Biology subjects

Doms, S.

Publications and source records attributed to Doms, S..

4 recordsLinked to original sources

bioRxiv2023

A mitochondrial sirtuin shapes the intestinal microbiota by controlling lysozyme expression

Sirtuins act as cellular sensors in the gut that control a substantial change in gut properties in response to environmental changes. Here we show that the only mitochondrial sirtuin of Drosophila, dSirt4, is strongly up-regulated by a protein-reduced diet. Flies with a dSirt4 defect show strong changes in the protein pattern and physiological properties of their intestine. One of the most notable effects was the strong induction of lysozyme gene expression in the intestine, which also translates into enhanced lysozyme activity. This effect was cell autonomous, as it was also observed in flies with dsirt4 was exclusively silenced in enterocytes of the intestine. Although this strongly increased lysozyme expression, it did not reduce total bacterial load in the intestine, but rather changed the composition of the microbiota by reducing the number of gram-positive bacteria. This effect on microbiota composition can be attributed to the dSirt4-dependent lysozyme expression, as it was absent in a lysozyme-deficient background. dSirt4 deficiency in enterocytes reduced lifespan of flies, which was also observed in those flies experiencing ectopic lysozyme overexpression in enterocytes. This implies that strong lysozyme expression leads to a dysbiotic state associated with reduced lifespan.

cell biology↗

bioRxiv2023

Comparative genomics of novel Bacteroides acidifaciens isolates reveals candidates for adaptation to host subspecies in house mice

The breadth of phenotypes influenced by the gut microbiome in multicellular hosts has attracted the keen and renewed interest of evolutionary biologists. Comparative studies suggest that coevolutionary processes may occur as hosts and their associated microbes (i.e., holobionts) diverge. The majority of studies to date however lack information beyond that of 16S rRNA gene profiling, and thus fail to capture potential underlying genomic changes among microbes. In this study, we conducted a comparative genomic analysis of 19 newly sampled Bacteroides acidifaciens isolates derived from the eastern and western house mouse subspecies, Mus musculus musculus and M. m. domesticus. Through a panel of genome-wide association (GWAS) analyses applied to pangenomic content, structural gene rearrangements, and SNPs, we reveal several candidates for adaptation to the host subspecies environment. The proportion of significant loci in each respective category is small, indicating low levels of differentiation according host subspecies. However, consistent signal is observed for genes involved in processes such as carbohydrate acquisition/utilization (SusD/RagB, amyA and amyS) and de novo purine nucleotide biosynthesis (purD), which serve as promising candidates for future experimental investigation in the house mouse as a model of holobiont evolution.

evolutionary biology↗

bioRxiv2021

High-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice provides novel insight on the impact of host genetics

Determining the forces that shape diversity in host-associated bacterial communities is critical to understanding the evolution and maintenance of metaorganisms. To gain deeper understanding of the role of host genetics in shaping gut microbial traits, we employed a powerful genetic mapping approach using inbred lines derived from the hybrid zone of two incipient house mouse species. Further, we uniquely performed our analysis on microbial traits measured at the gut mucosal interface, which is in more direct contact with host cells and the immune system. A high number of mucosa-associated bacterial taxa have significant heritability estimates; heritabilities are greater for 16S rRNA transcript-compared to gene copy-based traits, and interestingly, are positively correlated with cospeciation rate estimates. Genomewide association mapping identifies 443 loci influencing 123 taxa, with narrow genomic intervals pinpointing promising candidate genes and pathways. Importantly, we identified an enrichment of candidate genes associated with several human diseases, including inflammatory bowel disease, and functional categories including innate immunity and G-protein-coupled receptors. These results highlight key features of the genetic architecture of mammalian host-microbe interactions and how they diverge as new species form.

genetics↗

bioRxiv2019

Comparative analysis of amplicon and metagenomic sequencing methods reveals key features in the evolution of animal metaorganisms

BackgroundThe interplay between hosts and their associated microbiome is now recognized as a fundamental basis of the ecology, evolution and development of both players. These interdependencies inspired a new view of multicellular organisms as \"metaorganisms\". The goal of the Collaborative Research Center \"Origin and Function of Metaorganisms\" is to understand why and how microbial communities form long-term associations with hosts from diverse taxonomic groups, ranging from sponges to humans in addition to plants.\n\nMethodsIn order to optimize the choice of analysis procedures, which may differ according to the host organism and question at hand, we systematically compared the two main technical approaches for profiling microbial communities, 16S rRNA gene amplicon- and metagenomic shotgun sequencing across our panel of ten host taxa. This includes two commonly used 16S rRNA gene regions and two amplification procedures, thus totaling five different microbial profiles per host sample.\n\nConclusionWhile 16S rRNA gene-based analyses are subject to much skepticism, we demonstrate that many aspects of bacterial community characterization are consistent across methods and that metagenomic shotgun results are largely dependent on the employed pipeline. The resulting insight facilitates the selection of appropriate methods across a wide range of host taxa. Finally, by contrasting taxonomic and functional profiles and performing phylogenetic analysis, we provide important and novel insight into broad evolutionary patterns among metaorganisms, whereby the transition of animals from an aquatic to a terrestrial habitat marks a major event in the evolution of host-associated microbial composition.

microbiology↗