Cancer is a long-term illness that involves an imbalance in cellular and immune functions. It can be caused by a range of factors, including exposure to environmental carcinogens, poor diet, infections, and genetic alterations. Maintaining a healthy gut microbiome is crucial for overall health, and short-chain fatty acids (SCFAs) produced by gut microbiota play a vital role in this process. Recent research has established that alterations in the gut microbiome led to decreased production of SCFA's in lumen of the colon, which associated with changes in the intestinal epithelial barrier function, and immunity, are closely linked to colorectal cancer (CRC) development and its progression. SCFAs influence cancer progression by modifying epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA functions thereby affecting tumor initiation and metastasis. This suggests that restoring SCFA levels in colon through microbiota modulation could serve as an innovative strategy for CRC prevention and treatment. This review highlights the critical relationship between gut microbiota and CRC, emphasizing the potential of targeting SCFAs to enhance gut health and reduce CRC risk.

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.

The gut microbiome has a crucial role in cancer development and therapy through its interactions with the immune system and tumour microenvironment. Although evidence links gut microbiota composition to cancer progression, its precise role in modulating treatment responses remains unclear. In this Review, we summarize current knowledge on the gut microbiome's involvement in cancer, covering its role in tumour initiation and progression, interactions with chemotherapy, radiotherapy and targeted therapies, and its influence on cancer immunotherapy. We discuss the impact of microbial metabolites on immune responses, the relationship between specific bacterial species and treatment outcomes, and potential microbiota-based therapeutic strategies, including dietary interventions, probiotics and faecal microbiota transplantation. Understanding these complex microbiota-immune interactions is critical for optimizing cancer therapies. Future research should focus on defining microbial signatures associated with treatment success and developing targeted microbiome modulation strategies to enhance patient outcomes.

Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. It is associated with imbalanced gut microbiota. Probiotics can help restore this balance, potentially reducing the risk of CRC. However, the hostile environment and constant changes in the gastrointestinal tract pose significant challenges to the efficient delivery of probiotics to the colon. Traditional delivery methods are often insufficient due to their low viability and lack of targeting. To address these challenges, researchers are increasingly focusing on innovative encapsulation technologies. One such approach is single-cell encapsulation, which involves applying nanocoatings to individual probiotic cells. This technique can improve their resistance to the harsh gastrointestinal environment, enhance mucosal adhesion, and facilitate targeted release, thereby increasing the effectiveness of probiotic delivery. This article reviews the latest developments in probiotic encapsulation methods for targeted CRC treatment, emphasizing the potential benefits of emerging single-cell encapsulation techniques. It also analyzes and compares the advantages and disadvantages of current encapsulation technologies. Furthermore, it elucidates the underlying mechanisms through which probiotics can prevent and treat CRC, evaluates the efficacy and safety of probiotics in CRC treatment and adjuvant therapy, and discusses future directions and potential challenges in the targeted delivery of probiotics for CRC treatment and prevention.

Microbial communities are not simply remnants of the past but dynamic entities that continuously evolve under the selective pressures of nature, reflecting the intricate and adaptive processes of evolution. The microbiota residing in the various regions of the human body has numerous roles in different physiological processes such as nutrition, metabolism, immune regulation, etc. In the zeal of achieving empirical insights into the ambit of the gut microbiome, the research over the years led to the revelation of reciprocal interaction between the gut microbiome and the cognitive functioning of the human body. Dysbiosis in the gut microbial composition disturbs the homeostatic cognitive functioning of the human body. This dysbiosis has been associated with various chronic diseases, including brain cancer, such as glioma, glioblastoma, etc. This review explores the mechanistic role of dysbiosis-mediated progression of brain cancers and their subtypes. Moreover, it demonstrates the regulatory role of microbial metabolites produced by the gut microbiota, such as short-chain fatty acids, amino acids, lipids, etc., in the tumour progression. Further, we also provide valuable insights into the microbiota mediating the efficiency of therapeutic regimens, thereby leveraging gut microbiota as potential biomarkers and targets for improved treatment outcomes.

The gut microbiome plays a crucial role in modulating the efficacy and toxicity of cancer therapies, particularly in hematological malignancies. This review examines the dynamic interplay between gut microbiota and cancer treatments, such as chemotherapy, immunotherapy, and hematopoietic stem cell transplantation (HSCT). Disruptions in the gut microbiome, known as dysbiosis, are associated with adverse effects like gastrointestinal toxicity, neutropenia and cardiotoxicity during chemotherapy. Conversely, the supplementation of probiotics has shown potential in mitigating these side effects by enhancing gut barrier function and regulating immune responses. In HSCT, a higher diversity of gut microbiota is linked to better patient outcomes, including reduced graft-versus-host disease (GVHD) and improved survival rates. The microbiome also influences the efficacy of immunotherapies, such as immune checkpoint inhibitors and CAR-T cell therapy, by modulating immune pathways. Research suggests that certain bacteria, including Bifidobacterium and Akkermansia muciniphila, enhance therapeutic responses by promoting immune activation. Given these findings, modulating the gut microbiome could represent a novel strategy for improving cancer treatment outcomes. The growing understanding of the microbiome's impact on cancer therapy underscores its potential as a target for personalized medicine and offers new opportunities to optimize treatment efficacy while minimizing toxic side effects.

