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When smoke meets gut:deciphering the interactions between tobacco smoking and gut microbiota in disease development

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Science China(Life Sciences) 2024年第5期67卷 854-864页

作者： Bo Chen Guangyi Zeng Lulu Sun Changtao Jiang Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking UniversityBeijing 100191China State Key Laboratory of Women’s Reproductive Health and Fertility Promotion Peking UniversityBeijing 100191China Department of Endocrinology and Metabolism Peking University Third HospitalBeijing 100191China

Tobacco smoking is a prevalent and detrimental habit practiced worldwide,increasing the risk of various diseases,including chronic obstructive pulmonary disease(COPD),cardiovascular disease,liver disease,and cancer.Although previous research has explored the detrimental health effects of tobacco smoking,recent studies suggest that gut microbiota dysbiosis may play a critical role in these outcomes.Numerous tobacco smoke components,such as nicotine,are found in the gastrointestinal tract and interact with gut microbiota,leading to lasting impacts on host health and diseases.This review delves into the ways tobacco smoking and its various constituents influence gut microbiota composition and functionality.We also summarize recent advancements in understanding how tobacco smoking-induced gut microbiota dysbiosis affects host health.Furthermore,this review introduces a novel perspective on how changes in gut microbiota following smoking cessation may contribute to withdrawal syndrome and the degree of health improvements in smokers.

关键词： tobacco smoking gut microbiota dysbiosis nicotine smoking cessation

Advances in regulation and function of stearoyl-CoA desaturase 1 in cancer,from bench to bed

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Science China(Life Sciences) 2023年第12期66卷 2773-2785页

作者： Zhengyang Guo Xiao Huo Xianlong Li Changtao Jiang Lixiang Xue Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University and the Key Laboratory of Molecular Cardiovascular Science(Peking University)Ministry of EducationBeijing 100191China Peking University Third Hospital Cancer Center Department of Radiation OncologyPeking University Third HospitalBeijing 100191China

Stearoyl-CoA desaturase 1(SCD1)converts saturated fatty acids to monounsaturated fatty acids.The expression of SCD1 is increased in many cancers,and the altered expression contributes to the proliferation,invasion,stemness and chemoresistance of cancer cells.Recently,more evidence has been reported to further support the important role of SCD1 in cancer,and the regulation mechanism of SCD1 has also been focused.Multiple factors are involved in the regulation of SCD1,including metabolism,diet,tumor microenvironment,transcription factors,non-coding RNAs,and epigenetics modification.Moreover,SCD1 is found to be involved in regulating ferroptosis resistance.Based on these findings,SCD1 has been considered as a potential target for cancer treatment.However,the resistance of SCD1 inhibition may occur in certain tumors due to tumor heterogeneity and metabolic plasticity.This review summarizes recent advances in the regulation and function of SCD1 in tumors and discusses the potential clinical application of targeting SCD1 for cancer treatment.

关键词： cancer metabolism SCD1 fatty acid lipid metabolism ferroptosis ER stress drug resistance cancer therapy

Gut microbial-host-isozymes are new targets for diseases

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Science China Life Sciences 2024年第7期67卷 1525-1527页

作者： Zhiwei Zhang Kai Wang Changtao Jiang Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Female Fertility PromotionCenter for Reproductive MedicinePeking University Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking University

Gut microbiota can interact with the host through lots of media including small molecular metabolites and proteins(Cani,2019; Fan and Pedersen, 2021; Krautkramer et al., 2021). Recently, a new interaction pattern was identified, i.e.,gut microbiota can mimic the function of the host by producing a variety of enzymes with functions homologous to host enzymes,

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The role of the gut microbiome and its metabolites in metabolic diseases

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Protein & Cell 2021年第5期12卷 360-373页

作者： Jiayu Wu Kai Wang Xuemei Wang Yanli Pang Changtao Jiang Department of Obstetrics and Gynecology Center for Obesity and Metabolic Disease ResearchSchool of Basic Medical SciencesThird HospitalPeking UniversityBeijing 100191China Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking UniversityKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing 100191China

