Metabolomic changes in children with autism

BACKGROUND Autism spectrum disorder(ASD)is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors.Metabolomic profiling has emerged as a valuable tool for understanding the underlying metabolic dysregulations associated with ASD.AIM To comprehensively explore metabolomic changes in children with ASD,integrating findings from various research articles,reviews,systematic reviews,meta-analyses,case reports,editorials,and a book chapter.METHODS A systematic search was conducted in electronic databases,including PubMed,PubMed Central,Cochrane Library,Embase,Web of Science,CINAHL,Scopus,LISA,and NLM catalog up until January 2024.Inclusion criteria encompassed research articles(83),review articles(145),meta-analyses(6),systematic reviews(6),case reports(2),editorials(2),and a book chapter(1)related to metabolomic changes in children with ASD.Exclusion criteria were applied to ensure the relevance and quality of included studies.RESULTS The systematic review identified specific metabolites and metabolic pathways showing consistent differences in children with ASD compared to typically developing individuals.These metabolic biomarkers may serve as objective measures to support clinical assessments,improve diagnostic accuracy,and inform personalized treatment approaches.Metabolomic profiling also offers insights into the metabolic alterations associated with comorbid conditions commonly observed in individuals with ASD.CONCLUSION Integration of metabolomic changes in children with ASD holds promise for enhancing diagnostic accuracy,guiding personalized treatment approaches,monitoring treatment response,and improving outcomes.Further research is needed to validate findings,establish standardized protocols,and overcome technical challenges in metabolomic analysis.By advancing our understanding of metabolic dysregulations in ASD,clinicians can improve the lives of affected individuals and their families.

Metabolomic and structural brain connectomic evidence validating traditional Chinese medicine diagnostic classification of major depressive disorder

OBJECTIVE Major depressive disorder(MDD) is a highly heterogeneous mental illness.Further classification may help characterize its heterogeneity.The purpose of this study was to examine metabolomic and brain connectomic associations with traditional Chinese medicine(TCM) diagnostic classification of MDD.METHODS Fifty unmedicated depressed patients were classified into Liver Qi Stagnation(LQS,n=30) and Heart and Spleen Deficiency(HSD,n=20) subtypes according to TCM diagnosis.Healthy volunteers(n=28) were included as controls.Gas chromatography-mass spectrometry(GC-MS) and diffusion tensor imaging were used to detect serum and urinary metabolomic profiles and whole-brain white matter connectivity,respectively.RESULTS In metabolomic analysis,28 metabolites were identified for good separations between TCM subtypes and healthy controls in serum and urine samples.While both TCM subtypes had similar profiles in proteinogenic branched-chain amino acids and energy metabolism-related metabolites that were differentiated from healthy controls,the LQS subtype additionally differed from healthy controls in multiple amino acid metabolites that are involved in the biosynthesis of monoamine and amino acid neurotransmitters.Several metabolites are differentially associated with the two subtypes.In connectomic analysis,The LQS subtype showed significant differences in multiple network metrics of the angular gyrus,middle occipital gyrus,calcarine sulcus,and Heschl′ s gyrus when compared to the other two groups.The HSD subtype had markedly greater regional connectivity of the insula,parahippocampal gyrus,and posterior cingulate gyrus than the other two groups,and microstructural abnormalities of the frontal medial orbital gyrus and middle temporal pole.The insular betweenness centrality was strongly inversely correlated with the severity of depression and dichotomized the two subtypes at the optimal cutoff value with acceptable sensitivity and specificity.CONCLUSION The LQS subtype may represent an MDD subpopulation mainly characterized by abnormalities in the biosynthesis of monoamine and amino acid neurotransmitters,closer associations with stress-related pathophysiology,and aberrant connectivity of the audiovisual perception-related temporal-occipital network,whereas the HSD subtype is more closely associated with hyperconnectivity and microstructural abnormalities of the limbicparalimbic network.Certain metabolomic and connectomic variables are potential biomarkers for TCM diagnostic subtypes which is perhaps an alternative classification for depressive disorders.

