Biology subjects

Cenier, A.

Publications and source records attributed to Cenier, A..

5 recordsLinked to original sources

bioRxiv2026

Extensive genomic diversity in Desulfovibrio species reveals species-specific functional traits associated with disease

Desulfovibrio spp. are associated with inflammatory diseases and human health, yet limited representative genomes and isolates hinder our understanding of their role in disease. Here, we assembled a comprehensive database of 2,658 Desulfovibrio genomes across 90 diseases and 32 countries, including 24 human isolates. Genomic analyses showed extensive species diversity and revealed disease-associated functional traits, including flagellin and virulence genes (i.e. ureases). Flagellin-mediated Toll-like receptor 5 activation was species-specific and D. desulfuricans flagellin downregulated TGF-beta signalling in murine small intestinal organoids, suggesting impaired immune tolerance. Additionally, we investigated genomic capacity for hydrogen sulfide (H2S) production, a main Desulfovibrio metabolite. While health- and disease-associated Desulfovibrio spp. mainly encoded dissimilatory sulfate reduction, tetrathionate metabolism-encoding bacteria were exclusively detected in inflammatory bowel diseases, including Proteus mirabilis and Morganella morganii. Overall, our study provides a comprehensive genomic Desulfovibrio resource and identifies new links associating strain variation, functional traits and H2S-production with inflammatory diseases.

genomics↗

bioRxiv2025

Gene-centric metagenomic analyses reveal microbiome functional insights into diseases

The microbiome encodes millions of genes; however, understanding their role in human health remains challenging. Here, we developed MetaGEAR, a gene-centric analysis framework for metagenomic data. MetaGEAR constructs cohort-specific databases for efficient retrieval of gene annotations, abundances, and co-localization, while providing enhanced taxonomic resolution by integrating reference- and assembly-based approaches. This is combined with a Metagenomic Assembled Graph (MAGraph) capturing gene neighborhood information. Using MetaGEAR, we built a multi-cohort database comprising >33 million gene families to investigate microbiome functionality across 24 cohorts of inflammatory bowel disease, colorectal cancer, and healthy populations and identified disease signature genes. Furthermore, the MAGraph revealed mobile genetic elements acting as hubs for tetracycline resistance spreading among Enterococcus, Streptococcus, and Veillonella species. Also, a duplicated nitrate reduction operon in Klebsiella pneumoniae was linked to differential gene expression under stress and virulence-inducing conditions. In summary, gene-centric metagenomic analyses reveal important insights into microbiome functionality in diseases.

microbiology↗

bioRxiv2025

Microbial oral-gut translocation in advanced chronic liver disease is linked to exacerbation of intestinal barrier dysfunction and hepatic fibrosis

While microbiome perturbations are associated with advanced chronic liver disease (ACLD), microbial disease mechanisms are poorly understood. Using multi-omics analyses of paired saliva and faecal samples from an ACLD cohort, we identified next-to-identical oral and gut bacterial strains (including Veillonella and Streptococcus spp.) which increased in absolute abundance in the gut of ACLD patients. These translocators uniquely encoded a collagenase-like proteinase (prtC) with the potential for gut barrier disruption and prtC faecal abundance was a robust ACLD biomarker (auPR=0.91). CCl4-treated mice inoculated with Veillonella and Streptococcus prtC-encoding patient isolates showed exacerbation of gut barrier impairment and hepatic fibrosis. Furthermore, faecal collagenase activity was increased in ACLD patients and experimentally confirmed for the prtC gene from translocating Veillonella parvula. Overall, our study establishes mechanistic links between oral-gut translocation and ACLD pathobiology, and identifies the oral microbiome as an important contributing factor with potential for microbial diagnostics and therapeutics.

microbiology↗

bioRxiv2025

Flexibility and modulation of translation initiation in enterovirus genomes

Enteroviruses comprise a large group of mammalian pathogens that often utilize two open reading frames (ORFs) to encode their proteins: the upstream protein (UP) and the main polyprotein. In some enteroviruses, in addition to the canonical upstream AUG (uAUG), there is another AUG that may represent an alternative upstream initiation site. An analysis of enterovirus sequences containing additional upstream AUGs identified several clusters, including strains of pathogenic Enterovirus alphacoxsackie and E. coxsackiepol. Using ribosome profiling on coxsackievirus CVA-13 (E. coxsackiepol), we demonstrate that both upstream AUG codons can be used for translation initiation in infected cells. Moreover, we confirm translation from both upstream AUGs using a reporter system. Mutating the additional upstream AUG in the context of CVA-13 did not result in phenotypic changes in immortalized cell lines. However, the wild-type virus outcompeted this mutant in human intestinal organoids and differentiated neuronal systems, representing an advantage in physiologically relevant infection sites. Mutation of the stop codon of the shorter upstream ORF led to dysregulated translation of the other ORFs in the reporter system, suggesting a potential role for the additional uORF in modulating the expression level of the other ORFs. These findings demonstrate the remarkable plasticity of enterovirus IRES-mediated initiation and the competitive advantage of double-upstream-AUG-containing viruses in terminally differentiated intestinal organoids and neuronal systems.

microbiology↗

bioRxiv2022

Culture Associated DNA Methylation Changes Impact on Cellular Function of Human Intestinal Organoids

Background & AimsHuman intestinal epithelial organoids (IEO) are a powerful tool to model major aspects of intestinal development, health and diseases, as patient derived cultures retain many features found in-vivo. A necessary aspect of the organoid model is the requirement to expand cultures in-vitro through several rounds of passaging. This is of concern, as the passaging of cells has been shown to affect cell morphology, ploidy, and function. In this study, we address concerns around long term passaging of IEO to better characterise and define effects on cell morphology and function. MethodsHere we have analysed 173 human IEO from two sampling sites, terminal ileum and sigmoid colon and examined the effect of culture duration on DNA methylation (DNAm), gene expression and cellular function including their response to proinflammatory cytokines and in-vitro cell differentiation. ResultsOur analyses revealed a major effect of culture duration on DNAm, leading to significant changes at 61,337 loci representing approximately 8% of all CpGs tested. Although global cellular functions such as gut segment-specific gene expression remained stable, a subset of methylation changes correlated with altered gene expression at baseline as well as in response to inflammatory cytokine exposure and in-vitro differentiation. Importantly, epigenetic changes were found to be enriched in genomic regions associated with colonic cancer and distant to the site of replication indicating similarities to malignant transformation. ConclusionsOur study reveals culture-associated epigenetic, transcriptomic and functional changes in human mucosa derived IEO and highlights the importance of considering passage number as a potentially confounding factor. SynopsisThis work describes cell culture induced changes to DNA methylation, gene expression and cellular function in human IEO. Globally organoids lost DNA methylation with time in culture while DNA methylation also became generally more variable. This work suggests a shifted epigenetic profile in organoids cultured long-term.

genomics↗