Matrix metalloproteinases (MMPs) are key enzymes involved in extracellular matrix (ECM) remodeling, regulating a wide range of cellular and immune processes in both homeostatic and pathological conditions. Host-microbiota interactions play a critical role in maintaining ECM balance; however, during dysbiosis, this regulation is disrupted, leading to compromised barrier integrity, pathogen translocation into circulation, and the development of systemic diseases and cancer. This review highlights the bidirectional relationship between MMP expression/activity and microbiota dysbiosis, emphasizing tissue-specific alterations in MMP activity that contribute to disease progression. In addition, it integrates interdisciplinary evidence to illustrate the MMP-dependent mechanisms underlying various pathologies associated with oral and gut microbiome dysbiosis, including long-range effects through the gut-skin and gut-brain axes. Thus, this review introduces the emerging field of MatrixBiome, which explores the complex interactions between the ECM, microbiota, and host tissues. Finally, it also outlines therapeutic strategies to modulate MMP levels, either indirectly through microbiome-targeted approaches (e.g., prebiotics, probiotics, and postbiotics) or directly using MMP inhibitors, offering promising avenues for future clinical interventions.

Evidence suggests that various gut metabolites significantly impact breast cancer (BC) and its treatment. However, the underlying mechanisms remain poorly understood and require further investigation. In the present study, the current literature was reviewed to evaluate the roles of microbial metabolites in the development of BC and its response to treatment. Microbial metabolites, including secondary bile acids, short-chain fatty acids, amino acid metabolites, lipopolysaccharide, nisin and pyocyanin, serve crucial roles in the BC microenvironment. Microbial metabolites promote BC invasion, metastasis and recurrence by facilitating cellular movement, epithelial-mesenchymal transition, cancer stem cell function and diapedesis. Furthermore, certain metabolites, such as trimethylamine N-oxide and L-norvaline, can alter the pharmacokinetics of chemotherapeutic drugs. The present review highlights the possible involvement of microbial metabolites and bacteriocins in BC carcinogenesis, development and metastasis. These metabolites could provide new insights for BC treatment strategies and are considered potential therapeutic targets.

Oncologists increasingly recognize the microbiome as an important facilitator of health as well as a contributor to disease, including, specifically, cancer. Our knowledge of the etiologies, mechanisms, and modulation of microbiome states that ameliorate or promote cancer continues to evolve. The progressive refinement and adoption of "omic" technologies (genomics, transcriptomics, proteomics, and metabolomics) and utilization of advanced computational methods accelerate this evolution. The academic cancer center network, with its immediate access to extensive, multidisciplinary expertise and scientific resources, has the potential to catalyze microbiome research. Here, we review our current understanding of the role of the gut microbiome in cancer prevention, predisposition, and response to therapy. We underscore the promise of operationalizing the academic cancer center network to uncover the structure and function of the gut microbiome; we highlight the unique microbiome-related expert resources available at the City of Hope of Comprehensive Cancer Center as an example of the potential of team science to achieve novel scientific and clinical discovery.

The study aimed to investigate the causal relationships of gut microbiota (GM), ovarian cancer (OC), endometrial cancer (EC), and potential metabolite mediators using Mendelian randomization (MR) analysis.

Bidirectional two-sample MR analysis and reverse MR analysis of GM on OC/EC were employed to determine the causal effects of GM on OC/EC and the mediating role of blood metabolites in the relationship between GM and OC/EC, with results validated through sensitivity analysis.

We identified 6 pathogenic bacterial taxa associated with OC, including Euryarchaeota, Escherichia-Shigella, FamilyXIIIAD3011group, Prevotella9, and two unknown genera. Christensenellaceae R.7group, Tyzzerella3, and Victivallaceae were found to be protective against OC. The increase in EC risk was positively associated with Erysipelotrichia, Erysipelotrichaceae, Erysipelotrichales, and FamilyXI. Dorea, RuminococcaceaeUCG014, and Turicibacter exhibited a negative correlation with the EC risk. A total of 26 and 19 blood metabolites related to GM were identified, showing significant correlations with OC and EC, respectively. Cytosine was found to be an intermediate metabolite greatly associated with EC and FamilyXI. In reverse MR analysis, the FamilyXIIIAD3011group exhibited a significant bidirectional causal relationship with OC.

Our study revealed causal relationships of GM and intermediate metabolites with OC/EC, providing new avenues for understanding OC/EC and developing effective treatment strategies.

Prostate cancer is one of the most common malignant tumors among men worldwide, and current treatments still face many challenges. Therefore, researchers are continuously seeking new therapeutic methods to improve treatment efficacy and reduce side effects. Phenylacetylglutamine (PAGln), a common metabolite of the gut microbiota, has been reported to have anti-inflammatory and anti-tumor activities.

We assessed the impact of PAGln on prostate cancer using in vitro and in vivo models. Cell proliferation, migration, and invasion capabilities were evaluated through CCK8, EdU incorporation, and colony formation assays, as well as wound healing and Transwell assays. The in vivo anti-cancer effects of PAGln were evaluated using a BALB/c nude mouse xenograft model of prostate cancer and a lung metastatic tumor model established via tail vein injection. Molecular mechanisms were investigated through qRT-PCR and Western blot analysis.

