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

Familial aggregation is common in nasopharyngeal carcinoma (NPC), yet the impact of oral microbiome dysbiosis on this occurrence remains largely unexplored. We recruit 127 families (649 members, 1-5 patients each) and a case-control cohort of 337 individuals, validating findings in an additional cohort of 995 individuals. Significant microbial similarity is observed among family members, with family factors contributing most to microbiome variation, followed by cigarette smoking, age, and gender. Among multi-NPC families, especially those with three or more patients, we identify three NPC-enriched taxa with notable heritability, including Gemella sp. (heritability, h2 = 53.1%), Lautropia mirabilis (h2 = 38.8%), and Streptococcus sp. (h2 = 38.0%). Heritable bacteria present a markedly higher heritability in families with increased clustering of NPC and form closely interacting networks, suggesting their role in NPC familial aggregation. These findings open up possibilities for identifying high-risk individuals, enhancing clinical surveillance, and developing personalized prevention and treatment approaches of NPC through microbiome-based strategies.

The exact triggers of gallstone formation remain incompletely understood, but research indicates that microbial infection is a significant factor and can interfere with treatment. There is no consensus on the bile microbial culture profiles in previous studies, and determining the microbial profile could aid in targeted prevention and treatment. The primary aim of this study is to investigate the differences in microbial communities cultured from bile specimens of patients with gallstones.

We collected the clinical characteristics and bile microbial status of 9,939 gallstone patients. Statistical analysis was employed to assess the relationship between microbes and clinical features, and a random forest model was utilized to predict recurrence.

Results showed a higher proportion of females among patients, with the age group of 60-74 years being the most prevalent. The most common type of gallstone was solitary gallbladder stones. A total of 76 microbes were cultured from 5,153 patients, with Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis being the most frequently identified. Significant differences in microbial diversity and positive detection rates were observed across different age groups, types of gallstones, and recurrence status. Positive frequencies of E. coli, Enterococcus faecium, and K. pneumoniae varied significantly by age group and gallstone type. The microbial diversity in the recurrence group was significantly lower compared to the non-recurrence group. The recurrence rate was significantly higher in the group with single microbial species compared to those with no microbes or multiple microbes. For the recurrence group, there were significant differences in the frequencies of seven microbes (Aeromonas hydrophila, Enterococcus casseliflavus, Enterococcus faecium, E. coli, K. pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa) before and after recurrence, with these microbes appearing in a higher number of patients after recurrence. Regression analysis identified patient age, stone size, diabetes, venous thrombosis, liver cirrhosis, malignancy, coronary heart disease, and the number of microbial species as important predictors of recurrence. A random forest model constructed using these variables demonstrated good performance and high predictive ability (ROC-AUC = 0.862).

These findings highlight the significant role of microbial communities in gallstone formation and recurrence. Furthermore, the identified predictors of recurrence, including clinical factors and microbial diversity, may help develop personalized prevention and recurrence strategies for gallstone patients.

Human Papillomavirus (HPV) infections leading to a variety of diseases are a global public health issue.Despite the well-established link between HPV infection and cervical and anogenital cancers, there is ongoing debate regarding the relationship between HPV infection and colorectal cancer (CRC).

We evaluated the causal connection between HPV infection and CRC utilizing five Mendelian randomization (MR) methods. Genome-wide association studies (GWAS) datasets for HPV were obtained from the IEU Open GWAS project. A large summary of colorectal adenocarcinoma and colorectal cancer data from the FinnGen database was used as the outcome.

Our analysis revealed a significant association between genetically predicted HPV-16 infection and the risk of paternal colorectal adenocarcinoma (HPV-16: OR 1.058, 95% CI 1.013-1.102; p = 0.011), as well as CRC (HPV-16: OR 1.045, 95% CI 1.005-1.085; p = 0.025).

These findings provide compelling evidence for a causal effect of HPV infection on the development of CRC. Further investigations into the underlying mechanisms and elucidation of this association are necessary to identify viable interventions for the prevention and treatment of HPV-associated CRC.

Fusobacterium nucleatum, a gram-negative anaerobic bacterium abundantly found in the human oral cavity, is widely recognized as a key pathobiont responsible for the initiation and progression of periodontal diseases due to its remarkable aggregative capabilities. Numerous clinical studies have linked F. nucleatum with unfavorable prognostic outcomes in various malignancies. In further research, scholars have partially elucidated the mechanisms underlying F. nucleatum's impact on various types of cancer, thus gaining a certain comprehension of the role played by F. nucleatum in cancer. In this comprehensive review, we present an in-depth synthesis of the interplay between F. nucleatum and different cancers, focusing on aspects such as tumor initiation, metastasis, chemoresistance, and modulation of the tumor immune microenvironment and immunotherapy. The implications for cancer diagnosis and treatment are also summarized. The objective of this review is to enhance our comprehension of the intricate relationship between F. nucleatum and oncogenic pathogenesis, while emphasizing potential therapeutic strategies.

The microbiota plays a significant role in the tumor microenvironment, and its impact on tumor development and treatment outcome cannot be overlooked. Thus, it is essential to comprehend the interactions between the microbiota and the tumor microenvironment.

With the advent of next-generation sequencing, microbiota research has advanced significantly in recent years. The interaction between the intratumoral microbiota and the tumor microenvironment is an emerging area of research that holds great promise for understanding and treating solid tumor progression. This crosstalk between the intratumoral microbiota and the tumor microenvironment is a complex process that involves a multitude of factors, including the immune system, cellular signaling pathways, and metabolic processes. The origin of the intratumoral microbiota differs between various solid tumor, and the quantity and diversity of intratumoral microbiota also fluctuate significantly within each solid tumor.

