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Microbiome Dec 2022The gut microbiome promotes specific immune responses, and in turn, the immune system has a hand in shaping the microbiome. Cancer and autoimmune diseases are two major... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The gut microbiome promotes specific immune responses, and in turn, the immune system has a hand in shaping the microbiome. Cancer and autoimmune diseases are two major disease families that result from the contrasting manifestations of immune dysfunction. We hypothesized that the opposing immunological profiles between cancer and autoimmunity yield analogously inverted gut microbiome signatures. To test this, we conducted a systematic review and meta-analysis on gut microbiome signatures and their directionality in cancers and autoimmune conditions.
METHODOLOGY
We searched PubMed, Web of Science, and Embase to identify relevant articles to be included in this study. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements and PRISMA 2009 checklist. Study estimates were pooled by a generic inverse variance random-effects meta-analysis model. The relative abundance of microbiome features was converted to log fold change, and the standard error was calculated from the p-values, sample size, and fold change.
RESULTS
We screened 3874 potentially relevant publications. A total of 82 eligible studies comprising 37 autoimmune and 45 cancer studies with 4208 healthy human controls and 5957 disease cases from 27 countries were included in this study. We identified a set of microbiome features that show consistent, opposite directionality between cancers and autoimmune diseases in multiple studies. Fusobacterium and Peptostreptococcus were the most consistently increased genera among the cancer cases which were found to be associated in a remarkable 13 (+0.5 log fold change in 5 studies) and 11 studies (+3.6 log fold change in 5 studies), respectively. Conversely, Bacteroides was the most prominent genus, which was found to be increased in 12 autoimmune studies (+0.2 log fold change in 6 studies) and decreased in six cancer studies (-0.3 log fold change in 4 studies). Sulfur-metabolism pathways were found to be the most frequent pathways among the member of cancer-increased genus and species.
CONCLUSIONS
The surprising reproducibility of these associations across studies and geographies suggests a shared underlying mechanism shaping the microbiome across cancers and autoimmune diseases. Video Abstract.
Topics: Humans; Reproducibility of Results; Autoimmune Diseases; Neoplasms
PubMed: 36482486
DOI: 10.1186/s40168-022-01373-1 -
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 -
The American Journal of Gastroenterology Apr 2013The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The clinical and economic burden of Clostridium difficile infection (CDI) is significant. Recurrent CDI management has emerged as a major challenge with suboptimal response to standard therapy. Fecal microbiota transplantation (FMT) has been used as a treatment to reconstitute the normal microbial homeostasis and break the cycle of antibiotic agents that may further disrupt the microbiome. Given the lack of randomized-controlled trials (RCTs) and limitations in previous systematic reviews, we aimed to conduct a systematic review with robust methods to determine the efficacy and safety profile of FMT in CDI.
METHODS
An electronic search was conducted using MEDLINE (1946-March 2012), EMBASE (1974-March 2012) and Cochrane Central Register of Controlled Trials (2012). The search strategy was not limited by language. Abstract data were excluded and only completed studies that underwent the full, rigorous peer-review process were included. Studies that used FMT via any delivery modality for laboratory or endoscopically proven CDI with clinical resolution as primary outcome were included. A sample size of 10 or more patients was a further criterion. Elements of the Centre for Reviews and Dissemination checklist and the National Institute of Clinical Excellence quality assessment for case series checklist were employed to determine study quality. Eligibility assessment and data extraction were performed by two independent researchers. Both unweighted pooled resolution rates (UPR) and weighted pooled resolution rates (WPR) were calculated with corresponding 95% confidence intervals (CI) for overall studies, as well as predefined subgroups.
