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Nat Commun ; 10(1): 604, 2019 02 05.
Article in English | MEDLINE | ID: mdl-30723205

ABSTRACT

The gut microbiota contributes to host health and fitness, and imbalances in its composition are associated with pathology. However, what shapes microbiota composition is not clear, in particular the role of genetic factors. Previous work in Caenorhabditis elegans defined a characteristic worm gut microbiota significantly influenced by host genetics. The current work explores the role of central regulators of host immunity and stress resistance, employing qPCR and CFU counts to measure abundance of core microbiota taxa in mutants raised on synthetic communities of previously-isolated worm gut commensals. This revealed a bloom, specifically of Enterobacter species, in immune-compromised TGFß/BMP mutants. Imaging of fluorescently labeled Enterobacter showed that TGFß/BMP-exerted control operated primarily in the anterior gut and depended on multi-tissue contributions. Enterobacter commensals are common in the worm gut, contributing to infection resistance. However, disruption of TGFß/BMP signaling turned a normally beneficial Enterobacter commensal to pathogenic. These results demonstrate specificity in gene-microbe interactions underlying gut microbial homeostasis and highlight the pathogenic potential of their disruption.


Subject(s)
Bone Morphogenetic Proteins/immunology , Caenorhabditis elegans Proteins/immunology , Caenorhabditis elegans/immunology , Gastrointestinal Microbiome/immunology , Transforming Growth Factor beta/immunology , Animals , Animals, Genetically Modified , Bacteria/classification , Bacteria/genetics , Bacteria/growth & development , Bone Morphogenetic Proteins/genetics , Bone Morphogenetic Proteins/metabolism , Caenorhabditis elegans/genetics , Caenorhabditis elegans/microbiology , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Enterobacter/genetics , Enterobacter/immunology , Enterobacter/physiology , Gastrointestinal Microbiome/genetics , Gastrointestinal Microbiome/physiology , Homeostasis/immunology , Host Microbial Interactions/immunology , Mutation/immunology , Population Dynamics , RNA, Ribosomal, 16S/genetics , Signal Transduction/genetics , Signal Transduction/immunology , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism
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