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Drugs Sep 2021Clinical metagenomics (CMg) is the process of sequencing nucleic acid of clinical samples to obtain clinically relevant information such as the identification of...
Clinical metagenomics (CMg) is the process of sequencing nucleic acid of clinical samples to obtain clinically relevant information such as the identification of microorganisms and their susceptibility to antimicrobials. Over the last decades, sequencing and bioinformatic solutions supporting CMg have much evolved and an increasing number of case reports and series covering various infectious diseases have been published. Metagenomics is a new approach to infectious disease diagnosis that is currently being developed and is certainly one of the most promising for the coming years. However, most CMg studies are retrospective, and few address the potential impact CMg could have on patient management, including initiation, adaptation, or cessation of antimicrobials. In this narrative review, we have discussed the potential role of CMg in bacteriology, virology, mycology, and parasitology. Several reports and case-series confirm that CMg is an innovative tool with which one can (i) identify more microorganisms than with conventional methods in a single test, (ii) obtain results within hours, and (iii) tailor the antimicrobial regimen of patients. However, the cost-efficiency of CMg and its real impact on patient management are still to be determined.
Topics: Anti-Infective Agents; Communicable Diseases; Computational Biology; Humans; Metagenomics; Nucleic Acid Amplification Techniques
PubMed: 34328626
DOI: 10.1007/s40265-021-01572-4 -
International Journal of Environmental... Jul 2021The past decade has witnessed a surge in epidemiological studies that have explored the relationship between the oral microbiome and oral cancer. Owing to the diversity... (Review)
Review
The past decade has witnessed a surge in epidemiological studies that have explored the relationship between the oral microbiome and oral cancer. Owing to the diversity of the published data, a comprehensive systematic overview of the currently available evidence is critical. This review summarises the current evidence on the metagenomic studies on the oral microbiome in oral cancer. A systematic search was conducted in Medline and Embase databases to identify original studies examining the differences in the oral microbiome of oral cancer cases and controls. A total of twenty-six studies were identified that reported differences in microbial abundance between oral squamous cell carcinoma (OSCC) and controls. Although almost all the studies identified microbial dysbiosis to be associated with oral cancer, the detailed qualitative analysis did not reveal the presence/abundance of any individual bacteria or a consortium to be consistently enriched in OSCC samples across the studies. Interestingly, few studies reported a surge of periodontopathogenic taxa, especially , whereas others demonstrated a depletion of commensal taxa . Considerable heterogeneity could be identified in the parameters used for designing the studies as well as reporting the microbial data. If microbiome data needs to be translated in the future, to complement the clinical parameters for diagnosis and prognosis of oral cancer, further studies with the integration of clinical variables, adequate statistical power, reproducible methods, and models are required.
Topics: Carcinoma, Squamous Cell; Head and Neck Neoplasms; Humans; Metagenomics; Microbiota; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 34299675
DOI: 10.3390/ijerph18147224 -
Animal Microbiome Jun 2021Undesirable microbial infiltration into the female bovine reproductive tracts, for example during calving or mating, is likely to disturb the commensal microflora.... (Review)
Review
Undesirable microbial infiltration into the female bovine reproductive tracts, for example during calving or mating, is likely to disturb the commensal microflora. Persistent establishment and overgrowth of certain pathogens induce reproductive diseases, render the female bovine reproductive tract unfavourable for pregnancy or can result in transmission to the foetus, leading to death and abortion or birth abnormalities. This review of culture-independent metagenomics studies revealed that normal microflora in the female bovine reproductive tract is reasonably consistently dominated by bacteria from the phyla Bacteroidetes, Firmicutes, Proteobacteria, following by Actinobacteria, Fusobacteria and Tenericutes. Reproductive disease development in the female bovine reproductive tract was demonstrated across multiple studies to be associated with high relative abundances of bacteria from the phyla Bacteroidetes and Fusobacteria. Reduced bacterial diversity in the reproductive tract microbiome in some studies of cows diagnosed with reproductive diseases also indicated an association between dysbiosis and bovine reproductive health. Nonetheless, the bovine genital tract microbiome remains underexplored, and this is especially true for the male genital tract. Future research should focus on the functional aspects of the bovine reproductive tract microbiomes, for example their contributions to cattle fertility and susceptibility towards reproductive diseases.
PubMed: 34108039
DOI: 10.1186/s42523-021-00106-3 -
PeerJ 2021Vaginal microbiome studies frequently report diversity metrics and communities of microbiomes associated with reproductive health outcomes. Reports of (also known as...
