Authors: Pingmei Huang, Fenfen Ji, Alvin Ho-Kwan Cheung...

Peptostreptococcus stomatis (P. stomatis) is enriched in colorectal cancer (CRC), but its causality and translational implications in CRC are unknown. Here, we show that P. stomatis accelerates colonic tumorigenesis in Apc and azoxymethane/dextran sodium sulfate (AOM-DSS) models by inducing cell proliferation, suppressing apoptosis, and impairing gut barrier function. P. stomatis adheres to CRC cells through its surface protein fructose-1,6-bisphosphate aldolase (FBA) that binds to the integrin α6/β4 receptor on CRC cells, leading to the activation of ERBB2 and the downstream MEK-ERK-p90 cascade. Blockade of the FBA-integrin α6/β4 abolishes ERBB2-mitogen-activated protein kinase (MAPK) activation and the protumorigenic effect of P. stomatis. P. stomatis-driven ERBB2 activation bypasses receptor tyrosine kinase (RTK) blockade by EGFR inhibitors (cetuximab, erlotinib), leading to drug resistance in xenograft and spontaneous CRC models of KRAS-wild-type CRC. P. stomatis also abrogates BRAF inhibitor (vemurafenib) efficacy in BRAF-mutant CRC xenografts. Thus, we identify P. stomatis as an oncogenic bacterium and a contributory factor for non-responsiveness to RTK inhibitors in CRC.

Topics: Animals; Humans; Mice; Apoptosis; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Drug Resistance, Neoplasm; Fructose-Bisphosphate Aldolase; MAP Kinase Signaling System; Mitogen-Activated Protein Kinases; Peptostreptococcus; Receptor, ErbB-2; Tyrosine Kinase Inhibitors

PubMed: 39059397
DOI: 10.1016/j.chom.2024.07.001

Authors: Ling Zhang, Yuan Liu, Hua Jun Zheng...

The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic diseases and chronic inflammation, which is usually caused by bacteria and contributes to cancer. There may be a relationship between oral bacteria and oral squamous cell carcinoma (OSCC); however, this relationship has not been thoroughly characterized. Therefore, in this study, we compared the microbiota compositions between tumor sites and opposite normal tissues in buccal mucosal of 50 patients with OSCC using the 16S rDNA sequencing. Richness and diversity of bacteria were significantly higher in tumor sites than in the control tissues. Cancer tissues were enriched in six families (, and ) and 13 genera, including and . At the species level, the abundances of , and another five species were significantly increased, suggesting a potential association between these bacteria and OSCC. Furthermore, the functional prediction revealed that genes involved in bacterial chemotaxis, flagellar assembly and lipopolysaccharide (LPS) biosynthesis which are associated with various pathological processes, were significantly increased in the OSCC group. Overall, oral bacterial profiles showed significant difference between cancer sites and normal tissue of OSCC patients, which might be onsidered diagnostic markers and treatment targets. Our study has been registered in the Chinese clinical trial registry (ChiCTR1900025253, http://www.chictr.org.cn/index.aspx).

Topics: Bacteria; Carcinoma, Squamous Cell; DNA, Ribosomal; Female; Fusobacterium nucleatum; Humans; Lipopolysaccharides; Male; Microbiota; Middle Aged; Mouth; Mouth Mucosa; Peptostreptococcus; Prevotella intermedia; RNA, Ribosomal, 16S

PubMed: 32010645
DOI: 10.3389/fcimb.2019.00476

Authors: Marta Wlodarska, Chengwei Luo, Raivo Kolde...

Host factors in the intestine help select for bacteria that promote health. Certain commensals can utilize mucins as an energy source, thus promoting their colonization. However, health conditions such as inflammatory bowel disease (IBD) are associated with a reduced mucus layer, potentially leading to dysbiosis associated with this disease. We characterize the capability of commensal species to cleave and transport mucin-associated monosaccharides and identify several Clostridiales members that utilize intestinal mucins. One such mucin utilizer, Peptostreptococcus russellii, reduces susceptibility to epithelial injury in mice. Several Peptostreptococcus species contain a gene cluster enabling production of the tryptophan metabolite indoleacrylic acid (IA), which promotes intestinal epithelial barrier function and mitigates inflammatory responses. Furthermore, metagenomic analysis of human stool samples reveals that the genetic capability of microbes to utilize mucins and metabolize tryptophan is diminished in IBD patients. Our data suggest that stimulating IA production could promote anti-inflammatory responses and have therapeutic benefits.