The aim of this review is to provide a detailed summary of the intratumoral microbiota in various types of solid tumors. This will include an analysis of their origins, differences, and how they impact the progression of solid tumors. Furthermore, we will emphasize the significant potential that the intratumoral microbiota holds for the diagnosis and treatment of solid tumors.

Biomarkers in colorectal cancer (CRC) are of great interest in the current literature due to improvements in techniques such as liquid biopsy and next-generation sequencing (NGS). However, screening methods vary globally, with multi-target stool DNA (mt-sDNA) predominantly used in the USA and, more recently, the Cologuard Plus; biomarkers such as the Galectins family and septins show promise in early detection. Gut microbiome assessments, such as Fusobacterium nucleatum, are under intense exploration. Diagnostic tests, such as circulating DNA analysis via NGS, exhibit effectiveness and are being increasingly adopted. Circulating tumor cells emerge as potential alternatives to traditional methods in terms of diagnosis and prognosis. Predictive biomarkers are well established in guidelines; nonetheless, with the aid of machine learning and artificial intelligence, these biomarkers may be improved. This review critically explores the actual dynamic landscape of CRC biomarkers and future, promising biomarkers involved in screening, diagnosis, and prognosis.

Colorectal cancer (CRC) continuously ranks as the third most common cause of cancer-related deaths worldwide. Based on anatomical classifications and clinical diagnoses, CRC is classified into right-sided, left-sided, and rectal CRC. Importantly, the three types of positional-specific CRC affect the prognosis outcomes, thus indicating that positional-specific treatments for CRC are required. Emerging evidence suggests that besides host genetic and epigenetic alterations, gut mucosal microbiota is linked to gut inflammation, CRC occurrence, and prognoses. However, gut mucosal microbiota associated with positional-specific CRC are poorly investigated. Here, we report the gut mucosal microbiota profiles associated with these three types of CRC. Our analysis showed that the unique composition and biodiversity of bacterial taxa are linked to positional-specific CRC. We found that a combination of bacterial taxa can serve as potential biomarkers to distinguish the three types of CRC. Further investigations of the physiological roles of bacteria associated with positional-specific CRC may help understand the mechanism of CRC progression in different anatomical locations under the impact of gut mucosal microbiota.

Colorectal cancer (CRC) poses a global health threat, with the oral microbiome increasingly implicated in its pathogenesis. This study leverages Mendelian Randomization (MR) to explore causal links between oral microbiota and CRC using data from the China National GeneBank and Biobank Japan. By integrating multi-omics approaches, we aim to uncover mechanisms by which the microbiome influences cellular metabolism and cancer development.

We analyzed microbiome profiles from 2017 tongue and 1915 saliva samples, and GWAS data for 6692 CRC cases and 27178 controls. Significant bacterial taxa were identified via MR analysis. Single-cell RNA sequencing and enrichment analyses elucidated underlying pathways, and drug predictions identified potential therapeutics.

MR identified 19 bacterial taxa significantly associated with CRC. Protective effects were observed in taxa like RUG343 and Streptococcus_umgs_2425, while HOT-345_umgs_976 and W5053_sp000467935_mgs_712 increased CRC risk. Single-cell RNA sequencing revealed key pathways, including JAK-STAT signaling and tyrosine metabolism. Drug prediction highlighted potential therapeutics like Menadione Sodium Bisulfite and Raloxifene.

This study establishes the critical role of the oral microbiome in colorectal cancer development, identifying specific microbial taxa linked to CRC risk. Single-cell RNA sequencing and drug prediction analyses further elucidate key pathways and potential therapeutics, providing novel insights and personalized treatment strategies for CRC.

There is an accumulation of evidence that the human gut microbiota plays a role in maintaining health, and that an altered gut microbiota (sometimes called dysbiosis) associates with risk for many noncommunicable diseases. However, the dynamics of disease-linked bacteria in the gut and other body sites remain unclear. If microbiome alterations prove causative in particular diseases, therapeutic intervention may be possible. Furthermore, microbial signature taxa have been established for the diagnosis of some diseases like colon cancer. We identified 163 disease-enriched and 98 disease-depleted gut microbiome signature taxa at species-level resolution (signature species) from 10 meta-analyses of multiple diseases such as colorectal cancer, ulcerative colitis, Crohn's disease, irritable bowel syndrome, pancreatic cancer, and COVID-19 infection. Eight signature species were enriched and nine were depleted across at least half of the diseases studied. Compared with signature species depleted in diseases, a significantly higher proportion of disease-enriched signature species were identified as extra-intestinal (primarily oral) inhabitants, had been reported in bacteremia cases from the literature, and were aerotolerant anaerobes. These findings highlight the potential involvement of oral microbes, bacteremia isolates, and aerotolerant anaerobes in disease-associated gut microbiome alterations, and they have implications for patient care and disease management.

The gut microbiota influences the effectiveness and side effects of cancer treatments, particularly immunotherapy and associated immune-related complications. This important involvement of the microbiome is supported by the patients receiving antibiotics responding poorly to immunotherapy. Relatively few research has examined the underlying processes, and until recently, data regarding the detection of the microbial organisms that trigger these effects were inconsistent. Since then, a deeper comprehension of the processes of action and taxonomic classification of the relevant species has been attained. It's been demonstrated that certain bacterial species can enhance the body's reaction to immune checkpoint inhibitors through the release of distinct metabolites or products. Nonetheless, in certain patients who are not responding, Gram-negative bacteria may have a dominating suppressive impact. Patients' propensity to react to immunotherapy can be somewhat accurately predicted by machine learning techniques based on their microbiome makeup. Consequently, there has been an increase in interest in modifying the microbiome makeup to enhance patient reaction to medication. Clinical proof-of-concept studies demonstrate that dietary modifications or fecal microbiota transplantation (FMT) might be used therapeutically to increase the efficacy of immunotherapy in cancer patients. Current developments and new approaches for microbiota-based cancer treatments have been emphasized. In conclusion, preclinical research on animals and human clinical trials has made tremendous progress in our understanding of the function of the gut microbiome in health and illness. These investigations have shed light on the effects of food, FMT, probiotics, prebiotics, and microbiome-disease connections. However, there are still a lot of issues and restrictions that must be resolved before this research can be used in real-world clinical settings.

