Radioresistance is one of the main causes for local treatment failure in lung cancer. Nevertheless, the potential mechanisms of radioresistance in lung cancer have not been elucidated completely. Here, we discover a carcinoma-inhibiting protein called leucine zipper tumor suppressor 3 (LZTS3), which is low-expressed and related to adverse outcome in lung cancer. Moreover, our studies demonstrate that LZTS3 restrains cell proliferation and radioresistance in vitro and in vivo. Mechanistically, protein kinase CK1δ interacts with LZTS3, resulting in E3 ubiquitin ligase β-TrCP recognizes and binds to LZTS3. Thus, LZTS3 is degraded by the ubiquitin-proteasome pathway. We also identify two conserved degrons (DSGRNS and DSGRAS) are essential for the ubiquitinated degradation of LZTS3 by CK1δ and β-TrCP. More importantly, we detect that the CK1δ and β-TrCP-mediated degradation of LZTS3 facilitate the cell growth, proliferation and radioresistance in lung cancer. Collectivelly, our results suggest that LZTS3 regulates tumorigenesis and radioresistance in lung cancer depend on a CK1δ and β-TrCP-mediated ubiquitin-proteasome pathway. LZTS3 may be a new molecular target for lung cancer treatment.

Fucoidan, a water-soluble polysaccharide derived from marine organisms, has garnered significant attention for its ability to regulate gut microbiota and its anti-tumor properties. However, the existence of a correlation between the anti-tumor effect of fucoidan and its regulation of the gut microbiota remains unknown. In pursuit of this objective, we culled the gut microbiota of mice with broad-spectrum antibiotics to generate pseudo-sterile tumor-bearing mice. Subsequently, fecal microbial transplants were introduced into the pseudo-sterile tumor-bearing mice. The antitumor effects of fucoidan were found to be dependent on the gut microbiota. Fucoidan promoted the proliferation of Akkermansia, Bifidobacterium and Lactobacillus, which have immunomodulatory effects. Furthermore, through regulation of gut microbiota, fucoidan influenced the metabolic process of tryptophan and facilitated its conversion to indole-3-acetic acid. In addition, fucoidan decreased the kynurenine/tryptophan ratio in serum, increased the proportion of CD8+ T cells, and suppressed the expression level of IDO1 in tumor tissues. Our results confirm that fucoidan enhances anti-tumor immune responses and subsequently exhibits anti-tumor effects by modulating the gut microbiota. Our research contributes to the comprehension of the mechanism of anti-tumor effects of fucoidan and facilitates the development of fucoidan as a dietary supplement for cancer patients.

Microbiome modulation is one of the novel strategies in medicine with the greatest future to improve the health of individuals and reduce the risk of different conditions, including metabolic, immune, inflammatory, and degenerative diseases, as well as cancer. Regarding the latter, many studies have reported the role of the gut microbiome in carcinogenesis, formation and progression of colorectal cancer (CRC), as well as its response to different systemic therapies. Likewise, obesity, one of the most important risk factors for CRC, is also well known for its association with gut dysbiosis. Moreover, obesity and CRC display, apart from microbial dysbiosis, chronic inflammation, which participates in their pathogenesis. Although human and murine studies demonstrate the significant impact of the microbiome in regulating energy metabolism and CRC development, little is understood about the contribution of the microbiome to the development of obesity-associated CRC. Therefore, this systematic review explores the evidence for microbiome changes associated with these conditions and hypothesizes that this may contribute to the pathogenesis of obesity-related CRC. Two databases were searched, and different studies on the relationship among obesity, intestinal microbiota and CRC in clinical and preclinical models were selected. Data extraction was carried out by two reviewers independently, and 101 studies were finally considered. Findings indicate the existence of a risk association between obesity and CRC derived from metabolic, immune, and microbial disorders.

The use of nonfood prebiotics, probiotics, and synbiotics has approximately tripled in the last 20 years. It is necessary to examine the associations of these substances with all-cause and cause-specific mortality in a large prospective cohort.

This study included 53,333 adults from the National Health and Nutrition Examination Survey 1999-2018. All participants answered questions on the use of dietary supplements and medications, including prebiotics, probiotics, and synbiotics. Death outcomes were determined by linkage to National Death Index records through 31 December 2019. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality from all causes, heart diseases, cancer, and other causes.

During a mean follow-up of 10.6 years, 9117 deaths were documented, including 2364 heart disease deaths, 1964 cancer deaths, and 4700 other causes deaths. Compared to nonusers, nonfood prebiotic, probiotic, and synbiotic users had a 59% (HR 0.41, 95% CI 0.30 to 0.56), 56% (HR 0.44, 95% CI 0.26 to 0.74), 49% (HR 0.51, 95% CI 0.31 to 0.83), and 64% (HR 0.36, 95% CI 0.23 to 0.59) for lower risk of all-cause, cancer, heart disease, and other causes mortality, respectively. Moreover, the inverse association of the use of prebiotics, probiotics, and synbiotics with mortality was stronger in female participants and participants without hypertension.

The use of nonfood prebiotics, probiotics, and synbiotics is significantly associated with lower all-cause mortality, as well as deaths from heart disease, cancer, and other causes.

Background: The role of gut dysbiosis in the pathophysiology of atopic dermatitis (AD) through immune system (IS) imbalance is a novel line of investigation currently under discussion. This study aimed to characterize compare the composition and functional profile of the gut microbiota (GM) between adults with AD and healthy individuals. Methods: Observational cross-sectional study, where fecal samples from 70 adults (38 patients and 32 controls) were analyzed using metagenomics and bioinformatics. Results: Differences between the GM of patients with AD and healthy individuals were demonstrated. Reduced microbial diversity was found in subjects with AD. Bacterial species with lower abundance primarily belonged to the families Ruminococcaceae, Akkermansiaceae, and Methanobacteriaceae. Several microbial metabolic pathways were found to be decreased in patients with AD, including amino acid biosynthesis, vitamin biosynthesis, fatty acids and lipids biosynthesis, and energy metabolism. Conclusion: Adults with AD exhibited a distinct GM compared to healthy individuals. Changes were demonstrated both compositionally and functionally. Further investigation is mandatory to elucidate the potential link and causal relationship between gut dysbiosis and AD, which may be crucial for a deeper understanding of the disease's pathophysiology and the development of novel therapeutic approaches.