Liujunzi decoction ameliorats cisplatin-induced anorexia via adjusting metabolic disorders in rats

OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments,but its side effects often limit the clinical usage.Metabolic disorders are one of the side effects induced by cisplatin,which closely relate to the onset of chemotherapy-induced anorexia(CIA)in cancer patients but lacks effective controls.Liujunzi decoction(LJZD)is a traditional Chinese formula that has a promising effect in treating CIA.However,whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow.The present study evaluated the mechanism of cisplatin-induced metabolic disorders,and the effect of LJZD in ameliorating these disturbances.METHODS 42 male Sprague-Dawley(SD)rats(180-220 g)were randomly divided into 3 groups:normal control group(distilled water+saline),model group(distilled water+cisplatin),LJZD group(4.8 g·kg^(-1)Liujunzi decoction ingredients+cisplatin).Intragastrical administered each drug twice a day(7∶00-19∶00)since day 0 for 4 d,animals were intraperitoneal injected with cisplatin 6 mg·kg^(-1)1 h after administration while normal control groups were injected with same volume of saline.On day 3,each group was anesthetized with pentobarbital sodium 45 mg·kg^(-1)(ip),and blood samples were collected from aorta abdominalis.Then the samples were analyzed using an LC-ESI-MS/MS system.Significantly regulated metabolites between groups were determined by VIP≥1 and absolute Log2FC(fold change)≥1.Identified metabolites were mapped to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database using Metaboanalyst 5.0(https://www.metaboanalyst.ca/).RESULTS A total of 133,77 and 32 differential metabolites were filtrated in control vs model,control vs LJZD and model vs LJZD groups respectively.Comparing to control,the levels of hexadecanoic acid(Log2FC=6.3153),linoleic acid(Log2FC=5.3478),and 8,11-icosadienoic acid(Log2FC=5.2342)significantly increased,and the levels of N-acetyl-L-tyrosine(Log2FC=-2.6283),cinnamic acid(Log2FC=-2.3381),N-acetylphenylalanine(Log2FC=-2.2501)significantly decreased in model group.The KEGG pathway enrichments of these metabolites indicated that,cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism,which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid,unsaturated fatty acids,and phenylalanine.Compared to control,treatment of LJZD significantly increased the levels of 4-hydroxytryptamine(Log2FC=12.0186),hexadecanoic acid(Log2FC=5.7412),linoleic acid(Log2FC=5.1877)and significantly decreased the levels of N-acetylmethionine(Log2FC=-1.7317),2-aminoethanesulfinic acid(Log2FC=-1.6578),N-acetyl-L-tyrosine(Log2FC=-1.5355).And comparing to the model group,4-hydroxytryptamine(Log2FC=12.0186),7,12-diketocholic acid(Log2FC=2.0998),N-acetylneuraminic acid(Log2FC=2.0560)markedly increased,and 3-hydroxy-3-methylpentane-1(Log2FC=-1.9202),5-dioic acid(Log2FC=-1.7166),N-isovaleroylglycine,hexanoyl glycine(Log2FC=-1.4958)markedly decreased in LJZD group.It was worth noting that,there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups,which were the key metabolites of LJZD in treating CIA.Among these 23 common metabolites,there were 16 metabolites excluding the control vs LJZD group,that was,LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites.Cisplatin-induced downregulation of 11 metabolites such as hydrocinnamic acid,(±)12(13)epoxy-9Z-octadecenoic acid,cinnamic acid were upregulated after LJZD treatment,and cisplatin-induced upregulation of imidazoleacetic acid,2′-deoxycytidine-5′-monophosphate and other 5 metabolites were downregulated by LJZD.The KEGG pathway analysis indicated that the linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism were the most enriched metabolic pathway.Thus,cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism,and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA.CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabolism,biosynthesis of unsaturated fatty acids,and phenylalanine metabolism.The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments,relating to the regulation of linoleic acid metabolism,histidine metabolism,and pyrimidine metabolism.