The gut microbiota has been recognized as an important determinant in the initiation and progression of colorectal cancer (CRC), with recent studies shining light on the molecular mechanisms that may contribute to the interactions between microbes and the CRC microenvironment. Despite the increasing wealth of associations being established in the field, proving causality remains challenging. Obstacles include the high variability of the microbiome and its context, both across individuals and across time. Additionally, there is a lack of large and representative cohort studies with long-term follow-up and/or appropriate sampling methods for studying the mucosal microbiome. Finally, most studies focus on CRC, whereas interactions between host and bacteria in early events in carcinogenesis remain elusive, reinforced by the heterogeneity of CRC development. Here, we discuss these current most prominent obstacles, the recent developments, and research needs.

We aimed to identify specific anaerobic bacteria causing bacteraemia and a subsequent diagnosis of colorectal cancer.

A nationwide population-based cohort study, which included all episodes of defined specific anaerobic bacteraemia from 2010 (5,534,738 inhabitants) through 2020 (5,822,763 inhabitants) and all cases of colorectal cancer diagnosed from 2010 through 2021 in Denmark. We calculated the incidence and risk of colorectal cancer after bacteraemia with specific anaerobic bacteria using Escherichia coli bacteraemia as reference.

Nationwide data on colorectal cancer and specific anaerobic bacteraemia (100% complete, representing 11,124 episodes). The frequencies of colorectal cancer within one year following anaerobic bacteraemia were higher for species, which almost exclusively reside in the colon, such as Phocaeicola vulgatus/dorei (5.5%), Clostridium septicum (24.2%), and Ruminococcus gnavus (4.6%) compared to 0.6% in 50,650 E. coli bacteraemia episodes. Bacteroides spp. had a subhazard ratio for colorectal cancer of 3.9 (95% confidence interval [CI], 3.0 to 5.1) and for Clostridium spp. it was 8.9 (95% CI, 6.7 to 11.8, with C. septicum 50.0 [95% CI, 36.0 to 69.5]) compared to E. coli (reference).

This nationwide study identified specific colorectal cancer-associated anaerobic bacteria, which almost exclusively reside in the colon. Bacteraemia with these bacteria could be an indicator of colorectal cancer.

Pediatric solid tumors are a common malignant disease in children, and more and more studies have proved that there is an inseparable relationship between adult tumors and intestinal microbiome, but the changes in the intestinal microbiota of pediatric solid tumor (PST) patients have been scarcely examined. This study aims to examine the differences in the intestinal microbiota features between patients diagnosed with PST and healthy controls (HCs).

To elucidate the unique characteristics of the gut microbiota in pediatric patients with solid tumors, we recruited 23 PST patients and 20 HCs. A total of 43 stool samples were gathered, and then 16S rRNA sequencing was performed.

We noticed a noticeable pattern of elevated diversity in the gut microbiota within the PST groups. The differences in microbial communities among two groups were remarkable, regarding the analysis at the class level, the abundance of Bacilli was markedly increased in PST patients compared to HCs (P < 0.05), regarding the analysis at the genus level, The presence of Enterococcus was significantly higher in PST cases compared to HCs (P < 0.01), while Lachnospiraceae unclassified, Lachnospira, Haemophilus and Colidextribacter in PST cases, the abundance was significantly reduced. (P < 0.05), 6 genera, including Bacilli, Lactobacillales, Enterococcaceae and Morganella, showed a significant enrichment compared to healthy controls, while 10 genera, including Bilophila, Colidextribacter, Pasteurellales, Haemophilus, Lachnospiraceae unclassified, Lachnospira and Fusobacteriales, were significant reduction in the PST groups.

Our research conducted the characterization analysis of the gut microbiota in PST patients for the first time. More importantly, there are some notable differences in the gut microbiota between PST patients and healthy controls, which we believe is an interesting finding.

We aim to compare the effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on the gut microbiota through longitudinal analysis.

Healthy volunteers were randomly assigned to receive either PPI (n=23) or H2RA (n=26) daily for seven consecutive days. We collected oral (saliva) and faecal samples before and after the intervention for metagenomic next-generation sequencing. We analysed intervention-induced alterations in the oral and gut microbiome including microbial abundance and growth rates, oral-to-gut transmissions, and compared differences between the PPI and H2RA groups.

Both interventions disrupted the gut microbiota, with PPIs demonstrating more pronounced effects. PPI usage led to a significantly higher extent of oral-to-gut transmission and promoted the growth of specific oral microbes in the gut. This led to a significant increase in both the number and total abundance of oral species present in the gut, including the identification of known disease-associated species like Fusobacterium nucleatum and Streptococcus anginosus. Overall, gut microbiome-based machine learning classifiers could accurately distinguish PPI from non-PPI users, achieving an area under the receiver operating characteristic curve (AUROC) of 0.924, in contrast to an AUROC of 0.509 for H2RA versus non-H2RA users.

Our study provides evidence that PPIs have a greater impact on the gut microbiome and oral-to-gut transmission than H2RAs, shedding light on the mechanism underlying the higher risk of certain diseases associated with prolonged PPI use.

ChiCTR2300072310.

