphal (H) form, is found to be associated with carcinogenesis. The physicochemical properties and signal transduction pathways involved in the switch to the hyphal form overlap with those of tumor cell formation. Inhibiting differentiation causes apoptosis in fungi, whereas preventing apoptosis leads to cancer in multicellular organisms. Literature on the fungi-cancer linkage, though limited, is increasing rapidly. This review examines cancer-specific fungal communities, the impact of fungal microbiome on cancer cell progression, similarities between fungal differentiation and cells turning cancerous at biochemical and molecular levels, including the overlaps in signal transduction pathways between fungi and cancer. Based on the available evidence, we suggest that molecules inhibiting the yeast-hyphal transition in fungi can be combined with those targeting tumor cell apoptosis for effective cancer treatment. The review points out fertile research areas where mycologists and cancer researchers can collaborate to unravel common molecular mechanisms. Moreover, antibodies targeting fungal-specific chitin and glucan can be used for the selective neutralization of tumor cells. These new combinations of potential therapies are expected to facilitate the development of target-specific, less harmful and commercially feasible anticancer therapies. We bring together available evidence to argue that fungal infections could either trigger cancer or have a significant role in the development and progression of cancer. Hence, cancer-associated fungal populations could be utilized as a target for a combination therapy involving the integration of anticancer and antifungal drugs as well as inhibitors of fungal morphogenesis to develop more effective anticancer therapies.

Intratumoral microbiota have been identified as a component of the tumor microenvironment that regulates the metastatic behavior of tumors. They serve not only as indicators of tumor pathology but also as potential drug targets in cancer therapy. Herein, a multifunctional nanoplatform (DD@FEL) is prepared by combining antibiotic doxycycline (DOXY) that can combat intratumoral microbiota and the chemotherapeutic drug doxorubicin (DOX) in ergosterol-originated liposome. Specially, ergosterol is utilized as a substitute for cholesterol in liposomes to exert pharmacological activity. Mechanistically, DD@FEL leveraged DOXY to inhibit cancer metastasis based on the regulation of intratumoral microbiota, which synergizes with the chemotherapeutic effect of DOX, eventually inhibiting the progression of triple-negative breast cancer (TNBC). Verified both in vitro and in vivo, DD@FEL effectively exerts a cytotoxic effect on TNBC cells, delays the growth of primary TNBC, and attenuates the development of its lung metastasis, providing a promising therapeutic strategy to control both orthotopic and metastatic TNBC.

Matrix metalloproteinases (MMPs) are critical mediators of extracellular matrix remodeling, playing a pivotal role in the progression and metastasis of lung cancer. Emerging evidence indicates that bacterial pathogens, such as Streptococcus pneumoniae (SP), can modulate MMP activity and contribute to tumor progression. This study quantified SP abundance in lung cancer tissues and investigated its relationship with MMP-9 and MMP-2 expression, as well as its impact on clinical outcomes. SP DNA levels were assessed using droplet digital PCR, and MMP-9 and MMP-2 protein expression were evaluated by immunohistochemistry in 120 lung cancer samples. Elevated SP abundance was significantly associated with increased MMP-9 expression, advanced lung cancer stages, greater brain metastases burden, and reduced overall survival (P < 0.05). However, SP abundance showed no correlation with MMP-2 expression. These findings highlight a direct link between SP infection and lung cancer progression through MMP-9-mediated extracellular matrix degradation and metastatic spread. Targeting the SP-MMP-9 axis may represent a novel therapeutic approach to mitigate metastasis and improve patient outcomes in lung cancer.