基于肠道菌群和代谢组学探讨“脑肠共治”电针对孤独症大鼠的作用机制

目的观察“脑肠共治”电针对孤独症大鼠的社交能力及对肠道菌群、代谢产物的影响。方法采用丙戊酸钠腹腔注射法制备孤独症大鼠模型,选取造模成功的大鼠随机分为4组,每组10只,分别为模型组、基础电针组、针药结合组、脑肠共治电针组。另外选取10只正常大鼠为对照组。基础电针组予以电针百会、神庭、心俞;针药结合组在基础电针组的基础上再予以益生菌灌胃治疗;脑肠共治电针组在基础电针组基础上再结合电针足三里、曲池。均每日1次,连续4周。采用三箱社交实验评估行为学改变,16S rDNA测序分析肠道菌群分布情况,超高效液相色谱串联质谱分析血浆中的差异代谢组分,并结合Spearman相关性分析进行肠道菌群与代谢组学之间的关联分析。结果与对照组相比,模型组大鼠社交能力和社交新颖性均减弱(P<0.01);与模型组相比,基础电针组、针药结合组、脑肠共治电针组的社交新颖性增强(P<0.01);与基础电针组比较,针药结合组、脑肠共治电针组社交新颖性增强(P<0.01)。肠道菌群研究发现,与对照组比较,模型组的弯曲菌门相对丰度上调,嗜黏蛋白阿克曼菌相对丰度下调;而与模型组相比,针药结合组、脑肠共治电针组的弯曲菌门相对丰度下调,嗜黏蛋白阿克曼菌相对丰度上调。LEfSe分析发现,脑肠共治电针组与模型组共筛选出嗜黏蛋白阿克曼菌等21个关键菌,如与模型组比较,脑肠共治电针组可上调嗜黏蛋白阿克曼菌、卷曲乳杆菌,同时下调梭状芽胞杆菌等。代谢组学分析共筛选出12个差异代谢物,通路分析显示,其主要与氨基酸代谢、磷酸盐代谢、嘌呤代谢、花生四烯酸代谢等通路相关。结论电针百会、神庭、心俞、足三里、曲池对孤独症大鼠社交能力有明显的改善作用,调控肠道菌群如嗜黏蛋白阿克曼菌等菌属丰度,同时影响代谢物水平,且部分代谢物的改变与肠道菌群存在复杂相关性,可能与氨基酸代谢、磷酸盐代谢、嘌呤代谢、花生四烯酸代谢等通路相关。

不同运动方式干预对昼夜节律紊乱小鼠认知功能的影响——基于肠道菌群和非靶向代谢组学分析

目的研究不同运动方式干预对昼夜节律紊乱小鼠认知功能的影响,探讨肠道菌群及代谢与认知功能之间的相关性。方法采用轮回颠倒的光照周期暴露建立昼夜节律紊乱模型,将模型小鼠分为:安静组(DC)、中等强度持续训练(MICT)运动组(DM)和高强度间歇训练(HIIT)运动组(DH),另设对照组(CC),各组15只,经过6周运动干预后,运用HE染色观察结肠组织、Morris水迷宫检测认知功能、16S rRNA高通量测序检测肠道菌群以及LC-MS检测粪便代谢物。结果①DM组和DH组的腺体破坏程度有所减轻。②DM组和DH组平台潜伏期和初次抵达平台时间显著缩短,游泳距离减少,穿越站台次数和目标象限游泳时间百分比均显著增加。③DC组丰度较高的菌群为柔膜菌门和柔膜菌纲,DM组为瘤胃球菌科,DH组为Lutispora等。④DM组中肌酸、丁酸和甲硫氨酸等代谢物水平显著高于DC组,DH组中花生四烯酸等代谢物水平显著高于DC组。⑤肠道菌群中颤螺菌属、乳酸杆菌属与认知功能相关性显著,代谢物中姜黄素和油酸与认知功能相关性显著。结论MICT和HIIT可调节昼夜节律紊乱小鼠肠道菌群的结构和丰度,改善其认知功能,相关肠道菌群与代谢物参与运动改善昼夜节律紊乱小鼠认知功能的调节。

