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Clinical Microbiology and Infection :... Sep 2021Bacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bacteria colonizing the upper respiratory tract (URT) of young children play a key role in the pathogenesis of lower respiratory tract infection (LRTI).
OBJECTIVES
To systematically review the literature on the association between bacteria colonizing the URT and LRTI among young children.
DATA SOURCES
MEDLINE, Academic Search Premier, Africa-Wide Information and CINAHL, Scopus and Web of Science.
STUDY ELIGIBILITY CRITERIA
Studies published between 1923 and 2020, investigating URT bacteria from LRTI cases and controls.
PARTICIPANTS
Children under 5 years with and without acute LRTI.
METHODS
Three reviewers independently screened titles, abstracts and full texts. Meta-analysis was done using Mantel-Haenszel fixed- or random-effects models.
RESULTS
Most eligible studies (41/50) tested nasopharyngeal specimens when investigating URT bacteria. Most studies were of cross-sectional design (44/50). Twenty-four studies were performed in children in lower- or lower-middle-income countries (LMICs). There was higher prevalence of Haemophilus influenzae (pooled OR 1.60; 95% CI 1.23-2.07) and Klebsiella spp. (pooled OR 2.04; 95% CI 1.17-3.55) from URT specimens of cases versus controls. We observed a positive association between the detection of Streptococcus pneumoniae from URT specimens and LRTI after excluding studies where there was more antibiotic treatment prior to sampling in cases vs. controls (pooled OR 1.41; 95% CI 1.04-1.90). High density colonization with S. pneumoniae (>6.9 log copies/mL) was associated with an increased risk for LRTI. The associations between both Streptococcus and Haemophilus URT detection and LRTI were supported, at genus level, by 16S rRNA sequencing. Evidence for the role of Moraxella catarrhalis and Staphylococcus aureus was inconclusive.
CONCLUSIONS
Detection of H. influenzae or Klebsiella spp. in the URT was associated with LRTI, while evidence for association with S. pneumoniae was less conclusive. Longitudinal studies assessing URT microbial communities, together with environmental and host factors are needed to better understand pathogenesis of childhood LRTI.
Topics: Bacteria; Child; Child, Preschool; Cross-Sectional Studies; Humans; RNA, Ribosomal, 16S; Respiratory Tract Infections
PubMed: 34111578
DOI: 10.1016/j.cmi.2021.05.034 -
BJOG : An International Journal of... Jan 2020The aetiology and pathogenesis of endometriosis are still under investigation. There is evidence that there is a complex bidirectional interaction between endometriosis...
BACKGROUND
The aetiology and pathogenesis of endometriosis are still under investigation. There is evidence that there is a complex bidirectional interaction between endometriosis and the microbiome.
OBJECTIVE
To systematically review the available literature on the endometriosis-microbiome interaction, with the aim of guiding future inquiries in this emerging area of endometriosis research.
SEARCH STRATEGY
MEDLINE, Embase, Scopus and Web of Science were searched through May 2019. A manual search of reference lists of relevant studies was also performed.
SELECTION CRITERIA
Published and unpublished literature in any language describing a comparison of the microbiome state in mammalian hosts with and without endometriosis.
DATA COLLECTION AND ANALYSIS
Identified studies were screened and assessed independently by two authors. Data were extracted and compiled in a qualitative synthesis of the evidence.
MAIN RESULTS
Endometriosis appears to be associated with an increased presence of Proteobacteria, Enterobacteriaceae, Streptococcus spp. and Escherichia coli across various microbiome sites. The phylum Firmicutes and the genus Gardnerella also appear to have an association; however, this remains unclear.
CONCLUSIONS
The complex bidirectional relationship between the microbiome and endometriosis has begun to be characterised by the studies highlighted in this systematic review. Laboratory and clinical studies demonstrate that there are indeed differences in the microbiome composition of hosts with and without endometriosis.
TWEETABLE ABSTRACT
Review findings show endometriosis associated with increased Proteobacteria, Enterobacteriaceae, Streptococcus and Escherichia coli across various microbiome sites.