Gastric cancer (GC) prognosis is significantly influenced by intratumoral microbiomes, which modulate host-immune interactions. This study analyzed data from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to identify immune genes associated with GC prognosis and conducted prognostic immune subtypes. GC patients were classified into two distinct prognostic immune phenotypes C1 and C2 based on the non-negative matrix factorization consensus clusters. Phenotype C2 exhibited a better prognosis and distinct immune characteristics, including enhanced presence of Th2 and Th17 cells and improved response to chemotherapy. In contrast, phenotype C1 showed higher expression levels of PDCD1LG2 and TLR9, which were critical immune factors involved in immune regulation. Both phenotypes were linked to immune genes influencing intratumoral microbiomes and GC immunotherapy responses. A prediction risk model was constructed using the LASSO regression analysis and showed great prognostic value for GC patients. The key genes were correlated with immune cells and suppressed the function of the host immune system. The intratumoral microbiomes were strongly associated with the hosts' immune infiltration and significantly interacted with host immune genes to influence GC outcomes. Candidatus Nitrosotenuis plays a significant role in predicting the prognosis of GC patients. This research underscores the pivotal role of intratumoral microbiomes in GC prognosis and supports the development of future personalized therapeutic approaches.IMPORTANCEIncreasing evidence confirms the presence of intratumoral microbiomes. However, the role of the intratumoral microbiomes in the progression of gastric cancer and their relationship with the immune microenvironment remain unclear. Our study classified gastric cancer patients into two immune prognostic subtypes, C1 and C2, using non-negative matrix factorization consensus clusters. The C2 subtype exhibited a better prognosis and more pronounced immune characteristics. Microbiome analyses revealed associations between both subtypes and immune genes that affect intratumoral microbiomes and their responses to immunotherapy. The intratumoral microbiomes were closely linked with host immune infiltration and significantly interacted with immune genes, which influence the prognosis of gastric cancer. Notably, Candidatus Nitrosotenuis showed a significant prognostic value in gastric cancer patients. Our findings highlight the critical role of the intratumoral microbiomes in affecting gastric cancer prognosis and its interaction with the immune microenvironment, supporting future personalized therapeutic approaches.

Biological factors affect the human microbiome, highlighting the need for reasonably estimating sample sizes in future population studies.

We assessed the temporal stability of fecal microbiome diversity, species composition, and genes and functional pathways through shallow shotgun metagenome sequencing. Using intraclass correlation coefficients (ICC), we measured biological variability over 6 months. We estimated case numbers for 1:1 or 1:3 matched case-control studies, considering significance levels of 0.05 and 0.001 with 80% power, based on the collected fecal specimens per participant.

The fecal microbiome's temporal stability over 6 months varied (ICC < 0.6) for most alpha and beta diversity metrics. Heterogeneity was seen in species, genes, and pathways stability (ICC, 0.0-0.9). Detecting an OR of 1.5 per SD required 1,000 to 5,000 cases (0.05 significance for alpha and beta; 0.001 for species, genes, and pathways) with equal cases and controls. Low-prevalence species needed 15,102 cases, and high-prevalence species required 3,527. Similar needs applied to genes and pathways. In a 1:3 matched case-control study with one fecal specimen, 10,068 cases were needed for low-prevalence species and 2,351 for high-prevalence species. For ORs of 1.5 with multiple specimens, cases needed for low-prevalence species were 15,102 (one specimen), 8,267 (two specimens), and 5,989 (three specimens).

Detecting disease associations requires a large number of cases. Repeating prediagnostic samples and matching cases to more controls could decrease the needed number of cases for such detections.

Our results will help future epidemiologic study designs and implement well-powered microbiome studies.

Microalgae present a novel and multifaceted approach to cancer therapy by modulating the tumor-associated microbiome (TAM) and the tumor microenvironment (TME). Through their ability to restore gut microbiota balance, reduce inflammation, and enhance immune responses, microalgae contribute to improved cancer treatment outcomes. As photosynthetic microorganisms, microalgae exhibit inherent anti-tumor, antioxidant, and immune-regulating properties, making them valuable in photodynamic therapy and tumor imaging due to their capacity to generate reactive oxygen species. Additionally, microalgae serve as effective drug delivery vehicles, leveraging their biocompatibility and unique structural properties to target the TME more precisely. Microalgae-based microrobots further expand their therapeutic potential by autonomously navigating complex biological environments, offering a promising future for precision-targeted cancer treatments. We position microalgae as a multifunctional agent capable of modulating TAM, offering novel strategies to enhance TME and improve the efficacy of cancer therapies.

Recent studies have underscored a potential link between gut microbiota and urological tumors, yet the causal relationship with bladder cancer (BCa) and the role of metabolic pathways remain unclear.

Instrumental variables (IVs) for gut microbiota were obtained from genome-wide association studies (GWAS) conducted by the MiBioGen consortium (n = 18,340). GWAS data for BCa were sourced from a comprehensive genome-wide meta-analysis encompassing 23 cohorts. Mendelian randomization (MR) was employed to investigate the causal relationship between gut microbiota and BCa, utilizing inverse variance weighted (IVW) as the primary MR method. Additionally, metabolic pathways associated with these microbiota were analyzed to understand their functional roles in BCa pathogenesis. Sensitivity analyses were conducted to validate all MR results.