基于超高效液相色谱-质谱联用技术的慢性肾脏病骨代谢异常大鼠血清代谢组学研究

目的 通过超高效液相色谱-质谱(UHPLC-MS)联用技术探索慢性肾脏病骨代谢异常(CKD-BD)大鼠血清代谢组学变化。方法 该研究于2021年1月至2022年4月进行,选择16只8周龄SPF级SD雄性大鼠经过1周适应性喂养后,采用随机数字表法分为两组,每组8只。健康对照(NC)组:使用普通大鼠饲料喂养90 d;CKD-BD组:采用高磷高腺嘌呤饲料喂养60 d之后更换高磷饲料喂养30 d后处死,并通过生化检测及骨形态计量学方法对模型进行验证。造模成功后通过UHPLC-MS比较CKD-BD组大鼠与NC组大鼠血清代谢产物变化,通过多元统计分析等方法鉴定两组间差异代谢物,并通过生物信息学方法对差异代谢产物进行功能注释。结果 与NC组大鼠相比,CKD-BD组大鼠血肌酐、血磷显著升高,血钙显著降低(P<0.01)。骨形态计量学检测NC组大鼠骨矿化沉积率(MAR)为(1.90±0.61)μm/d,CKD-BD组大鼠MAR为(2.80±0.73)μm/d,差异有统计学意义(P<0.05)。NC组大鼠骨形成率/骨体积(BFR/BV)为(0.41±0.20)%/d,CKD-BD组大鼠BFR/BV为(1.25±0.41)%/d,差异有统计学意义(P<0.05)。代谢组学检测结果提示,与NC组相比,CKD-BD组糖基磷脂酰肌醇锚定蛋白合成等通路上调。自噬、胆汁酸合成分泌、胆固醇代谢、牛磺酸和次级牛磺酸代谢、甘油磷脂代谢等通路下调(P<0.05)。结论 通过UHPLC-MS技术比较CKD-BD大鼠与正常大鼠血清代谢产物,发现CKD疾病状态下血清代谢产物发生变化,CKD-BD组糖基磷脂酰肌醇锚定蛋白合成通路上调,与自噬相关的代谢通路下调,这些可能参与了CKD-BD发生。

基于海马代谢组学与16S rRNA测序探讨电针抗焦虑作用机制

目的通过海马代谢组学与16S rRNA测序等方法,探索电针抗焦虑作用机制。方法将大鼠随机分为正常组、模型组、电针组以及地西泮组。采用慢性束缚应激方法制备焦虑症大鼠模型。电针组造模期间同时进行“足三里”穴位电针干预,每次30 min,每天1次,持续21天。地西泮组每天灌胃地西泮,持续21天。造模结束后进行旷场实验以及高架十字迷宫实验观察大鼠行为学。随后进行病理染色观察大鼠海马脑区与结肠病理改变。代谢组学检测大鼠海马脑区代谢物改变。16S rRNA与短链脂肪酸分析检测大鼠肠道菌群与短链脂肪酸变化。Western blot检测大鼠结肠Occludin,海马TLR4、NF-κB P65和NLRP3蛋白含量表达变化。免疫荧光检测海马IBA-1、NLRP3和IL-1β蛋白表达。结果旷场实验结果显示,与正常组相比,模型组总活动距离(P<0.001)、中央区活动距离(P<0.01)和平均速度(P<0.01)下降,与模型组相比,电针组和地西泮组的总活动距离(P<0.05,P<0.001)、中央区活动距离(P<0.05,P<0.01)以及平均速度(P<0.05,P<0.01)均升高。高架十字迷宫实验结果显示,与正常组相比,模型组OE%(P<0.001)和OT%(P<0.001)降低,与模型组相比,电针组和地西泮组皆能升高OE%(P<0.05,P<0.001)和OT%(P<0.01,P<0.001)。海马HE染色结果显示正常组大鼠海马CA1区可见海马体各区域结构清楚,层次分明。模型组海马体可见CA1区有少量的神经细胞胞核皱缩深染,细胞边界不清晰,排列不规则,胞质呈空泡状。而给予电针和地西泮的干预分别能不同程度缓解上述病理现象;海马代谢组学结果显示电针能改善造模引起的海马代谢紊乱,其中主要涉及对牛磺酸和亚牛磺酸代谢调节;16S rRNA测序与短链脂肪酸检测结果显示电针能改善造模引起的肠道菌群紊乱,并且能调节血清LPS以及丁酸、己酸和戊酸水平。HE染色与Western blot结果发现模型组肠道出现病理损伤,并且与正常组相比,模型组结肠Occludin表达下降(P<0.05),而电针和地西泮的干预能改善结肠病理损伤,上调Occludin表达(P<0.05,P<0.05);免疫荧光结果显示,与正常组相比,模型组海马IBA-1、NLRP3和IL-1β表达水平上升(P<0.05,P<0.01,P<0.01),而与模型组相比,电针组和地西泮组能降低IBA-1(P<0.05,P<0.05)、NLRP3(P<0.05,P<0.05)和IL-1β(P<0.05,P<0.05)表达水平;Western blot结果显示,与正常组相比,模型组海马TLR4、NF-κB P65和NLRP3蛋白表达水平上升(P<0.05,P<0.001,P<0.05),与模型组相比,电针组和地西泮组能下调NF-κB P65(P<0.01,P<0.001)和NLRP3(P<0.05,P<0.05)蛋白表达水平。结论电针抗焦虑作用涉及对“微生物-肠-脑”轴的调节。

