Biology subjects

Moyes, D.

Publications and source records attributed to Moyes, D..

4 recordsLinked to original sources

bioRxiv2025

Development and Genome-level Microevolution of Oral Microbiome during Surface Colonization

The oral microbiome is essential to human health, yet its de novo ecological succession and microevolutionary dynamics remain poorly understood due to the absence of tractable in vivo models. Dental implants provide a unique opportunity to investigate these processes by establishing a defined time-zero for initial bacterial attachment. In this cohort study, we performed shotgun metagenomics on 95 subgingival plaque samples from 19 participants, including peri-implant sites at weeks 1-4 after crown placement and adjacent teeth as controls. Peri-implant and adjacent periodontal microbiomes exhibited distinct taxonomic and functional profiles. Even the same taxa had different functional potential across the two sites. These findings indicated that oral microbiome development is a niche-specific process with selective colonization rather than passive microbial translocation from adjacent sites. Longitudinal analysis identified three microbial community modules driving the succession of oral microbiome, including pioneer colonizers, constitutive species, and late commensals. Each module followed distinct temporal abundance patterns and played unique ecological roles throughout the succession process. Strain-level resolution revealed divergent microevolutionary trajectories: pioneer colonizers and late commensals exhibited higher cumulative mutation rates and greater strain heterogeneity overtime, with enrichment of nonsynonymous single nucleotide variants in genes related to virulence and metabolism, whereas constitutive species remained evolutionarily stable by contrast. Our study reveals that the development, succession, and microevolution of the oral microbiome is structured, niche-dependent, and modulated by inter-species facilitation and selective genomic adaptation. These findings advance the understanding of oral microbiome ecology and provide a conceptual foundation for manipulating microbial succession in health and disease.

microbiology↗

bioRxiv2023

Pathogenic entero- and salivatypes harbour changes in microbiome virulence and antimicrobial resistance genes with increasing chronic liver disease severity

Background & AimsLife-threatening complications of cirrhosis are triggered by bacterial infections, with the ever-increasing threat of antimicrobial resistance (AMR). Alterations in the gut microbiome in decompensated cirrhosis (DC) and acute-on-chronic liver failure (ACLF) are recognised to influence clinical outcomes, whilst the role of the oral microbiome is still being explored. Our aims were to simultaneously interrogate the gut and oral micro- and mycobiome in cirrhotic patients, and assess microbial community structure overlap in relation to clinical outcomes, as well as alterations in virulence factors and AMR genes. Methods18 healthy controls (HC), 20 stable cirrhotics (SC), 50 DC, 18 ACLF and 15 with non-liver sepsis (NLS) i.e. severe infection but without cirrhosis, were recruited at a tertiary liver centre. Shotgun metagenomic sequencing was undertaken from saliva (S) and faecal (F) samples (paired where possible). Salivatypes and enterotypes based on clustering of genera were calculated and compared in relation to cirrhosis severity and in relation to specific clinical parameters. Virulence and antimicrobial resistance genes (ARGs) were evaluated in both oral and gut niches, and distinct resistotypes identified. ResultsSpecific saliva- and enterotypes revealed a greater proportion of pathobionts with concomitant reduction in autochthonous genera with increasing cirrhosis severity, and in those with hyperammonemia. Overlap between oral and gut microbiome communities was observed and was significantly higher in DC and ACLF vs SC and HCs, independent of antimicrobial, beta-blocker and acid suppressant use. Two distinct gut microbiome clusters [ENT2/ENT3] harboured genes encoding for the phosphoenolpyruvate:sugar phosphotransferase system (PTS) system and other virulence factors in patients with DC and ACLF. Substantial numbers of ARGs (oral: 1,218 and gut: 672) were detected with 575 ARGs common to both sites. The cirrhosis resistome was significantly different to HCs, with three and four resistotypes identified for the oral and gut microbiome, respectively. DiscussionOral and gut microbiome profiles differ significantly with increasing severity of cirrhosis, with progressive dominance of pathobionts and loss of commensals. DC and ACLF have significantly worse microbial diversity than NLS, despite similar antimicrobial exposure, supporting the additive patho-biological effect of cirrhosis. The degree of microbial community overlap between sites, frequency of virulence factors and presence of ARGs, all increment significantly with hepatic decompensation. These alterations may predispose to higher infection risk, poorer response to antimicrobial therapy and worsening outcomes, and provide the rationale for developing non-antibiotic-dependent microbiome-modulating therapies.

physiology↗

bioRxiv2021

Integrative functional analysis uncovers metabolic differences between Candida species

Candida species are a dominant constituent of the human mycobiome and a better understanding of their metabolism from a fungal perspective can provide key insights into their ability to cause pathogenesis. Here, we have developed the BioFung database - a fungal specific tool for functional annotation using the KEGG database that provides an efficient method for annotation of protein-encoding gene. Analysis of carbohydrate-active enzyme (CAZymes) and BioFung, uncovered core and accessory features across Candida species demonstrating plasticity, adaptation to the environment and acquired features. Integerative functional analysis revealed that all Candida species can employ amino acid metabolism. However, metabolomics revealed that only a specific cluster of species (AGAu species - C. albicans, C. glabrata and C. auris) utilised amino acid metabolism. We identified critical metabolic pathways in the AGAu clusters with biomarkers and anti-fungal target potential in the CAZyme profile, polyamine, choline and fatty acid biosynthesis pathways. This study, combining genomic analysis, metabolomics and gene expression validation, highlights the metabolic diversity within AGAu species that underlies their remarkable ability to dominate the mycobiome and cause disease.

systems biology↗

bioRxiv2020

Host genetic and environmental factors shape the human gut resistome

BackgroundUnderstanding and controlling the spread of antimicrobial resistance is one of the greatest challenges of modern medicine. To this end many efforts focus on characterising the human resistome or the set of antibiotic resistance determinants within the microbiome of an individual. Aside from antibiotic use, other host environmental and genetic factors that may shape the resistome remain relatively underexplored. MethodsUsing gut metagenome data from 250 TwinsUK female twins, we quantified known antibiotic resistance genes to estimate gut microbiome antibiotic resistance potential for 41 types of antibiotics and resistance mechanisms. Using heritability modelling, we assessed the influence of host genetic and environmental factors on the gut resistome. We then explored links between gut resistome, host health and specific environmental exposures using linear mixed effect models adjusted for age, BMI, alpha diversity and family structure. ResultsWe considered gut microbiome antibiotic resistance to 21 classes of antibiotics, for which resistance genes were detected in over 90% of our population sample. Using twin modelling, we estimated that on average about 25% of resistome variability could be attributed to host genetic influences. Greatest heritability estimates were observed for resistance potential to acriflavine (70%), dalfopristin (51%), clindamycin (48%), aminocoumarin (48%) and the total score summing across all antibiotic resistance genes (38%). As expected, the majority of resistome variability was attributed to host environmental factors specific to an individual. We compared antibiotic resistance profiles to multiple environmental exposures, lifestyle and health factors. The strongest associations were observed with alcohol and vegetable consumption, followed by high cholesterol medication and antibiotic usage. Overall, inter-individual variation in host environment showed modest associations with antibiotic resistance profiles, and host health status had relatively minor signals. ConclusionOur results identify host genetic and environmental influences on the human gut resistome. The findings improve our knowledge of human factors that influence the spread of antibiotic resistance genes and may contribute towards helping to attenuate it.

microbiology↗