Showing papers by "Lesley Hoyles published in 2023"
TL;DR: In this article , a meta-analysis of publicly available repository data from studies of models of kidney disease in rodents, cohort variation far outweighed any effect of experimental kidney disease on the gut microbiota.
Abstract: Significance Statement Alterations in gut microbiota contribute to the pathophysiology of a diverse range of diseases, leading to suggestions that chronic uremia may cause intestinal dysbiosis that contributes to the pathophysiology of CKD. Various small, single-cohort rodent studies have supported this hypothesis. In this meta-analysis of publicly available repository data from studies of models of kidney disease in rodents, cohort variation far outweighed any effect of experimental kidney disease on the gut microbiota. No reproducible changes in animals with kidney disease were seen across all cohorts, although a few trends observed in most experiments may be attributable to kidney disease. The findings suggest that rodent studies do not provide evidence for the existence of “uremic dysbiosis” and that single-cohort studies are unsuitable for producing generalizable results in microbiome research. Background Rodent studies have popularized the notion that uremia may induce pathological changes in the gut microbiota that contribute to kidney disease progression. Although single-cohort rodent studies have yielded insights into host-microbiota relationships in various disease processes, their relevance is limited by cohort and other effects. We previously reported finding metabolomic evidence that batch-to-batch variations in the microbiome of experimental animals are significant confounders in an experimental study. Methods To attempt to identify common microbial signatures that transcend batch variability and that may be attributed to the effect of kidney disease, we downloaded all data describing the molecular characterization of the gut microbiota in rodents with and without experimental kidney disease from two online repositories comprising 127 rodents across ten experimental cohorts. We reanalyzed these data using the DADA2 and Phyloseq packages in R, a statistical computing and graphics system, and analyzed data both in a combined dataset of all samples and at the level of individual experimental cohorts. Results Cohort effects accounted for 69% of total sample variance (P<0.001), substantially outweighing the effect of kidney disease (1.9% of variance, P=0.026). We found no universal trends in microbial population dynamics in animals with kidney disease, but observed some differences (increased alpha diversity, a measure of within-sample bacterial diversity; relative decreases in Lachnospiraceae and Lactobacillus; and increases in some Clostridia and opportunistic taxa) in many cohorts that might represent effects of kidney disease on the gut microbiota. Conclusions These findings suggest that current evidence that kidney disease causes reproducible patterns of dysbiosis is inadequate. We advocate meta-analysis of repository data as a way of identifying broad themes that transcend experimental variation.
1 citations
TL;DR: In this paper , the authors describe the phenotypic and genotypic characteristics of 31 Pseudomonas aeruginosa isolates recovered from CAUTIs in an Egyptian hospital over a 3-month period.
Abstract: Catheter-associated urinary tract infections (CAUTIs) represent one of the major healthcare-associated infections, and Pseudomonas aeruginosa is a common Gram-negative bacterium associated with catheter infections in Egyptian clinical settings. The present study describes the phenotypic and genotypic characteristics of 31 P. aeruginosa isolates recovered from CAUTIs in an Egyptian hospital over a 3-month period. Genomes of isolates were of good quality and were confirmed to be P. aeruginosa by comparison to the type strain (average nucleotide identity, phylogenetic analysis). Clonal diversity among the isolates was determined; eight different sequence types were found (STs 244, 357, 381, 621, 773, 1430, 1667 and 3765), of which 357 and 773 are considered high-risk clones. Antimicrobial resistance (AMR) testing according to EUCAST guidelines showed the isolates were highly resistant to quinolones [ciprofloxacin (12/31, 38.7 %) and levofloxacin (9/31, 29 %) followed by tobramycin (10/31, 32.5 %)], and cephalosporins (7/31, 22.5 %). Genotypic analysis of resistance determinants predicted all isolates to encode a range of AMR genes, including those conferring resistance to aminoglycosides, β-lactamases, fluoroquinolones, fosfomycin, sulfonamides, tetracyclines and chloramphenicol. One isolate was found to carry a 422,938 bp pBT2436-like megaplasmid encoding OXA-520, the first report from Egypt of this emerging family of clinically important mobile genetic elements. All isolates were able to form biofilms, and were predicted to encode virulence genes associated with adherence, antimicrobial activity, antiphagocytosis, phospholipase enzymes, iron uptake, proteases, secretion systems, and toxins. The present study shows how phenotypic analysis alongside genomic analysis may help us understand the AMR and virulence profiles of P. aeruginosa contributing to CAUTIs in Egypt.