青蒿素对高果糖诱导的小鼠脂质代谢紊乱血清代谢组学研究

目的:分析高果糖饮食诱导的小鼠血清代谢物变化,探讨青蒿素改善高果糖饮食诱导的小鼠代谢紊乱的机制。方法:检测正常组、高果糖饮食组、青蒿素组及阳性药组小鼠血清葡萄糖、三酰甘油、胆固醇含量;采用超高效液相色谱-四极杆-飞行时间串联质谱法(UHPLC-Q-TOF MS)对各组小鼠血清进行代谢轮廓分析,进一步根据单变量统计分析筛选差异代谢物,对差异代谢物进行京都基因与基因组百科全书(KEGG)通路富集分析。结果:青蒿素显著降低了高果糖饮食诱导的小鼠血清三酰甘油上升。各组代谢轮廓出现改变。筛选出正离子模式下差异代谢物42个,负离子模式下差异代谢物45个。亚油酸代谢,逆行内源性大麻素信号转导,不饱和脂肪酸的生物合成等重要通路发生了显著改变。结论:青蒿素可以使高果糖饮食导致的代谢紊乱有所恢复,主要涉及脂质代谢。

睡眠障碍患者血浆代谢标志物研究

目的筛选睡眠障碍患者血液中的代谢标志物,并分析其异常代谢通路。方法选取2021年1—12月上海健康医学院附属嘉定区中心医院睡眠障碍患者30例(睡眠障碍组)、健康体检者30名(正常对照组)。收集所有研究对象的一般资料。采用超高效液相色谱串联质谱(UPLC-MS/MS)检测所有研究对象的血浆代谢物。依据VIP值、差异倍数(FC)和P值筛选出睡眠障碍组与正常对照组之间有显著意义的差异代谢物。对差异代谢物进行京都基因与基因组百科全书(KEGG)通路富集分析。结果共检出1656个代谢物,筛选出睡眠障碍组与正常对照组之间有显著意义的差异代谢物181个。正离子模式筛选出115个(表达上调61个、表达下调54个),VIP值居前10位的代谢物分别为乙二胺四乙酸、肉碱、N-(1-氨基-3,3-二甲基-1-氧代丁-2-基)-1-戊基-1h-吲哚-3-甲酰胺、[1-(环己基甲基)-1h-吲哚-3-羰基]-l-缬氨酸甲酯、二丁卡因、甘油磷酸胆碱、次黄嘌呤、棕榈酰血清素、去铁胺d2、亚麻酰肉碱。负离子模式筛选出66个(表达上调38个、表达下调28个),VIP值居前10位的代谢物分别为柠檬酸盐、牛磺酸、鼠李素、尿酸、丙酮酸盐、尿囊素、3',5'-环肌苷-磷酸、D-乳酸、(+)-6-氨基青霉烷酸、油酸。KEGG通路富集分析结果显示,差异代谢物涉及的通路为癌症的中枢碳代谢、腺苷三磷酸结合盒转运蛋白和蛋白质消化吸收等。结论筛选出睡眠障碍患者具有代表性的代谢物和代谢通路,可为睡眠障碍的诊断和治疗提供潜在的靶点。