PAGln inhibited the proliferation, migration, and invasion of prostate cancer (PCa) cells in vitro and suppressed the growth of prostate cancer in vivo. PAGln notably increased the mRNA levels of CCNG2 in PCa cells. Importantly, the knockdown of CCNG2 weakened the effects of PAGln on PCa cells. Mechanistic studies revealed that PAGln could promote the phosphorylation of β-catenin by upregulating CCNG2, thereby inhibiting the Wnt/β-catenin signaling pathway.

In summary, PAGln can effectively inhibit the proliferation, migration, and invasion of PCa by upregulating CCNG2 and suppressing the Wnt/β-catenin signaling pathway. These findings suggest that PAGln may serve as a promising therapeutic agent for prostate cancer.

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.

Colorectal cancer (CRC), an emerging public health concern, is one of the leading causes of cancer morbidity and mortality worldwide. An increasing body of evidence shows that dysfunction in metabolic reprogramming is a crucial characteristic of CRC progression. Specifically, metabolic reprogramming abnormalities in glucose, glutamine and lipid metabolism provide the tumour with energy and nutrients to support its rapid cell proliferation and survival. More recently, microRNAs (miRNAs) appear to be involved in the pathogenesis of CRC, including regulatory roles in energy metabolism. In addition, it has been revealed that dysbiosis in CRC might play a key role in impairing the host metabolic reprogramming processes, and while the exact interactions remain unclear, the link may lie with miRNAs. Hence, the aims of the current review include first, to delineate the metabolic reprogramming abnormalities in CRC; second, to explain how miRNAs mediate the aberrant regulations of CRC metabolic pathways; third, linking miRNAs with metabolic abnormalities and dysbiosis in CRC and finally, to discuss the roles of miRNAs as potential biomarkers.

An association between gut microbiota and the development of pancreatic ductal adenocarcinoma (PDAC) has been previously described. To better understand the bacterial microbiota changes accompanying PDAC promotion and progression stimulated by inflammation and fecal microbiota transplantation (FMT), we investigated stool and pancreatic microbiota by 16s RNA-based metagenomic analysis in mice with inducible acinar transgenic expressions of KrasG12D, and age- and sex-matched control mice that were exposed to inflammatory stimuli and fecal microbiota obtained from mice with PDAC. Time- and inflammatory-dependent stool and pancreatic bacterial composition alterations and stool alpha microbiota diversity reduction were observed only in mice with a Kras mutation that developed advanced pancreatic changes. Stool Actinobacteriota abundance and pancreatic Actinobacteriota and Bifidobacterium abundances increased. In contrast, stool abundance of Firmicutes, Verrucomicrobiota, Spirochaetota, Desulfobacterota, Butyricicoccus, Roseburia, Lachnospiraceae A2, Lachnospiraceae unclassified, and Oscillospiraceae unclassified decreased, and pancreatic detection of Alloprevotella and Oscillospiraceae uncultured was not observed. Furthermore, FMT accelerated tumorigenesis, gradually decreased the stool alpha diversity, and changed the pancreatic and stool microbial composition in mice with a Kras mutation. Specifically, the abundance of Actinobacteriota, Bifidobacterium and Faecalibaculum increased, while the abundance of genera such as Lachnospiraceace A2 and ASF356, Desulfovibrionaceace uncultured, and Roseburia has decreased. In conclusion, pancreatic carcinogenesis in the presence of an oncogenic Kras mutation stimulated by chronic inflammation and FMT dynamically changes the stool and pancreas microbiota. In particular, a decrease in stool microbiota diversity and abundance of bacteria known to be involved in short-fatty acids production were observed. PDAC mouse model can be used for further research on microbiota-PDAC interactions and towards more personalized and effective cancer therapies.

Hepatocellular carcinoma (HCC) is the most frequently occurring type of liver tumor and is considered one of the most common primary malignant neoplasms. The prognosis for HCC is dismal because of its complicated etiology and high level of medication resistance. Immunotherapy is presently regarded as one of the most effective therapeutic options for HCC; nevertheless, because of the disturbance of intestinal flora, immunotherapy shows low antitumor efficacy. An increasing body of research indicates that intestinal flora, particularly Akkermansia muciniphila (A. muciniphila), is vital for the treatment of tumors. Studies have demonstrated that the diminished effectiveness of immunotherapy in cancer patients is associated with a reduction in A. muciniphila levels, suggesting that increasing A. muciniphila levels significantly enhance the efficacy of immunotherapy. A. muciniphila functions as a gut probiotic and can treat and prevent a wide range of illnesses, including cancer. Consequently, preserving A. muciniphila abundance is enough to prevent and lower the danger of developing cancer disorders. In this review, we critically evaluate the current body of research on A. muciniphila, with a primary focus on its biological properties and functions. The different illnesses that A. muciniphila treats were then discussed, particularly the way it works with liver cancer. This review aims to give a novel treatment plan for patients with HCC as well as a theoretical foundation for improving HCC immunotherapy.