The MR analysis identified five gut microbiota taxa with a causal association with BCa, with the genus Bilophila notably promoting BCa. Metabolic pathway analysis revealed significant associations between specific pathways and BCa, suggesting that changes in amino acid and NAD metabolism might influence BCa development. Sensitivity analyses indicated no significant heterogeneity or horizontal pleiotropy among the IVs.

This study revealed the significant causal relationship between gut microbiota and BCa, particularly identifying Bilophila as a key pathogenic initiator. These findings elucidated the potential impact of metabolic pathways, especially amino acid and NAD metabolism, on the pathogenesis of BCa. They not only laid the foundation for innovative therapeutic strategies but also highlighted the immense potential of microbiota-based interventions in the prevention and treatment of BCa, paving the way for new directions in precision medicine.

This study introduces a deep learning-based strategy to automatically detect the L3 slice and segment abdominal tissues from computed tomography (CT) images. Accurate measurement of muscle and fat composition at the L3 level is critical as it can serve as a prognostic biomarker for cancer diagnosis and treatment. However, current manual approaches are time-consuming and prone to class imbalance, since L3 slices constitute only a small fraction of the entire CT dataset. In this study, we propose an optimization-incorporated strategy that integrates augmentation ratio and class weight adjustment as correction design variables within deep learning models. In this retrospective study, the CT dataset was privately collected from 150 prostate cancer and bladder cancer patients at the Department of Urology of Gangneung Asan Hospital. A ResNet50 classifier was used to detect the L3 slice, while standard Unet, Swin-Unet, and SegFormer models were employed to segment abdominal tissues. Bayesian optimization determines optimal augmentation ratios and class weights, mitigating the imbalanced distribution of L3 slices and abdominal tissues. Evaluation of CT data from 150 prostate and bladder cancer patients showed that the optimized models reduced the slice detection error to approximately 0.68 ± 1.26 slices and achieved a Dice coefficient of up to 0.987 ± 0.001 for abdominal tissue segmentation-improvements over the models that did not consider correction design variables. This study confirms that balancing class distribution and properly tuning model parameters enhances performance. The proposed approach may provide reliable and automated biomarkers for early cancer diagnosis and personalized treatment planning.

Studies have shown that the colonisation of active microorganisms is more conducive to the development of tumour immunotherapy, but intuitive evidence regarding shaping of the tumour immune microenvironment is lacking. In this study, we used Bifidobacterium longum subsp. longum (XZ01) to intervene in a colon cancer mouse model and found that its mechanism may be related to the interaction between the spatial distribution of microorganisms and tumour immunity. Through the visualisation method we established, for the first time, we showed that harmful active bacteria such as Streptococcus and Rhodococcus specifically accumulate in the middle and upper layers of tumour tissue. These bacteria likely participate in signalling pathways that affect macrophages by directly contacting or invading the macrophages, leading to a nondifferentiated state in macrophages and the loss of some immune functions. Furthermore, the accumulation of Streptococcus and Rhodococcus fragments in the deep layer of tumour tissue likely upregulates the expression of IL-10 in tumour tissue and inhibits other immune cells, such as CD8+ T cells, DC and NK cells. In contrast, XZ01 can specifically compete for the growth sites of Streptococcus and Rhodococcus in the middle and upper layers of tumour tissue and probably protects macrophages from being invaded by harmful bacteria. XZ01 directly regulates the polarisation of M0 macrophages towards the M1 phenotype by upregulating IFN-γ, thus activating tumour immunity to inhibit the growth of tumour cells. This study revealed that the influence of active microorganisms on the tumour immune microenvironment is crucial for effective immunotherapy intervention, potentially offering new targets for improving patient prognosis.

Neoadjuvant chemoimmunotherapy (NACI) has emerged as the standard treatment for early-stage triple-negative breast cancer (TNBC). However, reliable biomarkers for identifying patients who are likely to benefit from NACI are lacking. This study aims to develop an intratumoral microbiota-aided radiomics model for predicting pathological complete response (pCR) in patients with TNBC.

