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

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Science  30 Oct 2015:
Vol. 350, Issue 6260, pp. 558-563
DOI: 10.1126/science.aac6468

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The benefits of Escherichia coli

Infection and intestinal damage can trigger severe muscle wasting and loss of fat in mice. How this happens is poorly understood. Palaferri Schieber et al. discovered a protective Escherichia coli strain in their mouse colony. Mice intestinally colonized with the E. coli and infected with the food-poisoning bug Salmonella or with the lung pathogen Burkholderia did not waste away. Without the E. coli, similarly infected mice became fatally ill. The protective E. coli stimulated an innate immune mechanism that ensured that muscle-signaling pathways were not damaged by infection. Thus, the friendly E. coli allowed its host to tolerate and survive the pathogens.

Science, this issue p. 558

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.

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