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Science. 2015 Oct 30;350(6260):558-63. doi: 10.1126/science.aac6468.

Disease tolerance mediated by microbiome E. coli involves inflammasome and IGF-1 signaling.

Author information

1
Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
2
Integrative Genomics and Bioinformatics Core, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
3
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
4
Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
5
Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. jayres@salk.edu.

Abstract

Infections and inflammation can lead to cachexia and wasting of skeletal muscle and fat tissue by as yet poorly understood mechanisms. We observed that gut colonization of mice by a strain of Escherichia coli prevents wasting triggered by infections or physical damage to the intestine. During intestinal infection with the pathogen Salmonella Typhimurium or pneumonic infection with Burkholderia thailandensis, the presence of this E. coli did not alter changes in host metabolism, caloric uptake, or inflammation but instead sustained signaling of the insulin-like growth factor 1/phosphatidylinositol 3-kinase/AKT pathway in skeletal muscle, which is required for prevention of muscle wasting. This effect was dependent on engagement of the NLRC4 inflammasome. Therefore, this commensal promotes tolerance to diverse diseases.

Comment in

PMID:
26516283
PMCID:
PMC4732872
DOI:
10.1126/science.aac6468
[Indexed for MEDLINE]
Free PMC Article

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