Intratumoral microbiota are characterized by 16S rDNA sequencing and quantified through experimental assays. Single-cell RNA sequencing is performed to analyze the tumor microenvironment of tumors with various responses to NACI. Radiomics features are extracted from tumor regions on longitudinal magnetic resonance images (MRIs) scanned before and after NACI in the training set. On the basis of treatment response (pCR or non-pCR) and intratumoral microbiota scoring, we select key radiomics features and construct a fusion model integrating multi-timepoint (pre-NACI and post-NACI) MRI to predict the efficacy of immunotherapy, followed by independent external validation.

A total of 124 patients are enrolled, with 88 in the training set and 36 in the validation set. Tumors from patients who achieves pCR present a significantly greater intratumoral microbiota load than tumors from patients who achieve non-pCR (p < 0.05). Additionally, tumors in non-pCR group exhibit greater infiltration of tumor-associated SPP1+ macrophages, which is negatively correlated with the microbiota load. On the basis of intratumoral microbiota scoring, we select 17 radiomics features and use them to construct the fusion radiomics model. The fusion model achieves the highest AUC of 0.945 in the training set, outperforming pre-NACI (AUC = 0.875) and post-NACI (AUC = 0.917) models. In the validation set, this model maintains a superior AUC of 0.873, surpassing those of pre-NACI (AUC = 0.769) and post-NACI (AUC = 0.802) models. Clinically, the fusion model distinguishes patients who achieve pCR from those who do not with an accuracy of 77.8%. Decision curve analysis demonstrates the superior net clinical benefit of this model across varying risk thresholds.

Our intratumoral microbiota-aided radiomics model could serve as a powerful and noninvasive tool for predicting the response of patients with early-stage TNBC to NACI.

Colorectal cancer (CRC) remains a leading cause of cancer-related deaths worldwide, with its progression intricately linked to gut microbiota dysbiosis. Disruptions in microbial homeostasis contribute to tumor initiation, immune suppression, and inflammation, establishing the microbiota as a key therapeutic target. Fecal microbiota transplantation (FMT) has emerged as a transformative approach to restore microbial balance, enhance immune responses, and reshape the tumor microenvironment. This review explores the mechanisms underlying FMT's therapeutic potential, evaluates its advantages over other microbiota-based interventions, and addresses challenges such as donor selection, safety concerns, and treatment standardization. Looking forward, the integration of FMT into personalized CRC therapies requires robust clinical trials and the identification of predictive biomarkers to optimize its efficacy and safety.

Recent studies suggest that the human microbiome influence tumor development. Endometrial carcinoma (EC) is the sixth most common malignancy in women. Recent research has demonstrated the microbes play a critical role in the development and metastasis of EC. However, it remains unclear whether intratumoral microbes are associated with tumor microenvironment (TME) and prognosis of EC. In this study, we collected the EC microbiome data from cBioPortal and constructed a prognostic model based on Resident Microbiome of Endometrium (RME). We then examined the relationship between the RME score, immune cell infiltration, immunotherapy-related signature, and prognosis. The findings demonstrated the independent prognostic value of the RME score for EC. The group with low RME scores had higher enrichment of immune cells. Drug sensitivity analysis revealed that the RME score may serve as a potential predictor of chemotherapy efficacy. In conclusion, our research offers new perspectives on the relationships between tumor immunity and microbes.

Microecology refers to the ecosystem formed by human and microbial communities in the process of co-evolution, the microecological imbalance is associated with occurrence and development of multiple diseases, including lung cancer. In this review, we detailedly summarized the concept and roles of microecology, the relationship between microecology and human diseases, and related techniques in microecology studies. Importantly, we specially analyzed the correlations between microecology and lung cancer by focusing on gut microbiota, oral microbiota and lower respiratory tract microbiota, and further evaluated the effects of microbiota dysbiosis on chemotherapy and immunotherapy efficacy in lung cancer. At last, we discussed the potential mechanisms by which dysregulated microbiota promotes the genesis and development of lung cancer. Microecology-centered detection and intervention will improve the early diagnosis of lung cancer and provide new targets for the treatment of lung cancer.

Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with an increased risk of endometrial cancer, potentially mediated by vaginal microbiota dysbiosis and hormonal disturbances. This study investigates how hormonal imbalances in PCOS patients affect the vaginal microbiome and choline metabolism, thereby influencing endometrial cancer risk.