The gut-brain-cancer axis represents a novel and intricate connection between the gut microbiota, neurobiology, and cancer progression. Recent advances have accentuated the significant role of gut microbiota metabolites in modulating systemic processes that influence both brain health and tumorigenesis. This paper explores the emerging concept of metabolite-mediated modulation within the gut-brain-cancer connection, focusing on key metabolites such as short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, and lipopolysaccharides (LPS). While the gut microbiota's impact on immune regulation, neuroinflammation, and tumor development is well established, gaps remain in grasping how specific metabolites contribute to neuro-cancer interactions. We discuss novel metabolites with potential implications for neurobiology and cancer, such as indoles and polyamines, which have yet to be extensively studied. Furthermore, we review preclinical and clinical evidence linking gut dysbiosis, altered metabolite profiles, and brain tumors, showcasing limitations and research gaps, particularly in human longitudinal studies. Case studies investigating microbiota-based interventions, including dietary changes, fecal microbiota transplantation, and probiotics, demonstrate promise but also indicate hurdles in translating these findings to clinical cancer therapies. This paper concludes with a call for standardized multi-omics approaches and bi-directional research frameworks integrating microbiome, neuroscience, and oncology to develop personalized therapeutic strategies for neuro-cancer patients.

Prostate cancer (PCa) is the most commonly detected malignancy in men worldwide. PCa is a slow-growing cancer with the absence of symptoms at early stages. The pathogenesis has not been entirely understood including the key risk factors related to PCa development like diet and microbiota derived metabolites. Microbiota may influence the host's immunological responses, inflammatory responses, and metabolic pathways, which may be crucial for the development and metastasis. Similarly, short-chain fatty acids, methylamines, hippurate, bile acids, and other metabolites generated by microbiota may have potential roles in cancer inflammation and progression of cancer. Most studies have focused on the role of metabolites and their pathways involved in chronic inflammation, tumor initiation, proliferation, and progression. In summary, the review discusses the role of microbiota and microbial-derived metabolite-built strategies in inflammation and progression of the PCa.

The intestinal microbiota is a complex community of organisms present in the human gastrointestinal tract, some of which can produce short-chain fatty acids (SCFAs) through the fermentation of dietary fiber. SCFAs play a major role in mediating the intestinal microbiota's regulation of host immunity and intestinal homeostasis. Respiratory syncytial virus (RSV) can cause an imbalance between anti-inflammatory and proinflammatory responses in the host. In addition, changes in SCFA levels and the structure of the intestinal microbiota have been observed after RSV infection. Therefore, there may be a link between SCFAs and RSV infection, and SCFAs are expected to be therapeutic targets for RSV infection.

Breast cancer is the most common malignancy in women worldwide. Changes in the microbiota and their metabolites affect the occurrence and development of breast cancer; however, the specific mechanisms are not clear. Gut microbes and their metabolites influence the development of breast cancer by regulating the tumor immune response, estrogen metabolism, chemotherapy, and immunotherapy effects. It was previously thought that there were no microorganisms in breast tissue, but it is now thought that there are microorganisms in breast cancer that can affect the outcome of the disease. This review builds on existing research to comprehensively analyze the role of gut and intratumoral microbiota and their metabolites in the development and metastasis of breast cancer. We also explore the potential function of the microbiota as biomarkers for prognosis and therapeutic response, highlighting the need for further research to clarify the causal relationship between the microbiota and breast cancer. We hope to provide new ideas and directions for the development of new methods for breast cancer treatment.

The primary source of short-chain fatty acids (SCFAs), now recognized as critical mediators of host health, particularly in the context of neurobiology and cancer development, is the gut microbiota's fermentation of dietary fibers. Recent research highlights the complex influence of SCFAs, such as acetate, propionate, and butyrate, on brain cancer progression. These SCFAs impact immune modulation and the tumor microenvironment, particularly in brain tumors like glioma. They play a critical role in regulating cellular processes, including apoptosis, cell differentiation, and inflammation. Moreover, studies have linked SCFAs to maintaining the integrity of the blood-brain barrier (BBB), suggesting a protective role in preventing tumor infiltration and enhancing anti-tumor immunity. As our understanding of the gut-brain axis deepens, it becomes increasingly important to investigate SCFAs' therapeutic potential in brain cancer management. Looking into how SCFAs affect brain tumor cells and the environment around them could lead to new ways to prevent and treat these diseases, which could lead to better outcomes for people who are dealing with these challenging cancers.

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.

Globally, one of the most prevalent cancers is colorectal cancer (CRC). Chemotherapy and surgery are two common conventional CRC therapies that are frequently ineffective and have serious adverse effects. Thus, there is a need for complementary and different therapeutic approaches. The use of microbial metabolites to trigger epigenetic alterations as a way of preventing CRC is one newly emerging field of inquiry. Small chemicals called microbial metabolites, which are made by microbes and capable of altering host cell behaviour, are created. Recent research has demonstrated that these metabolites can lead to epigenetic modifications such as histone modifications, DNA methylation, and non-coding RNA regulation, which can control gene expression and affect cellular behaviour. This review highlights the current knowledge on the epigenetic modification for cancer treatment, immunomodulatory and anti-carcinogenic attributes of microbial metabolites, gut epigenetic targeting system, and the role of dietary fibre and gut microbiota in cancer treatment. It also focuses on short-chain fatty acids, especially butyrates (which are generated by microbes), and their cancer treatment perspective, challenges, and limitations, as well as state-of-the-art research on microbial metabolites-induced epigenetic changes for CRC inhibition. In conclusion, the present work highlights the potential of microbial metabolites-induced epigenetic modifications as a novel therapeutic strategy for CRC suppression and guides future research directions in this dynamic field.

