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Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota

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Frontiers of Medicine 2018年第6期12卷 645-657页

作者： Ruiting Han Junli Ma houkai li Functional Metabolomic and Gut Microbiome Laboratory Institute of Interdisciplinary Integrative Biomedical ResearchShanghai University of Traditional Chinese MedicineShanghai 201203China

Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical “Two-hit” theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a “metabolic organ” that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.

关键词： gut microbiota NAFLD obesity insulin resistance bile acids probiotic

环磷酰胺诱导的小鼠免疫低下模型的方法学考察及金樱子提取物联合益生菌调节免疫功能的研究

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中国免疫学杂志 2024年第8期40卷 1701-1708页

作者：刘泽坤马俊丽李艳郑宁宁盛丽莉李后开上海中医药大学中药学院上海201203

目的:建立更符合人体免疫低下状态的小鼠模型,并基于此模型考察金樱子、益生菌以及二者联合用药对免疫功能的调节作用。方法:采用不同给药剂量、时间和实验终点的环磷酰胺建立小鼠免疫低下模型,并与氢化可的松及环孢素A诱导的免疫低下... 详细信息

目的:建立更符合人体免疫低下状态的小鼠模型,并基于此模型考察金樱子、益生菌以及二者联合用药对免疫功能的调节作用。方法:采用不同给药剂量、时间和实验终点的环磷酰胺建立小鼠免疫低下模型,并与氢化可的松及环孢素A诱导的免疫低下模型对比,确立了25 mg/kg环磷酰胺隔日共注射7次,无恢复期的免疫低下小鼠模型;流式细胞术检测小鼠脾脏淋巴细胞(CD4^(+)T细胞、CD8^(+)T细胞、CD19^(+)B细胞)比例变化;qRT-PCR检测小鼠脾脏炎症因子(IL-1β、IL-6)mRNA表达。结果:80 mg/kg环磷酰胺连续注射3 d后,胸腺萎缩,脾脏肿大,脾脏中CD4^(+)T细胞、CD8^(+)T细胞、CD19^(+)B细胞比例下降,IL-1β及IL-6 mRNA表达上调;25 mg/kg环磷酰胺隔日注射共7次后,胸腺和脾脏萎缩,脾脏中CD4^(+)T及CD8^(+)T细胞比例呈升高趋势,IL-1β及IL-6 mRNA表达上调;环磷酰胺造模后恢复1周或2周,小鼠免疫器官重量和指数、脾脏淋巴细胞比例、脾脏炎症细胞因子mRNA表达均显著恢复;金樱子联合益生菌可显著恢复环磷酰胺导致的CD4^(+)T细胞上调以及炎症因子IL-1β上调。结论:本研究建立了25 mg/kg环磷酰胺隔日注射共7次,无恢复期的免疫低下小鼠模型,并基于此模型发现金樱子联合益生菌具有一定的正向免疫调节作用。

关键词：免疫功能低下环磷酰胺动物模型药物评价

山药多糖延缓秀丽隐杆线虫衰老的药效评价及作用机制研究

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世界中医药 2024年第4期19卷 473-480页

作者：刘泽坤贺小芳洪颖盛丽莉李后开上海中医药大学中药学院上海201203

目的:基于秀丽隐杆线虫模型考察山药多糖的抗衰老药效并探究其作用机制。方法:基于秀丽隐杆线虫模型,利用寿命、咽泵频率、身体活动频率、脂褐素荧光、抗压性实验、活性氧荧光、抗氧化酶活性等指标考察山药多糖的抗衰老药理活性;通过转... 详细信息

目的:基于秀丽隐杆线虫模型考察山药多糖的抗衰老药效并探究其作用机制。方法:基于秀丽隐杆线虫模型,利用寿命、咽泵频率、身体活动频率、脂褐素荧光、抗压性实验、活性氧荧光、抗氧化酶活性等指标考察山药多糖的抗衰老药理活性;通过转录组数据分析,探究山药多糖的抗衰老药效机制。结果:山药多糖可以显著延长线虫的寿命,缓解衰老过程中咽泵频率以及身体活动频率的下降,降低衰老过程中脂褐素及活性氧积累并提高线虫的抗压能力和抗氧化活性。转录组学京都基因和基因组百科全书(KEGG)通路分析发现,内分泌系统、细胞的生长和凋亡通路发生了显著的变化。山药多糖调控了30个与衰老相关的基因表达,且差异基因主要显著富集在自噬、哺乳动物雷帕霉素靶蛋白(mTOR)及胰岛素信号通路。结论:山药多糖具有抗衰老药理活性,转录组学数据揭示这种抗衰老作用可能与自噬、mTOR及胰岛素信号通路有关。