In this observational study, 70 women were enrolled, including 36 with PCOS and 34 controls. We analyzed their vaginal microbiota, lipid metabolism, and endometrial transcriptome using 16S rRNA sequencing, untargeted lipidomics, and transcriptomic sequencing.

The PCOS group showed significant differences in vaginal microbiota composition, notably an increase in LPS-producing Prevotella spp. Functional analyses indicated activation of LPS biosynthesis and inflammatory signaling pathways. Lipidomics revealed disrupted choline metabolism, with alterations in phosphocholine and total choline levels. Transcriptomic data highlighted the up-regulation of inflammatory and metabolic dysregulation pathways.

Hormonal imbalances in PCOS contribute to significant changes in the vaginal microbiome and metabolic pathways, increasing the risk of endometrial cancer. These findings suggest potential therapeutic targets for reducing cancer risk in this population.

Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive malignancy with a dismal prognosis, and gaps remain in understanding the determinants influencing disease outcomes.

To characterise the gut microbiota feature and identify potential probiotics that could ameliorate the development of NKTCL.

This cross-sectional study employed shotgun metagenomic sequencing to profile the gut microbiota in two Chinese NKTCL cohorts, with validation conducted in an independent Korean cohort. Univariable and multivariable Cox proportional hazards analyses were applied to assess associations between identified marker species and patient outcomes. Tumour-suppressing effects were investigated using comprehensive in vivo and in vitro models. In addition, metabolomics, RNA sequencing, chromatin immunoprecipitation sequencing, Western blot analysis, immunohistochemistry and lentiviral-mediated gene knockdown system were used to elucidate the underlying mechanisms.

We first unveiled significant gut microbiota dysbiosis in NKTCL patients, prominently marked by a notable reduction in Faecalibacterium prausnitzii which correlated strongly with shorter survival among patients. Subsequently, we substantiated the antitumour properties of F. prausnitzii in NKTCL mouse models. Furthermore, F. prausnitzii culture supernatant demonstrated significant efficacy in inhibiting NKTCL cell growth. Metabolomics analysis revealed butyrate as a critical metabolite underlying these tumour-suppressing effects, validated in three human NKTCL cell lines and multiple tumour-bearing mouse models. Mechanistically, butyrate suppressed the activation of Janus kinase-signal transducer and activator of transcription pathway through enhancing histone acetylation, promoting the expression of suppressor of cytokine signalling 1.

These findings uncover a distinctive gut microbiota profile in NKTCL and provide a novel perspective on leveraging the therapeutic potential of F. prausnitzii to ameliorate this malignancy.

In microbiome research, data sparsity represents a prevalent and formidable challenge. Sparse data not only compromises the accuracy of statistical analyses but also conceals critical biological relationships, thereby undermining the reliability of the conclusions. To tackle this issue, we introduce a machine learning approach for microbiome data imputation, termed TphPMF. This technique leverages Probabilistic Matrix Factorization, incorporating phylogenetic relationships among microorganisms to establish Bayesian prior distributions. These priors facilitate posterior predictions of potential non-biological zeros. We demonstrate that TphPMF outperforms existing microbiome data imputation methods in accurately recovering missing taxon abundances. Furthermore, TphPMF enhances the efficacy of certain differential abundance analysis methods in detecting differentially abundant (DA) taxa, particularly showing advantages when used in conjunction with DESeq2-phyloseq. Additionally, TphPMF significantly improves the precision of cross-predicting disease conditions in microbiome datasets pertaining to type 2 diabetes and colorectal cancer.

Intestinal crypts harbour a specific microbiota but whether and how these bacteria regulate intestinal stem cells (ISCs) or influence colorectal cancer (CRC) development is unclear. Here we screened crypt-resident bacteria in organoids and found that indole acetic acid (IAA) secreted by Acinetobacter radioresistens inhibits ISC turnover. A. radioresistens inhibited cellular proliferation in tumour slices from CRC patients and inhibited intestinal tumorigenesis and spheroid initiation in APCMin/+ mice. Targeted clearance of A. radioresistens from colonic crypts using bacteriophage increased EphB2 expression and consequently promoted cellular proliferation, ISC turnover and tumorigenesis in mouse models of CRC. The protective effects of A. radioresistens were abrogated upon deletion of trpC to prevent IAA production, or upon intestine-specific aryl hydrocarbon receptor (AhR) knockout, identifying an IAA-AhR-Wnt-β-catenin signalling axis that promotes ISC homeostasis. Our findings reveal a protective role for an intestinal crypt-resident microbiota member in tumorigenesis.