In the last decade, it has been discovered that intestinal flora can affect various organ-specific cancers by altering the body's energy balance, synthesizing genetic toxins and small signaling molecules, and initiating and modulating immune responses. In this review, we will focus on elucidating the role of intestinal flora based on its molecular mechanisms and its possible impact on head and neck cancers in the near future, and explore how it may be a novel approach to treating head and neck cancers in the future.

Lymph node metastasis (LNM) is a key factor in the prognosis of papillary thyroid carcinoma (PTC). This study explores the effect of intratumoral bacteria on LNM in PTC. The intrathyroidal microbiome is analyzed in 55 PTC patients by 16S rRNA gene sequencing. The CCK8 and Transwell assays determine the impact of bacteria on the proliferation and migration abilities of PTC cells. Xenograft tumor and bacterial colonization experiments are carried out using nude mice. We show that Lactobacillus is significantly decreased in PTC lesions from patients with LNM. Lactobacillus johnsonii (L. johnsonii) suppresses the proliferation and migration capability of PTC cells in vitro and in vivo. Bacterial gut colonization of L. johnsonii increases its abundance in tumors and inhibits PTC growth and LNM. These findings suggest that L. johnsonii can be harnessed for the development of innovative therapeutic strategies for PTC.

In order to decipher the relationship between gut microbiota imbalance and cancer, this paper reviewed the role of intestinal microbiota in anticancer therapy and related mechanisms, discussed the current research status of gut microbiota as a biomarker of cancer, and finally summarized the reasonable means of regulating gut microbiota to assist cancer therapy. Overall, our study reveals that the gut microbiota can serve as a potential target for improving cancer management.

Growing evidence reveals that the tumor microbiome-comprising distinct microbial communities within neoplastic tissues-exerts a profound influence on cancer initiation, progression, and therapeutic response. These microbes actively reshape the tumor microenvironment (TME) through metabolite secretion, the modulation of immune pathways, and direct interactions with host cells, thereby affecting tumor biology and therapeutic outcomes. Despite substantial heterogeneity among cancer types, recent insights underscore the tumor microbiome's potential as both a diagnostic/prognostic biomarker and a targetable component for innovative treatments. In this review, we synthesize emerging knowledge on the mechanistic roles of tumor-associated microbiota in shaping the TME, with a focus on how these discoveries can guide novel therapeutic strategies. We further explore interdisciplinary advances, including the convergence of microbiomics and nanotechnology, to enhance drug delivery, circumvent resistance, and foster TME remodeling. By highlighting these cutting-edge developments, our review underscores the transformative potential of integrating tumor microbiome research into precision oncology and advancing more personalized cancer therapies.

In recent years, numerous reports have been published regarding the relationship between the gut microbiota and the tumor immune microenvironment (TIME). However, to date, no systematic study has been conducted on the relationship between gut microbiota and the TIME using bibliometric methods.

To describe the current global research status on the correlation between gut microbiota and the TIME, and to identify the most influential countries, research institutions, researchers, and research hotspots related to this topic.

We searched for all literature related to gut microbiota and TIME published from January 1, 2014, to May 28, 2024, in the Web of Science Core Collection database. We then conducted a bibliometric analysis and created visual maps of the published literature on countries, institutions, authors, keywords, references, etc., using CiteSpace (6.2R6), VOSviewer (1.6.20), and bibliometrics (based on R 4.3.2).

In total, 491 documents were included, with a rapid increase in the number of publications starting in 2019. The country with the highest number of publications was China, followed by the United States. Germany has the highest number of citations in literature. From a centrality perspective, the United States has the highest influence in this field. The institutions with the highest number of publications were Shanghai Jiao Tong University and Zhejiang University. However, the institution with the most citations was the United States National Cancer Institute. Among authors, Professor Giorgio Trinchieri from the National Institutes of Health has the most local impact in this field. The most cited author was Fan XZ. The results of journal publications showed that the top three journals with the highest number of published papers were Frontiers in Immunology, Cancers, and Frontiers in Oncology. The three most frequently used keywords were gut microbiota, tumor microenvironment, and immunotherapy.

This study systematically elaborates on the research progress related to gut microbiota and TIME over the past decade. Research results indicate that the number of publications has rapidly increased since 2019, with research hotspots including "gut microbiota", "tumor microenvironment" and "immunotherapy". Exploring the effects of specific gut microbiota or derived metabolites on the behavior of immune cells in the TIME, regulating the secretion of immune molecules, and influencing immunotherapy are research hotspots and future research directions.

Radiotherapy (RT) is one of the major cornerstones in managing gastrointestinal (GI) cancers. However, several side effects, such as intestinal inflammation, mucosal injury, and dysbiosis, often compromise this. The gut microbiota increasingly attracts much interest as an essential modulator of RT effects influencing immune responses and tissue repair. Through short-chain fatty acids such as butyrate, representatives of certain bacterial species play a crucial role under normal conditions, keeping the mucosal integrity intact and reducing oxidative stress-mediated damage. Dysbiosis, a state where diminished microbial diversity and increased pathogenic species in the microbiota are seen, amplifies RT-induced toxicity in patients. Clinical investigations highlight that microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, hold the means to augment RT efficacy and lessen toxicity. Increased microflora diversity and specific microbial profiles have yielded serious patient improvements. Advanced RT methods use stereotactic body radiotherapy combined with microbiota modulation as a promising technique to shield healthy tissue and maximize immune-mediated antitumor effects. Additionally, there is an implication in tumor behavior regulated by the intratumoral microbiota regarding the response to radiotherapy. Notably, the modulation of gut and tumor microbiota provides an avenue to optimize RT benefits in GI cancers, underscoring the importance of personalized therapy.

Gliomas, particularly high-grade gliomas such as glioblastoma, represent a major challenge due to their poor prognosis. While dietary factors have been proposed as potential modulators of glioma risk, causal inference has been hindered by confounding and reverse causality in observational studies. This study employs Mendelian randomization to investigate the causal relationship between dietary factors and glioma risk.

