Time-restricted feeding protects against septic liver injury by reshaping gut microbiota and metabolite 3-hydroxybutyrate
Hu JJ, Deng F, Sun QS, Xiong QM, Min Y, Feng SY, Lin ZB, Chen PH, Hu Z, Wu L, Chen XF, Xie S, Liu WF, Li C, Liu KX
Gut microbes · 27 citas
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiación independiente
- Universidad u hospital
- Southern Medical University
- Universidad u hospital
- Nanfang Hospital
Según 2 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2025-04-13 · Gut Microbes · vol. 17 · número 1 · pág. 2486515
- Editorial
- Landes Bioscience
- Citado
- 27 citas · más que el 99% de estudios similares · 14.4× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 66 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Diet and metabolism studies · Dietary Effects on Health · Gut microbiota and health
- Palabras clave
- Biology, Metabolite, Gut flora, Microbiology, Probiotic, Liver injury, Metabolome, Bacteria, Immunology, Pharmacology, Biochemistry, Genetics
- MeSH
- liver, animals, mice, inbred c57bl, mice, knockout, humans, mice, sepsis, liver diseases, disease models, animal, 3-hydroxybutyric acid, male, gastrointestinal microbiome
15 autores
- Jingjuan Hu🇨🇳Nanfang Hospital; Southern Medical University
- Fan Deng🇨🇳Nanfang Hospital; Southern Medical University
- Qi‐Shun Sun🇨🇳Nanfang Hospital; Southern Medical University
- Qingming Xiong🇨🇳Nanfang Hospital; First People's Hospital of Foshan; Southern Medical University
- Yue Min🇨🇳Nanfang Hospital; Southern Medical University
- Siyuan Feng🇨🇳Nanfang Hospital; Southern Medical University
- Zebin Lin🇨🇳Nanfang Hospital; Southern Medical University
- P. K. Chen🇨🇳Nanfang Hospital; Southern Medical University
- Zhen Hu🇨🇳Nanfang Hospital; Southern Medical University
- Ling Wu🇨🇳Nanfang Hospital; Southern Medical University
- Xiaofeng Chen🇨🇳Nanfang Hospital; Southern Medical University
- Sun Xie🇨🇳Nanfang Hospital; Southern Medical University
- Weifeng Liu🇨🇳Nanfang Hospital; Southern Medical University
- Cai Li🇨🇳Nanfang Hospital; Southern Medical University
- Ke‐Xuan Liu🇨🇳 · autor de correspondenciaNanfang Hospital; Southern Medical University
Resumen
El texto original del estudio, en el idioma en que se publicó.
Liver injury is an independent risk factor for multiple organ dysfunction and high mortality in patients with sepsis. However, the pathological mechanisms and therapeutic strategies for sepsis-associated liver injury have not been fully elucidated. Time-restricted feeding (TRF) is a promising dietary regime, but its role in septic liver injury remains unknown. Using 16S rRNA gene sequencing, Q200 targeted metabolomics, transcriptomics, germ-free mice, Hmgcs2/Lpin1 gene knockout mice, and Aml12 cells experiments, we revealed that TRF can mitigate septic liver injury by modulating the gut microbiota, particularly by increasing Lactobacillus murinus (L. murinus) abundance, which was significantly reduced in septic mice. Further study revealed that live L. murinus could markedly elevate serum levels of metabolite 3-hydroxybutyrate (3-HB) and alleviate sepsis-related injury, while the knockout of the key enzyme for 3-HB synthesis (3-hydroxy-3-methylglutaryl-CoA synthase 2, Hmgcs2) in the liver negated this protective effect. Additionally, serum 3-HB levels were significantly positively correlated with L. murinus abundance and negatively correlated with liver injury indicators in septic patients, demonstrating a strong predictive value for septic liver injury (AUC = 0.8429). Mechanistically, 3-HB significantly inhibited hepatocyte ferroptosis by activating the PI3K/AKT/mTOR/LPIN1 pathway, reducing ACSL4, MDA, LPO, and Fe2+ levels. This study demonstrates that TRF reduces septic liver injury by modulating gut microbiota to increase L. murinus, which elevates 3-HB to activate PI3K/AKT/mTOR/LPIN1 and inhibit hepatocyte ferroptosis. Overall, this study elucidates the protective mechanism of TRF against septic liver injury and identifies 3-HB as a potential therapeutic target and predictive biomarker, thereby providing new insights into the clinical management and diagnosis of septic liver injury.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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