As one part of the innate immune response to external stimuli, chronic inflammation increases the risk of various cancers, and tumor-promoting inflammation is considered one of the enabling characteristics of cancer development. Recently, there has been growing evidence on the role of anti-inflammation therapy in cancer prevention and treatment. And researchers have already achieved several noteworthy outcomes. In the review, we explored the underlying mechanisms by which inflammation affects the occurrence and development of cancer. The pro- or anti-tumor effects of these inflammatory factors such as interleukin, interferon, chemokine, inflammasome, and extracellular matrix are discussed. Since FDA-approved anti-inflammation drugs like aspirin show obvious anti-tumor effects, these drugs have unique advantages due to their relatively fewer side effects with long-term use compared to chemotherapy drugs. The characteristics make them promising candidates for cancer chemoprevention. Overall, this review discusses the role of these inflammatory molecules in carcinogenesis of cancer and new inflammation molecules-directed therapeutic opportunities, ranging from cytokine inhibitors/agonists, inflammasome inhibitors, some inhibitors that have already been or are expected to be applied in clinical practice, as well as recent discoveries of the anti-tumor effect of non-steroidal anti-inflammatory drugs and steroidal anti-inflammatory drugs. The advantages and disadvantages of their application in cancer chemoprevention are also discussed.

The endometrial microbiota exerts a crucial role in maintaining the health of the female reproductive system. As such, in this study, we have examined the composition of the microbiota in endometrium tissues with and without endometriosis, with the objective of identifying key species that may potentially contribute to the progression of endometriosis.

We obtained endometrial tissues from 43 women diagnosed as either having endometriosis or not. Subsequently, we utilized a diverse array of techniques, including fluorescence in situ hybridization (FISH), immunohistochemistry (utilizing anti-LPS and anti-LTA antibodies), transmission electron microscopy (TEM), and 16S rRNA sequencing, to undertake a comprehensive examination of the presence of microorganisms in the endometrium and their potential role in endometriosis.

Our findings consistently indicated the existence of bacteria in both normal endometrium tissues and those affected by endometriosis. By employing the fluorescent co-staining technique, we observed the colocalization of macrophages and bacteria in both tissue types. Notably, we discovered a significant increase in microbial diversity in endometrial tissue from women with endometriosis compared to normal endometrial tissues. Additionally, we identified 13 species that were more abundant in the normal group, such as Acinetobacter guillouiae. In contrast, seven species were prominent in the endometriosis group, with Faecalibacterium prausnitzii being a notable one. Finally, our results suggest that Faecalibacterium prausnitzii may play an essential role in the progression of endometriosis.

We carried out a comprehensive analysis of the endometrial microbial landscape in endometriosis tissue and revealed that Faecalibacterium prausnitzii is a pivotal species that may potentially play a crucial role in the pathogenesis of endometriosis.

An increasing number of studies indicate that the gut, cervical, and vaginal microbiota may play crucial roles in the development of cervical cancer (CC). However, the interactions between the microbiota and the host are yet unknown. To address this gap, a systematic review and meta-analysis were conducted to assess the microbiota alterations in a variety of body locations, including the gut and genital tract.

Electronic searches of PubMed, Embase, Web of Science, and the Cochrane Library were conducted to retrieve eligible papers published from January 1, 2014, to January 1, 2024 (PROSPERO: CRD42024554433). This study was restricted to English-language studies reporting on alpha diversity, beta diversity, and relative abundance, as well as on patients with CC whose microbiota had been analyzed via next-generation sequencing technologies. To assess the risk of bias (RoB), we utilized the Newcastle‒Ottawa Quality Assessment Scale (NOS) and the ROBINS-I tool. For the meta-analysis, we employed Review Manager 5.4.