TL;DR: In this paper , a phage capable of killing clinically relevant members of the K. oxytoca complex (KoC) was identified, which represents a novel virus family (proposed name Dilsviridae).
Abstract: This study aimed to characterize the lytic phage vB_KmiS-Kmi2C, isolated from sewage water on a GES-positive strain of Klebsiella michiganensis.Comparative phylogenetic and network-based analyses were used to characterize the genome of phage vB_KmiS-Kmi2C (circular genome of 42 234 bp predicted to encode 55 genes), demonstrating it shared little similarity with other known phages. The phage was lytic on clinical strains of K. oxytoca (n = 2) and K. michiganensis (n = 4), and was found to both prevent biofilm formation and disrupt established biofilms produced by these strains.We have identified a phage capable of killing clinically relevant members of the K. oxytoca complex (KoC). The phage represents a novel virus family (proposed name Dilsviridae) and genus (proposed name Dilsvirus).
TL;DR: The preterm infant microbiota is dominated by enterobacteriaceae (Escherichia, Klebsiella or Enterobacter spp.), Enterococcus and Staphylococcus spp. as discussed by the authors showed that a Klebsia/Enterococcus-dominated faecal microbiota is associated with an increased risk of developing necrotizing enterocolitis.
Abstract: The preterm infant microbiota is dominated by Enterobacteriaceae (Escherichia, Klebsiella or Enterobacter spp.), Enterococcus and Staphylococcus spp. Recent work has demonstrated the development of this microbiota is predictable and driven by simple microbe–microbe interactions. Because of their systemic immaturity, including an underdeveloped immune system, preterm infants are susceptible to a range of infections. Numerous retrospective studies have examined the association of the preterm gut microbiota with diseases such as necrotizing enterocolitis (NEC), early-onset sepsis and late-onset sepsis. To date, no single bacterium has been associated with infection in these infants, but a Klebsiella/Enterococcus-dominated faecal microbiota is associated with an increased risk of developing NEC. Staphylococci aid and enterococci inhibit establishment/maintenance of gastrointestinal Klebsiella populations in preterm infants, though the mechanisms underlying these interactions are poorly understood. Klebsiella spp. recovered from healthy and sick preterm infants display similar antimicrobial resistance and virulence profiles, giving no clues as to why some infants develop potentially life-threatening diseases while others do not. The identification of cytotoxin-producing Klebsiella oxytoca sensu lato in the gut microbiota of some preterm infants has led to the suggestion that these bacteria may contribute to NEC in a subset of neonates. This mini review highlights current knowledge on Klebsiella spp. contributing to the preterm gut microbiota and provides insights into areas of research that warrant further attention.
TL;DR: The preterm infant microbiota is dominated by enterobacteriaceae (Escherichia, Klebsiella or Enterobacter spp.), Enterococcus and Staphylococcus spp. as discussed by the authors showed that a Klebsia/Enterococcus-dominated faecal microbiota is associated with an increased risk of developing necrotizing enterocolitis.
Abstract: The preterm infant microbiota is dominated by Enterobacteriaceae (Escherichia, Klebsiella or Enterobacter spp.), Enterococcus and Staphylococcus spp. Recent work has demonstrated the development of this microbiota is predictable and driven by simple microbe–microbe interactions. Because of their systemic immaturity, including an underdeveloped immune system, preterm infants are susceptible to a range of infections. Numerous retrospective studies have examined the association of the preterm gut microbiota with diseases such as necrotizing enterocolitis (NEC), early-onset sepsis and late-onset sepsis. To date, no single bacterium has been associated with infection in these infants, but a Klebsiella/Enterococcus-dominated faecal microbiota is associated with an increased risk of developing NEC. Staphylococci aid and enterococci inhibit establishment/maintenance of gastrointestinal Klebsiella populations in preterm infants, though the mechanisms underlying these interactions are poorly understood. Klebsiella spp. recovered from healthy and sick preterm infants display similar antimicrobial resistance and virulence profiles, giving no clues as to why some infants develop potentially life-threatening diseases while others do not. The identification of cytotoxin-producing Klebsiella oxytoca sensu lato in the gut microbiota of some preterm infants has led to the suggestion that these bacteria may contribute to NEC in a subset of neonates. This mini review highlights current knowledge on Klebsiella spp. contributing to the preterm gut microbiota and provides insights into areas of research that warrant further attention.