Breast cancer (BC), a major cause of death among women worldwide, has traditionally been linked to genetic and environmental factors. However, emerging research highlights the gut microbiome's significant role in shaping BC development, progression, and treatment outcomes. This review explores the intricate relationship between the gut microbiota and the breast tumor microenvironment, emphasizing how these microbes influence immune responses, inflammation, and metabolic pathways. Certain bacterial species in the gut either contribute to or hinder BC progression by producing metabolites that affect hormone metabolism, immune system pathways, and cellular signaling. An imbalance in gut bacteria, known as dysbiosis, has been associated with a heightened risk of BC, with metabolites like short-chain fatty acids (SCFAs) and enzymes such as β-glucuronidase playing key roles in this process. Additionally, the gut microbiota can impact the effectiveness of chemotherapy, as certain bacteria can degrade drugs like gemcitabine and irinotecan, leading to reduced treatment efficacy. Understanding the complex interactions between gut bacteria and BC may pave the way for innovative treatment approaches, including personalized microbiome-targeted therapies, such as probiotics and fecal microbiota transplants, offering new hope for more effective prevention, diagnosis, and treatment of BC.

Colorectal cancer (CRC) is the third most prevalent cancer. Ongoing research aims to uncover the causes of CRC, with a growing focus on the role of gut microbiota (GM) in carcinogenesis. The GM influences CRC development, progression, treatment efficacy, and therapeutic toxicities. For example, Fusobacterium nucleatum and Escherichia coli can regulate microbial gene expression through the incorporation of human small noncode RNA and potentially contribute to cancer progression. Metallic nanoparticles (MNPs) have both negative and positive impacts on GM, depending on their type. Several studies state that titanium dioxide may increase the diversity, richness, and abundance of probiotics bacteria, whereas other studies demonstrate dose-dependent GM dysbiosis. The MNPs offer cytotoxicity through the modulation of MAPK signaling pathways, NF-kB signaling pathways, PI3K/Akt signaling pathways, extrinsic signaling pathways, intrinsic apoptosis, and cell cycle arrest at G1, G2, or M phase. MNPs enhance drug delivery, enable targeted therapy, and may restore GM. However, there is a need to conduct well-designed clinical trials to assess the toxicity, safety, and effectiveness of MNPs-based CRC therapies.

Recent progress on the underlying biological mechanisms of healthy longevity has propelled the field from elucidating genetic modification of healthy longevity hallmarks to defining mechanisms of gut microbiota influencing it. Importantly, the role of gut microbiota in the healthy longevity of the host may provide unprecedented opportunities to decipher the plasticity of lifespan on a natural evolutionary scale and shed light on using microbiota-targeted strategies to promote healthy aging and combat age-related diseases. This review investigates how gut microbiota affects healthy longevity, focusing on the mechanisms through which gut microbiota modulates it. Specifically, we focused on the ability of gut microbiota to enhance the intestinal barrier integrity, provide protection from inflammaging, ameliorate nutrientsensing pathways, optimize mitochondrial function, and improve defense against age-related diseases, thus participating in enhancing longevity and healthspan.

The adipose tissue is a complex organ that can play endocrine, metabolic, and immune regulatory roles in cancer. In particular, adipocytes provide metabolic substrates for cancer cell proliferation and produce signaling molecules that can stimulate cell adhesion, migration, invasion, angiogenesis, and inflammation. Cancer cells, in turn, can reprogram adipocytes towards a more inflammatory state, resulting in a vicious cycle that fuels tumor growth and evolution. These mechanisms are enhanced in obesity, which is associated with the risk of developing certain tumors. Diet, an exogenous source of lipids with pro- or anti-inflammatory functions, has also been connected to cancer risk. This review analyzes how adipocytes and lipids are involved in tumor development and progression, focusing on the relationship between obesity and cancer. In addition, we discuss how diets with varying lipid intakes can affect the disease outcomes. Finally, we introduce novel metabolism-targeted treatments and adipocyte-based therapies in oncology.

