Disease tolerance mediated by microbiome E. coli involves inflammasome and IGF-1 signaling
Open accessAbstract
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.
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Oral supplementation of Escherichia coli significantly decreases the expression of MAFbx and MuRF1 in B. thailandensis, S. Typhimurium or dextran sulfate sodium-induced muscle atrophy via the activation of the IGF-1/PI3K/Akt signaling pathway in skeletal muscle tissues.
“Oral supplementation Escherichia coli significantly decreases the expression of MAFbx and MuRF1 in B. thailandensis, S. Typhimurium or dextran sulfate sodium-induced muscle atrophy via the activation of the IGF-1/PI3K/Akt signaling pathway in skeletal muscle tissues [160].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [160]
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- Authors
- Schieber, A. M. P., Lee, Y. M., Chang, M. W., Leblanc, M., Collins, B., Downes, M., Evans, R. M., & Ayres, J. S.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Schieber, Alexandria M. Palaferri
- Lee, Yujung Michelle
- Ayres, Janelle S.
- ORCID
- Venue
- Science
- Published
- 2015-10-30
- Volume
- 350
- Issue
- 6260
- Pages
- 558-563
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4732872
- OpenAlex
- W2285543512
- Cited by
- 189
- References
- 44
- Citations by year
- 2026: 3 · 2025: 16 · 2024: 13 · 2023: 13 · 2022: 16 · 2021: 16 · 2020: 20 · 2019: 18 · 2018: 25 · 2017: 24 · 2016: 23 · 2015: 2
- FWCI
- 10.71
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01AI114929, DK0577978, CA014195)
- Howard Hughes Medical Institute
- Samuel Waxman Cancer Research Foundation
- Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002)
- NOMIS Foundation
- Searle Scholar Foundation
- Ray Thomas Edward Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- disease tolerance, gut microbiota, commensal Escherichia coli, muscle atrophy, cachexia, NLRC4 inflammasome, insulin-like growth factor I, PI3K/Akt signaling, Salmonella typhimurium, Burkholderia thailandensis, intestinal infection, skeletal muscle, inflammation
- MeSH terms
- Animals, Calcium-Binding Proteins, Escherichia coli, Insulin-Like Growth Factor I, Intestines, Mice, Inbred C57BL, Salmonella Infections, Salmonella typhimurium, Muscle, Skeletal, Burkholderia, Burkholderia Infections, Wasting Syndrome, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt, Mice, Biosynthetic Pathways, Phosphatidylinositol 3-Kinase, Inflammasomes, Microbiota
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