RESULTS
Eleven studies with a total of 273 CDI patients treated with FMT were identified; no RCTs were found as none have been published. Two-hundred and forty-five out of 273 patients experienced clinical resolution (UPR 89.7%; WPR 89.1% (95% CI 84 to 93%)). There was no statistically significant heterogeneity between studies (Cochran Q test P=0.13, I(2)=33.7%). A priori subgroup analysis suggested that lower gastrointestinal FMT delivery (UPR 91.4%; WPR 91.2% (95% CI 86 to 95%)) led to a trend towards higher clinical resolution rates than the upper gastrointestinal route (UPR 82.3%; WPR 80.6% (95% CI 69-90%)) (proportion difference of WPR was 10.6% (95% CI -0.6 to 22%)). No difference in clinical outcomes was detected between anonymous vs. patient selected donors. There were no reported adverse events associated with FMT and follow-up was variable from weeks to years.
CONCLUSIONS
FMT holds considerable promise as a therapy for recurrent CDI but well-designed, RCTs and long-term follow-up registries are still required. These are needed to identify the right patient, efficacy and safety profile of FMT before this approach can be widely advocated.
Topics: Biological Therapy; Clostridioides difficile; Enterocolitis, Pseudomembranous; Feces; Humans; Metagenome; Treatment Outcome
PubMed: 23511459
DOI: 10.1038/ajg.2013.59 -
Frontiers in Cellular and Infection... 2023Clinical values of metagenomic next-generation sequencing (mNGS) in patients with severe pneumonia remain controversial. Therefore, we conduct this meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clinical values of metagenomic next-generation sequencing (mNGS) in patients with severe pneumonia remain controversial. Therefore, we conduct this meta-analysis to evaluate the diagnostic performance of mNGS for pathogen detection and its role in the prognosis of severe pneumonia.
METHODS
We systematically searched the literature published in PubMed, Embase, Cochrane Library, Web of Science, Clinical Trials.gov, CNKI, Wanfang Data, and CBM from the inception to the 28th September 2022. Relevant trials comparing mNGS with conventional methods applied to patients with severe pneumonia were included. The primary outcomes of this study were the pathogen-positive rate, the 28-day mortality, and the 90-day mortality; secondary outcomes included the duration of mechanical ventilation, the length of hospital stay, and the length of stay in the ICU.
RESULTS
Totally, 24 publications with 3220 patients met the inclusion criteria and were enrolled in this study. Compared with conventional methods (45.78%, 705/1540), mNGS (80.48%, 1233/1532) significantly increased the positive rate of pathogen detection [ = 6.81, 95% (4.59, 10.11, < 0.001]. The pooled 28-day and 90-day mortality in mNGS group were 15.08% (38/252) and 22.36% (36/161), respectively, which were significantly lower than those in conventional methods group 33.05% (117/354) [ = 0.35, 95% (0.23, 0.55), < 0.001, = 0%] and 43.43%(109/251) [ = 0.34, 95% (0.21, 0.54), < 0.001]. Meanwhile, adjusted treatment based on the results of mNGS shortened the length of hospital stay [MD = -2.76, 95% (- 3.56, - 1.96), P < 0.001] and the length of stay in ICU [ = -4.11, 95% (- 5.35, - 2.87), < 0.001].
CONCLUSION
The pathogen detection positive rate of mNGS was much higher than that of conventional methods. Adjusted treatment based on mNGS results can reduce the 28-day and 90-day mortality of patients with severe pneumonia, and shorten the length of hospital and ICU stay. Therefore, mNGS advised to be applied to severe pneumonia patients as early as possible in addition to conventional methods to improve the prognosis and reduce the length of hospital stay.
Topics: Humans; High-Throughput Nucleotide Sequencing; Hospitals; Metagenome; Metagenomics; Pneumonia; Sensitivity and Specificity
PubMed: 37091676
DOI: 10.3389/fcimb.2023.1106859 -
Journal of Oral & Maxillofacial Research 2016To describe the microbial profiles of peri-implant diseases and the main detection methods. (Review)
Review
OBJECTIVES
To describe the microbial profiles of peri-implant diseases and the main detection methods.