It is well known that an unhealthy lifestyle is a major risk factor for metabolic diseases,while in recent years,accumulating evidence has demonstrated that the gut microbiome and its metabolites also play a crucial role in the onset and development of many metabolic diseases,including obesity,type 2 diabetes,nonalcoholic fatty liver disease,cardiovascular disease and so on.Numerous microorganisms dwell in the gastrointestinal tract,which is a key interface for energy acquisition and can metabolize dietary nutrients into many bioactive substances,thus acting as a link between the gut microbiome and its host.The gut microbiome is shaped by host genetics,immune responses and dietary factors.The metabolic and immune potential of the gut microbiome determines its significance in host health and diseases.Therefore,targeting the gut microbiome and relevant metabolic pathways would be effective therapeutic treatments for many metabolic diseases in the near future.This review will summarize information about the role of the gut microbiome in organism metabolism and the relationship between gut microbiome-derived metabolites and the pathogenesis of many metabolic diseases.Furthermore,recent advances in improving metabolic diseases by regulating the gut microbiome will be discussed.

关键词： gut microbiome metabolism metabolite immune regulation metabolic diseases

Role of gut microbiota in the development of non-alcoholic fatty liver disease

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Liver Research 2019年第1期3卷 25-30页

作者： Xuemei Wang Jialin Xia Changtao Jiang Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking UniversityThe Key Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijingChina

Non-alcoholic fatty liver disease(NAFLD)is a chronic liver disease characterized by hepatic steatosis in the absence of other causes,such as chronic alcohol consumption,that cause secondary hepatic fat accumulation.NAFLD has become the most common liver disease worldwide over the past two decades,and the prevalence of NAFLD is 20e30%in Western countries.However,the mechanism of NAFLD re-mains unclear.The gut microbiota plays an important role in the metabolism of the host;in fact,it has been implicated in inflammatory diseases,metabolic syndrome and cardiovascular disease.Accumu-lating evidence has indicated that gut microbiota component changes are linked to human obesity,in-sulin resistance(IR),type 2 diabetes and NAFLD.Here,we provide insight into the role of gut microbiota,especially bile salt hydrolase(BSH)in modulating the bile acid pool and farnesoid X receptor(FXR),which promotes the synthesis of ceramide and contributes to the development of NAFLD.

关键词： Non-alcoholic fatty liver disease(NAFLD) Gut microbiota Bile acid Farnesoid X receptor(FXR) Ceramide Bile salt hydrolase(BSH)

Microbial transformations of bile acids and their receptors in the regulation of metabolic dysfunction-associated steatotic liver disease

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Liver Research 2023年第3期7卷 165-176页

作者： Yuhua Gao Jun Lin Chuan Ye Siqi Guo Changtao Jiang Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking Universityand the Key Laboratory of Molecular Cardiovascular Science(Peking University)Ministry of EducationBeijingChina Center of Basic Medical Research Institute of Medical Innovation and ResearchThird HospitalPeking UniversityBeijingChina Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking UniversityBeijingChina

Bile acids(BAs)play important roles in the digestion of dietary fats and molecular signal transduction,and modulation of the BA composition usually affects the progression of metabolic diseases.While the liver produces primary BAs,the gut microbiota modifies these products into various forms that greatly increase their diversity and biological functions.Mechanistically,BAs can regulate their own metabolism and transport as well as other key aspects of metabolic processes via dedicated BA receptors.Disruption of BA transport and homeostasis leads to the progression of liver diseases,including metabolic dysfunction-associated steatotic liver disease(MASLD)and hepatocellular carcinoma(HCC).Here,we summarize the microbial transformations of BAs and their downstream signaling in the development of metabolic diseases and present new insights into novel therapeutic strategies targeting BA pathways that may contribute to these diseases.

关键词： Bile acids(BAs) Gut microbiota Metabolic dysfunction-associated steatotic liver disease(MASLD) Metabolic dysfunction-associated steatohepatitis(MASH) Hepatocellular carcinoma(HCC) Farnesoid X receptor(FXR) G protein-coupled bile acid receptor 1(TGR5)

Metabolic disorder in the progression of heart failure

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Science China(Life Sciences) 2019年第9期62卷 1153-1167页