The gut microbiota are known to play an important role in host health and disease. Alterations in the gut microbiota composition can disrupt the stability of the gut ecosystem, which may result in noncommunicable chronic diseases (NCCDs). Remodeling the gut microbiota through personalized nutrition is a novel therapeutic avenue for both disease control and prevention. However, whether there are commonly used gut microbiota-targeted diets and how gut microbiota-diet interactions combat NCCDs and improve health remain questions to be addressed. Lactoferrin (LF), which is broadly used in dietary supplements, acts not only as an antimicrobial in the defense against enteropathogenic bacteria but also as a prebiotic to propagate certain probiotics. Thus, LF-induced gut microbiota alterations can be harnessed to induce changes in host physiology, and the underpinnings of their relationships and mechanisms are beginning to unravel in studies involving humans and animal models.

The profound influence of microbiota in cancer initiation and progression has been under the spotlight for years, leading to numerous researches on cancer microbiome entering clinical evaluation. As promising biomarkers and therapeutic targets, the critical involvement of microbiota in cancer clinical practice has been increasingly appreciated. Here, recent progress in this field is reviewed. We describe the potential of tumor-associated microbiota as effective diagnostic and prognostic biomarkers, respectively. In addition, we highlight the relationship between microbiota and the therapeutic efficacy, toxicity, or side effects of commonly utilized treatments for cancer, including chemotherapy, radiotherapy, and immunotherapy. Given that microbial factors influence the cancer treatment outcome, we further summarize some dominating microbial interventions and discuss the hidden risks of these strategies. This review aims to provide an overview of the applications and advancements of microbes in cancer clinical relevance.

Current studies on the immune microenvironment of colorectal cancer (CRC) were mostly limited to the tissue level, lacking relevant studies in the peripheral blood, and failed to describe its alterations in the whole process of adenocarcinoma formation, especially of adenoma carcinogenesis. Here, we constructed a large-scale population cohort and used the CyTOF to explore the changes of various immune cell subsets in peripheral blood of CRC. We found monocytes and basophils cells were significantly higher in adenocarcinoma patients. Compared with early-stage CRC, effector CD4+T cells and naive B cells were higher in patients with lymph node metastasis, whereas the basophils were lower. We also performed random forest algorithm and found monocytes play the key role in carcinogenesis. Our study draws a peripheral blood immune cell landscape of the occurrence and development of CRC at the single-cell level and provides a reference for other researchers.

Colorectal cancer is one of the most frequently diagnosed forms of cancer, and it is associated with several common symptoms and signs such as rectal bleeding, altered bowel habits, abdominal pain, anemia, and unintentional weight loss. Sciatica, a debilitating condition in which the patient experiences paresthesia and pain in the dermatome of associated lumbosacral nerve roots or sciatic nerve distribution, is not considered one of these. Here we present a case of colorectal cancer manifesting symptoms of sciatica alone.

A 68-year-old male presented with progressive lower back pain radiating to his left thigh and calf over L5/S1 dermatome. Sciatica was suspected and initially underwent conservative treatment with analgesics. However, the symptoms progressed and MRI revealed an epidural abscess surprisingly. Surgical debridement was performed and pus culture isolated Streptococcus gallolyticus. Based on the strong association of S. gallolyticus with colorectal cancer, the presence of this pathogen prompted further tumor evaluation, even in the absence of the typical symptoms and signs. This investigation ultimately leads to the diagnosis of sigmoid adenocarcinoma.

Although rare, sciatica caused by S. gallolyticus infection of the spinal epidural space may serve as the initial presentation of colorectal cancer. Physicians should be aware of the strong association between S. gallolyticus and colorectal cancer. Based on what we currently know about the condition; a thorough systematic assessment of occult neoplasia for patients with S. gallolyticus infection is recommended.

Anaerobic bacteria, existing on human skin and mucous membranes, can cause severe infections with complications or mortality. We examined the clinical characteristics of patients infected with Fusobacterium spp. and assessed their antibiotic susceptibility.

Clinical data were collated from patients diagnosed with Fusobacterium infections in a Japanese university hospital between 2014 and 2023. Antibiotic susceptibility tests were conducted following the Clinical and Laboratory Standards Institute guidelines.

We identified 299 Fusobacterium isolates. The median age was 61 years (range, 14-95 years), with females constituting 43.1% of the patients. Most infections were community-acquired (84.6%, 253/299). Multiple bacterial strains were isolated simultaneously in 74.6% of cases. One-fourth of the patients had solid organ malignancies (25.4%, 76/299), and 14.5% (11/76) of those had colorectal cancer. The 30-day mortality rate was 1.3%. Fusobacterium species were isolated from blood cultures in 6% (18/299) of the patients. Patients, aged 75 years or older, with cerebrovascular disease or hematologic malignancy exhibited significantly higher prevalence of blood culture isolates in univariate analysis. Each Fusobacterium species had its characteristic infection site. Approximately 5% F. nucleatum and F. necrophorum isolates showed penicillin G resistance. Moxifloxacin resistance was observed in varying degrees across strains, ranging from 4.6 to 100% of isolates. All isolates were sensitive to β-lactam/β-lactamase inhibitors, carbapenems, and metronidazole.

We show a link between Fusobacterium species and solid organ malignancies. We observed resistance to penicillin, cefmetazole, clindamycin, and moxifloxacin, warranting caution in their clinical use. This study offers valuable insights for managing Fusobacterium infections and guiding empirical treatments.

Recent observational studies revealed an association between gut microbiota and aging, but whether gut microbiota are causally associated with the aging process remains unknown. We used a two-sample Mendelian randomization approach to investigate the causal association between gut microbiota and biological age acceleration using the largest available gut microbiota GWAS summary data from the MiBioGen consortium and GWAS data on biological age acceleration. We further conducted sensitivity analysis using MR-PRESSO, MR-Egger regression, Cochran Q test, and reverse MR analysis. Streptococcus (IVW, β = 0.16, p = 0.0001) was causally associated with Bioage acceleration. Eubacterium (rectale group) (IVW, β = 0.20, p = 0.0190), Sellimonas (IVW, β = 0.06, p = 0.019), and Lachnospira (IVW, β = -0.18, p = 0.01) were suggestive of causal associations with Bioage acceleration, with the latter being protective. Actinomyces (IVW, β = 0.26, p = 0.0083), Butyricimonas (IVW, β = 0.21, p = 0.0184), and Lachnospiraceae (FCS020 group) (IVW, β = 0.24, p = 0.0194) were suggestive of causal associations with Phenoage acceleration. This Mendelian randomization study found that Streptococcus was causally associated with Bioage acceleration. Further randomized controlled trials are needed to investigate its role in the aging process.