BACKGROUND
Vaginal microbiome studies frequently report diversity metrics and communities of microbiomes associated with reproductive health outcomes. Reports of (also known as Group B Streptococcus or GBS), the leading cause of neonatal infectious morbidity and mortality, are notably lacking from the studies of the vaginal microbiome, despite being a known contributor to preterm birth and other complications. Therefore, the purpose of this systematic review was to explore the frequency of GBS reporting in vaginal microbiome literature pertaining to pregnancy and to examine methodological bias that contributes to differences in species and genus-level microbiome reporting. Lack of identification of GBS via sequencing-based approaches due to methodologic or reporting bias may result incomplete understanding of bacterial composition during pregnancy and subsequent birth outcomes.
METHODOLOGY
A systematic review was conducted following the PRISMA guideline. Three databases (PubMed, CINAHL, and Web of Science) were used to identify papers for review based on the search terms "vaginal microbiome", "pregnancy", and "16S rRNA sequencing". Articles were evaluated for methods of DNA extraction and sequencing, 16S region, taxonomy classification database, number of participants or vaginal specimens, and pregnancy trimester.
RESULTS
Forty-five research articles reported employing a metagenomic approach or 16S approach for vaginal microbiome analysis during pregnancy that explicitly reported taxonomic composition and were included in this review. Less than 30% of articles reported the presence of GBS ( = 13). No significant differences in methodology were identified between articles that reported versus did not report GBS. However, there was large variability across research methods used for vaginal microbiome analysis and species-level bacterial community reporting.
CONCLUSION
Considerable differences in study design and data formatting methods may contribute to underrepresentation of GBS, and other known pathogens, in existing vaginal microbiome literature. Previous studies have identified considerable variation in methodology across vaginal microbiome studies. This study adds to this body of work because in addition to laboratory or statistical methods, how results and data are shared (e.g., only analyzing genus level data or 20 most abundant microbes), may hinder reproducibility and limit our understanding of the influence of less abundant microbes. Sharing detailed methods, analysis code, and raw data may improve reproducibility and ability to more accurately compare microbial communities across studies.
PubMed: 34046261
DOI: 10.7717/peerj.11437 -
Journal of Clinical Microbiology Aug 2021Metagenomic sequencing is frequently claimed to have the potential to revolutionize microbiology through rapid species identification and antimicrobial resistance (AMR)... (Meta-Analysis)
Meta-Analysis
Metagenomic sequencing is frequently claimed to have the potential to revolutionize microbiology through rapid species identification and antimicrobial resistance (AMR) prediction. We assess the progress toward these developments. We perform a systematic review and meta-analysis of all published literature on culture-independent metagenomic sequencing for pathogen-agnostic infectious disease diagnostics up to 12 August 2020. Methodologic bias and applicability were assessed using the tool Quadas-2. (Prospero CRD42020163777). A total of 2,023 clinical samples from 13/21 eligible diagnostic test accuracy studies were included in the meta-analysis. Reference standards were culture, molecular testing, clinical decision, or a composite measure. Sensitivity and specificity in the most widely investigated sample types were 90% (95% confidence interval [CI], 78% to 96%) and 86% (45% to 98%) for blood, 75% (54% to 89%) and 96% (72% to 100%) for cerebrospinal fluid (CSF), and 84% (79% to 88%) and 67% (38% to 87%) for orthopedic samples, respectively. We identified a limited use of controls, especially negative controls which were used in only 62% (13/21) of studies. AMR prediction and comparison to phenotypic results were undertaken in four studies; categorical agreement was 88%(80% to 97%), and very major and major error rates were 24% (8% to 40%) and 5% (0% to 12%), respectively. Better human DNA depletion methods are required; a median 91% (interquartile range [IQR], 82% to 98%; range, 76% to 98%) of sequences was classified as human. The median (IQR; range) time from sample to result was 29 hours (24 to 94; 4 to 144 hours). The reported consumable cost per sample ranged from $130 to $685. There is scope for improving the quality of reporting in clinical metagenomic studies. Although our results are limited by the heterogeneity displayed, our results reflect a promising outlook for clinical metagenomics. Methodological improvements and convergence around protocols and best practices may improve performance in the future.
Topics: Communicable Diseases; Diagnostic Tests, Routine; Humans; Metagenome; Metagenomics; Sensitivity and Specificity
PubMed: 33910965
DOI: 10.1128/JCM.02916-20 -
Frontiers in Bioengineering and... 2021Global environmental contamination with a complex mixture of xenobiotics has become a major environmental issue worldwide. Many xenobiotic compounds severely impact the...
