OBJECTIVE:To investigate the effects of Jinlida granules(津力达颗粒,JLD)on body weight,glucose tolerance,intestinal inflammation and barrier function in high-fat diet(HFD)-induced obese rats and explore the regulation...OBJECTIVE:To investigate the effects of Jinlida granules(津力达颗粒,JLD)on body weight,glucose tolerance,intestinal inflammation and barrier function in high-fat diet(HFD)-induced obese rats and explore the regulation of the gut microbiota as a potential treatment mechanism.METHODS:Sprague-Dawley rats were divided into control,HFD,low-dose JLD(L-JLD),high-dose JLD(HJLD),and sitagliptin groups.The rats,with the exception of those in the control group,were fed a HFD to establish an obesity model while simultaneously receiving 0.5%carboxymethyl cellulose,L-JLD,H-JLD or sitagliptin for 25 weeks.We assessed body weight,conducted oral glucose tolerance tests,and analysed faecal samples using metagenomic sequencing.Haematoxylin-eosin(HE),Masson and immunohistochemical(IHC)staining were employed to evaluate histological changes in the colon tissue.Immunofluorescence(IF)staining was used to measure the expression levels of Zonula occludens-1(ZO-1)and Claudin-1 in colon tissue.The colon tissue was also subjected to transcriptomic evaluation.RESULTS:JLD treatment significantly reduced body weight and enhanced glucose tolerance in obese rats.It alleviated colonic tissue damage,decreased collagen deposition,inhibited macrophage infiltration,and increased the expression of the tight junction proteins ZO-1 and Claudin-1.Metagenomic analysis revealed JLDinduced shifts in the gut microbiota composition(increasing the abundance of Turicibacter,Faecalibaculum,Coriobacteriaceae and Lactobacillus reuteri),enriching beneficial bacteria and metabolic pathways(increasing the biosynthesis of various secondary metabolites,ascorbate and aldarate metabolism,oxidative phosphorylation,C5-branched dibasic acid metabolism and beta-alanine metabolism).Transcriptomic analysis revealed downregulation of inflammatory and immune pathways(inhibition of the tumour necrosis factor signalling pathway,advanced glycation end products-receptor for advanced glycation end products signalling pathway,toll-like receptor signalling pathway,and interleukin-17 signalling pathway),suggesting a comprehensive modulatory effect of JLD on intestinal health and metabolic function.CONCLUSIONS:JLD granules effectively improve glucose tolerance and ameliorate obesity-related intestinal dysfunctions in HFD-induced obese rats.These benefits are likely mediated through the modulation of the gut microbiota,the suppression of intestinal inflammation,the enhancement of barrier function,and the attenuation of proinflammatory pathways.Our findings offer novel insights into the therapeutic potential of JLD,emphasizing its role in integrating gut microbiota management into the treatment of metabolic disorders.展开更多
目的本研究旨在通过16S rRNA高通量测序技术探讨五苓散对腹泻型肠易激综合征(diarrhea predominant-irritable bowel syndrome,IBS-D)小鼠肠道菌群的调节作用。方法18只SPF级雄性小鼠随机分为正常组、模型组和五苓散组,每组6只。采用番...目的本研究旨在通过16S rRNA高通量测序技术探讨五苓散对腹泻型肠易激综合征(diarrhea predominant-irritable bowel syndrome,IBS-D)小鼠肠道菌群的调节作用。方法18只SPF级雄性小鼠随机分为正常组、模型组和五苓散组,每组6只。采用番泻叶灌胃结合急性束缚应激的方法制备IBS-D模型。造模成功后,五苓散组小鼠给予五苓散7.93 g/(kg·d),正常组和模型组给予等剂量蒸馏水,2次/d,连续4 d。治疗结束后,我们分别收集各组小鼠肠道内容物,进行肠道酶活性及肠道菌群的特征分析。结果肠道酶活性分析显示,造模后小鼠肠道内淀粉酶(P=0.298)、蛋白酶(P=0.017)和乳糖酶活性均下降(P<0.001);五苓散治疗后小鼠肠道内淀粉酶(P=0.213)、蛋白酶(P=0.085)和乳糖酶(P<0.001)活性均上升。肠道菌群分析显示,IBS-D小鼠肠道菌群发生明显改变;五苓散治疗后肠道菌群的丰富度与物种多样性均有所恢复。厚壁菌门(Firmicutes)、变形菌门(Proteobacteria)、蓝细菌门(Cyanobacteria)、酸杆菌门(Acidobacteria)、uncultured_bacterium_o_Chloroplast、链球菌属(Streptococcus)和乳杆菌属(Lactobacillus)在五苓散治疗后相对丰度虽有变化,但差异均无统计学意义(P<0.05)。经五苓散治疗后,IBS-D小鼠肠道菌群厚壁菌门/拟杆菌门相对丰度比值(F/B值)显著下降(P=0.013)。通过PICRUSt2对肠道功能进行预测,发现五苓散治疗IBS-D可能通过影响代谢途径(metabolic pathways)、次生代谢物的生物合成(biosynthesis of secondary metabolites)、抗生素的生物合成(biosynthesis of antibiotics)、不同环境中的微生物代谢(microbial metabolism in diverse environments)、氨基酸的生物合成(biosynthesis of amino acids)等代谢通路发挥作用。结论五苓散可能通过恢复肠道酶活性、调节肠道菌群组成结构及功能进而发挥对IBS-D的治疗作用,为五苓散治疗IBS-D提供了新的临床防治思路。展开更多