TL;DR: In this article , a multicentre, prospective observational study was conducted of colorectal cancer patients undergoing primary surgical resection in the UK and Czech Republic, and 13 mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa.
Abstract: Abstract Background and aims The gut microbiota is implicated in the pathogenesis of colorectal cancer (CRC). We aimed to map the CRC mucosal microbiota and metabolome and define the influence of the tumoral microbiota on oncological outcomes. Methods A multicentre, prospective observational study was conducted of CRC patients undergoing primary surgical resection in the UK ( n = 74) and Czech Republic ( n = 61). Analysis was performed using metataxonomics, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), targeted bacterial qPCR and tumour exome sequencing. Hierarchical clustering accounting for clinical and oncological covariates was performed to identify clusters of bacteria and metabolites linked to CRC. Cox proportional hazards regression was used to ascertain clusters associated with disease-free survival over median follow-up of 50 months. Results Thirteen mucosal microbiota clusters were identified, of which five were significantly different between tumour and paired normal mucosa. Cluster 7, containing the pathobionts Fusobacterium nucleatum and Granulicatella adiacens , was strongly associated with CRC ( P FDR = 0.0002). Additionally, tumoral dominance of cluster 7 independently predicted favourable disease-free survival (adjusted p = 0.031). Cluster 1, containing Faecalibacterium prausnitzii and Ruminococcus gnavus , was negatively associated with cancer ( P FDR = 0.0009), and abundance was independently predictive of worse disease-free survival (adjusted p = 0.0009). UPLC-MS analysis revealed two major metabolic (Met) clusters. Met 1, composed of medium chain (MCFA), long-chain (LCFA) and very long-chain (VLCFA) fatty acid species, ceramides and lysophospholipids, was negatively associated with CRC ( P FDR = 2.61 × 10 −11 ); Met 2, composed of phosphatidylcholine species, nucleosides and amino acids, was strongly associated with CRC ( P FDR = 1.30 × 10 −12 ), but metabolite clusters were not associated with disease-free survival ( p = 0.358). An association was identified between Met 1 and DNA mismatch-repair deficiency ( p = 0.005). FBXW7 mutations were only found in cancers predominant in microbiota cluster 7. Conclusions Networks of pathobionts in the tumour mucosal niche are associated with tumour mutation and metabolic subtypes and predict favourable outcome following CRC resection.
TL;DR: In this paper , a phage capable of killing clinically relevant members of the Klebsiella oxytoca complex (KoC) was identified, which represents a novel virus family (proposed name Dilsviridae).
Abstract: AIMS This study aimed to characterise the lytic phage vB_KmiS-Kmi2C, isolated from sewage water on a GES-positive strain of Klebsiella michiganensis. METHODS AND RESULTS Comparative phylogenetic and network-based analyses were used to characterise the genome of phage vB_KmiS-Kmi2C (circular genome of 42,234 bp predicted to encode 55 genes), demonstrating it shared little similarity with other known phages. The phage was lytic on clinical strains of K. oxytoca (n=2) and K. michiganensis (n=4), and was found to both prevent biofilm formation and disrupt established biofilms produced by these strains. CONCLUSIONS We have identified a phage capable of killing clinically relevant members of the Klebsiella oxytoca complex (KoC). The phage represents a novel virus family (proposed name Dilsviridae) and genus (proposed name Dilsvirus). SIGNIFICANCE AND IMPACT OF THE STUDY Identification a novel lytic phage active against clinically relevant strains of the KoC provides an alternative to antibiotics to treat these increasingly antimicrobial-resistant opportunistic pathogens. The unusual way in which the phage can disrupt established biofilms may allow us to identify novel phage-based approaches for biofilm remediation in the future.