Evidence supports significant interactions among microbes, immune cells, and tumor cells in at least 10%-20% of human cancers, emphasizing the importance of further investigating these complex relationships. However, the implications and significance of tumor-related microbes remain largely unknown. Studies have demonstrated the critical roles of host microbes in cancer prevention and treatment responses. Understanding interactions between host microbes and cancer can drive cancer diagnosis and microbial therapeutics (bugs as drugs). Computational identification of cancer-specific microbes and their associations is still challenging due to the high dimensionality and high sparsity of intratumoral microbiome data, which requires large datasets containing sufficient event observations to identify relationships, and the interactions within microbial communities, the heterogeneity in microbial composition, and other confounding effects that can lead to spurious associations. To solve these issues, we present a bioinformatics tool, microbial graph attention (MEGA), to identify the microbes most strongly associated with 12 cancer types. We demonstrate its utility on a dataset from a consortium of nine cancer centers in the Oncology Research Information Exchange Network. This package has three unique features: species-sample relations are represented in a heterogeneous graph and learned by a graph attention network; it incorporates metabolic and phylogenetic information to reflect intricate relationships within microbial communities; and it provides multiple functionalities for association interpretations and visualizations. We analyzed 2,704 tumor RNA sequencing samples and MEGA interpreted the tissue-resident microbial signatures of each of 12 cancer types. MEGA can effectively identify cancer-associated microbial signatures and refine their interactions with tumors.

Studying the tumor microbiome in high-throughput sequencing data is challenging because of the extremely sparse data matrices, heterogeneity, and high likelihood of contamination. We present a new deep learning tool, MEGA, to refine the organisms that interact with tumors.

Colorectal diseases such as colorectal cancer (CRC) and inflammatory bowel disease (IBD) have become one of the most common public health concerns worldwide due to the increasing incidence. Environmental factors are one of the important causes of colorectal diseases, as they can affect the intestinal barrier function, immune response and microbiota, causing intestinal inflammation and tumorigenesis. Triphenyl phosphate (TPHP), a widely used organophosphorus flame retardant that can leach and accumulate in various environmental media and biota, can enter the human intestine through drinking water and food. However, the effects of TPHP on colorectal health have not been well understood. In this study, we investigated the adverse influence of TPHP exposure on colorectal cells (in vitro assay) and C57BL/6 mice (in vivo assay), and further explored the potential mechanism underlying the association between TPHP and colorectal disease. We found that TPHP exposure inhibited cell viability, increased apoptosis and caused G1/S cycle arrest of colorectal cells. Moreover, TPHP exposure damaged colorectal tissue structure, changed immune-related gene expression in the colorectal transcriptome, and disrupted the composition of colorectal microbiota. Importantly, we found that TPHP exposure upregulated chemokine CXCL10, which was involved in colorectal diseases. Our study revealed that exposure to TPHP had significant impacts on colorectal health, which may possibly stem from alterations in host immunity and the structure of the colorectal microbial community.

Colorectal cancer (CRC) is the second leading cause of cancer-related death, mostly due to metastatic disease and the fact that many patients already show signs of metastasis at the time of first diagnosis. Current CRC therapies negatively impact patients' quality of life and have little to no effect on combating the tumor once the dissemination has started. Danio rerio (zebrafish) is a popular animal model utilized in cancer research. One of its main advantages is the ease of xenograft transplantation due to the fact that zebrafish larvae lack the adaptative immune system, guaranteeing the impossibility of rejection. In this review, we have presented the many works that choose zebrafish xenograft as a tool for the study of CRC, highlighting the methods used as well as the promising new therapeutic molecules that have been identified due to this animal model.

Excess body weight (EBW) increases the risk of colorectal cancer (CRC) and is linked to lower colonoscopy compliance. Here, we extensively analyzed 981 metagenome samples from multiple cohorts to pinpoint the specific microbial signatures and their potential capability distinguishing EBW patients with CRC. The gut microbiome displayed considerable variations between EBW and lean CRC. We identify 44 and 37 distinct multi-kingdom microbial species differentiating CRC and controls in EBW and lean populations, respectively. Unique bacterial-fungal associations are also observed between EBW-CRC and lean-CRC. Our analysis revealed specific microbial functions in EBW-CRC, including D-Arginine and D-ornithine metabolism, and lipopolysaccharide biosynthesis. The best-performing classifier for EBW-CRC, comprising 12 bacterial and three fungal species, achieved an AUROC of 0.90, which was robustly validated across three independent cohorts (AUROC = 0.96, 0.94, and 0.80). Pathogenic microbial species, Anaerobutyricum hallii, Clostridioides difficile and Fusobacterium nucleatum, are EBW-CRC specific signatures. This work unearths the specific multi-kingdom microbial signatures for EBW-CRC and lean CRC, which may contribute to precision diagnosis and treatment of CRC.