Topics: Animals; Anti-Inflammatory Agents; Bacteria; Bacteroides; Clostridiales; Colon; Cytokines; Dysbiosis; Humans; Indoles; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Mice; Mucin-2; Mucins; Organoids; Peptostreptococcus; Symbiosis

PubMed: 28704649
DOI: 10.1016/j.chom.2017.06.007

Meta-Analysis

Authors: Nagavardhini Avuthu, Chittibabu Guda

Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. The dysbiotic gut microbiota and its metabolite secretions play a significant role in CRC development and progression. In this study, we identified microbial and metabolic biomarkers applicable to CRC using a meta-analysis of metagenomic datasets from diverse geographical regions. We used LEfSe, random forest (RF), and co-occurrence network methods to identify microbial biomarkers. Geographic dataset-specific markers were identified and evaluated using area under the ROC curve (AUC) scores and random effect size. Co-occurrence networks analysis showed a reduction in the overall microbial associations and the presence of oral pathogenic microbial clusters in CRC networks. Analysis of predicted metabolites from CRC datasets showed the enrichment of amino acids, cadaverine, and creatine in CRC, which were positively correlated with CRC-associated microbes (Peptostreptococcus stomatis, Gemella morbillorum, Bacteroides fragilis, spp., Fusobacterium nucleatum, Solobacterium moorei, and Clostridium symbiosum), and negatively correlated with control-associated microbes. Conversely, butyrate, nicotinamide, choline, tryptophan, and 2-hydroxybutanoic acid showed positive correlations with control-associated microbes ( < 0.05). Overall, our study identified a set of global CRC biomarkers that are reproducible across geographic regions. We also reported significant differential metabolites and microbe-metabolite interactions associated with CRC. This study provided significant insights for further investigations leading to the development of noninvasive CRC diagnostic tools and therapeutic interventions. Several studies showed associations between gut dysbiosis and CRC. Yet, the results are not conclusive due to cohort-specific associations that are influenced by genomic, dietary, and environmental stimuli and associated reproducibility issues with various analysis approaches. Emerging evidence suggests the role of microbial metabolites in modulating host inflammation and DNA damage in CRC. However, the experimental validations have been hindered by cost, resources, and cumbersome technical expertise required for metabolomic investigations. In this study, we performed a meta-analysis of CRC microbiota data from diverse geographical regions using multiple methods to achieve reproducible results. We used a computational approach to predict the metabolomic profiles using existing CRC metagenomic datasets. We identified a reliable set of CRC-specific biomarkers from this analysis, including microbial and metabolite markers. In addition, we revealed significant microbe-metabolite associations through correlation analysis and microbial gene families associated with dysregulated metabolic pathways in CRC, which are essential in understanding the vastly sporadic nature of CRC development and progression.

Topics: Biomarkers; Colorectal Neoplasms; Dysbiosis; Gastrointestinal Microbiome; Humans; Reproducibility of Results

PubMed: 35766483
DOI: 10.1128/spectrum.00013-22

Authors: Neha Sharma, Kaveh Zivari, Avleen Kaur...

Fish bone-induced pancreatitis is an uncommon cause of pancreatitis, with only a few reported cases in the literature. The patients with the highest risk for fish bone-induced pancreatitis include those from cultures where unfilleted fish is a culinary delicacy. The etiology of foreign body-induced pancreatitis is very common, secondary to inflammation of the duodenal papilla or bile duct obstruction. CT imaging is key for visualization of the fish bone, as radiography rarely detects fish bones. Complications of fish bone-induced pancreatitis include thrombosis of the superior mesenteric vein, bacteremia (with ), pancreatic granuloma, and gastrointestinal perforation. Management of fish bone-induced pancreatitis includes either endoscopic resection or exploratory laparotomy, followed by supportive care until pancreatitis resolves. Here, we present a case of pancreatitis secondary to accidental fish bone ingestion, identified during upper gastrointestinal endoscopy and managed by bone removal and supportive care.

PubMed: 35891822
DOI: 10.7759/cureus.26191

Authors: Pamela Vernocchi, Tommaso Gili, Federica Conte...

Several studies in recent times have linked gut microbiome (GM) diversity to the pathogenesis of cancer and its role in disease progression through immune response, inflammation and metabolism modulation. This study focused on the use of network analysis and weighted gene co-expression network analysis (WGCNA) to identify the biological interaction between the gut ecosystem and its metabolites that could impact the immunotherapy response in non-small cell lung cancer (NSCLC) patients undergoing second-line treatment with anti-PD1. Metabolomic data were merged with operational taxonomic units (OTUs) from 16S RNA-targeted metagenomics and classified by chemometric models. The traits considered for the analyses were: (i) condition: disease or control (CTRLs), and (ii) treatment: responder (R) or non-responder (NR). Network analysis indicated that indole and its derivatives, aldehydes and alcohols could play a signaling role in GM functionality. WGCNA generated, instead, strong correlations between short-chain fatty acids (SCFAs) and a healthy GM. Furthermore, commensal bacteria such as , Rikenellaceae, , Peptostreptococcaceae, Mogibacteriaceae and Clostridiaceae were found to be more abundant in CTRLs than in NSCLC patients. Our preliminary study demonstrates that the discovery of microbiota-linked biomarkers could provide an indication on the road towards personalized management of NSCLC patients.