Urinary tract infections (UTIs) are one of the most common bacterial infections, affecting more than 150 million people each year in the world. UTIs have grown exponentially in the last few years. They represent a major load for both individuals and society. The highest incidence (about 55-60%) concerns women. Many pathogens are involved in UTIs, most of which are derived from the gut. Recent studies, together with recent diagnostic techniques (such as quantitative culture of urine or next-generation sequencing), have improved the knowledge of microbial communities in the urinary tract. It turned out that gut dysbiosis is strictly involved in the pathogenesis of UTIs. In particular, the human gut is the natural habitat for Escherichia coli (E. coli), the main bacterium responsible for UTIs. The overgrowth of E. coli pathogenic strains represents a risk factor for them. Furthermore, the human gut microbiota acts as a "global reservoir" for genes conferring resistance to clinically relevant antibiotics, thus influencing the treatment of UTIs. In addition, differently from the past, the idea of a sterile urinary environment has been replaced by the characterization of a urinary microbiome. The aim of our review is to explore recent studies on the association between gut microbiota and urinary microbiome and to summarize the current knowledge about the effects of interactions between gut and urinary microbial communities in the pathogenesis of UTIs, considering UTIs more as a "gut disease" and not only a urinary disease and providing new insight into the therapeutic options such as the use of probiotics.

Social separation, or the absence of social support, can cause physical and psychological health issues. Social separation is crucial for the welfare of the Yangtze finless porpoise (YFP) in captivity because they face many challenges like frequent social separation, noise from visitors, and animal replacement, which can cause psychological and physiological stress. This research is aimed at assessing the potential negative impacts of social separation on the gut microbiome and metabolome of captive YFP, focusing on the potential imbalances caused by mother-calf separation. The study found that social separation did not alter the alpha and beta diversity of the gut microbes but increased the abundance of disease-associated taxa such as Romboutsia, Terrisporobacter, and Clostridium_sensu_stricto_13 in the MC (mother-calf) group while increasing Paeniclostridium and Clostridium_sensu_stricto_1 associated with host health in the MS (mother-separated) group. The fecal metabolome underwent significant changes during social separation, with stress-associated metabolites like kainic acid, phenethylamine glucuronide, and paxilline upregulated in the MC group and host health-associated metabolites like butyric acid, 6-hydroxyhexanoic acid, and fosinopril downregulated in the MS group. In addition, there was a strong association between the fecal microbiome and the metabolome of captive YFPs. The study enhances our comprehension of the detrimental effects of social separation, which result in disruptions in the gut microbiome and fecal metabolome. The study is aimed at introducing a new method for assessing the health and welfare of endangered mammals in captivity.

Lung cancer accounts for the large majority of cancer incidence and mortality worldwide for decades. The dysbiotic microbiome and its metabolite secretions in the gut have been regarded as the dominant biological factors in oncogenesis, development, and progression, adding probiotic components of which have come to be potential therapeutic regimes. However, there still exists little knowledge about whether probiotic microorganisms in lower airways inhibit lung cancer by lung microenvironment remodulation. In this study, we performed bioinformatics analysis from previous sequencing data and specific microbiome databases to identify the potent protective microbes in lower airways, followed by bacterial cultivation and morphological verifications in vitro. We found that Paenibacillus odorifer was correlated closely with the anti-tumorous by-product acetic acid in lower respiratory tract. Additionally, the enrichment of this microorganism in the health, rather than in lung neoplasms from public data sets, further confirmed its protective activity in preserving pulmonary homeostasis. Colony cultivation of this strain and targeted metabolite analysis indicated that Paenibacillus odorifer proliferation was weakened at 37°C but lasted longer than it did at the optimal temperature. And performing as a candidate origin of acetic acid, this strain was liable to inhibit the growth of lung cancer cells in time- and dose-dependent approaches which was validated by colony formation assays. These results suggested that Paenibacillus odorifer functions as a candidate probiotic in lower airways to restrict lung cancer cell growth by releasing protective molecules, indicating a potential preventive microbial strategy.IMPORTANCEVarious types of microorganisms in lower respiratory tracts protect local homeostasis against oncogenesis. Although extensive efforts engaged in gut microbiome-mediated pulmonary carcinogenesis, emerging evidence suggested the crucial role of microbial metabolites from respiratory tracts in modulating carcinogenesis-related host inflammation and DNA damage in lung cancer, which was still not fully understood in lower respiratory tract microbes and its metabolite-mediated microecological environment homeostasis in preventing or alleviating lung cancer. In this study, we analyzed the lower respiratory tract microbiome and SCFAs expression among different lung segments from the same participants, further identifying that Paenibacillus odorifer was correlated closely with anti-tumorous by-product, acetate acid in lower respiratory tract by multi-omics analysis. And previous experiments showed this strain could inhibit the growth of lung cancer cells in vitro. These findings indicated that Paenibacillus odorifer in lower respiratory tracts might perform as a candidate probiotic against lung carcinogenesis by releasing protective factor acetate, which further presented a promising diagnostic and interventional approach in clinical settings of lung cancer.

Carbon-13 isotopomics of triacylglycerol (TAG) fatty acids or free fatty acids in biological matrices holds considerable potential in food authentication, forensic investigations, metabolic studies, and medical research. However, challenges arise in the isotopic analysis of short- and medium-chain (C4 to C10) fatty acid methyl esters (SMCFAMEs) through gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). The high volatility of these esters results in losses during their preparation, leading to isotopic fractionation. Moreover, the methoxy group added to acyl chains requires the correction of δ13C values, thereby increasing the uncertainty of the final results. Analyzing free fatty acids (FFAs) addresses both issues encountered with SMCFAMEs. To achieve this objective, we have developed a new protocol enabling the isotopomics of individual fatty acids (FAs) by GC-C-IRMS. The same experiment also provides the FA profile, i.e., the relative percentage of each FA in the TAG hydrolysate or its concentration in the studied matrix. The method exhibited high precision, as evidenced by the repeatability and within-lab reproducibility of results when tested on TAGs from both animal and vegetal origins. Compared to the analysis of FAMEs by GC-C-IRMS, the current procedure also brings several improvements in alignment with the principles of green analytical chemistry and green sample preparation. Thus, we present a two-in-one method for 13C-isotopomic and metabolomic biomarker quantitation within quasi-universal TAG compounds, encompassing the short- and medium-acyl chains.