MATERIAL AND METHODS
A literature search was performed in MEDLINE via PubMed database to identify studies on microbial composition of peri-implant surfaces in humans published in the last 5 years. Studies had to have clear implant status definition for health, peri-implant mucositis and/or peri-implantitis and specifically study microbial composition of the peri-implant sulcus.
RESULTS
A total of 194 studies were screened and 47 included. Peri-implant sites are reported to be different microbial ecosystems compared to periodontal sites. However, differences between periodontal and peri-implant health and disease are not consistent across all studies, possibly due to the bias introduced by the microbial detection technique. New methods non species-oriented are being used to find 'unexpected' microbiota not previously described in these scenarios.
CONCLUSIONS
Microbial profile of peri-implant diseases usually includes classic periodontopathogens. However, correlation between studies is difficult, particularly because of the use of different detection methods. New metagenomic techniques should be promoted for future studies to avoid detection bias.
PubMed: 27833735
DOI: 10.5037/jomr.2016.7310 -
Frontiers in Physiology 2021Our understanding of human gut microbiota has expanded in recent years with the introduction of high-throughput sequencing methods. These technologies allow for the...
Our understanding of human gut microbiota has expanded in recent years with the introduction of high-throughput sequencing methods. These technologies allow for the study of metagenomic, metatranscriptomic, and metabolomic bacterial alterations as they relate to human disease. Work in this area has described the human gut microbiome in both healthy individuals and those with chronic gastrointestinal diseases, such as eosinophilic esophagitis (EoE). A systematic review of the current available literature on metagenomic, metatranscriptomic, and metabolomic changes in EoE was performed. This review was performed following the PRISMA guidelines for reporting systematic reviews and meta-analyses. All relevant publications up to March 2021 were retrieved using the search engines PubMed, Google Scholar, and Web of Science. They were then extracted, assessed, and reviewed. Only original studies published in English were included. A total of 46 potential manuscripts were identified for review. Twelve met criteria for further review based on relevance screening and 9 met criteria for inclusion, including 6 studies describing the microbiome in EoE and 3 detailing metabolomic/tissue biochemistry alterations in EoE. No published studies examined metatranscriptomic changes. Samples for microbiome analysis were obtained via esophageal biopsy ( = 3), esophageal string test ( = 1), salivary sampling ( = 1), or stool specimen ( = 1). Samples analyzing tissue biochemistry were obtained via esophageal biopsy ( = 2) and blood plasma ( = 1). There were notable differences in how samples were collected and analyzed. Metabolomic and tissue biochemical alterations were described using Raman spectroscopy, which demonstrated distinct differences in the spectral intensities of glycogen, lipid, and protein content compared to controls. Finally, research in proteomics identified an increase in the pro-fibrotic protein thrombospondin-1 in patients with EoE compared with controls. While there are notable changes in the microbiome, these differ with the collection technique and method of analysis utilized. Techniques characterizing metabolomics and tissue biochemistry are now being utilized to further study patients with EoE. The lack of published data related to the human microbiome, metagenome, metatranscriptome, and metabolome in patients with EoE highlights the need for further research in these areas.
PubMed: 34566693
DOI: 10.3389/fphys.2021.731034 -
Cancers May 2023Oesophagogastric cancer is the fifth most common cancer worldwide, with poor survival outcomes. The role of bacteria in the pathogenesis of oesophagogastric cancer... (Review)
Review
OBJECTIVE
Oesophagogastric cancer is the fifth most common cancer worldwide, with poor survival outcomes. The role of bacteria in the pathogenesis of oesophagogastric cancer remains poorly understood.
DESIGN
A systematic search identified studies assessing the oesophagogastric cancer microbiome. The primary outcome was to identify bacterial enrichment specific to oesophagogastric cancer. Secondary outcomes included appraisal of the methodology, diagnostic performance of cancer bacteria and the relationship between oral and tissue microbiome.
