Jing Lv, He-Ping Zhao, Yan Yu, Ji-Han Wang, Xiao-Jun Zhang, Zhi-Qi Guo, Wen-Yan Jiang, Kai Wang, Lei Guo
{"title":"从肠道微生物生态学到脂质稳态:解码肠道微生物群在血脂异常发病机制和干预中的作用。","authors":"Jing Lv, He-Ping Zhao, Yan Yu, Ji-Han Wang, Xiao-Jun Zhang, Zhi-Qi Guo, Wen-Yan Jiang, Kai Wang, Lei Guo","doi":"10.3748/wjg.v31.i30.108680","DOIUrl":null,"url":null,"abstract":"<p><p>Dyslipidemia, a complex disorder characterized by systemic lipid profile abnormalities, affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease. Mounting evidence has established the gut microbiota (GM) as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation, immunometabolic regulation, and bioactive metabolite signaling. However, the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment. Mechanistically, GM perturbations disrupt lipid homeostasis <i>via</i> lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction, short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis, bile acid-farnesoid X receptor/Takeda G protein-coupled receptor 5 axis dysfunction altering cholesterol flux, microbial β-oxidation intermediates impairing mitochondrial energetics, and host-microbiota non-coding RNA crosstalk regulating lipogenic genes. This comprehensive review systematically examines three critical dimensions, including bidirectional GM-lipid axis interactions, molecular cascades bridging microbial ecology to metabolic dysfunction, and translational applications of GM modulation through precision probiotics, structure-specific prebiotics, and a metabolically optimized fecal microbiota transplantation protocol. Notwithstanding these advances, critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing. Future directions require longitudinal multi-omic studies, gnotobiotic models for mechanistic validation, and machine learning-driven personalized microbiota profiling. This synthesis provides a framework for developing microbiota-centric strategies targeting dyslipidemia pathophysiology, with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 30","pages":"108680"},"PeriodicalIF":5.4000,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404133/pdf/","citationCount":"0","resultStr":"{\"title\":\"From gut microbial ecology to lipid homeostasis: Decoding the role of gut microbiota in dyslipidemia pathogenesis and intervention.\",\"authors\":\"Jing Lv, He-Ping Zhao, Yan Yu, Ji-Han Wang, Xiao-Jun Zhang, Zhi-Qi Guo, Wen-Yan Jiang, Kai Wang, Lei Guo\",\"doi\":\"10.3748/wjg.v31.i30.108680\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Dyslipidemia, a complex disorder characterized by systemic lipid profile abnormalities, affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease. Mounting evidence has established the gut microbiota (GM) as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation, immunometabolic regulation, and bioactive metabolite signaling. However, the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment. Mechanistically, GM perturbations disrupt lipid homeostasis <i>via</i> lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction, short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis, bile acid-farnesoid X receptor/Takeda G protein-coupled receptor 5 axis dysfunction altering cholesterol flux, microbial β-oxidation intermediates impairing mitochondrial energetics, and host-microbiota non-coding RNA crosstalk regulating lipogenic genes. This comprehensive review systematically examines three critical dimensions, including bidirectional GM-lipid axis interactions, molecular cascades bridging microbial ecology to metabolic dysfunction, and translational applications of GM modulation through precision probiotics, structure-specific prebiotics, and a metabolically optimized fecal microbiota transplantation protocol. Notwithstanding these advances, critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing. Future directions require longitudinal multi-omic studies, gnotobiotic models for mechanistic validation, and machine learning-driven personalized microbiota profiling. This synthesis provides a framework for developing microbiota-centric strategies targeting dyslipidemia pathophysiology, with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.</p>\",\"PeriodicalId\":23778,\"journal\":{\"name\":\"World Journal of Gastroenterology\",\"volume\":\"31 30\",\"pages\":\"108680\"},\"PeriodicalIF\":5.4000,\"publicationDate\":\"2025-08-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404133/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3748/wjg.v31.i30.108680\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3748/wjg.v31.i30.108680","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
From gut microbial ecology to lipid homeostasis: Decoding the role of gut microbiota in dyslipidemia pathogenesis and intervention.
Dyslipidemia, a complex disorder characterized by systemic lipid profile abnormalities, affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease. Mounting evidence has established the gut microbiota (GM) as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation, immunometabolic regulation, and bioactive metabolite signaling. However, the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment. Mechanistically, GM perturbations disrupt lipid homeostasis via lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction, short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis, bile acid-farnesoid X receptor/Takeda G protein-coupled receptor 5 axis dysfunction altering cholesterol flux, microbial β-oxidation intermediates impairing mitochondrial energetics, and host-microbiota non-coding RNA crosstalk regulating lipogenic genes. This comprehensive review systematically examines three critical dimensions, including bidirectional GM-lipid axis interactions, molecular cascades bridging microbial ecology to metabolic dysfunction, and translational applications of GM modulation through precision probiotics, structure-specific prebiotics, and a metabolically optimized fecal microbiota transplantation protocol. Notwithstanding these advances, critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing. Future directions require longitudinal multi-omic studies, gnotobiotic models for mechanistic validation, and machine learning-driven personalized microbiota profiling. This synthesis provides a framework for developing microbiota-centric strategies targeting dyslipidemia pathophysiology, with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.
期刊介绍:
The primary aims of the WJG are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in gastroenterology and hepatology.