Evidence indicates that there are significant alterations in gut microbiota diversity and composition in patients with hematological malignancies. The present study investigated the oral and intestinal microbiome in patients with chronic lymphocytic leukemia (CLL) (n=81) and age-matched healthy volunteers (HVs; n=21) using 16S ribosomal RNA next-generation sequencing. Changes in both oral and gut microbiome structures were identified, with a high abundance of Proteobacteria and depletion of Bacteroidetes in CLL as compared to HVs. Oral and stool samples of patients with CLL revealed a significant change in the abundance of short-chain fatty acid-producing genera in comparison with HVs. Furthermore, the relative abundance of oral and intestine Bacteroidetes was significantly decreased in patients with CLL with negative prognostic features, including unmutated immunoglobulin heavy chain gene (IGHV). Notably, an increased abundance of gut Firmicutes was found to be associated with high expression of CD38. Finally, the present study suggested the log Firmicutes/Bacteroidota ratio as a novel intestinal microbiome signature associated with a shorter time to first treatment in individuals with CLL. The findings indicate that oral and gut microbial diversity in CLL might point to the inflammatory-related modulation of the clinical course of the disease.

The gut microbiome is an important and the largest endocrine organ linked to the microbes of the GI tract. The bacterial, viral and fungal communities are key regulators of the health and disease status in a host at hormonal, neurological, immunological, and metabolic levels. The useful microbes can compete with microbes exhibiting pathogenic behavior by maintaining resistance against their colonization, thereby maintaining eubiosis. As diagnostic tools, metagenomic, proteomic and genomic approaches can determine various microbial markers in clinic for early diagnosis of colorectal cancer (CRC). Probiotics are live non-pathogenic microorganisms such as lactic acid bacteria, Bifidobacteria, Firmicutes and Saccharomyces that can help maintain eubiosis when administered in appropriate amounts. In addition, the type of dietary intake contributes substantially to the composition of gut microbiome. The use of probiotics has been found to exert antitumor effects at preclinical levels and promote the antitumor effects of immunotherapeutic drugs at clinical levels. Also, modifying the composition of gut microbiota by Fecal Microbiota Transplantation (FMT), and using live lactic acid producing bacteria such as Lactobacillus, Bifidobacteria and their metabolites (termed postbiotics) can contribute to immunomodulation of the tumor microenvironment. This can lead to tumor-preventive effects at early stages and antitumor effects after diagnosis of CRC. To conclude, probiotics are presumably found to be safe to use in humans and are to be studied further to promote their appliance at clinical levels for management of CRC.

Emerging evidence highlights the crucial role of gastrointestinal microbiota in the pathogenesis of gastric cancer. Helicobacter pylori (H. pylori) infection stands out as a primary pathogenic factor. However, interventions such as anti-H. pylori therapy, gastric surgeries, immunotherapy, and chronic inflammation significantly remodel the gastric microbiome, implicating a broader spectrum of microorganisms in cancer development. These microbial populations can modulate gastric carcinogenesis through various mechanisms, including sustained chronic inflammation, bacterial genotoxins, alterations in short-chain fatty acids, elevated gastrointestinal bile acids, impaired mucus barrier function, and increased concentrations of N-nitrosamines and lactic acid. The dynamic changes in gut microbiota also critically influence the outcomes of anti-cancer therapies by modifying drug bioavailability and metabolism, thus affecting therapeutic efficacy and side effect profiles. Additionally, the effectiveness of radiotherapy can be significantly impacted by gut microbiota alterations. Novel therapeutic strategies targeting the microbiome, such as dietary interventions, probiotic and synbiotic supplementation, and fecal microbiota transplantation, are showing promise in cancer treatment. Understanding the intricate relationship between the gut microbiota and gastric cancer is essential for developing new, evidence-based approaches to the prevention and treatment of this malignancy.

Prostate cancer (PCa) is one of the most prevalent malignancies in males worldwide. Increasing research attention has focused on the PCa microenvironment, which plays a crucial role in tumor progression and therapy resistance. This review aims to provide a comprehensive overview of the key components of the PCa microenvironment, including immune cells, vascular systems, stromal cells, and microbiota, and explore their implications for diagnosis and treatment.

Keywords such as "prostate cancer", "tumor microenvironment", "immune cells", "vascular system", "stromal cells", and "microbiota" were used for literature retrieval through online databases including PubMed and Web of Science. Studies related to the PCa microenvironment were selected, with a particular focus on those discussing the roles of immune cells, vascular systems, stromal cells, and microbiota in the development, progression, and treatment of PCa. The selection criteria prioritized peer-reviewed articles published in the last five years, aiming to summarize and analyze the latest research advancements and clinical relevance regarding the PCa microenvironment.