关键词：山药多糖秀丽隐杆线虫抗衰老寿命抗氧化转录组学自噬胰岛素信号通路

Amygdala, an important regulator for food intake

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Frontiers in Biology 2011年第1期6卷 82-85页

作者： Qian ZHANG houkai li Feifan GUO Key Laboratory of Nutrition and Metabolism Institute for Nutritional SciencesShanghai Institutes for Biological SciencesChinese Academy of Sciencesthe Graduate School of the Chinese Academy of SciencesShanghai 200031China

Amygdala plays a critical role in the regulation of emotional behavior and food *** are short chains of amino acids secreted by neurons as intercellular messengers,which regulate different functions such as emotion,food intake,learning and *** this review,we summarize the recent progress on the regulation of food intake by amygadala,which is mediated by those neuropeptides known to be critical in the regulation of this process.

关键词： amygdala food intake neuropeptide

Functional Metabolomics Reveals that Astragalus Polysaccharides Improve lipids Metabolism through Microbial Metabolite 2-Hydroxybutyric Acid in Obese Mice

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Engineering 2022年第2期8卷 111-122页

作者： Bingbing li Ying Hong Yu Gu Shengjie Ye Kaili Hu Jian Yao Kan Ding Aihua Zhao Wei Jia houkai li Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China University of Hawaii Cancer Center HonoluluHI 96813USA

Polysaccharides are widely present in herbs with multiple activities,especially immunity regulation and metabolic benefits for metabolic ***,the underlying mechanisms are not well *** metabolomics is increasingly used to investigate systemic effects on the host by iden-tifying metabolites with particular *** study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides(APS)by adopting a functional metabolomics *** effects of APS were determined in eight-week high-fat diet(HFD)-fed obese ***,gas chromatography–time-of-flight mass spectrometry(GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues,and liquid chromatography–tandem mass spectrom-etry(LC–MS/MS)-based targeted metabolomics was *** potential functions of the metabo-lites were tested with in vitro and in vivo models of metabolic *** results first confirmed the metabolic benefits of APS in obese ***,metabolomics analysis revealed that APS supplemen-tation reversed the HFD-induced metabolic changes,and identified 2-hydroxybutyric acid(2-HB)as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by *** study indicated that 2-HB inhibited oleic acid(OA)-induced triglyceride(TG)*** was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 ***,it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose(HFHS)-fed *** conclusion,our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation,which modulated lipid metabolism both in vitro and in *** results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides.

关键词： Astragalus polysaccharides(APS) Functional metabolomics 2-Hydroxybutyric acid Obesity

Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid

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Journal of Pharmaceutical Analysis 2020年第6期10卷 560-570页

作者： Ningning Zheng Yu Gu Ying Hong lili Sheng linlin Chen Feng Zhang Jie Hou Weidong Zhang Zean Zhang Wei Jia houkai li Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghai201203China College of Basic Medical Sciences Dalian Medical UniversityDalian116044China School of Pharmacy Second Military Medical UniversityShanghai200433China Center for Drug Safety Evaluation and Research Shanghai University of Traditional Chinese MedicineShanghai201203China University of Hawaii Cancer Center HonoluluHI96813USA Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200233China

liver injury caused by acetaminophen(AP)overdose is a leading public health *** APinduced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone(NAPQI),a toxic metabolite of AP,resulting in cell damage,emerging evidence indicates that AP-induced liver injury is also associated with gut ***,the gut microbiota-involved mechanism remains largely *** our study,we found that vancomycin(Vac)pretreatment(100 mg/kg,twice a day for 4 days)attenuated AP-induced liver injury,altered the composition of gut microbiota,and changed serum metabolic ***,we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid(2-HB),which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH *** current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.

关键词： revealed liver injury Gut microbiota Acetaminophen Vancomycin 2-Hydroxybutyric acid

Microbial and transcriptomic profiling reveals diet-related alterations of metabolism in metabolic disordered mice

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Microbial and transcriptomic profiling reveals diet-related ...

Cold exposure promotes coronavirus infection by altering the gut microbiota and lipid metabolism to reduce host immunity

中国营养学会第十五届全国营养科学大会

作者： Weize Zhu Ying Hong Yan li Jing Zhong Xiaofang He Ningning Zheng lili Sheng houkai li Shanghai University of Traditional Chinese Medicine Huzhou Central Hospital

