Exposing new taxonomic variation with inflammation — a murine model-specific genome database for gut microbiome researchers

Microbiome

Research

Ikaia Leleiwi¹  Kelly C. Wrighton²  Brian M. M. Ahmer³  Anice Sabag-Daigle³  Linnea F. M. Kop⁴  Rory M. Flynn⁵  Mikayla A. Borton⁵  Michael Shaffer⁵  Rebecca A. Daly⁵  Lindsey M. Solden⁵  Katherine Kokkinias⁶  Josué Rodriguez-Ramos⁷ 

[1] Department of Cell and Molecular Biology, The Colorado State University, Fort Collins, CO, USA;Department of Soil and Crop Sciences, The Colorado State University, Fort Collins, CO, USA;Department of Cell and Molecular Biology, The Colorado State University, Fort Collins, CO, USA;Department of Soil and Crop Sciences, The Colorado State University, Fort Collins, CO, USA;Graduate Degree Program in Ecology, The Colorado State University, Fort Collins, CO, USA;Department of Microbiology, Immunology, and Pathology, The Colorado State University, Fort Collins, CO, USA;Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA;Department of Microbiology, RIBES, Radbound University, Nijmegen, The Netherlands;Department of Microbiology and Biophysics, The Ohio State University, Columbus, OH, USA;Department of Soil and Crop Sciences, The Colorado State University, Fort Collins, CO, USA;Department of Soil and Crop Sciences, The Colorado State University, Fort Collins, CO, USA;Department of Microbiology, Immunology, and Pathology, The Colorado State University, Fort Collins, CO, USA;Department of Soil and Crop Sciences, The Colorado State University, Fort Collins, CO, USA;Graduate Degree Program in Ecology, The Colorado State University, Fort Collins, CO, USA;

关键词: CBA/J mouse;    Salmonella;    Metagenome;    Pathogen;    Pathobiome;   

DOI  :  10.1186/s40168-023-01529-7

 received in 2022-11-04, accepted in 2023-03-21,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe murine CBA/J mouse model widely supports immunology and enteric pathogen research. This model has illuminated Salmonella interactions with the gut microbiome since pathogen proliferation does not require disruptive pretreatment of the native microbiota, nor does it become systemic, thereby representing an analog to gastroenteritis disease progression in humans. Despite the value to broad research communities, microbiota in CBA/J mice are not represented in current murine microbiome genome catalogs.ResultsHere we present the first microbial and viral genomic catalog of the CBA/J murine gut microbiome. Using fecal microbial communities from untreated and Salmonella-infected, highly inflamed mice, we performed genomic reconstruction to determine the impacts on gut microbiome membership and functional potential. From high depth whole community sequencing (~ 42.4 Gbps/sample), we reconstructed 2281 bacterial and 4516 viral draft genomes. Salmonella challenge significantly altered gut membership in CBA/J mice, revealing 30 genera and 98 species that were conditionally rare and unsampled in non-inflamed mice. Additionally, inflamed communities were depleted in microbial genes that modulate host anti-inflammatory pathways and enriched in genes for respiratory energy generation. Our findings suggest decreases in butyrate concentrations during Salmonella infection corresponded to reductions in the relative abundance in members of the Alistipes. Strain-level comparison of CBA/J microbial genomes to prominent murine gut microbiome databases identified newly sampled lineages in this resource, while comparisons to human gut microbiomes extended the host relevance of dominant CBA/J inflammation-resistant strains.ConclusionsThis CBA/J microbiome database provides the first genomic sampling of relevant, uncultivated microorganisms within the gut from this widely used laboratory model. Using this resource, we curated a functional, strain-resolved view on how Salmonella remodels intact murine gut communities, advancing pathobiome understanding beyond inferences from prior amplicon-based approaches. Salmonella-induced inflammation suppressed Alistipes and other dominant members, while rarer commensals like Lactobacillus and Enterococcus endure. The rare and novel species sampled across this inflammation gradient advance the utility of this microbiome resource to benefit the broad research needs of the CBA/J scientific community, and those using murine models for understanding the impact of inflammation on the gut microbiome more generally.8oDwaJeBPqYs8E78ifbGCvVideo Abstract

【 授权许可】

CC BY   
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

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