The PCa microenvironment is highly complex and dynamic, with immune cells contributing to immunosuppressive conditions, stromal cells promoting tumor growth, and microbiota potentially affecting androgen metabolism. Vascular systems support angiogenesis, which fosters tumor expansion. Understanding these components offers insight into the mechanisms driving PCa progression and opens avenues for novel therapeutic strategies targeting the tumor microenvironment.

A deeper understanding of the PCa microenvironment is crucial for advancing diagnostic techniques and developing precision therapies. This review highlights the potential of targeting the microenvironment to improve patient outcomes, emphasizing its significance in the broader context of PCa research and treatment innovation.

Gynecologic cancers develop from the female reproductive organs. Microbial dysbiosis in the gut and oral cavity can communicate with each other through various ways, leading to mucosal destruction, inflammatory response, genomic instability, and ultimately inducing cancer and worsening. Here, we introduce the mechanisms of interactions between gut and oral microbiota and their changes in the development of gynecologic tumors. In addition, new therapeutic approaches based on microbiota modulation are discussed.

Cancer remains a multifactorial disease with an increased mortality rate around the world for the past several decades. Despite advancements in treatment strategies, lower survival rates, drug-associated side effects, and drug resistance create a need for novel anticancer agents. Ample evidence shows that imbalances in the gut microbiota are associated with the formation of cancer and its progression. Altering the gut microbiota via probiotics and their metabolites has gained attention among the research community as an alternative therapy to treat cancer. Probiotics exhibit health benefits as well as modulate the immunological and cellular responses in the host. Apart from probiotics, their secreted products like bacteriocins, exopolysaccharides, short-chain fatty acids, conjugated linoleic acid, peptidoglycan, and other metabolites are found to possess anticancer activity. The beneficiary role of these postbiotic compounds is widely studied for characterizing their mechanism and mode of action that reduces cancer growth. The present review mainly focuses on the postbiotic components that are employed against cancer with their reported mechanism of action. It also describes recent research works carried out so far with specific strain and anticancer activity of derived compounds both in vitro and in vivo, validating that the probiotic approach would pave an alternative way to reduce the burden of cancer.

The human microbiome has recently emerged as a focal point in cancer research, specifically in anti-tumor immunity, immunotherapy, and chemotherapy. This review explores microbial-derived metabolites, emphasizing their crucial roles in shaping fundamental aspects of cancer treatment. Metabolites such as short-chain fatty acids (SCFAs), Trimethylamine N-Oxide (TMAO), and Tryptophan Metabolites take the spotlight, underscoring their diverse origins and functions and their profound impact on the host immune system. The focus is on SCFAs' remarkable ability to modulate immune responses, reduce inflammation, and enhance anti-tumor immunity within the intricate tumor microenvironment (TME). The review critically evaluates TMAO, intricately tied to dietary choices and gut microbiota composition, assessing its implications for cancer susceptibility, progression, and immunosuppression. Additionally, the involvement of tryptophan and other amino acid metabolites in shaping immune responses is discussed, highlighting their influence on immune checkpoints, immunosuppression, and immunotherapy effectiveness. The examination extends to their dynamic interaction with chemotherapy, emphasizing the potential of microbial-derived metabolites to alter treatment protocols and optimize outcomes for cancer patients. A comprehensive understanding of their role in cancer therapy is attained by exploring their impacts on drug metabolism, therapeutic responses, and resistance development. In conclusion, this review underscores the pivotal contributions of microbial-derived metabolites in regulating anti-tumor immunity, immunotherapy responses, and chemotherapy outcomes. By illuminating the intricate interactions between these metabolites and cancer therapy, the article enhances our understanding of cancer biology, paving the way for the development of more effective treatment options in the ongoing battle against cancer.

The intricate interplay between the host and its microbiota has garnered increasing attention in the past decade. Specifically, the emerging recognition of microorganisms within diverse cancer tissues, previously presumed sterile, has ignited a resurgence of enthusiasm and research endeavors. Four potential migratory routes have been identified as the sources of intratumoral microbial "dark matter," including direct invasion of mucosal barriers, spreading from normal adjacent tissue, hematogenous spread, and lymphatic drainage, which contribute to the highly heterogeneous features of intratumor microbiota. Importantly, multitudes of studies delineated the roles of intratumor microbiota in cancer initiation and progression, elucidating underlying mechanisms such as genetic alterations, epigenetic modifications, immune dysfunctions, activating oncogenic pathways, and inducing metastasis. With the deepening understanding of intratumoral microbial composition, novel microbiota-based strategies for early cancer diagnosis and prognostic stratification continue to emerge. Furthermore, intratumor microbiota exerts significant influence on the efficacy of cancer therapeutics, particularly immunotherapy, making it an enticing target for intervention in cancer treatment. In this review, we present a comprehensive discussion of the current understanding pertaining to the developmental history, heterogeneous profiles, underlying originations, and carcinogenic mechanisms of intratumor microbiota, and uncover its potential predictive and intervention values, as well as several inevitable challenges as a target for personalized cancer management strategies.