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

Full bibliography

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

Resource type
Title
Western diet regulates immune status and the response to LPS-driven sepsis independent of diet-associated microbiome
Abstract
<p>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.</p>
Publication
Proceedings of the National Academy of Sciences
Pages
201814273
Date
2019/02/06
Journal Abbr
PNAS
Language
en
DOI
10.1073/pnas.1814273116
ISSN
0027-8424, 1091-6490
Accessed
2019-02-14T04:12:23Z
Library Catalog
Rights
© 2019 . Published under the PNAS license.
Citation
Napier, B. A., Andres-Terre, M., Massis, L. M., Hryckowian, A. J., Higginbottom, S. K., Cumnock, K., … Monack, D. M. (2019). Western diet regulates immune status and the response to LPS-driven sepsis independent of diet-associated microbiome. Proceedings of the National Academy of Sciences, 201814273. https://doi.org/10.1073/pnas.1814273116
Processing time: 0.05 seconds