Dissecting the brain with spatially resolved multi-omics

Recent studies have highlighted spatially resolved multi-omics technologies,including spatial genomics,transcriptomics,proteomics,and metabolomics,as powerful tools to decipher the spatial heterogeneity of the brain.Here,we focus on two major approaches in spatial transcriptomics(next-generation sequencing-based technologies and image-based technologies),and mass spectrometry imaging technologies used in spatial proteomics and spatial metabolomics.Furthermore,we discuss their applications in neuroscience,including building the brain atlas,uncovering gene expression patterns of neurons for special behaviors,deciphering the molecular basis of neuronal communication,and providing a more comprehensive explanation of the molecular mechanisms underlying central nervous system disorders.However,further efforts are still needed toward the integrative application of multi-omics technologies,including the real-time spatial multi-omics analysis in living cells,the detailed gene profile in a whole-brain view,and the combination of functional verification.

Metabolomics in Schizophrenia and Major Depressive Disorder

Defining pathophenotype, a systems level consequence of a disease genotype, together with environmental and stochastic influences, is an arduous task in psychiatry. It is also an appealing goal, given growing need for appreciation of brain disorders biological complexity, aspiration for diagnostic tests development and ambition to identify novel drug targets. Here, we focus on the Schizophrenia and Major Depressive Disorder and highlight recent advances in metabolomics research. As a systems biologytool, metabolomics holds a promise to take part in elucidating interactions between genes and environment, in complex behavioral traits and psychopathology risk translational research.

Gastrointestinal Microbiome and related metabolites in Depression and Antidepressants - a comprehensive review

Depression,a prevalent mood disorder,has emerged as a significant health concern in society.While the exact cause of depression remains incompletely understood,there is substantial evidence linking the gastrointestinal microbiome and its metabolites to this condition.Through combined multi-omics analysis,it has been observed that the composition of the gastrointestinal microbiome,including Firmicutes,Bacteroidetes,and Actinobacteria,undergoes significant alterations in depressed individuals.Moreover,the production of short-chain fatty acids,tryptophan,and bile acids by these gut microbes is also found to be modified in depression.Furthermore,studies have demonstrated that antidepressant medications exert their therapeutic effects by interacting with the gastrointestinal microbiome and their metabolites.This review provides an overview of the association between the gastrointestinal microbiome,related metabolites,and depression.It highlights the potential of these factors to serve as mechanisms of action for antidepressant medications.Additionally,the review summarizes the commonly used technical tools in depression research.

2型糖尿病气阴两虚证大鼠尿液代谢组学研究

目的 通过尿液非靶向代谢组学方法,从代谢差异标志物及代谢通路方面,探讨成年SD大鼠2型糖尿病气阴两虚证的中医证候内在的生物物质基础。方法 将SD大鼠随机分为正常组和2型糖尿病(diabetes mellitus type 2,T2DM)气阴两虚证组,采用高脂高糖饲料饲喂、小剂量链脲佐菌素(streptozocin, STZ)35 mg/kg腹腔注射结合青皮附子散颗粒剂灌胃的方法建立T2DM气阴两虚证模型。利用液质联用(Liquid Chromatography-Mass Spectrometry, LC-MS)技术进行尿液非靶代谢组学分析,运用主成分分析(Principal Component Analysis, PCA)和偏最小二乘法判别分析(Partial Least Squares Discriminant Analysis, PLS-DA),KEGG数据库、HMDB数据库、LIPIDMaps数据库和液相色谱与串联质谱联用(liquid chromatography tandem mass spectrometry, LC-MS/MS)等鉴定潜在的生物标志物进行通路富集分析。结果 发现与糖尿病发生相关的代谢物变化涉及碳水化合物代谢9条,脂质代谢12条,氨基酸代谢9条,能量代谢2条。结论 糖尿病气阴两虚证生物模型存在碳水化合物代谢、脂质代谢、氨基酸代谢、生物能量代谢紊乱,代谢组学研究方法有助于揭示中医证候的微观物质基础。