Global environmental contamination with a complex mixture of xenobiotics has become a major environmental issue worldwide. Many xenobiotic compounds severely impact the environment due to their high toxicity, prolonged persistence, and limited biodegradability. Microbial-assisted degradation of xenobiotic compounds is considered to be the most effective and beneficial approach. Microorganisms have remarkable catabolic potential, with genes, enzymes, and degradation pathways implicated in the process of biodegradation. A number of microbes, including , and , have been isolated and characterized, and have shown exceptional biodegradation potential for a variety of xenobiotic contaminants from soil/water environments. Microorganisms potentially utilize xenobiotic contaminants as carbon or nitrogen sources to sustain their growth and metabolic activities. Diverse microbial populations survive in harsh contaminated environments, exhibiting a significant biodegradation potential to degrade and transform pollutants. However, the study of such microbial populations requires a more advanced and multifaceted approach. Currently, multiple advanced approaches, including metagenomics, proteomics, transcriptomics, and metabolomics, are successfully employed for the characterization of pollutant-degrading microorganisms, their metabolic machinery, novel proteins, and catabolic genes involved in the degradation process. These technologies are highly sophisticated, and efficient for obtaining information about the genetic diversity and community structures of microorganisms. Advanced molecular technologies used for the characterization of complex microbial communities give an in-depth understanding of their structural and functional aspects, and help to resolve issues related to the biodegradation potential of microorganisms. This review article discusses the biodegradation potential of microorganisms and provides insights into recent advances and omics approaches employed for the specific characterization of xenobiotic-degrading microorganisms from contaminated environments.
PubMed: 33644024
DOI: 10.3389/fbioe.2021.632059 -
MSystems Feb 2021Reproducibility is a major issue in microbiome studies, which is partly caused by missing consensus about data analysis strategies. The complex nature of microbiome...
Reproducibility is a major issue in microbiome studies, which is partly caused by missing consensus about data analysis strategies. The complex nature of microbiome data, which are high-dimensional, zero-inflated, and compositional, makes them challenging to analyze, as they often violate assumptions of classic statistical methods. With advances in human microbiome research, research questions and study designs increase in complexity so that more sophisticated data analysis concepts are applied. To improve current practice of the analysis of microbiome studies, it is important to understand what kind of research questions are asked and which tools are used to answer these questions. We conducted a systematic literature review considering all publications focusing on the analysis of human microbiome data from June 2018 to June 2019. Of 1,444 studies screened, 419 fulfilled the inclusion criteria. Information about research questions, study designs, and analysis strategies were extracted. The results confirmed the expected shift to more advanced research questions, as one-third of the studies analyzed clustered data. Although heterogeneity in the methods used was found at any stage of the analysis process, it was largest for differential abundance testing. Especially if the underlying data structure was clustered, we identified a lack of use of methods that appropriately addressed the underlying data structure while taking into account additional dependencies in the data. Our results confirm considerable heterogeneity in analysis strategies among microbiome studies; increasingly complex research questions require better guidance for analysis strategies. The human microbiome has emerged as an important factor in the development of health and disease. Growing interest in this topic has led to an increasing number of studies investigating the human microbiome using high-throughput sequencing methods. However, the development of suitable analytical methods for analyzing microbiome data has not kept pace with the rapid progression in the field. It is crucial to understand current practice to identify the scope for development. Our results highlight the need for an extensive evaluation of the strengths and shortcomings of existing methods in order to guide the choice of proper analysis strategies. We have identified where new methods could be designed to address more advanced research questions while taking into account the complex structure of the data.
PubMed: 33622856
DOI: 10.1128/mSystems.01154-20 -
Reviews in Medical Virology Sep 2021Viruses are postulated as primary candidate triggers of islet autoimmunity (IA) and type 1 diabetes (T1D), based on considerable epidemiological and experimental... (Meta-Analysis)
Meta-Analysis Review
Viruses are postulated as primary candidate triggers of islet autoimmunity (IA) and type 1 diabetes (T1D), based on considerable epidemiological and experimental evidence. Recent studies have investigated the association between all viruses (the 'virome') and IA/T1D using metagenomic next-generation sequencing (mNGS). Current associations between the early life virome and the development of IA/T1D were analysed in a systematic review and meta-analysis of human observational studies from Medline and EMBASE (published 2000-June 2020), without language restriction. Inclusion criteria were as follows: cohort and case-control studies examining the virome using mNGS in clinical specimens of children ≤18 years who developed IA/T1D. The National Health and Medical Research Council level of evidence scale and Newcastle-Ottawa scale were used for study appraisal. Meta-analysis for exposure to specific viruses was performed using random-effects models, and the strength of association was measured using odds ratios (ORs) and 95% confidence intervals (CIs). Eligible studies (one case-control, nine nested case-control) included 1,425 participants (695 cases, 730 controls) and examined IA (n = 1,023) or T1D (n = 402). Meta-analysis identified small but significant associations between IA and number of stool samples positive for all enteroviruses (OR 1.14, 95% CI 1.00-1.29, p = 0.05; heterogeneity χ = 1.51, p = 0.68, I = 0%), consecutive positivity for enteroviruses (1.55, 1.09-2.20, p = 0.01; χ = 0.19, p = 0.91, I = 0%) and number of stool samples positive specifically for enterovirus B (1.20, 1.01-1.42, p = 0.04; χ = 0.03, p = 0.86, I = 0%). Virome analyses to date have demonstrated associations between enteroviruses and IA that may be clinically significant. However, larger prospective mNGS studies with more frequent sampling and follow-up from pregnancy are required to further elucidate associations between early virus exposure and IA/T1D.
