Genome-wide mapping of gene-microbe interactions in the murine lung microbiota based on quantitative microbial profiling

Animal Microbiome

Research

S. Ibrahim¹  Y. Gupta²  John F. Baines³  B. M. Hermes³  C. J. Chung³  Meriem Belheouane⁴ 

[1] College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, UAE;Division of Nephrology, Department of Medicine, Columbia University Irving Medical Center, 10032, New York, NY, USA;Max Planck Institute for Evolutionary Biology, August-Thienemann-Str. 2, 24306, Plön, Germany;Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Arnold-Heller-Str. 3, 24105, Kiel, Germany;Max Planck Institute for Evolutionary Biology, August-Thienemann-Str. 2, 24306, Plön, Germany;Section of Evolutionary Medicine, Institute for Experimental Medicine, Kiel University, Arnold-Heller-Str. 3, 24105, Kiel, Germany;Research Center Borstel, Evolution of the Resistome, Leibniz Lung Center, Parkallee 1-40, 23845, Borstel, Germany;

关键词: Mouse;    Lung microbiota;    Host genetics;    QTL mapping;    Quantitative microbial profiling;    Lactobacillus;    Interleukin 10;   

DOI  :  10.1186/s42523-023-00250-y

 received in 2022-11-22, accepted in 2023-05-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMammalian lungs comprise a complex microbial ecosystem that interacts with host physiology. Previous research demonstrates that the environment significantly contributes to bacterial community structure in the upper and lower respiratory tract. However, the influence of host genetics on the makeup of lung microbiota remains ambiguous, largely due to technical difficulties related to sampling, as well as challenges inherent to investigating low biomass communities. Thus, innovative approaches are warranted to clarify host-microbe interactions in the mammalian lung.ResultsHere, we aimed to characterize host genomic regions associated with lung bacterial traits in an advanced intercross mouse line (AIL). By performing quantitative microbial profiling (QMP) using the highly precise method of droplet digital PCR (ddPCR), we refined 16S rRNA gene amplicon-based traits to identify and map candidate lung-resident taxa using a QTL mapping approach. In addition, the two abundant core taxa Lactobacillus and Pelomonas were chosen for independent microbial phenotyping using genus-specific primers. In total, this revealed seven significant loci involving eight bacterial traits. The narrow confidence intervals afforded by the AIL population allowed us to identify several promising candidate genes related to immune and inflammatory responses, cell apoptosis, DNA repair, and lung functioning and disease susceptibility. Interestingly, one genomic region associated with Lactobacillus abundance contains the well-known anti-inflammatory cytokine Il10, which we confirmed through the analysis of Il10 knockout mice.ConclusionsOur study provides the first evidence for a role of host genetic variation contributing to variation in the lung microbiota. This was in large part made possible through the careful curation of 16S rRNA gene amplicon data and the incorporation of a QMP-based methods. This approach to evaluating the low biomass lung environment opens new avenues for advancing lung microbiome research using animal models.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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