代谢组学用于多囊卵巢综合征代谢紊乱的研究进展

多囊卵巢综合征(polycystic ovary syndrome,PCOS)是青春期及育龄妇女最常见的内分泌代谢紊乱性疾病之一,以雄激素分泌过多、排卵功能障碍和多囊卵巢形态(polycysticovarymorphology,PCOM)为关键特征,主要表现为月经周期紊乱、不孕、多毛或/和痤疮。大多数PCOS患者伴有肥胖,并同时存在糖、脂、氨基酸等方面代谢紊乱。PCOS其病理生理学及发病机制尚不清楚,下丘脑-垂体-卵巢轴失衡被认为是PCOS的重要病理生理基础。代谢组学的应用为PCOS研究提供新视角,能够发现差异性代谢物,从而确定糖、脂、氨基酸代谢等途径代谢紊乱的潜在生物标记物,为PCOS治疗及发病机制寻求突破点。

基于色谱质谱联用技术的中医痰湿体质的代谢组学研究

目的:寻找中医痰湿体质血清标志性代谢物及其引起的代谢通路变化,结合糖脂代谢、胰岛素抵抗指数等指标,探讨中医痰湿体质形成、发展等各阶段的病理特征以及中医关于"肥人多痰湿"的发病机制。方法:收集正常组平和质、超重组非痰湿质和痰湿质、肥胖组痰湿质的血清样本,分析比较4组间体脂参数(体重指数BMI、腰围WC、腰臀比WHR)、血脂(TG、CHOL、HDLC、LDLC)、空腹血糖(FPG)、空腹胰岛素(FINS)、胰岛素抵抗指数(Homa-IR),并分别与中医痰湿体质积分作相关性分析。应用高效液相色谱-四级杆-飞行时间质谱联用(HPLC-Q-TOF/MS)的代谢组学技术为基础、使用多元数据统计分析寻找痰湿体质的血清差异代谢物,进一步探讨中医痰湿体质内在的病理学特征及相关疾病的发病机制。结果:BMI、WC、WHR、TG随着组别依次呈现逐渐增大的趋势,HDL-C则逐渐减小,肥胖组痰湿质的FINS、Homa-IR指数显著高于正常组平和质(P<0.01);全组中医痰湿体质积分与BMI、WC、WHR、TG水平呈显著正相关(P<0.05);与HDL-C水平呈显著负相关(P<0.01);超重组非痰湿质显著性差异表达血清代谢物有8种,超重组痰湿质有9种,肥胖组痰湿质有9种(P<0.05)。结论:痰湿质肥胖症存在着显著的体脂分布异常、脂代谢紊乱、胰岛素水平过高、高胰岛素抵抗等病理特征,提示中医痰湿体质是肥胖症的易患体质;中医痰湿体质存在显著性差异表达血清代谢物。

基于代谢组学的抽动障碍患儿血清生物标志物研究

目的运用代谢组学的方法研究抽动障碍(tic disorder,TD)患儿血清代谢产物差异,总结TD患儿血清相关生物标志物特点,探析TD的生物学实质,分析其代谢通路及生物学意义,为TD的诊断及进一步研究提供思路。方法选取2019年10月—2020年3月期间于北京中医药大学东方医院儿科门诊确诊为TD的患儿30例(TD组),同时选取同一时期体检健康儿童30例设为正常组。采用液-质联用技术(LC-MC)、气-质联用技术(GC-MC)和化学计量学分析研究技术,检测TD患儿血清代谢物变化,筛选出TD代谢生物标记物。结果筛选出与TD相关的生物标记物为甘油三酯、L-苯丙氨酸-L-脯氨酸、乳糖神经酰胺、白三烯、2-甲基-3-酮戊酸、L-胱氨酸、硫酸脱氢异雄酮、聚乙烯等50余种,主要涉及甘油磷脂代谢、亚油酸代谢、花生四烯酸代谢等代谢通路。结论所筛选的生物标记物及其代谢通路,可作为TD患儿独特的代谢图谱,成为TD的诊断依据及进一步研究靶点。