作者： Xiuxiu Zhang Huiying Liu Juan Gao Min Zhu Yupeng Wang Changtao Jiang Ming Xu Department of Cardiology and Institute of Vascular Medicine Peking University Third Hospital/ NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory PeptidesKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing Key Laboratory of Cardiovascular Receptors ResearchBeijing 100191China Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking UniversityKey Laboratory of Molecular Cardiovascular ScienceMinistry of Education and Beijing Key Laboratory of Cardiovascular Receptors ResearchBeijing 100191China State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Heart failure(HF) is a major clinical concern owing to its high prevalence and high mortality.Metabolomics,an effective approach to predict diagnostic biomarkers and to explore the altered metabolic pathways in pathogenesis,has been extensively applied in evaluating the course of diseases.In this study,we used this approach to analyse the abundance of metabolites,with liquid chromatograph-mass spectrometer,in plasma samples from rats with transverse aortic constriction(TAC) and patients at different stages of HF.We compared the metabolic parameters within and between TAC rats and patients.An apparent metabolic shift was observed in rats,from compensated hypertrophy stage to decompensated hypertrophy stage,and in patients with HF,from stage A to stage B and subsequently stage C.Diagnostic biomarkers were predicted by comparing the variable importance in the projection scores and fold change analysis within and between rats and patients.Enrichment pathway analysis and network analysis provided an overview of the largely disturbed metabolic pathways,and those interfered at different stages and across species were confirmed.The significantly changed metabolites and pathways revealed the underlying mechanisms of HF pathogenesis,hinted at novel potential biomarkers,and provided potential therapeutic intervention targets for HF.

关键词： heart failure metabolomics TAC HF stages A–C biomarker pathway analysis

Disruption of adipocyte HIF-1α improves atherosclerosis through the inhibition of ceramide generation

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1899-1912页

作者： Pengcheng Wang Guangyi Zeng Yu Yan Song-yang Zhang Yongqiang Dong Yangming Zhang Xingzhong Zhang Huiying Liu Zhipeng Zhang Changtao Jiang Yanli Pang Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking UniversityKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationBeijing 100191China Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191 China Center for Reproductive Medicine Department of Obstetrics and GynecologyPeking University Third HospitalBeijing 100191 China Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking UniversityBeijing 100191China General Surgery Department Peking University Third HospitalBeijing 100191China

Atherosclerosis is a chronic multifactorial cardiovascular disease.Western diets have been reported to affect atherosclerosis through regulating adipose function.In high cholesterol diet-fed ApoE^(−/−)mice,adipocyte HIF-1αdeficiency or direct inhibition of HIF-1αby the selective pharmacological HIF-1αinhibitor PX-478 alleviates high cholesterol diet-induced atherosclerosis by reducing adipose ceramide generation,which lowers cholesterol levels and reduces inflammatory responses,resulting in improved dyslipidemia and atherogenesis.Smpd3,the gene encoding neutral sphingomyelinase,is identified as a new target gene directly regulated by HIF-1αthat is involved in ceramide generation.Injection of lentivirus-SMPD3 in epididymal adipose tissue reverses the decrease in ceramides in adipocytes and eliminates the improvements on atherosclerosis in the adipocyte HIF-1α-deficient mice.Therefore,HIF-1αinhibition may constitute a novel approach to slow atherosclerotic progression.

关键词： HIF-1a SMPD3 Ceramide PX-478 Adipocyte Cholesterol Inflammatory responses Atherosclerosis

Gut microbiota,immunity,and bile acid metabolism:decoding metabolic disease interactions

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Life Metabolism 2023年第6期2卷 9-27页

作者： Qixiang Zhao Jiayu Wu Yong Ding Yanli Pang Changtao Jiang Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking UniversityBeijing 100191China

In recent decades,the global prevalence of metabolic syndrome has surged,posing a significant public health challenge.Metabolic disorders,encompassing diabetes,obesity,nonalcoholic fatty liver disease,and polycystic ovarian syndrome,have been linked to alterations in the gut microbiota.Nonetheless,the connection between gut microbiota and host metabolic diseases warrants further investigation.In this review,we delve into the associations between various metabolic disorders and the gut microbiota,focusing on immune responses and bile acid(BA)metabolism.Notably,T helper cells,innate lymphoid cells,macrophages,and dendritic cells have been shown to modulate host metabolism through interactions with intestinal microorganisms and the release of cytokines.Furthermore,secondary BA metabolites,derived from the microbiota,are involved in the pathogenesis of metabolic diseases via the farnesoid X receptor and Takeda G protein-coupled receptor 5.By covering both aspects of this immune system-microorganism axis,we present a comprehensive overview of the roles played by the gut microbiota,microbiota-derived BA metabolites,and immune responses in metabolic diseases,as well as the interplay between these systems.

关键词： intestinal microbiota metabolic disease immunity bile acids