ArticleProceedings of the National Academy of Sciences of the United States of America2019
Western diet regulates immune status and the response to LPS-driven sepsis independent of diet-associated microbiome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- The obesity paradox in murine sepsis models: a systematic review and meta-analysis.Anaesthesiology intensive therapy · 2025Pooled it
- Adherence to the EAT-Lancet Diet and Risk of Sepsis: A Prospective Cohort Study from the UK Biobank.NPJ science of food · 2026Article
- Gut microbiota and pediatric eye diseases: current insights, mechanistic underpinnings, and future outlook.Frontiers in nutrition · 2026Review
- Fiber-deprived diet weakens lung defense against antimicrobial-resistantGut microbes reports · 2026Article
- Review
- A high-lipid diet leads to greater pathology and lower tolerance during infection.The Journal of experimental biology · 2025Article
- Nutrition, Gut Microbiota, and Epigenetics in the Modulation of Immune Response and Metabolic Health.Cardiology and cardiovascular medicine · 2025Article
- Nutritional Strategies for the Treatment and Prevention of Sepsis Outside the Intensive Care Unit.Nutrients · 2024Review
- Western diets and chronic diseases.Nature medicine · 2024Review
- Immunological insights into hypertension: unraveling triggers and potential therapeutic avenues.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- Effects of Age and Diet on Triglyceride Metabolism in Mice.bioRxiv : the preprint server for biology · 2024Article
- Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice.Nature communications · 2024Article
- Association of early dietary fiber intake and mortality in septic patients with mechanical ventilation based on MIMIC IV 2.1 database: a cohort study.Nutrition journal · 2024Article
- Fermented Sprouts ofPharmaceutics · 2023Article
- Review
- miR-181c, a potential mediator for acute kidney injury in a burn rat model with following sepsis.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2023Article
- A new frontier for fat: dietary palmitic acid induces innate immune memory.Immunometabolism (Cobham, Surrey) · 2023Review
- [Immunomodulation by nutritional intervention in critically ill patients].Die Anaesthesiologie · 2023Review
- Pyruvate Dehydrogenase Kinase 2 Accelerates Endotoxin Shock by Promoting Mitogen-Activated Protein Kinase Activation.Inflammation · 2023Article
- Contributions of the microbiota to the systemic inflammatory response.Microbiota and host · 2023Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.