糖脂代谢紊乱机制研究及中医药防治的进展

中医药在防治糖脂代谢紊乱方面具有多靶点、多通路、联合增效、协同交互的特点。近年来,中医药在探索糖脂代谢紊乱机制研究方面不断深入和细化,实验设计更加系统化,并且紧密结合了包括转录组学、代谢组学、蛋白组学等先进的研究技术,为阐释药物有效成分的作用靶点提供了有力的科学依据。此外,近年微生物组学也成为糖脂代谢紊乱机制研究的热点之一,学者通过高通量测序技术,揭示中药通过调节肠道菌群结构,改善糖脂代谢紊乱的生物学基础,为明确中医药防治代谢性疾病的干预靶点提供了更广阔的思路。作者系统梳理了近3年中医药防治糖脂代谢紊乱的相关研究,针对其现状及特点予以总结和述评。

Multi-omics: Opportunities for research on mechanism of type 2 diabetes mellitus

Type 2 diabetes mellitus(T2DM)is a burdensome global disease.In-depth understanding of its mechanism will help to optimize diagnosis and treatment,which reduces the burden.Multi-omics research has unparalleled advantages in contributing to the overall understanding of the mechanism of this chronic metabolic disease.In the past two decades,the study of multi-omics on T2DMrelated intestinal flora perturbation and plasma dyslipidemia has shown tremendous potential and is expected to achieve major breakthroughs.The regulation of intestinal flora in diabetic patients has been confirmed by multiple studies.The use of metagenomics,16S RNA sequencing,and metabolomics has comprehensively identified the overall changes in the intestinal flora and the metabolic disturbances that could directly or indirectly participate in the intestinal flora-host interactions.Lipidomics combined with other“omics”has characterized lipid metabolism disorders in T2DM.The combined application and crossvalidation of multi-omics can screen for dysregulation in T2DM,which will provide immense opportunities to understand the mechanisms behind T2DM.

Disciplined sleep for healthy living: Role of noradrenaline

Sleep is essential for maintaining normal physiological processes. It has been broadly divided into rapid eye movement sleep(REMS) and non-REMS(NREMS); one spends the least amount of time in REMS. Sleep(both NREMS and REMS) disturbance is associated with most altered states, disorders and pathological conditions. It is affected by factors within the body as well as the environment, which ultimately modulate lifestyle.Noradrenaline(NA) is one of the key molecules whose level increases upon sleep-loss, REMS-loss in particular and it induces several REMS-loss associated effects and symptoms. The locus coeruleus(LC)-NAergic neurons are primarily responsible for providing NA throughout the brain. As those neurons project to and receive inputs from across the brain, they are modulated by lifestyle changes, which include changes within the body as well as in the environment. We have reviewed the literature showing how various inputs from outside and within the body integrate at the LC neuronal level to modulate sleep(NREMS and REMS) and vice versa. We propose that these changes modulate NA levels in the brain, which in turn is responsible for acute as well as chronic psychosomatic disorders and pathological conditions.

重度抑郁症的代谢组学生物标志物研究进展

重度抑郁症(MDD)是世界范围内主要的精神疾病,对社会造成了巨大的经济和情感压力。生物标志物的发现不仅有助于改进抑郁症的诊断和加速新药研发,而且可以用来预测抑郁症发生的可能性,推进MDD个性化治疗的进程。近年来,代谢组学技术的快速发展以及它在疾病诊断方面的广泛应用,为进一步筛选MDD相关生物标志物提供了可能。本文将基于血液、尿液、脑脊液代谢组学总结和讨论MDD代谢组学生物标志物的研究进展,目的是使研究人员能够在已有研究基础上作出新的发现,并期望MDD生物标志物早日在临床中发挥重要作用,以改善MDD患者的生活质量。