RESULTS
A total of 9295 articles were identified, and 87 studies were selected for analysis. Five genera were enriched in gastric cancer: , , , and . No clear trends were observed in oesophageal adenocarcinoma. , and were abundant in oesophageal squamous cell carcinoma. Functional analysis supports the role of immune cells, localised inflammation and cancer-specific pathways mediating carcinogenesis. STORMS reporting assessment identified experimental deficiencies, considering batch effects and sources of contamination prevalent in low-biomass samples.
CONCLUSIONS
Functional analysis of cancer pathways can infer tumorigenesis within the cancer-microbe-immune axis. There is evidence that study design, experimental protocols and analytical techniques could be improved to achieve more accurate and representative results. Whole-genome sequencing is recommended to identify key metabolic and functional capabilities of candidate bacteria biomarkers.
PubMed: 37345006
DOI: 10.3390/cancers15102668 -
International Urogynecology Journal May 2022The objective was to systemically review the current literature on the association of gut, vaginal, and urinary dysbiosis in female patients with overactive bladder...
INTRODUCTION AND HYPOTHESIS
The objective was to systemically review the current literature on the association of gut, vaginal, and urinary dysbiosis in female patients with overactive bladder (OAB).
METHODS
We performed a comprehensive literature search following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) protocols for systematic reviews. In the EMBASE, CINAHL, and Medline databases, a search was conducted using key words such as "microbiome," "microbiota," "microflora," "overactive bladder," "urge," "gut," "vaginal." Articles were screened using the online tool www.covidence.org . Two independent reviewers screened studies at each stage and resolved conflicts together. We excluded papers that discussed pediatric patients and animal studies. In total, 13 articles met this criterion, which included 6 abstracts.
RESULTS
After identifying 817 unique references, 13 articles met the criteria for data extraction. Articles were published from 2017 to 2021. No study reported the same microbiota abundance, even in healthy individuals. Overall, there was a loss of bacterial diversity in OAB patients compared with controls. Additionally, the bacterial composition of the controls and OAB patients was not significantly different, especially if the urine was collected midstream. Overall, the composition of the microbiome is dependent on the specimen collection methodology, and the metagenomic sequencing technique utilized. OAB urine microbiome is more predisposed to alteration from the gut or vaginal influences than in controls.
CONCLUSIONS
Current evidence suggested a potential relationship among gut, vaginal, and urinary microbiome in OAB patients, but there are very limited studies.
Topics: Bacteria; Child; Female; Humans; Microbiota; Urinary Bladder, Overactive; Urinary Tract; Vagina
PubMed: 35237854
DOI: 10.1007/s00192-022-05127-3 -
BMC Medical Informatics and Decision... Dec 2023Invasive detection methods such as liver biopsy are currently the gold standard for diagnosing liver cirrhosis and can be used to determine the degree of liver fibrosis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Invasive detection methods such as liver biopsy are currently the gold standard for diagnosing liver cirrhosis and can be used to determine the degree of liver fibrosis and cirrhosis. In contrast, non-invasive diagnostic methods, such as ultrasonography, elastography, and clinical prediction scores, can prevent patients from invasiveness-related discomfort and risks and are often chosen as alternative or supplementary diagnostic methods for liver fibrosis or cirrhosis. However, these non-invasive methods cannot specify the pathological grading and early diagnosis of the lesions. Recent studies have revealed that gut microbiome-based machine learning can be utilized as a non-invasive diagnostic technique for liver cirrhosis or fibrosis, but there is no evidence-based support. Therefore, this study conducted a systematic review and meta-analysis for the first time to investigate the accuracy of machine learning based on the gut microbiota in the prediction of liver fibrosis and cirrhosis.
METHODS
A comprehensive and systematic search of publications published before April 2th, 2023 in PubMed, Cochrane Library, Embase, and Web of Science was conducted for relevant studies on the application of gut microbiome-based metagenomic sequencing modeling technology to the diagnostic prediction of liver cirrhosis or fibrosis. A bivariate mixed-effects model and Stata software 15.0 were adopted for the meta-analysis.