Topics: Endometriosis; Female; Gastrointestinal Microbiome; Humans; Menstrual Cycle; Menstruation Disturbances; RNA, Ribosomal, 16S
PubMed: 31454452
DOI: 10.1111/1471-0528.15916 -
The Lancet. Microbe Nov 2022Data from animal models suggest a role of early-life gut microbiota in lung immune development, and in establishing susceptibility to respiratory infections and asthma... (Review)
Review
Data from animal models suggest a role of early-life gut microbiota in lung immune development, and in establishing susceptibility to respiratory infections and asthma in humans. This systematic review summarises the association between infant (ages 0-12 months) gut microbiota composition measured by genomic sequencing, and childhood (ages 0-18 years) respiratory diseases (ie, respiratory infections, wheezing, or asthma). Overall, there was evidence that low α-diversity and relative abundance of particular gut-commensal bacteria genera (Bifidobacterium, Faecalibacterium, Ruminococcus, and Roseburia) are associated with childhood respiratory diseases. However, results were inconsistent and studies had important limitations, including insufficient characterisation of bacterial taxa to species level, heterogeneous outcome definitions, residual confounding, and small sample sizes. Large longitudinal studies with stool sampling during the first month of life and shotgun metagenomic approaches to improve bacterial and fungal taxa resolution are needed. Standardising follow-up times and respiratory disease definitions and optimising causal statistical approaches might identify targets for primary prevention of childhood respiratory diseases.
Topics: Infant; Humans; Infant, Newborn; Child, Preschool; Child; Adolescent; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Feces; Bacteria; Asthma; Respiration Disorders; Respiratory Tract Infections
PubMed: 35988549
DOI: 10.1016/S2666-5247(22)00184-7 -
Microbiome Mar 2017Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Necrotizing enterocolitis (NEC) is a catastrophic disease of preterm infants, and microbial dysbiosis has been implicated in its pathogenesis. Studies evaluating the microbiome in NEC and preterm infants lack power and have reported inconsistent results.
METHODS AND RESULTS
Our objectives were to perform a systematic review and meta-analyses of stool microbiome profiles in preterm infants to discern and describe microbial dysbiosis prior to the onset of NEC and to explore heterogeneity among studies. We searched MEDLINE, PubMed, CINAHL, and conference abstracts from the proceedings of Pediatric Academic Societies and reference lists of relevant identified articles in April 2016. Studies comparing the intestinal microbiome in preterm infants who developed NEC to those of controls, using culture-independent molecular techniques and reported α and β-diversity metrics, and microbial profiles were included. In addition, 16S ribosomal ribonucleic acid (rRNA) sequence data with clinical meta-data were requested from the authors of included studies or searched in public data repositories. We reprocessed the 16S rRNA sequence data through a uniform analysis pipeline, which were then synthesized by meta-analysis. We included 14 studies in this review, and data from eight studies were available for quantitative synthesis (106 NEC cases, 278 controls, 2944 samples). The age of NEC onset was at a mean ± SD of 30.1 ± 2.4 weeks post-conception (n = 61). Fecal microbiome from preterm infants with NEC had increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes prior to NEC onset. Alpha- or beta-diversity indices in preterm infants with NEC were not consistently different from controls, but we found differences in taxonomic profiles related to antibiotic exposure, formula feeding, and mode of delivery. Exploring heterogeneity revealed differences in microbial profiles by study and the target region of the 16S rRNA gene (V1-V3 or V3-V5).
CONCLUSIONS
Microbial dysbiosis preceding NEC in preterm infants is characterized by increased relative abundances of Proteobacteria and decreased relative abundances of Firmicutes and Bacteroidetes. Microbiome optimization may provide a novel strategy for preventing NEC.
Topics: Bacteria; Bacteroides; Dysbiosis; Enterocolitis, Necrotizing; Feces; Firmicutes; Gastrointestinal Microbiome; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intestines; Proteobacteria; RNA, Ribosomal, 16S
PubMed: 28274256
DOI: 10.1186/s40168-017-0248-8 -
BJOG : An International Journal of... Jan 2020Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of...
BACKGROUND
Persistent infection with high-risk human papillomavirus can lead to cervical dysplasia and cancer. Recent studies have suggested associations between the composition of the vaginal microbiota, infection with human papillomavirus (HPV) and progression to cervical dysplasia and cancer.
OBJECTIVE
To assess how specific cervico-vaginal microbiota compositions are associated with HPV infection, cervical dysplasia and cancer, we conducted a systematic review and network meta-analysis (registered in PROSPERO: CRD42018112862).
SEARCH STRATEGY
PubMed, Web of science, Embase and Cochrane database.
SELECTION CRITERIA
All original studies describing at least two community state types of bacteria (CST), based on molecular techniques enabling identification of bacteria, and reporting the association with HPV infection, cervical dysplasia and/or cervical cancer.
DATA COLLECTION AND ANALYSIS
For the meta-analysis, a network map was constructed to provide an overview of the network relationships and to assess how many studies provided direct evidence for the different vaginal microbiota compositions and HPV, cervical dysplasia or cancer. Thereafter, the consistency of the model was assessed, and forest plots were constructed to pool and summarise the available evidence, presenting odds ratios and 95% confidence intervals.