A two-sample MR framework was applied, utilizing genome-wide association study data for 22 dietary exposures and glioma risks, including both GBM and non-GBM subtypes. Instrumental variables (genetic variants) were identified for each dietary factor to address confounding and pleiotropy. Causal inference was conducted using inverse-variance weighted regression, complemented by MR-Egger and MR-PRESSO analyses to assess and correct for potential pleiotropy.

A positive causal association was observed between the intake of cooked vegetables and the GBM risk (OR = 6.55, 95% CI: 1.86-23.12, p = 0.00350). While alcohol intake demonstrated a protective effect for non-GBM risk (OR = 0.770, 95% CI: 0.61-0.97, p = 0.029), beer was substantially linked to an increased risk of non-GBM gliomas (OR = 4.82, 95% CI: 1.84-12.59, p = 0.0014). Other dietary factors did not exhibit significant causal associations.

These findings suggest that certain dietary factors, including cooked vegetable intake, beer consumption, and alcohol intake, may exert a causal influence on glioma risk. This study provides new insights into the potential dietary determinants of glioma and underscores the need for further investigation into modifiable risk factors for glioma prevention.

While Gangba sheep being well known for their unique flavour and nutritional value, harsh environmental factors negatively affect their growth and development, leading to poor productivity. The gastrointestinal tract microbiota plays an important role in host nutrient absorption and metabolism. The identification of dynamic changes in the gastrointestinal microbial communities and their functions is an important step towards improving animal production performance and health.

A comprehensive multi-omics survey of the microbial communities of the Gangba sheep gastrointestinal tract was performed under three distinct feeding strategies: natural grazing, semi-grazing with supplementation, and barn feeding. The dynamic changes, cross-kingdom partnerships and functional potential profiles were analysed and the results revealed that the feeding strategies had a greater impact on the microbial communities than the site of the gastrointestinal tract. The different microbial associations among the groups were revealed by co-occurrence networks based on the amplicon sequence variants (ASVs). Moreover, a Gangba sheep gastrointestinal microbial genomic catalogue was constructed for the first time, including 1146 metagenome-assembled genomes (MAGs) with completeness > 50% and contamination < 10%, among which, 504 bacterial and 15 archaeal MAGs were of high quality with completeness > 80% and contamination < 10%. About 40% of the high-quality MAGs displaying enzyme activity were related to the microbial species that contribute to plant biomass degradation. Most of these enzymes were expressed in rumen metatranscriptome datasets, especially in Prevotella spp. and Ruminococcus spp., suggesting that gastrointestinal microbial communities in ruminants play major roles in the digestion of plant biomass to provide nutrition and energy for the host.

These findings suggest that feeding strategies are the primary cause of changes in the gastrointestinal microbiome. Diversification of livestock feed might be an effective strategy to maintain the diversity and ecological multifunctionality of microbial communities in the gastrointestinal tract. Additionally, the catalogue of microbial genomes and the encoded biomass-degrading enzymes identified here provide insights into the potential microbial functions of the gastrointestinal tract of Gangba sheep at high altitudes. This paves the way for microbial interventions to improve the growth performance, productivity and product quality of ruminant livestock. Video Abstract.

The human body harbors a vast array of microorganisms. Changes in the microbial ecosystem can potentially lead to diseases, including cancer. Traditionally, research has focused more on the gut microbiota and its influence on cancer. However, with the advancement of sequencing technologies, scholars have discovered that microorganisms within kidney tissues are significant components of tumor tissues. Intratumoral microorganisms may affect tumor growth and development through certain mechanisms, influence the function of immune cells, or impact the effectiveness of chemotherapy or immunotherapy in patients. This paper reviews the latest progress in the research on intratumoral microorganisms in renal cancer (RCa). It summarizes the types and distribution characteristics of these microorganisms, discusses the close association between specific viral infections (such as HPV and EBV) and RCa, and highlights the role of microorganisms in the pathogenesis of RCa. This review provides new perspectives for understanding the pathogenic mechanisms of RCa, thereby offering potential clinical applications.

Hypothalamic inflammation often coincides with cancer and cachexia-anorexia. Prior work established the significance of tumor-derived inflammatory factors in triggering hypothalamic inflammation, yet the precise mechanisms remained elusive. Here, we demonstrate that prostaglandin E2 (PGE2), produced in the tumor via cyclooxygenase-2 (COX-2), plays a pivotal role in this context. PGE2 itself directly exerts pro-inflammatory effects on the hypothalamus through the EP4 receptor, while also augmenting hypothalamic inflammation via NF-κB pathways in the presence of host gut-derived pathogen-associated molecular patterns (PAMPs). In tumor-bearing mice, we confirm this synergistic interaction between tumor-derived COX-2/PGE2 and host-derived lipopolysaccharide (LPS) in amplifying hypothalamic inflammation. Supporting this mechanism we find that the tumor-specific knockout of COX-2 attenuates hypothalamic inflammation and improves survival in mice. Together, these findings highlight the mechanisms of tumor-associated COX-2 in fuelling hypothalamic inflammation. They also emphasize the potential of tumor-specific COX-2 inhibition and targeting gut permeability as a novel therapeutic strategy for improving clinical outcomes in cancer patients.

Immune checkpoint inhibitors commonly cause gastrointestinal immune-related adverse effects. These patients also carry an increased risk of concomitant infections. This 66-year-old man with immune checkpoint inhibitor colitis was discovered to have concurrent Yersinia and Cytomegalovirus colitis. Such infections may mimic or complicate disease course. Hence, clinicians must monitor patient symptoms, have a low threshold for infectious testing and colonoscopy, and consider treatment strategies to mitigate their risk.

Microbiome and radiotherapy represent bidirectionally interacting entities. The human microbiome has emerged as a pivotal modulator of the efficacy and toxicity of radiotherapy; however, a reciprocal effect of radiotherapy on microbiome composition alterations has also been observed. This review explores the relationship between the microbiome and extracranial solid tumors, particularly focusing on the bidirectional impact of radiotherapy on organ-specific microbiome. This article aims to provide a systematic review on the radiotherapy-induced microbial alteration in-field as well as in distant microbiomes. In this review, particular focus is directed to the oral and gut microbiome, its role in the development and progression of cancer, and how it is altered throughout radiotherapy. This review concludes with recommendations for future research, such as exploring microbiome modification to optimize radiotherapy-induced toxicities or enhance its anti-cancer effects.