The insights into interactions between host genetics and gut microbiome (GM) in colorectal tumor susceptibility (CTS) remains lacking. We used Collaborative Cross mouse population model to identify genetic and microbial determinants of Azoxymethane-induced CTS. We identified 4417 CTS-associated single nucleotide polymorphisms (SNPs) containing 334 genes that were transcriptionally altered in human colorectal cancers (CRCs) and consistently clustered independent human CRC cohorts into two subgroups with different prognosis. We discovered a set of genera in early-life associated with CTS and defined a 16-genus signature that accurately predicted CTS, the majority of which were correlated with human CRCs. We identified 547 SNPs associated with abundances of these genera. Mediation analysis revealed GM as mediators partially exerting the effect of SNP UNC3869242 within Duox2 on CTS. Intestine cell-specific depletion of Duox2 altered GM composition and contribution of Duox2 depletion to CTS was significantly influenced by GM. Our findings provide potential novel targets for personalized CRC prevention and treatment.

Skeletal muscle atrophy is a hallmark of cachexia, a wasting condition typical of chronic pathologies, that still represents an unmet medical need. Bone morphogenetic protein (BMP)-Smad1/5/8 signaling alterations are emerging drivers of muscle catabolism, hence, characterizing these perturbations is pivotal to develop therapeutic approaches. We identified two promoters of "BMP resistance" in cancer cachexia, specifically the BMP scavenger erythroferrone (ERFE) and the intracellular inhibitor FKBP12. ERFE is upregulated in cachectic cancer patients' muscle biopsies and in murine cachexia models, where its expression is driven by STAT3. Moreover, the knock down of Erfe or Fkbp12 reduces muscle wasting in cachectic mice. To bypass the BMP resistance mediated by ERFE and release the brake on the signaling, we targeted FKBP12 with low-dose FK506. FK506 restores BMP-Smad1/5/8 signaling, rescuing myotube atrophy by inducing protein synthesis. In cachectic tumor-bearing mice, FK506 prevents muscle and body weight loss and protects from neuromuscular junction alteration, suggesting therapeutic potential for targeting the ERFE-FKBP12 axis.

Gram-positive bacilli represent a diverse species of bacteria that range from commensal flora to pathogens implicated in severe and life-threatening infection. Following the isolation of Gram-positive bacilli from blood cultures, the time to species identification may take upward of 24 hours, leaving clinicians to conjecture whether they may represent a contaminant (inadvertent inoculation of commensal flora) or pathogenic organism. In this study, we sought to identify patient variables that could help predict the isolation of contaminant versus pathogenic Gram-positive bacilli from blood cultures.

Retrospective cohort study.

One quaternary academic medical center affiliated with the University of Toronto.

Adult inpatients were admitted to hospital over a 5-year period (May 2014 to December 2019).

A total of 260 unique Gram-positive bacilli blood culture results from adult inpatients were reviewed and analyzed in both a univariable and multivariable model.

Malignancy (aOR 2.78, 95% CI 1.33-5.91, p = 0.007), point increments in the Quick Sepsis Related Organ Failure Assessment score for sepsis (aOR 2.25, 95% CI 1.50-3.47, p < 0.001), peptic ulcer disease (aOR 5.63, 95% CI 1.43-21.0, p = 0.01), and the receipt of immunosuppression prior to a blood culture draw (aOR 3.80, 95% CI 1.86-8.01, p < 0.001) were associated with an increased likelihood of speciating pathogenic Gram-positive bacilli from blood cultures such as Clostridium species and Listeria monocytogenes.

Such predictors can help supplement a clinician's assessment on determining when empirical therapy is indicated when faced with Gram-positive bacilli from blood cultures and may direct future stewardship interventions for responsible antimicrobial prescribing.

The associations between cancer and bacteria/fungi have been extensively studied, but the implications of cancer-associated viruses have not been thoroughly examined. In this study, we comprehensively characterized the cancer virome of tissue samples across 31 cancer types, as well as blood samples from 23 cancer types. Our findings demonstrated the presence of viral DNA at low abundances in both tissue and blood across major human cancers, with significant differences in viral community composition observed among various cancer types. Furthermore, Cox regression analyses conducted on four cancers, including Head and Neck squamous cell carcinoma (HNSC), Kidney renal clear cell carcinoma (KIRC), Stomach adenocarcinoma (STAD), and Uterine Corpus Endometrial Carcinoma (UCEC), revealed strong correlation between viral composition/abundance in tissues and patient survival. Additionally, we identified virus-associated prognostic signatures (VAPS) for these four cancers, and discerned differences in the interplay between VAPS and dominant bacteria in tissues among patients with varying survival risks. Notably, clinically relevant analyses revealed prognostic capacities of the VAPS in these four cancers. Taken together, our study provides novel insights into the role of viruses in tissue in the prognosis of multiple cancers and offers guidance on the use of tissue viruses to stratify prognosis for patients with cancer.

Colorectal cancer (CRC) can compromise the mucosal barrier and subsequently allow a route for bacterial invasion into the portal system or systemic circulation. Despite preliminary data suggesting that patients who experienced pyogenic liver abscess (PLA) have higher CRC incidence rates, data from outside the Southeast Asian population are sparse.

To investigate whether there is an association between PLA and the subsequent incidence of diagnosed CRC using the Veterans Health Administration (VHA) cohort.

A patient-level matched retrospective cohort study was conducted at 127 VHA hospitals across the US from January 1, 2003, to December 31, 2020. Patients were followed up to 10 years from PLA diagnosis. Data analysis was performed from April 14, 2002, to October 31, 2023. All patients who were admitted to VHA hospitals with a diagnosis of PLA were included. For each patient with PLA, up to 3 controls without diagnosis of PLA, matching age, sex, and health care facility, were selected.

Pyogenic liver abscess.

The primary outcome was CRC diagnosis during the follow-up period. A multivariable Fine-Gray subdistribution regression model with time-dependent coefficient was used to estimate the time-varying hazard ratio (HR) of CRC incidence while accounting for mortality as a competing event.