MAIN RESULTS
Vaginal microbiota dominated by non-Lactobacilli species or Lactobacillus iners were associated with three to five times higher odds of any prevalent HPV and two to three times higher for high-risk HPV and dysplasia/cervical cancer compared with Lactobacillus crispatus.
CONCLUSIONS
These findings suggest an association between certain bacterial community types of the vaginal microbiota and HPV infection and HPV-related disease. This may be useful for guiding treatment options or serve as biomarkers for HPV-related disease.
TWEETABLE ABSTRACT
This network meta-analysis suggests an association between different vaginal bacterial community types and the risk of HPV.
Topics: Female; Humans; Lactobacillus; Microbiota; Network Meta-Analysis; Papillomaviridae; Papillomavirus Infections; RNA, Ribosomal, 16S; Uterine Cervical Neoplasms; Vagina; Uterine Cervical Dysplasia
PubMed: 31237400
DOI: 10.1111/1471-0528.15854 -
Theranostics 2021Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and...
Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, . In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, . Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.
Topics: Autophagy; Humans; Macroautophagy; Mitophagy; Organelles
PubMed: 33391472
DOI: 10.7150/thno.49860 -
Frontiers in Plant Science 2020Plants dedicate a high amount of energy and resources to the production of ribosomes. Historically, these multi-protein ribosome complexes have been considered static...
Plants dedicate a high amount of energy and resources to the production of ribosomes. Historically, these multi-protein ribosome complexes have been considered static protein synthesis machines that are not subject to extensive regulation but only read mRNA and produce polypeptides accordingly. New and increasing evidence across various model organisms demonstrated the heterogeneous nature of ribosomes. This heterogeneity can constitute specialized ribosomes that regulate mRNA translation and control protein synthesis. A prominent example of ribosome heterogeneity is seen in the model plant, , which, due to genome duplications, has multiple paralogs of each ribosomal protein (RP) gene. We support the notion of plant evolution directing high RP paralog divergence toward functional heterogeneity, underpinned in part by a vast resource of ribosome mutants that suggest specialization extends beyond the pleiotropic effects of single structural RPs or RP paralogs. Thus, Arabidopsis is a highly suitable model to study this phenomenon. Arabidopsis enables reverse genetics approaches that could provide evidence of ribosome specialization. In this review, we critically assess evidence of plant ribosome specialization and highlight steps along ribosome biogenesis in which heterogeneity may arise, filling the knowledge gaps in plant science by providing advanced insights from the human or yeast fields. We propose a data analysis pipeline that infers the heterogeneity of ribosome complexes and deviations from canonical structural compositions linked to stress events. This analysis pipeline can be extrapolated and enhanced by combination with other high-throughput methodologies, such as proteomics. Technologies, such as kinetic mass spectrometry and ribosome profiling, will be necessary to resolve the temporal and spatial aspects of translational regulation while the functional features of ribosomal subpopulations will become clear with the combination of reverse genetics and systems biology approaches.
PubMed: 32670337
DOI: 10.3389/fpls.2020.00948 -
Ageing Research Reviews Nov 2022Modifications of RNA, collectively called the "epitranscriptome", might provide novel biomarkers and innovative targets for interventions in geroscience but are just... (Review)
Review
Modifications of RNA, collectively called the "epitranscriptome", might provide novel biomarkers and innovative targets for interventions in geroscience but are just beginning to be studied in the context of ageing and stress resistance. RNA modifications modulate gene expression by affecting translation initiation and speed, miRNA binding, RNA stability, and RNA degradation. Nonetheless, the precise underlying molecular mechanisms and physiological consequences of most alterations of the epitranscriptome are still only poorly understood. We here systematically review different types of modifications of rRNA, tRNA and mRNA, the methodology to analyze them, current challenges in the field, and human disease associations. Furthermore, we compiled evidence for a connection between individual enzymes, which install RNA modifications, and lifespan in yeast, worm and fly. We also included resistance to different stressors and competitive fitness as search criteria for genes potentially relevant to ageing. Promising candidates identified by this approach include RCM1/NSUN5, RRP8, and F33A8.4/ZCCHC4 that introduce base methylations in rRNA, the methyltransferases DNMT2 and TRM9/ALKBH8, as well as factors involved in the thiolation or A to I editing in tRNA, and finally the mA machinery for mRNA.
Topics: Aging; AlkB Homolog 8, tRNA Methyltransferase; Animals; Humans; Methyltransferases; MicroRNAs; RNA, Messenger; RNA, Ribosomal; RNA, Transfer; Saccharomyces cerevisiae
PubMed: 35908668
DOI: 10.1016/j.arr.2022.101700 -
Pharmacological Reviews Oct 2020RNA-based therapies, including RNA molecules as drugs and RNA-targeted small molecules, offer unique opportunities to expand the range of therapeutic targets. Various...