In recent years, the microbiome has shown an integral role in cancer immunotherapy and has become a prominent and widely studied topic. A full understanding of the interactions between the tumor microbiome and various immunotherapies offers opportunities for immunotherapy of cancer. This review scrutinizes the composition of the tumor microbiome, the mechanism of microbial immune regulation, the influence of tumor microorganisms on tumor metastasis, and the interaction between tumor microorganisms and immunotherapy. In addition, this review also summarizes the challenges and opportunities of immunotherapy through tumor microbes, as well as the prospects and directions for future related research. In conclusion, the potential of microbial immunotherapy to enhance treatment outcomes for cancer patients should not be underestimated. Through this review, it is hoped that more research on tumor microbial immunotherapy will be done to better solve the treatment problems of cancer patients.

Immunotherapy, which uses the body's immune system to fight cancer cells, has gained attention recently as a breakthrough in cancer treatment. Although significant progress has been made, obstacles still exist since cancers are skilled at avoiding immune monitoring. The gut microbiota is being looked at more and more in modern research as a critical component in improving the results of immunotherapy. Through modulating both innate and adaptive immune responses, the gut microbiome has a significant impact on cancer immunotherapy. The effectiveness of treatment and the way the immune system responds are significantly influenced by some microorganisms and the metabolites they produce, especially short-chain fatty acids. On the other hand, dysbiosis and persistent inflammation in the gut environment might unintentionally accelerate the growth of tumors, which makes the complex relationship between the makeup of the microbiota and cancer treatment more challenging. Gut microbiota plays a crucial role in immunotherapy effectiveness. Improved microbial diversity leads to better treatment responses, with some taxa like Bacteroides and Ruminococcaceae being linked to better responses to immune checkpoint inhibitors. Dysbiotic conditions can worsen immune-related side effects and reduce treatment effectiveness. Strategies manipulating gut microbiota, such as fecal microbiota transplantation, antibiotic therapies, and dietary interventions, could optimize immunotherapy response and prognosis. However, standardizing these interventions for different cancer types and patient populations is challenging due to individual microbiome differences. Future research should combine microbiome research with AI and rigorous clinical trials for individualized cancer treatments.

Background/Objectives: Research on the relationship between gut microbiota (GM) and atopic dermatitis (AD) has seen a growing interest in recent years. The aim of this systematic review was to determine whether differences exist between the GM of adults with AD and that of healthy adults (gut dysbiosis). Methods: We conducted a systematic review based on the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed using PubMed, EMBASE, and Web of Science. Observational and interventional studies were analyzed. Results: Although the studies showed heterogeneous results, some distinguishing characteristics were found in the intestinal microbial composition of adults with dermatitis. Even though no significant differences in diversity were found between healthy and affected adults, certain microorganisms, such as Bacteroidales, Enterobacteriaceae, and Clostridium (perfringens), were more characteristic of the fecal microbiota in adults with AD. Healthy individuals exhibited lower abundances of aerobic bacteria and higher abundances of short-chain fatty acid-producing species and polyamines. Clinical trials showed that the consumption of probiotics (Bifidobacterium and/or Lactobacillus), fecal microbiota transplants, and balneotherapy modified the fecal microbiota composition of participants and were associated with significant improvements in disease management. Conclusions: In anticipation of forthcoming clinical trials, it is essential to conduct meta-analyses that comprehensively evaluate the effectiveness and safety of interventions designed to modify intestinal flora in the context of AD. Preliminary evidence suggests that certain interventions may enhance adult AD management.

Chemotherapy is crucial in the management of tumors, but challenges such as chemoresistance and adverse reactions frequently lead to therapeutic delays or even premature cessation. A growing body of research underscores a profound connection between the gut microbiota (GM) and cancer chemotherapy (CC). This paper aims to pinpoint highly influential publications and monitor the current landscape and evolving trends within the realm of GM/CC research.

On October 1st, 2024, a comprehensive search for GM/CC publications spanning the past 20 years from 2004 to 2023 was conducted utilizing the Web of Science Core Collection (WoSCC). The scope encompassed both articles and reviews, and the data was subsequently extracted. To gain insights into the evolution and dynamics of this research field, we employed bibliometric analysis tools such as the Bibliometrix R package, VOSviewer, and Microsoft Excel to visualize and analyze various dimensions, including prominent journals, leading authors, esteemed institutions, contributing countries/regions, highly cited papers, and frequently occurring keywords.

A total of 888 papers were obtained. The number of publications about GM/CC studies has increased gradually. China and the United States published the largest number of papers. The INSERM was in the leading position in publishers. The most productive authors were Zitvogel L from France. Cancers had the largest number of papers. Citation analysis explained the historical evolution and breakthroughs in GM/CC research. Highly cited papers and common keywords illustrated the status and trends of GM/CC research. Four clusters were identified, and the hot topics included the role of the GM in the efficacy and toxicity of CC, the targeting of the GM to improve the outcome of CC, the mechanism by which the GM affects CC, and the correlation of the GM with carcinogenesis and cancer therapy. Metabolism, GM-derived metabolites, tumor microenvironment, immunity, intestinal barrier, tumor microbiota and Fusobacterium nucleatum may become the new hotspots and trends of GM/CC research.

This study analyzed global publications and bibliometric characteristics of the links between GM and CC, identified highly cited papers in GM/CC, provided insight into the status, hotspots, and trends of global GM/CC research, and showed that the GM can be used to predict the efficacy and toxicity of CC and modifying the GM can improve the outcomes of chemotherapeutics, which may inform clinical researchers of future directions.