Topics: Autoimmunity; Child; Diabetes Mellitus, Type 1; High-Throughput Nucleotide Sequencing; Humans; Infant; Prospective Studies; Virome
PubMed: 33378601
DOI: 10.1002/rmv.2209 -
Pancreatology : Official Journal of the... Jan 2021Altered intestinal microbiota has been reported in pancreatic disorders, however, it remains unclear whether these changes alter the course of disease in patients with...
BACKGROUND
Altered intestinal microbiota has been reported in pancreatic disorders, however, it remains unclear whether these changes alter the course of disease in patients with acute (AP) and chronic pancreatitis (CP), or whether these disease states alter the environment to enable pathogenic microbial composition changes to occur. We undertook a systematic review to characterize the gut microbiome in pancreatitis patients.
METHODS
MEDLINE and EMBASE were searched for studies on microbiota in pancreatitis published from January 1, 2000 to June 5, 2020. Animal studies, reviews, case reports, and non-English articles were excluded. A frequency analysis was performed for outcomes reported in ≥2 studies and studies were analyzed for risk of bias and quality of evidence.
RESULTS
22 papers met inclusion criteria; 15 included AP, 7 included CP. No studies were appropriately designed to assess whether alterations in the gut microbiome exacerbate pancreatitis or develop as a result of pancreatitis. We did identify several patterns of microbiome changes that are associated with pancreatitis. The gut microbiome demonstrated decreased alpha diversity in 3/3 A P studies and 3/3 C P studies. Beta diversity analysis revealed differences in bacterial community composition in the gut microbiome in 2/2 A P studies and 3/3 C P studies. Functionally, gut microbiome changes were associated with infectious pathways in AP and CP. Several studies suffered from high risk of bias and inadequate quality.
CONCLUSIONS
Detecting differences in microbial composition associated with AP and CP may represent a diagnostic tool. Appropriately controlled longitudinal studies are needed to determine whether microbiome changes are causative or reactive in pancreatitis.
Topics: Gastrointestinal Microbiome; Humans; Pancreatitis; Pancreatitis, Chronic
PubMed: 33376062
DOI: 10.1016/j.pan.2020.12.013 -
PloS One 2020Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis and its early diagnosis is very difficult leading to present with severe disability or die.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis and its early diagnosis is very difficult leading to present with severe disability or die. The current study aimed to assess the accuracy of metagenomic next generation sequencing (mNGS) for TBM, and to identify a new test for the early diagnosis of TBM.
METHODS
We searched for articles published in Embase, PubMed, Cochrane Library, China National Knowledge Infrastructure, and Wanfang Data up to June 30, 2020 for studies that assessed the efficacy of mNGS for the diagnosis of TBM. Then, the accuracy between mNGS and a composite reference standard (CRS) in these articles was compared using the meta-analysis approach.
RESULTS
Four independent studies with 342 samples comparing mNGS and a CRS were included in this study. The sensitivity of mNGS for TBM diagnosis ranged from 27% to 84%. The combined sensitivity of mNGS was 61%, and the I2 value was 92%. Moreover, the specificity of mNGS for TBM diagnosis ranged from 96% to 100%. The combined specificity of mNGS was 98%, and the I2 value was 74%. The heterogeneity between studies in terms of sensitivity and specificity was significant. The area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) of mNGS for TBM was 0.98.
CONCLUSIONS
The sensitivity of mNGS for TBM diagnosis was moderate. Furthermore, the specificity was extremely high, and the AUC of the SROC indicated a very good diagnostic efficacy. mNGS could be used as an early diagnostic method for TBM, however, the results should be treated with caution for the heterogeneity between studies was extremely significant.
SYSTEMATIC REVIEW REGISTRATION
INPLASY202070100.
Topics: China; Early Diagnosis; High-Throughput Nucleotide Sequencing; Humans; Metagenome; Metagenomics; Mycobacterium tuberculosis; ROC Curve; Reference Standards; Sensitivity and Specificity; Tuberculosis, Meningeal
PubMed: 33259541
DOI: 10.1371/journal.pone.0243161