Thirty-six eligible studies were included in this review. The Chao1 index (SMD = 0.96, [95% CI: 0.71, 1.21], I2 = 0%) and the Shannon index (SMD = 1.02, [95% CI: 0.53, 1.50], I2 = 85%) values from vaginal samples were significantly greater in patients than in the controls. In the cervical samples, the Shannon index value (SMD = 1.29, [95% CI: 0.61, 1.97], I2 = 93%) significantly increased, whereas the Chao1 index value did not significantly differ (SMD = 0.50, [95% CI: -0.46, 1.46], I2 = 89%). The Shannon index value (SMD = 0.25, [95% CI: -0.22, 0.72], I2 = 38%) did not significantly differ across the gut samples. The majority of studies (19/25) indicated that the patients and noncancer controls differed significantly in terms of beta diversity. Cancer-associated changes were observed, with a dramatic decrease in the Lactobacillus genus and significant increases in pathogenic bacteria, including the Anaerococcus, Peptostreptococcus, Porphyromonas, Prevotella, and Sneathia genera. Additionally, the impact of antineoplastic therapies on microbial diversity was inconsistently reported across several studies.

This systematic review elucidates the microbiota alterations associated with the prevalence of CC and its response to anti-tumor therapies, aiming to provide insights for future research directions and precision medicine strategies to enhance women's quality of life.

CRD42024554433.

The number of female lung adenocarcinoma patients is increasing annually, but these patients are difficult to diagnose in the early stage without obvious clinical symptoms, leading to late-stage diagnoses and poor outcomes. Recent studies have shown that the lung microbiota is closely related to the occurrence and development of lung cancer, especially the characteristic changes in the lung microbiota of lung cancer patients, which opens a new research direction for the diagnosis and treatment of lung cancer. This study aimed to analyze the characteristics of the lung flora in different stages of female lung adenocarcinoma.

16 S rRNA sequencing technology was used to analyze the alpha diversity, beta diversity, composition, and function of the pulmonary flora in female patients with benign lesions (n = 7), adenocarcinoma in situ (n = 16), microinvasive adenocarcinoma (n = 31), and invasive adenocarcinoma (n = 25).

Progression to invasive lung adenocarcinoma is correlated with reduced alpha diversity in the lung flora. Compared with the other stages, only the invasive adenocarcinoma stage had significant differences in the beta diversity of the lung flora. At the phylum and genus levels, the abundance of major flora species decreased significantly as the disease progressed to the invasive adenocarcinoma stage, whereas the abundance of Bacillus spp. increased significantly. The abundance of phenotypes with mobile elements, biofilm-forming ability, oxidative stress tolerance, parthenogenetic anaerobic properties, and pathogenicity was significantly greater in invasive adenocarcinomas. The abundance of metabolic pathways was significantly lower in invasive adenocarcinomas.

Invasive adenocarcinoma has a unique flora structure characterized by decreased flora diversity and abundance and an increase in specific flora (e.g., Bacillus). In terms of bacterial function, adaptability and pathogenicity increased, and metabolic pathway activity decreased.

Gut microbiota is associated with endometrial cancer (EC); however, the causal relationship remains unexplored. This study attempted to explore the relationship between gut microbiota and EC using Mendelian randomization (MR) methods.

In this two-sample MR analysis, we used MiBioGen's gut microbiota data as the exposure and three datasets from European populations with EC as the outcome. The EC datasets included general EC, endometrioid histology, and non-endometrioid histology. Single nucleotide polymorphism (SNP) was used as the instrumental variable. Inverse variance weighted (IVW), multiplicative random effects IVW (MRE-IVW), Maximum likelihood (ML), MR Egger, MR-PRESSO, and the weighted median were used to perform MR analysis. Sensitivity analysis was conducted to assess the reliability of the results.

In this MR analysis of three EC datasets, specific gut microbiota were identified as potentially associated with different pathological types of EC. For general EC (ID: ebi-a-GCST006464), Family.Acidaminococcaceae (OR = 1.23, 95%CI: 1.02-1.48) and genus.Butyrivibrio (OR = 1.08, 95%CI: 1.01-1.16) were identified as risk factors, while genus.Ruminococcaceae UCG014 (OR = 0.82, 95%CI: 0.69-0.98) and genus.Turicibacter (OR = 0.84, 95%CI: 0.73-0.97) appeared to have protective effects. For endometrioid histology EC (ID: ebi-a-GCST006465), Family.Acidaminococcaceae (OR = 1.27, 95%CI: 1.01-1.59) and genus.Butyrivibrio (OR = 1.10, 95%CI: 1.01-1.19) were identified as risk factors, while several microbiota, including Family.Lactobacillaceae, genus.Coprococcus3, genus.Dorea, genus.Flavonifractor, genus.Lactobacillus, genus.Paraprevotella, and genus.Turicibacter, were identified as protective factors. For non-endometrioid histology EC (ID: ebi-a-GCST006466), Family.Rhodospirillaceae (OR = 1.41, 95%CI: 1.01-1.96) and genus.Peptococcus (OR = 1.43, 95%CI: 1.07-1.91) were identified as risk factors, while no significant protective factors were identified.