The discoveries of the oncomicrobiome (intratumoral microbiome) and oncomicrobiota (intratumoral microbiota) represent significant advances in tumor research and have rapidly become of key interest to the field. Within tumors, microorganisms such as bacteria, fungi, viruses, and archaea form the oncomicrobiota and are primarily found within tumor cells, immunocytes, and the intercellular matrix. The oncomicrobiome exhibits marked heterogeneity and is associated with tumor initiation, progression, metastasis, and treatment response. Interactions between the oncomicrobiome and the immune system can modulate host antitumor immunity, influencing the efficacy of immunotherapies. Oncomicrobiome research also faces numerous challenges, including overcoming methodological issues such as low target abundance, susceptibility to contamination, and biases in sample handling and analysis methods across different studies. Furthermore, studies of the oncomicrobiome may be confounded by baseline differences in microbiomes among populations driven by both environmental and genetic factors. Most studies to date have revealed associations between the oncomicrobiome and tumors, but very few have established mechanistic links between the two. This review introduces the relevant concepts, detection methods, sources, and characteristics of the oncomicrobiome. We then describe the composition of the oncomicrobiome in common tumors and its role in shaping the tumor microenvironment. We also discuss the current problems and challenges to be overcome in this rapidly progressing field.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered an unprecedented public health crisis known as the coronavirus disease 2019 (COVID-19) pandemic. Gastrointestinal (GI) symptoms develop in patients during acute infection and persist after recovery from airway distress in a chronic form of the disease (long COVID). A high incidence of irritable bowel syndrome (IBS) manifested by severe abdominal pain and defecation pattern changes is reported in COVID patients. Although COVID is primarily considered a respiratory disease, fecal shedding of SARS-CoV-2 antigens positively correlates with bowel symptoms. Active viral infection in the GI tract was identified by human intestinal organoid studies showing SARS-CoV-2 replication in gut epithelial cells. In this review, we highlight the key findings in post-COVID bowel symptoms and explore possible mechanisms underlying the pathophysiology of the illness. These mechanisms include mucosal inflammation, gut barrier dysfunction, and microbiota dysbiosis during viral infection. Viral shedding through the GI route may be the primary factor causing the alteration of the microbiome ecosystem, particularly the virome. Recent evidence in experimental models suggested that microbiome dysbiosis could be further aggravated by epithelial barrier damage and immune activation. Moreover, altered microbiota composition has been associated with dysregulated serotonin pathways, resulting in intestinal nerve hypersensitivity. These mechanisms may explain the development of post-infectious IBS-like symptoms in long COVID. Understanding how coronavirus infection affects gut pathophysiology, including microbiome changes, would benefit the therapeutic advancement for managing post-infectious bowel symptoms.

The homeostasis of the microbiota is essential for human health. In particular, the gut microbiota plays a critical role in the regulation of the immune system. Thus, faecal microbiota transplantation (FMT), a technology that has rapidly developed in the last decade, has specifically been utilised for the treatment of intestinal inflammation and has recently been found to be able to treat tumours in combination with immunotherapy. FMT has become a breakthrough in enhancing the response rate to immunotherapy in cancer patients by altering the composition of the patient's gut microbiota. This review discusses the mechanisms of faecal microorganism effects on tumour development, drug treatment efficacy, and adverse effects and describes the recent clinical research trials on FMT. Moreover, the factors influencing the efficacy and safety of FMT are described. We summarise the possibilities of faecal transplantation in the treatment of tumours and its complications and propose directions to explore the development of FMT.

The human microbiome is the complex ecosystem consisting of trillions of microorganisms that play a key role in developing the immune system and nutrient metabolism. Alterations in the gut microbiome have been linked to cancer initiation, progression, metastasis, and response to treatment. Accumulating evidence suggests that levels of vitamins and minerals influence the gut environment and may have implications for cancer risk and progression. Bifidobacterium has been reported to reduce the colorectal cancer risk by binding to free iron. Additionally, zinc ions have been shown to activate the immune cells and enhance the effectiveness of immunotherapy. Higher selenium levels have been associated with a reduced risk of several cancers, including colorectal cancer. In contrast, enhanced copper uptake has been implicated in promoting cancer progression, including colon cancer. The interaction between cancer and gut bacteria, as well as dysbiosis impact has been studied in animal models. The interplay between prebiotics, probiotics, synbiotics, postbiotics and gut bacteria in cancer offers the diverse physiological benefits. We also explored the particular probiotic formulations like VSL#3, Prohep, Lactobacillus rhamnosus GG (LGG), etc., for their ability to modulate immune responses and reduce tumor burden in preclinical models. Targeting the gut microbiome through antibiotics, bacteriophage, microbiome transplantation-based therapies will offer a new perspective in cancer research. Hence, to understand this interplay, we outline the importance of micronutrients with an emphasis on the immunomodulatory function of the microbiome and highlight the microbiome's potential as a target for precision medicine in cancer treatment.

Fusobacterium nucleatum (Fn) has been extensively studied for its connection to colorectal cancer (CRC) and its potential role in chemotherapy resistance. Studies indicate that Fn is commonly found in CRC tissues and is associated with unfavorable prognosis and treatment failure. It has been shown that Fn promotes chemoresistance by affecting autophagy, a cellular process that helps cells survive under stressful conditions. Additionally, Fn targets specific signaling pathways that activate particular microRNAs and modulate the response to chemotherapy. Understanding the current molecular mechanisms and investigating the importance of Fn-inducing chemoresistance could provide valuable insights for developing novel therapies. This review surveys the role of Fn in tumor proliferation, metastasis, and chemoresistance in CRC, focusing on its effects on the tumor microenvironment, gene expression, and resistance to conventional chemotherapy drugs. It also discusses the therapeutic implications of targeting Fn in CRC treatment and highlights the need for further research.

Radiotherapy is an effective method of treating cancer and affects 50% of patients. Intensity-modulated radiotherapy (IMRT) is a modernized method of classical radiation used in the treatment of laryngeal cancer. Treatment with intent to preserve the larynx is not always safe or complication-free. The microbiome may significantly influence the effectiveness of oncological treatment, especially radiotherapy, and may also be modified by the toxic response to radiation.

The aim of the study was to prospectively assess the microbiome and its influence on radiotherapy toxicity in patients with laryngeal cancer.