A total of 8286 patients with PLA (male, 96.5%; mean [SD] age, 65.8 [11.9] years) and 23 201 patient-level matched controls (male, 96.3%; mean age, 65.3 [11.7] years) were included. A diagnosis of CRC was found in a significantly higher proportion of patients with PLA compared with controls (1.9% [159 of 8286] vs 0.8% [196 of 23 201]; P < .001). The incidence of CRC was significantly higher among patients with PLA during the first 3 years from PLA diagnosis (HR, 3.64; 95% CI, 2.70-4.91 at 0.5 years; HR, 2.51; 95% CI, 1.93-3.26 at 1 year; HR, 1.74; 95% CI, 1.33-2.28 at 2 years; and HR, 1.41; 95% CI, 1.05-1.89 at 3 years), but not significant after 3 years. This association was not observed among patients whose PLA was likely secondary to cholangitis or cholecystitis (HR, 1.78; 95% CI, 0.89-3.56 at 0.5 years).

In this patient-level matched retrospective cohort study, a significantly higher incidence of CRC was observed up to 3 years from PLA diagnosis. The findings suggest that offering CRC screening for patients with cryptogenic PLA may be useful, especially patients who have not been screened according to guidelines.

With advances in metagenomic sequencing technologies, there are accumulating studies revealing the associations between the human gut microbiome and some human diseases. These associations shed light on using gut microbiome data to distinguish case and control samples of a specific disease, which is also called host disease status classification. Importantly, using learning-based models to distinguish the disease and control samples is expected to identify important biomarkers more accurately than abundance-based statistical analysis. However, available tools have not fully addressed two challenges associated with this task: limited labeled microbiome data and decreased accuracy in cross-studies. The confounding factors, such as the diet, technical biases in sample collection/sequencing across different studies/cohorts often jeopardize the generalization of the learning model.

To address these challenges, we develop a new tool GDmicro, which combines semi-supervised learning and domain adaptation to achieve a more generalized model using limited labeled samples. We evaluated GDmicro on human gut microbiome data from 11 cohorts covering 5 different diseases. The results show that GDmicro has better performance and robustness than state-of-the-art tools. In particular, it improves the AUC from 0.783 to 0.949 in identifying inflammatory bowel disease. Furthermore, GDmicro can identify potential biomarkers with greater accuracy than abundance-based statistical analysis methods. It also reveals the contribution of these biomarkers to the host's disease status.

https://github.com/liaoherui/GDmicro.

Colorectal cancer (CRC) is one of the most common causes of death in the world. The multi-drug resistance, especially in metastatic colorectal cancer, drives the development of new strategies that secure a positive outcome and reduce undesirable side effects. Nanotechnology has made an impact in addressing some pharmacokinetic and safety issues related to administration of free therapeutic agents. However, demands of managing complex biointerfacing require equally complex methods for introducing stimuli-responsive or targeting elements. In order to procure a more efficient solution to the overcoming of biological barriers, the physiological functions of cancer cell plasma and exosomal membranes provided the source of highly functionalized coatings. Biomimetic nanovehicles based on colorectal cancer (CRC) membranes imparted enhanced biological compatibility, immune escape and protection to diverse classes of therapeutic molecules. When loaded with therapeutic load or used as a coating for other therapeutic nanovehicles, they provide highly efficient and selective cell targeting and uptake. This review presents a detailed overview of the recent application of homotypic biomimetic nanovehicles in the management of CRC. We also address some of the current possibilities and challenges associated with the CRC membrane biomimetics.

Invasive infection with Streptococcus bovis/Streptococcus equinus complex (SBSEC) bacteria is associated with underlying colorectal neoplasia. However, the link between intestinal or fecal colonization with SBSEC isolates or antibody responses to SBSEC members and colorectal cancer is not thoroughly investigated in the literature.

We searched the PubMed, EMBASE, and Web of Science databases for case-control studies as well as retrospective or prospective cohort studies reporting an association between SBSEC bacteria and colorectal neoplasia.

We identified 22 studies (15 case-control and 7 cohort) that met our inclusion criteria. Among the cohort studies, patients with SBSEC bacteremia were 3.73 times more likely to have underlying colorectal cancer compared with individuals with no bacteremia (relative risk [RR], 3.73; 95% CI, 2.79-5.01), whereas the risk of underlying colorectal adenoma in patients with SBSEC bacteremia was not significantly increased (RR, 5.00; 95% CI, 0.83-30.03). In case-control studies, patients with colorectal cancer were 2.27 times more likely to have evidence of intestinal or fecal colonization with SBSEC isolates (odds ratio [OR], 2.27; 95% CI, 1.11-4.62) and immunoglobulin G (IgG) antibody responses to SBSEC antigens (OR, 2.27; 95% CI, 1.06-4.86) compared with controls. Patients with colorectal adenoma were not more likely to be colonized with SBSEC isolates compared with controls (OR, 1.12; 95% CI, 0.55-2.25).

Apart from the well-established association of SBSEC bacteremia and underlying colorectal cancer, intestinal or fecal colonization with SBSEC isolates and IgG antibody responses to SBSEC antigens were higher in patients with colorectal cancer compared with controls. Neither bacteremia from SBSEC isolates nor colonization with SBSEC bacteria was associated with underlying colorectal adenoma.

The intestinal microbiota participates in host physiology and pathology through metabolites, in which short-chain fatty acids (SCFAs) are considered principal products and have extensive influence on intestine homeostasis. It has been reported that skin ulceration syndrome (SUS), the disease of Apostichopus japonicus caused by Vibrio splendidus, is associated with the alteration of the intestinal microbiota composition.

To investigate whether the intestinal microbiota affects A. japonicus health via SCFAs, in this study, we focus on the SCFA profiling and intestinal barrier function in A. japonicus treated with V. splendidus.

