Circulating Microbial Cell-Free DNA in Health and Disease

Article Immunology

Microbial Cell-Free DNA Identifies the Causative Pathogen in Infective Endocarditis and Remains Detectable Longer Than Conventional Blood Culture in Patients with Prior Antibiotic Therapy

Emily M. Eichenberger et al.

Summary: Microbial cell-free DNA accurately identifies the microbial etiology of infective endocarditis, and sequential mcfDNA levels may help estimate the patient's burden of infection and response to treatment.

CLINICAL INFECTIOUS DISEASES (2023)

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Article Immunology

Plasma Microbial Cell-free DNA Next-generation Sequencing in the Diagnosis and Management of Febrile Neutropenia

Esther Benamu et al.

Summary: This study evaluated the ability of Karius microbial cell-free DNA sequencing test (KT) to identify infectious etiologies in patients with febrile neutropenia (FN) and its impact on antimicrobial treatment. The results showed that KT was able to detect organisms that were not identified by conventional microbiological tests, and it had the potential to improve the diagnosis and optimize the antimicrobial therapy for FN.

CLINICAL INFECTIOUS DISEASES (2022)

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Article Immunology

Microbial Cell-Free DNA Identifies Etiology of Bloodstream Infections, Persists Longer Than Conventional Blood Cultures, and Its Duration of Detection Is Associated With Metastatic Infection in Patients With Staphylococcus aureus and Gram-Negative Bacteremia

Emily M. Eichenberger et al.

Summary: In patients with bacteremia, microbial cell-free DNA can be detected for a longer period of time compared to conventional blood cultures, and the duration of detection is associated with an increased risk of metastatic infection.

CLINICAL INFECTIOUS DISEASES (2022)

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Review Immunology

Cell-Free Tumor DNA (cf-tDNA) Liquid Biopsy: Current Methods and Use in Brain Tumor Immunotherapy

Jack Wadden et al.

Summary: Gliomas are brain tumors derived from mutations in glial brain cells. The development of precise diagnostics and novel targeted immunotherapies for gliomas is crucial. Radiographic imaging, the most common diagnostic technique, has limitations in molecular information and can be confounded by inflammation. Recently, circulating cell free tumor DNA (cf-tDNA) has been investigated as a promising biomarker for glioma diagnosis and disease monitoring. However, the low concentrations of cf-tDNA and the presence of the blood-brain barrier pose challenges to its recovery and analysis. This mini review summarizes the current trends and future prospects of various approaches for cf-tDNA detection and analysis.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Microbiology

Peripheral Blood Microbiome Analysis via Noninvasive Prenatal Testing Reveals the Complexity of Circulating Microbial Cell-Free DNA

Xunliang Tong et al.

Summary: A baseline for microbial cfDNA in healthy individuals is urgently needed for proper interpretation of microbial cfDNA sequencing results. This study utilized the standard low-pass whole-genome-sequencing-based NIPT to establish a microbial cfDNA baseline in healthy people. The complexity of circulating microbial cfDNA was revealed, indicating the need for a more comprehensive interpretation of microbial cfDNA sequencing results, especially regarding geographic patterns and coexistence networks.

MICROBIOLOGY SPECTRUM (2022)

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Review Medicine, General & Internal

Circulating Bacterial DNA: A New Paradigm for Cancer Diagnostics

Tamara Glyn et al.

Summary: Cell-free DNA analysis, including investigation of circulating bacterial DNA, shows promise in cancer screening, diagnosis, and treatment monitoring. It can distinguish between cancer patients and healthy controls and has potential prognostic value. However, improvements in laboratory and bioinformatics analyses are needed, and the clinical relevance of circulating bacterial DNA for each cancer type is yet to be determined. Despite these challenges, cell-free DNA analysis presents an exciting prospect for future liquid biopsy screening and diagnostics in cancer.

FRONTIERS IN MEDICINE (2022)

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Article Infectious Diseases

Plasma metagenomic next-generation sequencing of microbial cell-free DNA detects pathogens in patients with suspected infected pancreatic necrosis

Donghuang Hong et al.