Statistically significant risk factors for complications after radiotherapy were the percentage of Porphyromonas of at least 6.7%, the percentage of Fusobacterium of at least 2.6% and the percentage of Catonella of at least 2.6%.

The importance of the microbiome in oncology has been confirmed in many studies. Effective radiotherapy treatment and the prevention of radiation-induced oral mucositis is a challenge in oncology. The microbiome may be an important part of personalized cancer treatment. The assessment of the microbiome of patients diagnosed with cancer may provide the opportunity to predict the response to treatment and its effectiveness. The influence of the microbiome may be important in predicting the risk group for radiotherapy treatment failure. The possibility of modifying the microbiome may become a goal to improve the prognosis of patients with laryngeal cancer. Fusobacterium, Porphyromonas and Catonella are important risk factors for radiation-induced oral mucositis in patients with laryngeal cancer.

The human body represents the habitat of trillions of symbiotic microorganisms, collectively known as human microbiota, approximately half of which residing in the gut. The development of next-generation sequencing techniques has boosted the profiling of human microbiota in recent years. A growing body of evidence seems to support a strict relationship between the disruption of the mutualistic relationship between the microbiota and the host (i.e., dysbiosis) and the development of several diseases, including breast malignancies. Breast cancer still represents the most frequent cause of cancer-related death in women. Its complex relationship with gut microbiota is the object of a growing body of evidence. In fact, the interaction with the host immune system and a direct impact of gut microbiota on estrogen, lipid and polyphenols metabolism, seem to potentially affect breast tumor development, progression and response to treatments. In this review, in an attempt to help oncologists navigating this rapidly-evolving research field, we provide an essential overview on the taxonomy, main analytical techniques and terminology most commonly adopted. We discuss what is currently known regarding the interaction between gut microbiota and breast cancer and potential efforts to harness this complex interplay for therapeutic purposes, and revise main ongoing studies. We also briefly provide an overview on breast cancer intratumoral microbiota and its potential role beyond gut microbiota.

The gut microbiome has emerged as a crucial player in modulating cancer therapies, including radiotherapy. In the case of breast cancer, the interplay between the microbiome and radiotherapy-derived metabolites may enhance therapeutic outcomes and minimize adverse effects. In this review, we explore the bidirectional relationship between the gut microbiome and breast cancer. We explain how gut microbiome composition influences cancer progression and treatment response, and how breast cancer and its treatments influence microbiome composition. A dual role for radiotherapy-derived metabolites is explored in this article, highlighting both their therapeutic benefits and potential hazards. By integrating genomics, metabolomics, and bioinformatics tools, we present a comprehensive overview of these interactions. The study provides real-world insight through case studies and clinical trials, while therapeutic innovations such as probiotics, and dietary interventions are examined for their potential to modulate the microbiome and enhance treatment effectiveness. Moreover, ethical considerations and patient perspectives are discussed, ensuring a comprehensive understanding of the subject. Towards revolutionizing treatment strategies and improving patient outcomes, the review concludes with future research directions. It also envisions integrating microbiome and metabolite research into personalized breast cancer therapy.

The tumour microenvironment represents a novel frontier in oncological research. Over the past decade, accumulating evidence has underscored the importance of the tumour microenvironment (TME), including tumour cells, stromal cells, immune cells, and various secreted factors, which collectively influence tumour growth, invasion, and responses to therapeutic agents. Immune cells within the TME are now widely acknowledged to play pivotal roles in tumour development and treatment. While some perspectives have posited that immune cells within the TME facilitate tumour progression and confer resistance to therapeutic interventions, contrasting conclusions also exist. Affirmative and negative conclusions appear to be context dependent, and a unified consensus has yet to be reached. The burgeoning body of research on the relationship between the gut microbiota and tumours in recent years has led to a growing understanding. Most studies have indicated that specific components of the gut microbiota, such as unique bacterial communities or specific secretory factors, play diverse roles in regulating immune cells within the TME, thereby influencing the prognosis and outcomes of cancer treatments. A detailed understanding of these factors could provide novel insights into the TME and cancer therapy. In this study, we aimed to synthesise information on the interactions between the gut microbiota and immune cells within the TME, providing an in-depth exploration of the potential guiding implications for future cancer therapies.

Breast cancer remains one of the leading causes of death among women worldwide, and recent research highlights its growing connection to alterations in the microbiota. This review delves into the intricate relationship between microbiotas and breast cancer, exploring its presence in healthy breast tissue, its changes during cancer progression, and its considerable impact on both the tumor microenvironment (TME) and the tumor immune microenvironment (TIME). We extensively analyze how the microbiota influences cancer growth, invasion, metastasis, resistance to drugs, and the evasion of the immune system, with a special focus on its effects on the TIME. Furthermore, we investigate distinct microbial profiles associated with the four primary molecular subtypes of breast cancer, examining how the microbiota in tumor tissues compares with that in adjacent normal tissues. Emerging studies suggest that microbiotas could serve as valuable diagnostic and prognostic biomarkers, as well as targets for therapy. This review emphasizes the urgent need for further research to improve strategies for breast cancer prevention, diagnosis, and treatment. By offering a detailed examination of the microbiota's critical role in breast cancer, this review aims to foster the development of novel microbiota-based approaches for managing the disease.

cancer of unknown primary site (CUP) is a heterogeneous group of cancers in which metastases are found, and the primary tumor is not detected with available diagnostic methods. CUP is a disease that has not been fully researched, and its biology is unclear. The clinical characteristics of CUP are variable, but the prognosis of patients is usually unfavorable, and the possibilities of radical treatment are limited. The microbiome is the genes and gene products of microorganisms residing in a human body. In recent years, thanks to the use of next-generation sequencing, it is possible to assess the impact of the microbiome on human body functions. Head and neck cancers, due to the rich microbiome of this area, are influenced by it, and dysbiosis may be a risk factor for the development of cancer. Objective of this work: the aim of this study was to evaluate prognostic factors, clinical features including the microbiome, and treatment outcomes in patients with cancer of unknown primary site.