Metabolic syndrome(MetS) is a complex disease that determined by a cluster of interactional factors, of which, gut microbiota plays a critical role in regulating host metabolism. However, why different diets with the same energy led to divergent degree of MetS remains uncertain. This study explored the effect of diet on host metabolism from the perspective of dynamic changes of gut microbiota composition over time. Methods Mice were fed with two kind of high-energy diets, high sucrose diet(HSD) and high fat diet(HFD), for 4, 8, and 12 weeks to determine the dynamic associations between the microbiota and MetS, and hepatic transcriptomic profile was studied to explore dietary effect on liver gene expression. In addition, fecal microbiota transplantation(FMT) was performed to study the different effect of HSD or HFDaltered gut microbiota on host metabolism in the recipient mice. Results Our result showed that HFD led to more severe MetS than HSD in all studied time points, including more body weight gain, more severe hepatic steatosis and insulin resistance. However, HSD induced higher serum triglycerides level than HFD throughout the entire study. Gut microbiota 16 S rRNA gene sequencing showed that HFD rapidly and steadily reduced species richness, altered microbiota structure and function, and increased the abundance of bacteria responsible for fatty acid metabolism and inflammatory signaling, but reduced bacterial sugar-related metabolism in a time-dependent manner. In contrast, HSD had less effect on regulating gut microbiota structure. HSD activated microbial sugar metabolism and reduced insulin regulation signal at only early stage, but activated both primary and secondary bile acid biosynthesis at only late stage. Alistipes and Bacteroides genera, the abundance of which were significantly increased in HFD than HSD and Con group at all three time points, were positively correlated with obesity, hyperlipidemia, liver steatosis, and insulin resistance. However, [

关键词： metabolic syndrome high-energy diet gut microbiota metabolism

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Frigid Zone Medicine 2023年第4期3卷 216-231,I0002-I0006页

作者： Gaosong Wu Yuhao Zhang Ningning Zheng Saisai Tian Jingyu liao Wanqi Le houkai li Weidong Zhang Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghai 201203China School of Traditional Chinese Pharmacy China Pharmaceutical UniversityNanjing 211198China School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Phytochemistry School of PharmacySecond Military Medical UniversityShanghai 200433China Institute of Medicinal Plant Development Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China

Objective:Cold exposure has been suggested to be advantageous for the spread and infection of the coronavirus,and the gut microbiota influences the severity of the infection by modulating host inflammatory and immune ***,it remains unclear whether the promotion of viral infection through cold exposure is linked to the gut ***:In this study,we performed an unbiased analysis of gut microbiota,serum,and lung tissue metabolome changes in cold-exposed and virus-infected mice,alongside the assessment of immune-inflammatory indicators in serum and lung ***:The results revealed that both cold exposure and viral infection significantly decreased the percentage of peripheral blood lymphocytes(CD4^(+)T cells,CD8^(+)T cells,and B cell)and increased the expression of inflammatory factors(IL-6,IL-1β,TNF-α,and IFN-γ).Meanwhile,cold exposure disrupted the homeostasis of gut microbiota,elevating the abundance of pathogenic bacteria(Staphylococcus)and diminishing the abundance of beneficial bacteria(Alistipes).Notably,in virus-infected mice exposed to a cold environment,the reduction in the abundance of beneficial bacteria Alistipes was more pronounced than in cases of single virus infection and cold *** of altered serum and lung tissue metabolites highlighted glycerophospholipids,fatty acids,and eicosanoids as the most affected metabolites by cold *** metabolites,closely associated with virus infection,exhibited a significant correlation with immune-inflammatory ***:These findings establish a mechanistic connection between cold exposure and virus infection,suggesting that cold exposure-induced dysregulation of gut microbiota and lipid metabolism diminishes host immunity,promoting virus infection.

关键词： cold exposure coronavirus infection gut microbiota lipid metabolism immune

生物质热解固体热载体高温烟气加热装置设计与试验

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农业工程学报 2017年第4期33卷 89-95页

作者：王绍庆李志合吴厚凯李宁柏雪源山东理工大学农业工程与食品科学学院/山东省清洁能源工程技术研究中心淄博255049

固体热载体加热生物质是生物质热解制取生物油的工艺手段之一。为解决固体热载体间接加热方式升温慢、效率低问题,设计了一种流化床生物质燃烧的热烟气直接加热固体热载体装置,分析了其结构与原理,开展了固体热载体升温性能和流化床燃... 详细信息

固体热载体加热生物质是生物质热解制取生物油的工艺手段之一。为解决固体热载体间接加热方式升温慢、效率低问题,设计了一种流化床生物质燃烧的热烟气直接加热固体热载体装置,分析了其结构与原理,开展了固体热载体升温性能和流化床燃烧器的燃烧特性试验研究,并对试验结果进行了热平衡分析。结果表明:流化床高温烟气加热陶瓷球热载体的平均热能利用率为66.3%,流化床燃烧生物质粉产生的高温烟气能够满足热载体加热装置对热源的需求,热载体加热器内的热量传递方式主要是对流换热。陶瓷球热载体与加热器内高温烟气的对流传热系数为475 W/(m^2·℃)。研究对结果对解决生物质热解液化技术中的固体热载体加热升温关键问题具有重要指导意义。

关键词：生物质燃烧加热装置流化床固体热载体