Summary: In this study, the diagnostic value of plasma metagenomic next-generation sequencing (mNGS) based on circulating microbial cell-free DNA in patients with suspected infected pancreatic necrosis (IPN) was evaluated. The study found that plasma mNGS can identify IPN-related pathogens with a high degree of conformity to culture results of IPN drains. Additionally, the study found that patients with positive mNGS results had worse clinical outcomes.

BMC INFECTIOUS DISEASES (2022)

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Article Medical Laboratory Technology

Cell-Free DNA as Biomarker for Sepsis by Integration of Microbial and Host Information

Qiuyu Jing et al.

Summary: In this study, the researchers explored multiple aspects of cfDNA in septic and nonseptic ICU patients. They found that septic patients had increased cfDNA quantity and altered human cfDNA fragmentation pattern. The researchers also used a machine learning model to integrate all the information and achieved improved performance in diagnosing sepsis and predicting clinical outcomes for ICU patients.

CLINICAL CHEMISTRY (2022)

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Review Medicine, General & Internal

New Perspectives on the Importance of Cell-Free DNA Biology

Abel J. Bronkhorst et al.

Summary: Cell-free DNA (cfDNA) fragments in body fluids represent a vast reservoir of information that can be used for the development of diagnostic and monitoring assays for various diseases. However, the complexity and instability of cfDNA present challenges for research and development.

DIAGNOSTICS (2022)

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Article Economics

Budget Impact of Microbial Cell-Free DNA Testing Using the Karius®Test as an Alternative to Invasive Procedures in Immunocompromised Patients with Suspected Invasive Fungal Infections

Ann T. MacIntyre et al.

Summary: This analysis aimed to assess the budget implications of using the Karius (R) Test in patients suspected of invasive fungal infection in an average state in the USA from a healthcare payer perspective. The results show that the introduction of the Karius Test is associated with a cost saving of US$2277 per patient; when multiplied by the estimated number of cases per year, the cost saving is US$17,039,666.

APPLIED HEALTH ECONOMICS AND HEALTH POLICY (2021)

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Review Medicine, General & Internal

Donor-Derived Cell-Free DNA in Kidney Transplantation as a Potential Rejection Biomarker: A Systematic Literature Review

Adrian Martuszewski et al.

Summary: This paper summarises the promising results related to cfDNA in transplant patients, highlighting the potential of donor-derived cell-free DNA in early diagnosis of transplant injury to prevent premature graft loss.

JOURNAL OF CLINICAL MEDICINE (2021)

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Article Oncology

Alterations of circulating bacterial DNA in colorectal cancer and adenoma: A proof-of-concept study

Qian Xiao et al.

Summary: This study demonstrated alterations of circulating bacterial DNA in colorectal neoplasia patients, indicating its potential as non-invasive biomarkers for colorectal neoplasia screening and early diagnosis, which could play a significant role in disease diagnosis and treatment.

CANCER LETTERS (2021)

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Article Respiratory System

Circulating microbial cell-free DNA is associated with inflammatory host-responses in severe pneumonia

Haopu Yang et al.

Summary: The study found that culture-positive patients with severe pneumonia had higher levels of mcfDNA, which were independently associated with plasma levels of inflammatory biomarkers. These results suggest that host-microbe interactions play a key role in patients with severe pneumonia and warrant further investigation.

THORAX (2021)

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Review Genetics & Heredity

The Nexus of cfDNA and Nuclease Biology

Diana S. C. Han et al.

Summary: Cell-free DNA (cfDNA) serves as a widely used noninvasive biomarker in the diagnosis and prognosis of diseases. The balance between cfDNA generation and clearance is crucial in maintaining health and managing diseases, with plasma nuclease activity linked to various pathologies and changes in cfDNA fragmentation. Further research on factors influencing cfDNA levels and fragmentomic profiles provides insights into the biology of cfDNA.

TRENDS IN GENETICS (2021)

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Review Oncology

The gut microbiome: what the oncologist ought to know

K. A. Lee et al.

Summary: The gut microbiome (GM) plays a crucial role in human pathologies and has become a focus in oncology research, with emerging evidence supporting its effects on cancer development and responses to therapies. Understanding of the complex interrelationships between GM, cancer, the immune system, nutrition, and medication is based on clinical trials, observational studies, and evolving understanding of cancer biology.