in the study group, increased numbers of bacteria of the phyla Bacteroides, Fusobacteria, Bacillota, Actinomycetota, Actinobacteria, and Candidatus were detected, while Firmicutes and Proteobacteria were detected in smaller numbers. Independent predictors of CUP occurrence were the following: leukocyte count of at most 6.49 × 103/mm, bacteria from the Proteobacteria phylum in the microbiome below 11.6%, Firmicutes below 22.1%, and Actinobacteria at least 11.0%. Increased numbers of Porphyromonas and Fusobacterium bacteria were associated with the risk of radiotherapy complications and shortened survival rate.

clinical diagnosis and treatment of patients with CUP is complicated and difficult due to the lack of consensus on this issue. Treatment and prognosis of patients with CUP is unsatisfactory. The clinical value of the influence of the microbiome on the development, course, and treatment of cancer is becoming increasingly important. The microbiome may become a marker of response to anticancer treatment and the risk of its complications. Immunity modulation with the microbiome provides opportunities for further research on improving the effectiveness of oncological treatment. Fusobacterium and Porphyromonas seem to be the bacteria most important for the development of cancer, also worsening the prognosis of patients by increasing the risk of complications of radiotherapy and shortening the survival rate of patients. Streptococcus and Lactobacillus seem to be bacteria that reduce the risk of cancer, reduce the risk of complications, and improve the prognosis of patients. Total protein deficiency and elevated inflammatory markers are also important predictors of cancer risk.

The tumor microenvironment (TME) is a critical determinant in the initiation, progression, and treatment outcomes of various cancers. Comprising of cancer-associated fibroblasts (CAF), immune cells, blood vessels, and signaling molecules, the TME is often likened to the soil supporting the seed (tumor). Among its constituents, tumor-associated macrophages (TAMs) play a pivotal role, exhibiting a dual nature as both promoters and inhibitors of tumor growth. This review explores the intricate relationship between TAMs and the TME, emphasizing their diverse functions, from phagocytosis and tissue repair to modulating immune responses. The plasticity of TAMs is highlighted, showcasing their ability to adopt either protumorigenic or anti-tumorigenic phenotypes based on environmental cues. In the context of cancer, TAMs' pro-tumorigenic activities include promoting angiogenesis, inhibiting immune responses, and fostering metastasis. The manuscript delves into therapeutic strategies targeting TAMs, emphasizing the challenges faced in depleting or inhibiting TAMs due to their multifaceted roles. The focus shifts towards reprogramming TAMs to an anti-tumorigenic M1-like phenotype, exploring interventions such as interferons, immune checkpoint inhibitors, and small molecule modulators. Noteworthy advancements include the use of CSF1R inhibitors, CD40 agonists, and CD47 blockade, demonstrating promising results in preclinical and clinical settings. A significant section is dedicated to Chimeric Antigen Receptor (CAR) technology in macrophages (CAR-M cells). While CAR-T cells have shown success in hematological malignancies, their efficacy in solid tumors has been limited. CAR-M cells, engineered to infiltrate solid tumors, are presented as a potential breakthrough, with a focus on their development, challenges, and promising outcomes. The manuscript concludes with the exploration of third-generation CAR-M technology, offering insight into in-vivo reprogramming and nonviral vector approaches. In conclusion, understanding the complex and dynamic role of TAMs in cancer is crucial for developing effective therapeutic strategies. While early-stage TAM-targeted therapies show promise, further extensive research and larger clinical trials are warranted to optimize their targeting and improve overall cancer treatment outcomes.

Metagenomic time-course studies provide valuable insights into the dynamics of microbial systems and have become increasingly popular alongside the reduction in costs of next-generation sequencing technologies. Normalization is a common but critical preprocessing step before proceeding with downstream analysis. To the best of our knowledge, currently there is no reported method to appropriately normalize microbial time-series data. We propose TimeNorm, a novel normalization method that considers the compositional property and time dependency in time-course microbiome data. It is the first method designed for normalizing time-series data within the same time point (intra-time normalization) and across time points (bridge normalization), separately. Intra-time normalization normalizes microbial samples under the same condition based on common dominant features. Bridge normalization detects and utilizes a group of most stable features across two adjacent time points for normalization. Through comprehensive simulation studies and application to a real study, we demonstrate that TimeNorm outperforms existing normalization methods and boosts the power of downstream differential abundance analysis.

The importance of the complex interplay between the microbiome and mucosal immunity, particularly within the respiratory tract, has gained significant attention due to its potential implications for the severity and progression of lung diseases. Therefore, this review summarizes the specific interactions through which the respiratory tract-specific microbiome influences mucosal immunity and ultimately impacts respiratory health. Furthermore, we discuss how the microbiome affects mucosal immunity, considering tissue-specific variations, and its capacity in respiratory diseases containing asthma, chronic obstructive pulmonary disease, and lung cancer. Additionally, we investigate the external factors which affect the relationship between respiratory microbiome and mucosal immune responses. By exploring these intricate interactions, this review provides valuable insights into the potential for microbiome-based interventions to modulate mucosal immunity and alleviate the severity of respiratory diseases.

Despite ongoing breakthroughs in novel anticancer therapies, chemotherapy remains a mainstream therapeutic modality in different types of cancer. Unfortunately, chemotherapy-related toxicity (CRT) often leads to dose limitation, and even results in treatment termination. Over the past few years, accumulating evidence has indicated that the gut microbiota is extensively engaged in various toxicities initiated by chemotherapeutic drugs, either directly or indirectly. The gut microbiota can now be targeted to reduce the toxicity of chemotherapy. In the current review, we summarized the clinical relationship between the gut microbiota and CRT, as well as the critical role of the gut microbiota in the occurrence and development of CRT. We then summarized the key mechanisms by which the gut microbiota modulates CRT. Furthermore, currently available strategies to mitigate CRT by targeting the gut microbiota were summarized and discussed. This review offers a novel perspective for the mitigation of diverse chemotherapy-associated toxic reactions in cancer patients and the future development of innovative drugs or functional supplements to alleviate CRT via targeting the gut microbiota.