RESULTS
Ten studies were included in the present study, involving 11 prediction trials and 838 participants, 403 of whom were fibrotic and cirrhotic patients. Meta-analysis showed the pooled sensitivity (SEN) = 0.81 [0.75, 0.85], specificity (SEP) = 0.85 [0.77, 0.91], positive likelihood ratio (PLR) = 5.5 [3.6, 8.7], negative likelihood ratio (NLR) = 0.23 [0.18, 0.29], diagnostic odds ratio (DOR) = 24 [14, 41], and area under curve (AUC) = 0.86 [0.83-0.89]. The results demonstrated that machine learning methods had excellent potential to analyze gut microbiome data and could effectively predict liver cirrhosis or fibrosis. Machine learning provides a powerful tool for non-invasive prediction and diagnosis of liver cirrhosis or liver fibrosis, with broad clinical application prospects. However, these results need to be interpreted with caution due to limited clinical data.
CONCLUSION
Gut microbiome-based machine learning can be utilized as a practical, non-invasive technique for the diagnostic prediction of liver cirrhosis or fibrosis. However, most of the included studies applied the random forest algorithm in modeling, so a diversified prediction system based on microorganisms is needed to improve the non-invasive detection of liver cirrhosis or fibrosis.
Topics: Humans; Gastrointestinal Microbiome; Liver Cirrhosis; Fibrosis; Machine Learning
PubMed: 38115019
DOI: 10.1186/s12911-023-02402-1 -
Microorganisms Dec 2022The 5- and 10-year implant success rates in dentistry are nearly 90%. Prevalence of peri-implant diseases is 10% for peri-implantitis and 50% for peri-implant mucositis....
The 5- and 10-year implant success rates in dentistry are nearly 90%. Prevalence of peri-implant diseases is 10% for peri-implantitis and 50% for peri-implant mucositis. To better understand these inflammatory pathologies of infectious origin, it is important to know if the composition of the peri-implant microbiota is comparable with the periodontal microbiota in healthy and pathological conditions. New generation sequencing (NGS) is a recent metagenomic method that analyzes the overall microorganisms present in an ecological niche by exploiting their genome. These methods are of two types: 16S rRNA sequencing and the shotgun technique. For several years, they have been used to explore the oral, periodontal, and, more specifically, peri-implant microbiota. The aim of this systematic review is to analyze the recent results of these new explorations by comparing the periodontal and peri-implant microbiota in patients with healthy and diseased sites and to explore the microbiological characteristics of peri-implantitis. A better knowledge of the composition of the peri-implant microbiota would enable us to optimize our therapeutic strategies. An electronic systematic search was performed using the medical databases PubMed/Medline, Cochrane Library, and ScienceDirect, and . The selected articles were published between January 2015 and March 2021. Inclusion criteria included clinical studies comparing healthy and pathological periodontal and peri-implant microbiota exclusively using 16S rRNA sequencing or shotgun sequencing, with enrolled populations free of systemic pathology, and studies without substantial bias. Eight articles were selected and reviewed. All of them used 16S rRNA sequencing exclusively. The assessment of these articles demonstrates the specific character of the peri-implant microbiota in comparison with the periodontal microbiota in healthy and pathological conditions. Indeed, peri-implant diseases are defined by dysbiotic bacterial communities that vary from one individual to another, including known periodontopathogens such as () and genera less mentioned in the periodontal disease pattern such as . Examination of peri-implant microbiota with 16S rRNA sequencing reveals differences between the periodontal and peri-implant microbiota under healthy and pathological conditions in terms of diversity and composition. The pattern of dysbiotic drift is preserved in periodontal and peri-implant diseases, but when comparing the different types of pathological sites, the peri-implant microbiota has a specificity in the presence of bacteria proper to peri-implantitis and different relative proportions of the microorganisms present.
PubMed: 36557719
DOI: 10.3390/microorganisms10122466