Western diet regulates immune status and the response to LPS-driven sepsis independent of diet-associated microbiome.

Autor:	Napier BA; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Andres-Terre M; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Massis LM; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Hryckowian AJ; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Higginbottom SK; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Cumnock K; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Casey KM; Department of Comparative Medicine, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Haileselassie B; Department of Pediatrics, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Lugo KA; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Schneider DS; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Sonnenburg JL; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305., Monack DM; Department of Microbiology and Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305; dmonack@stanford.edu.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2019 Feb 26; Vol. 116 (9), pp. 3688-3694. Date of Electronic Publication: 2019 Feb 11.
DOI:	10.1073/pnas.1814273116
Abstrakt:	Sepsis is a deleterious immune response to infection that leads to organ failure and is the 11th most common cause of death worldwide. Despite plaguing humanity for thousands of years, the host factors that regulate this immunological response and subsequent sepsis severity and outcome are not fully understood. Here we describe how the Western diet (WD), a diet high in fat and sucrose and low in fiber, found rampant in industrialized countries, leads to worse disease and poorer outcomes in an LPS-driven sepsis model in WD-fed mice compared with mice fed standard fiber-rich chow (SC). We find that WD-fed mice have higher baseline inflammation (metaflammation) and signs of sepsis-associated immunoparalysis compared with SC-fed mice. WD mice also have an increased frequency of neutrophils, some with an "aged" phenotype, in the blood during sepsis compared with SC mice. Importantly, we found that the WD-dependent increase in sepsis severity and higher mortality is independent of the microbiome, suggesting that the diet may be directly regulating the innate immune system through an unknown mechanism. Strikingly, we could predict LPS-driven sepsis outcome by tracking specific WD-dependent disease factors (e.g., hypothermia and frequency of neutrophils in the blood) during disease progression and recovery. We conclude that the WD is reprogramming the basal immune status and acute response to LPS-driven sepsis and that this correlates with alternative disease paths that lead to more severe disease and poorer outcomes. Competing Interests: The authors declare no conflict of interest.
Databáze:	MEDLINE
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