Radiation enteritis remains a major challenge for radiotherapy against abdominal and pelvic malignancies. Nevertheless, there is no approved effective therapy to alleviate irradiation (IR)-induced gastrointestinal (GI) toxicity. In the current study, Cannabidiol (CBD) was found to mitigate intestinal injury by GPX4-mediated ferroptosis resistance upon IR exposure. RNA-sequencing was employed to investigate the underlying mechanism involved in the radio-protective effect of CBD, wherein runt-related transcription factor 3 (RUNX3) and its target genes were changed significantly. Further experiment showed that the transactivation of GPX4 triggered by the direct binding of RUNX3 to its promoter region, or by stimulating the transcriptional activity of NF-κB via RUNX3-mediated LILRB3 upregulation was critical for the anti-ferroptotic effect of CBD upon IR injury. Specially, CBD was demonstrated to be a molecular glue skeleton facilitating the heterodimerization of RUNX3 with its transcriptional chaperone core-biding factor β (CBFβ) thereby promoting their nuclear localization and the subsequent transactivation of GPX4 and LILRB3. In short, our study provides an alternative strategy to counteract IR-induced enteritis during the radiotherapy on abdominal/pelvic neoplasms.

Diet plays a critical role in shaping the gut microbiome, which in turn regulates molecular activities in the colonic mucosa. The state and composition of the gut microbiome are key factors in the development of colorectal cancer. An altered gut microbiome, linked to weakened immune responses and the production of carcinogenic substances, is a significant contributor to colorectal cancer pathogenesis. Dietary changes that involve low-fiber and phytomolecule intake, coupled with higher consumption of red meat, can raise the risk of colorectal cancer. Salutary filaments, which reach the colon undigested, are metabolized by the gut microbiome, producing short-chain fatty acids. Short-chain fatty acids possess beneficial anti-inflammatory and antiproliferative properties that promote colon health. A well-balanced microbiome, supported by beneficial fibers and phytochemicals, can regulate the activation of proto-oncogenes and oncogenic pathways, thereby reducing cell proliferation. Recent research suggests that an overabundance of specific microbes, such as Fusobacterium nucleatum, may contribute to adverse changes in the colonic mucosa. Positive lifestyle adjustments have been demonstrated to effectively inhibit the growth of harmful opportunistic organisms. Synbiotics, which combine probiotics and prebiotics, can protect the intestinal mucosa by enhancing immune responses and decreasing the production of harmful metabolites, oxidative stress, and cell proliferation. This narrative review provides a concise understanding of evolving evidence regarding how diet influences the gut microbiome, leading to the restoration of the colonic epithelium. It underscores the importance of a healthy, plant-based diet and associated supplements in preventing colorectal cancer by enhancing gut microbiome health.

Gut microbiota contributes to the homeostasis of immune system and is related to various diseases such as tumorigenesis. Ferroptosis, a new type of cell death, is also involved in the disease pathogenesis. Recent studies have found the correlations of gut microbiota mediated ferroptosis and immune cell death. Gut microbiota derived immunosuppressive metabolites, which can promote differentiation and function of immune cells, tend to inhibit ferroptosis through their receptors, whereas inflammatory metabolites from gut microbiota also affect the differentiation and function of immune cells and their ferroptosis. Thus, it is possible for gut microbiota to regulate immune cell ferroptosis. Indeed, gut microbiota metabolite receptor aryl hydrocarbon receptor (AhR) can affect ferroptosis of intestinal intraepithelial lymphocytes, leading to disease pathogenesis. Since immune cell ferroptosis in tumor microenvironment (TME) affects the occurrence and development of tumor, the modulation of gut microbiota in these cell ferroptosis might influence on the tumorigenesis, and also immunotherapy against tumors. Here we will summarize the recent advance of ferroptosis mediated by gut microbiota metabolites, which potentially acts as regulator(s) on immune cells in TME for therapy against tumor.

Recent years have seen an outstanding growth in the understanding of connections between diet-induced obesity, dysbiosis and alterations in the tumor microenvironment. Now we appreciate that gut dysbiosis can exert important effects in distant target tissues via specific microbes and metabolites. Multiple studies have examined how diet-induced obese state is associated with gut dysbiosis and how gut microbes direct various physiological processes that help maintain obese state in a bidirectional crosstalk. Another tightly linked factor is sustained low grade inflammation in tumor microenvironment that is modulated by both obese state and dysbiosis, and influences tumor growth as well as response to immunotherapy. Our review brings together these important aspects and explores their connections. In this review, we discuss how obese state modulates various components of the breast tumor microenvironment and gut microbiota to achieve sustained low-grade inflammation. We explore the crosstalk between different components of tumor microenvironment and microbes, and how they might modulate the response to immunotherapy. Discussing studies from multiple tumor types, we delve to find common microbial characteristics that may positively or negatively influence immunotherapy efficacy in breast cancer and may guide future studies.

Cancer remains a public health concern worldwide, with its incidence increasing worldwide and expected to continue growing during the next decades. The microbiome has emerged as a central factor in human health and disease, demonstrating an intricate relationship between the microbiome and cancer. Although some microbiomes present within local tissues have been shown to restrict cancer development, mainly by interacting with cancer cells or the host immune system, some microorganisms are harmful to human health and risk factors for cancer development. This review summarizes the recent evidence concerning the microbiome and some of the most common cancer types (i.e., lung, head and neck, breast, gastric, colorectal, prostate, and cervix cancers), providing a general overview of future clinical approaches and perspectives.

Although immune checkpoint inhibitors (anti-PD-1 antibody, anti-PD-L1 antibody, and anti-CTLA-4 antibody) have displayed considerable success in the treatment of malignant tumors, the therapeutic effect is still unsatisfactory for a portion of patients. Therefore, it is imperative to develop strategies to enhance the effect of these ICIs. Increasing evidence strongly suggests that the key to this issue is to transform the tumor immune microenvironment from a state of no or low immune infiltration to a state of high immune infiltration and enhance the tumor cell-killing effect of T cells. Therefore, some combination strategies have been proposed and this review appraise a summary of 39 strategies aiming at enhancing the effectiveness of ICIs, which comprise combining 10 clinical approaches and 29 foundational research strategies. Moreover, this review improves the comprehensive understanding of combination therapy with ICIs and inspires novel ideas for tumor immunotherapy.