RNA-based therapies, including RNA molecules as drugs and RNA-targeted small molecules, offer unique opportunities to expand the range of therapeutic targets. Various forms of RNAs may be used to selectively act on proteins, transcripts, and genes that cannot be targeted by conventional small molecules or proteins. Although development of RNA drugs faces unparalleled challenges, many strategies have been developed to improve RNA metabolic stability and intracellular delivery. A number of RNA drugs have been approved for medical use, including aptamers (e.g., pegaptanib) that mechanistically act on protein target and small interfering RNAs (e.g., patisiran and givosiran) and antisense oligonucleotides (e.g., inotersen and golodirsen) that directly interfere with RNA targets. Furthermore, guide RNAs are essential components of novel gene editing modalities, and mRNA therapeutics are under development for protein replacement therapy or vaccination, including those against unprecedented severe acute respiratory syndrome coronavirus pandemic. Moreover, functional RNAs or RNA motifs are highly structured to form binding pockets or clefts that are accessible by small molecules. Many natural, semisynthetic, or synthetic antibiotics (e.g., aminoglycosides, tetracyclines, macrolides, oxazolidinones, and phenicols) can directly bind to ribosomal RNAs to achieve the inhibition of bacterial infections. Therefore, there is growing interest in developing RNA-targeted small-molecule drugs amenable to oral administration, and some (e.g., risdiplam and branaplam) have entered clinical trials. Here, we review the pharmacology of novel RNA drugs and RNA-targeted small-molecule medications, with a focus on recent progresses and strategies. Challenges in the development of novel druggable RNA entities and identification of viable RNA targets and selective small-molecule binders are discussed. SIGNIFICANCE STATEMENT: With the understanding of RNA functions and critical roles in diseases, as well as the development of RNA-related technologies, there is growing interest in developing novel RNA-based therapeutics. This comprehensive review presents pharmacology of both RNA drugs and RNA-targeted small-molecule medications, focusing on novel mechanisms of action, the most recent progress, and existing challenges.
Topics: Aptamers, Nucleotide; Betacoronavirus; COVID-19; Chemistry Techniques, Analytical; Clustered Regularly Interspaced Short Palindromic Repeats; Coronavirus Infections; Drug Delivery Systems; Drug Development; Drug Discovery; Humans; MicroRNAs; Oligonucleotides, Antisense; Pandemics; Pneumonia, Viral; RNA; RNA, Antisense; RNA, Messenger; RNA, Ribosomal; RNA, Small Interfering; RNA, Viral; Ribonucleases; Riboswitch; SARS-CoV-2
PubMed: 32929000
DOI: 10.1124/pr.120.019554 -
Parasitology Research Apr 2017Cryptosporidiosis caused by Cryptosporidium spp. is an important parasitic disease that can be life-threatening for children and immunocompromised patients. This... (Meta-Analysis)
Meta-Analysis Review
Cryptosporidiosis caused by Cryptosporidium spp. is an important parasitic disease that can be life-threatening for children and immunocompromised patients. This systematic review and meta-analysis was designed to determine the prevalence rate of Cryptosporidium infection and related risk factors among the Iranian general population. We searched electronic databases including Google Scholar, PubMed, Science Direct, Scopus and Proquest for articles in English and SID, Magiran, IranMedex, and IranDoc for articles in Persian. Out of 4816 studies identified in the electronic search, 94 articles were eligible for inclusion in the systematic review and meta-analysis. The prevalence rate of cryptosporidiosis by using the random effect model among children, healthy people, and gastroenteritis and immunocompromised patients in Iran was estimated as 3.65, 2.94, 1.29, and 4.54%, respectively. Findings of a phylogenetic analysis inferred by gp60 and 18S ribosomal RNA markers indicated that most of the infection rate belonged to C. parvum (particularly subtype IIaA15G2R1) and C. hominis among understudied groups. The present study is the first systematic review and meta-analysis providing a comprehensive view of the prevalence of human cryptosporidiosis and its related risk factors in Iran. It seems that the awareness of Cryptosporidium prevalence, risk factors, and disease complications may be required for developing effective strategies to prevent infection.
Topics: Adjuvants, Immunologic; Adolescent; Adult; Aged; Animals; Child; Child, Preschool; Cryptosporidiosis; Cryptosporidium; Databases, Factual; Female; Gastroenteritis; Humans; Immunocompromised Host; Infant; Infant, Newborn; Iran; Male; Middle Aged; Phylogeny; Prevalence; RNA, Ribosomal, 18S; Risk Factors; Sialoglycoproteins; Young Adult
PubMed: 28110441
DOI: 10.1007/s00436-017-5376-3