This two-sample MR study has identified gut microbiota with potential causal relationships with EC, varying by pathological type. These findings provide new insights into the pathogenesis of EC and suggest directions for future research on diagnosis and treatment strategies.

Mitophagy plays a critical role in maintaining mitochondrial quality and cellular homeostasis. But the specific contribution of mitophagy-related E3 ubiquitin ligases to prognoses remains largely unexplored. In this study, we identified a novel mitophagy-related E3 ubiquitin ligase prognostic signature using least absolute shrinkage and selector operator (LASSO) and multivariate Cox regression analyses in breast cancer. Based on median risk scores, patients were divided into high-risk and low-risk groups. Functional enrichment analyses were conducted to explore the biological differences between the two groups. Immune infiltration, drug sensitivity, and mitochondrial-related phenotypes were also analyzed to evaluate the clinical implications of the model. A four-gene signature (ARIH1, SIAH2, UBR5, and WWP2) was identified, and Kaplan-Meier analysis demonstrated that the high-risk group had significantly worse overall survival (OS). The high-risk patients exhibited disrupted mitochondrial metabolism and immune dysregulation with upregulated immune checkpoint molecules. Additionally, the high-risk group exhibited higher sensitivity to several drugs targeting the Akt/PI3K/mTORC1 signaling axis. Accompanying mitochondrial metabolic dysregulation, mtDNA stress was elevated, contributing to activation of the senescence-associated secretory phenotype (SASP) in the high-risk group. In conclusion, the identified signature provides a robust tool for risk stratification and offers insights into the interplay between mitophagy, immune modulation, and therapeutic responses for breast cancer.

Over the past few years, the tumor microbiome is increasingly recognized for its multifaceted involvement in cancer initiation, progression, and metastasis. With the application of 16S ribosomal ribonucleic acid (16S rRNA) sequencing, the intratumoral microbiome, also referred to as tumor-intrinsic or tumor-resident microbiome, has also been found to play a significant role in the tumor microenvironment (TME). Understanding their complex functions is critical for identifying new therapeutic avenues and improving treatment outcomes. This review first summarizes the origins and composition of these microbial communities, emphasizing their adapted diversity across a diverse range of tumor types and stages. Moreover, we outline the general mechanisms by which specific microbes induce tumor initiation, including the activation of carcinogenic pathways, deoxyribonucleic acid (DNA) damage, epigenetic modifications, and chronic inflammation. We further propose the tumor microbiome may evade immunity and promote angiogenesis to support tumor progression, while uncovering specific microbial influences on each step of the metastatic cascade, such as invasion, circulation, and seeding in secondary sites. Additionally, tumor microbiome is closely associated with drug resistance and influences therapeutic efficacy by modulating immune responses, drug metabolism, and apoptotic pathways. Furthermore, we explore innovative microbe-based therapeutic strategies, such as engineered bacteria, oncolytic virotherapy, and other modalities aimed at enhancing immunotherapeutic efficacy, paving the way for microbiome-centered cancer treatment frameworks.

Dietary polyphenols are garnering attention in the scientific community due to their potential health-beneficial properties and preventative effects against chronic diseases, viz. cardiovascular diseases, diabetes, obesity, and neurodegenerative diseases. Polyphenols are antioxidants that change microbial composition by suppressing pathogenic bacteria and stimulating beneficial bacteria. The interaction of polyphenols with dietary fibers affects their bioaccessibility in the upper and lower parts of the digestive tract. Dietary fibers, polyphenols, their conjugates, and their metabolites modulate microbiome population and diversity. Consuming polyphenol-rich dietary fibers such as pomegranate, cranberry, berries, and tea improves gut health. A complex relationship exists between polyphenol-rich diets and gut microbiota for functioning in human health. In this review, we provide an overview of the interactions of dietary polyphenols, fibers, and gut microbiota, improving the understanding of the functional properties of dietary polyphenols.