We found that V. splendidus could destroy the mid-intestine integrity and downregulate the expression of tight junction proteins ZO-1 and occludin in A. japonicus, which further dramatically decreased microorganism abundance and altered SCFAs contents. Specifically, acetic acid is associated with the largest number of microorganisms and has a significant correlation with occludin and ZO-1 among the seven SCFAs. Furthermore, our findings showed that acetic acid could maintain the intestinal barrier function by increasing the expression of tight junction proteins and rearranging the tight junction structure by regulating F-actin in mid-intestine epithelial cells. Thus, our results provide insights into the effects of the gut microbiome and SCFAs on intestine barrier homeostasis and provide essential knowledge for intervening in SUS by targeting metabolites or the gut microbiota.

Colorectal cancer (CRC) is a significant global health burden with a rising incidence worldwide. Distinct bacterial populations are associated with CRC development and progression, and it is thought that the relationship between CRC and associated gut bacteria changes during the progression from normal epithelium to benign adenoma and eventually malignant carcinoma and metastasis. This study compared the interaction of CRC-associated species Enterotoxigenic Bacteroides fragilis, Enterococcus faecalis and Fusobacterium nucleatum and one probiotic species, Escherichia coli Nissle 1917 with a colorectal adenoma (S/RG/C2) and a colorectal adenocarcinoma (HCT116) derived cell line. Gentamicin protection assays showed that all species displayed higher attachment to benign tumour monolayers when compared to malignant monolayers. However, invasion of 3/4 species was higher in the HCT116 cells than in the adenoma cells. All species were found to persist within tumour cell monolayers for a minimum of 48 h under standard aerobic cell culture conditions, with persistence significantly higher in HCT116 cells. Downstream assays were performed to analyse the behaviour of S/RG/C2 and HCT116 cells post-infection and revealed that all species increased the tumour cell yield of both cell lines. The migratory and invasive potential of HCT116 cells was increased after infection with F. nucleatum; however, no species significantly altered these characteristics in S/RG/C2 cells. These results add to the growing evidence for the involvement of microorganisms in CRC progression and suggest that these interactions may be dependent on tumour cell-specific characteristics.

Modifications in the gut microbiota may be a crucial factor in the efficacy of canagliflozin (Cana) in managing patients with type 2 diabetes mellitus (T2DM). However, the interplay between oral and ocular surface microbiota and this treatment remains poorly explored.

This study aimed to assess alterations in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment in patients with T2DM.

In this 30-day, controlled before-and-after study, 21 treatment-naïve patients with T2DM received sole treatment with Cana (100 mg/day), and were matched with 10 healthy controls based on gender and age. Using 16S rRNA sequencing, changes in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment were assessed and compared with those of healthy controls. Concurrently, diabetes-related clinical parameters were recorded over the study period. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR200034878).

A noticeable shift was observed in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment. The post-Cana treatment gut microbiota was more similar to that of the healthy controls. Network correlation analysis revealed that modifications in the gut, oral, and ocular surface microbiota were related to changes in clinical parameters, especially for the ocular surface microbiota.

A significant decrease in fasting plasma glucose (8.22 ± 2.19 vs 6.87 ± 1.09 mmol/L), glycated serum protein [291.00 (264.00, 353.00) vs 275.00 (251.00, 342.50) μmol/L], hemoglobin A1c (7.39 ± 1.18 vs 7.12 ± 1.33%), body mass index (25.32 ± 2.99 vs 24.83 ± 2.95 kg/m2), systolic blood pressure (129.05 ± 17.51 vs 123.43 ± 14.82 mmHg), and urinary creatinine [158.40 (74.75, 219.15) vs 79.70 (56.25, 138.10) μmmol/kg] levels was noted after 30-day Cana monotherapy (P < 0.05).

Treatment with Cana resulted in an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria, particularly Lachnospiraceae UCG 004, Bacteroides, and Lachnospiraceae NK4A136 group.

After Cana treatment, a significant increase of Prevotella and Veillonella, both of which are known to be closely associated with SCFAs, was observed.

Post-Cana administration, the ocular surface microbiota exhibited the most distinct changes in structure and composition. Remarkably, the majority of the increased ocular surface microbiota could produce SCFAs within the gut microbiota.

Cana effectively improved the dysregulated glucose metabolism in patients with T2DM. This improvement can potentially be attributed to the restoration of balance among the gut, oral, and ocular surface microbial communities.

https://www.chictr.org.cn/showproj.html?proj=56487, identifier ChiCTR2000034878.

External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers (YORCs) for profiles potentially correlative with disease etiology and biology.

YORC is rapidly increasing, with 1 in 4 new rectal cancer cases occurring under the age of 50 years. Its etiology is unknown.

YORC (<50 y old) or later-onset rectal cancer (LORC, ≥50 y old) patients underwent pretreatment biopsied of tumor and tumor-adjacent normal (TAN) tissue. After whole genome sequencing, metagenomic analysis quantified microbial communities comparing tumors versus TANs and YORCs versus LORCs, controlling for multiple testing. Response to neoadjuvant therapy (NT) was categorized as major pathological response (MPR, ≤10% residual viable tumor) versus non-MPR.

Our 107 tumors, 75 TANs from 37 (35%) YORCs, and 70 (65%) LORCs recapitulated bacterial species were previously associated with colorectal cancers (all P <0.0001). YORC and LORC tumoral microbiome signatures were distinct. After NT, 13 patients (12.4%) achieved complete pathologic response, whereas MPR occurred in 47 patients (44%). Among YORCs, MPR was associated with Fusobacterium nucleaum , Bacteroides dorei, and Ruminococcus bromii (all P <0.001), but MPR in LORC was associated with R. bromii ( P <0.001). Network analysis of non-MPR tumors demonstrated a preponderance of oral bacteria not observed in MPR tumors.

Microbial signatures were distinct between YORC and LORC. Failure to achieve an MPR was associated with oral bacteria in tumors. These findings urge further studies to decipher correlative versus mechanistic associations but suggest a potential for microbial modulation to augment current treatments.