基金Supported by the National Key Research and Development Program'Modernization Research of Traditional Chinese Medicine':Cardiovascular Event Chain(Metabolic Syndrome,Atherosclerosis,Myocardial Infarction,Arrhythmia,Heart Failure)(No.2017YFC700500)the Key R&D Program of Hebei:Traditional Chinese Medicine Innovation Project:Clinical Research on the Treatment of Diabetes Foot with Collateral Drugs and the Mechanism of Its Influence on Collateral Vessel Reconstruction(No.223777155D)+1 种基金the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine:Clinical Study on Jinlida Granules in Treating Intestinal Dysfunction of diabetes and Its Effect on Short Chain Fatty Acids(No.2023179)the Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine:Clinical Study on Tongluo Therapy for Diabetes Foot and Its Influence on Microcirculation(No.2018200)。
文摘OBJECTIVE:To investigate the effects of Jinlida granules(津力达颗粒,JLD)on body weight,glucose tolerance,intestinal inflammation and barrier function in high-fat diet(HFD)-induced obese rats and explore the regulation of the gut microbiota as a potential treatment mechanism.METHODS:Sprague-Dawley rats were divided into control,HFD,low-dose JLD(L-JLD),high-dose JLD(HJLD),and sitagliptin groups.The rats,with the exception of those in the control group,were fed a HFD to establish an obesity model while simultaneously receiving 0.5%carboxymethyl cellulose,L-JLD,H-JLD or sitagliptin for 25 weeks.We assessed body weight,conducted oral glucose tolerance tests,and analysed faecal samples using metagenomic sequencing.Haematoxylin-eosin(HE),Masson and immunohistochemical(IHC)staining were employed to evaluate histological changes in the colon tissue.Immunofluorescence(IF)staining was used to measure the expression levels of Zonula occludens-1(ZO-1)and Claudin-1 in colon tissue.The colon tissue was also subjected to transcriptomic evaluation.RESULTS:JLD treatment significantly reduced body weight and enhanced glucose tolerance in obese rats.It alleviated colonic tissue damage,decreased collagen deposition,inhibited macrophage infiltration,and increased the expression of the tight junction proteins ZO-1 and Claudin-1.Metagenomic analysis revealed JLDinduced shifts in the gut microbiota composition(increasing the abundance of Turicibacter,Faecalibaculum,Coriobacteriaceae and Lactobacillus reuteri),enriching beneficial bacteria and metabolic pathways(increasing the biosynthesis of various secondary metabolites,ascorbate and aldarate metabolism,oxidative phosphorylation,C5-branched dibasic acid metabolism and beta-alanine metabolism).Transcriptomic analysis revealed downregulation of inflammatory and immune pathways(inhibition of the tumour necrosis factor signalling pathway,advanced glycation end products-receptor for advanced glycation end products signalling pathway,toll-like receptor signalling pathway,and interleukin-17 signalling pathway),suggesting a comprehensive modulatory effect of JLD on intestinal health and metabolic function.CONCLUSIONS:JLD granules effectively improve glucose tolerance and ameliorate obesity-related intestinal dysfunctions in HFD-induced obese rats.These benefits are likely mediated through the modulation of the gut microbiota,the suppression of intestinal inflammation,the enhancement of barrier function,and the attenuation of proinflammatory pathways.Our findings offer novel insights into the therapeutic potential of JLD,emphasizing its role in integrating gut microbiota management into the treatment of metabolic disorders.
文摘目的本研究旨在通过16S rRNA高通量测序技术探讨五苓散对腹泻型肠易激综合征(diarrhea predominant-irritable bowel syndrome,IBS-D)小鼠肠道菌群的调节作用。方法18只SPF级雄性小鼠随机分为正常组、模型组和五苓散组,每组6只。采用番泻叶灌胃结合急性束缚应激的方法制备IBS-D模型。造模成功后,五苓散组小鼠给予五苓散7.93 g/(kg·d),正常组和模型组给予等剂量蒸馏水,2次/d,连续4 d。治疗结束后,我们分别收集各组小鼠肠道内容物,进行肠道酶活性及肠道菌群的特征分析。结果肠道酶活性分析显示,造模后小鼠肠道内淀粉酶(P=0.298)、蛋白酶(P=0.017)和乳糖酶活性均下降(P<0.001);五苓散治疗后小鼠肠道内淀粉酶(P=0.213)、蛋白酶(P=0.085)和乳糖酶(P<0.001)活性均上升。肠道菌群分析显示,IBS-D小鼠肠道菌群发生明显改变;五苓散治疗后肠道菌群的丰富度与物种多样性均有所恢复。厚壁菌门(Firmicutes)、变形菌门(Proteobacteria)、蓝细菌门(Cyanobacteria)、酸杆菌门(Acidobacteria)、uncultured_bacterium_o_Chloroplast、链球菌属(Streptococcus)和乳杆菌属(Lactobacillus)在五苓散治疗后相对丰度虽有变化,但差异均无统计学意义(P<0.05)。经五苓散治疗后,IBS-D小鼠肠道菌群厚壁菌门/拟杆菌门相对丰度比值(F/B值)显著下降(P=0.013)。通过PICRUSt2对肠道功能进行预测,发现五苓散治疗IBS-D可能通过影响代谢途径(metabolic pathways)、次生代谢物的生物合成(biosynthesis of secondary metabolites)、抗生素的生物合成(biosynthesis of antibiotics)、不同环境中的微生物代谢(microbial metabolism in diverse environments)、氨基酸的生物合成(biosynthesis of amino acids)等代谢通路发挥作用。结论五苓散可能通过恢复肠道酶活性、调节肠道菌群组成结构及功能进而发挥对IBS-D的治疗作用,为五苓散治疗IBS-D提供了新的临床防治思路。