BRITISH JOURNAL OF CANCER (2021)

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Article Orthopedics

Sequencing of Circulating Microbial Cell-Free DNA Can Identify Pathogens in Periprosthetic Joint Infections

Adriana P. Echeverria et al.

Summary: This study demonstrates that microbial cfDNA from pathogens causing periprosthetic joint infections can be detected in peripheral blood and accurately identified through sequencing, providing a promising adjunct to tissue cultures for improved pathogen detection and quicker speciation. Additionally, cfDNA sequencing may offer a novel method for monitoring infection clearance during treatment.

JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME (2021)

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Review Oncology

Gut microbiota-mediated immunomodulation in tumor

Xinyi Liu et al.

Summary: The gut microbiota is closely associated with cancer and modulating the microbiome can improve therapeutic responses, although the exact mechanisms remain unclear. Further research is needed before introducing gut microbiota into clinical practice.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2021)

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Article Obstetrics & Gynecology

Cell-free fetal DNA testing and its correlation with prenatal indications

Jing-wei Wang et al.

Summary: The study evaluated the performance of NIPT in different clinical indications, demonstrating extremely high sensitivity and specificity for T21 and providing evidence for other abnormal chromosomal karyotypes.

BMC PREGNANCY AND CHILDBIRTH (2021)

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Article Multidisciplinary Sciences

Bacterial DNAemia is associated with serum zonulin levels in older subjects

Giorgio Gargari et al.

Summary: The presence of bacterial DNA in the blood of older subjects is significantly correlated with markers of intestinal permeability, with most of the bacterial DNA belonging to the genus Pseudomonas. These findings suggest that the permeability of cell layers may play a crucial role in bacterial migration into the bloodstream.

SCIENTIFIC REPORTS (2021)

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Article Biotechnology & Applied Microbiology

Detection of cell-free microbial DNA using a contaminant-controlled analysis framework

Enrique Zozaya-Valdes et al.

Summary: The human microbiome plays a crucial role in cancer, with commensal microbial DNA potentially serving as a new cancer biomarker. This study identified cell-free microbial DNA in the plasma of metastatic melanoma patients, highlighting the importance of controlling for contamination and providing a framework for accurate detection of cfmDNA for future biomarker studies.

GENOME BIOLOGY (2021)

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Letter Respiratory System

Plasma microbial cell-free DNA load is associated with mortality in patients with COVID-19

Georgios D. Kitsios et al.

RESPIRATORY RESEARCH (2021)

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Review Endocrinology & Metabolism

Blood Microbiota and Circulating Microbial Metabolites in Diabetes and Cardiovascular Disease

Ganesan Velmurugan et al.

TRENDS IN ENDOCRINOLOGY AND METABOLISM (2020)

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Article Oncology

Evaluation of Plasma Microbial Cell-Free DNA Sequencing to Predict Bloodstream Infection in Pediatric Patients With Relapsed or Refractory Cancer

Kathryn P. Goggin et al.

JAMA ONCOLOGY (2020)

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Article Microbiology

Assessment of the Clinical Utility of Plasma Metagenomic Next-Generation Sequencing in a Pediatric Hospital Population

Rose A. Lee et al.

JOURNAL OF CLINICAL MICROBIOLOGY (2020)

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Article Multidisciplinary Sciences

Detection of microbial cell-free DNA in maternal and umbilical cord plasma in patients with chorioamnionitis using next generation sequencing

Russell G. Witt et al.

PLOS ONE (2020)

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Article Multidisciplinary Sciences

Cell free DNA from respiratory pathogens is detectable in the blood plasma of Cystic Fibrosis patients

Sara L. Rassoulian Barrett et al.

SCIENTIFIC REPORTS (2020)

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Article Multidisciplinary Sciences

Microbiome analyses of blood and tissues suggest cancer diagnostic approach

Gregory D. Poore et al.