Topics: Akkermansia; Alcohols; Aldehydes; Antineoplastic Agents, Immunological; Bacteroides; Carcinoma, Non-Small-Cell Lung; Clostridiaceae; Databases, Genetic; Disease Progression; Drug Monitoring; Fatty Acids, Volatile; Gastrointestinal Microbiome; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Immunotherapy; Indoles; Lung Neoplasms; Metabolome; Metagenomics; Peptostreptococcus; Precision Medicine; Programmed Cell Death 1 Receptor; RNA, Ribosomal, 16S; Signal Transduction

PubMed: 33227982
DOI: 10.3390/ijms21228730

Review

Authors: C A Spiegel

Bacterial vaginosis (BV) is the most common of the vaginitides affecting women of reproductive age. It appears to be due to an alteration in the vaginal ecology by which Lactobacillus spp., the predominant organisms in the healthy vagina, are replaced by a mixed flora including Prevotella bivia, Prevotella disiens, Porphyromonas spp., Mobiluncus spp., and Peptostreptococcus spp. All of these organisms except Mobiluncus spp. are also members of the endogenous vaginal flora. While evidence from treatment trials does not support the notion that BV is sexually transmitted, recent studies have shown an increased risk associated with multiple sexual partners. It has also been suggested that the pathogenesis of BV may be similar to that of urinary tract infections, with the rectum serving as a reservoir for some BV-associated flora. The organisms associated with BV have also been recognized as agents of female upper genital tract infection, including pelvic inflammatory disease, and the syndrome BV has been associated with adverse outcome of pregnancy, including premature rupture of membranes, chorioamnionitis, and fetal loss; postpartum endometritis; cuff cellulitis; and urinary tract infections. The mechanisms by which the BV-associated flora causes the signs of BV are not well understood, but a role for H2O2-producing Lactobacillus spp. in protecting against colonization by catalase-negative anaerobic bacteria has been recognized. These and other aspects of BV are reviewed.

Topics: Female; Humans; Vaginosis, Bacterial

PubMed: 1747864
DOI: 10.1128/CMR.4.4.485

Authors: Sukanya Sudhaharan, Padmasri Chavali, Lakshmi Vemu...

BACKGROUND AND OBJECTIVES

Brain abscess remains a potentially fatal central nervous system (CNS) disease, especially in developing countries. Anaerobic abscess is difficult to diagnose because of cumbersome procedures associated with the isolation of anaerobes.

MATERIALS AND METHODS

This is a hospital-based retrospective microbiological analysis of 430 brain abscess materials (purulent aspirates and/or tissue), for anaerobic organisms, that were received between 1987-2014, by the Microbiology Laboratory in our Institute.

RESULTS

Culture showed growth of bacteria 116/430 (27%) of the cases of which anaerobes were isolated in 48/116 (41.1%) of the cases. Peptostreptococcus (51.4 %), was the predominant organism isolated in four cases followed by Bacteroides and Peptococcus species.

CONCLUSION

Early diagnosis and detection of these organisms would help in the appropriate management of these patients.

PubMed: 27307977
DOI: No ID Found

Review

Authors: Charmaine Ng, Haojun Li, William K K Wu...

Colorectal cancer (CRC) is a common cancer globally. It is a complex disease influenced by genetic and environmental factors. Early studies on familial cases have identified major genes involved in CRC, such as proto-oncogenes and , and tumour-suppressor genes and . These genes have provided valuable insight into the molecular pathogenesis of CRC, and some have made ways to clinical utility to help diagnose cancer syndromes, prognosticate oncological outcomes and predict treatment responses. While these genetic factors are important, recent studies have suggested contribution of microorganisms to colorectal carcinogenesis. Observational studies, animal experiments and translational works have identified several microorganisms as potential carcinogenic bacteria, such as and . With the advent of sequencing technology and bioinformatics, more genomic and metagenomic factors are being uncovered as important players in CRC carcinogenesis. This article aims to review recent genomic and metagenomic discoveries relating to CRC.

PubMed: 31949936
DOI: 10.21037/jgo.2019.06.04