NATURE (2020)

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Review Microbiology

Achromobacter Infections and Treatment Options

Burcu Isler et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2020)

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Review Biochemistry & Molecular Biology

Putative Origins of Cell-Free DNA in Humans: A Review of Active and Passive Nucleic Acid Release Mechanisms

Stefan Grabuschnig et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Surgery

Alterations in blood microbiota after colonic cancer surgery

J. H. Soby et al.

BJS OPEN (2020)

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Article Critical Care Medicine

Enhanced Performance of Next-Generation Sequencing Diagnostics Compared With Standard of Care Microbiological Diagnostics in Patients Suffering From Septic Shock

Silke Grumaz et al.

CRITICAL CARE MEDICINE (2019)

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Article Medical Laboratory Technology

Association between blood microbiome and type 2 diabetes mellitus: A nested case-control study

Jing Qiu et al.

JOURNAL OF CLINICAL LABORATORY ANALYSIS (2019)

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Article Multidisciplinary Sciences

Circulating Microbiota-Based Metagenomic Signature for Detection of Hepatocellular Carcinoma

Eun Ju Cho et al.

SCIENTIFIC REPORTS (2019)

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Article Oncology

Detection of Microbial 16S rRNA Gene in the Serum of Patients With Gastric Cancer

Zhaogang Dong et al.

FRONTIERS IN ONCOLOGY (2019)

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Article Multidisciplinary Sciences

Application of cell-free DNA sequencing in characterization of bloodborne microbes and the study of microbe-disease interactions

Kuo-Ping Chiu et al.

PEERJ (2019)

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Article Microbiology

Multi-Method Characterization of the Human Circulating Microbiome

Emma Whittle et al.

FRONTIERS IN MICROBIOLOGY (2019)

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Article Genetics & Heredity

Analysis of microbial sequences in plasma cell-free DNA for early-onset breast cancer patients and healthy females

Yu-Feng Huang et al.

BMC MEDICAL GENOMICS (2018)

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Article Infectious Diseases

Liquid biopsy for infectious diseases: sequencing of cell-free plasma to detect pathogen DNA in patients with invasive fungal disease

David K. Hong et al.

DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE (2018)

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Article Multidisciplinary Sciences

Numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free DNA

Mark Kowarsky et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017)

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Article Hematology

Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing

Sandrine Paisse et al.

TRANSFUSION (2016)

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Article Microbiology

Bloodstream Infections

Raquel M. Martinez et al.

MICROBIOLOGY SPECTRUM (2016)

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Review Cell Biology

Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut

Andrea Michielan et al.

MEDIATORS OF INFLAMMATION (2015)

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Review Microbiology

The dormant blood microbiome in chronic, inflammatory diseases

Marnie Potgieter et al.

FEMS MICROBIOLOGY REVIEWS (2015)

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Article Biology

Reagent and laboratory contamination can critically impact sequence-based microbiome analyses

Susannah J. Salter et al.

BMC BIOLOGY (2014)

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Review Gastroenterology & Hepatology

Pathological bacterial translocation in liver cirrhosis

Reiner Wiest et al.

JOURNAL OF HEPATOLOGY (2014)

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Article Multidisciplinary Sciences

Elevated Levels of Circulating DNA in Cardiovascular Disease Patients: Metagenomic Profiling of Microbiome in the Circulation

Vasudevan Dinakaran et al.

PLOS ONE (2014)

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Article Physiology

Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system

Daniel Rittirsch et al.

AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY (2013)

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Article Infectious Diseases

Molecular investigation of bacterial communities on the inner and outer surfaces of peripheral venous catheters

L. Zhang et al.

EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES (2013)

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Review Dentistry, Oral Surgery & Medicine

Periodontal health status and bacteraemia from daily oral activities: systematic review/meta-analysis

Inmaculada Tomas et al.

JOURNAL OF CLINICAL PERIODONTOLOGY (2012)

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Review Medical Laboratory Technology

The microbiome of the lung

James M. Beck et al.

TRANSLATIONAL RESEARCH (2012)

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Article Microbiology

Aspergillus lentulus sp nov., a new sibling species of A-fumigatus

SA Balajee et al.

EUKARYOTIC CELL (2005)

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Circulating Microbial Cell-Free DNA in Health and Disease

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