Metabolites最新文献

{"title":"Metabolomics Reveal Key Metabolic Pathway Responses to Anxiety State Regulated by Serotonin in <i>Portunus trituberculatus</i>.","authors":"Wei Zhai, Yuanyuan Fu, Lei Liu, Xinlian Huang, Sixiang Wang","doi":"10.3390/metabo14100568","DOIUrl":"https://doi.org/10.3390/metabo14100568","url":null,"abstract":"<p><strong>Background: </strong>Anxiety refers to the pathological persistence and intensification of emotional responses to danger, affecting health from psychological and physical aspects. Serotonin is an important neurotransmitter involved in the onset of anxiety.</p><p><strong>Methods and results: </strong>To explore the biological changes in the formation of anxiety in crustaceans under the regulation of serotonin, we applied the open field-like test method for assessing anxiety states of larval <i>Portunus trituberculatus</i>, a highly aggressive crustacean species with a more simple neural structure compared with rodents and mammals. Compared with the control group, serotonin treatment resulted in a significant decrease in the time spent by the larvae in the central zone, suggesting anxiety-like behavior. Clonazepam treatment reversed this result and provided further evidence that the behavior of larval <i>P. trituberculatus</i> displayed anxiety. Moreover, a non-targeted metabolomic analysis found a significant alteration in the metabolites involved in tryptophan metabolism pathways associated with anxiety, including L-kynurenine, N-acetyl serotonin, and serotonin. These metabolites are involved in the serotonin pathway, the kynurenine pathway, and other pathways that affect anxiety through tryptophan metabolism. There were no significant differences in tryptophan metabolism levels between the control and clonazepam treatment groups.</p><p><strong>Conclusions: </strong>Our results demonstrate the possible existence of anxiety-like behavior in the larvae of <i>P. trituberculatus</i> from two perspectives. Being a species with a simpler neural structure than that of mammals, the larvae of <i>P. trituberculatus</i> offer a convenient model for studying the mechanisms of anxiety in crustaceans.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics Approach to Identify Biomarkers of Acute and Subacute Mastitis in Milk Samples: A Pilot Case-Control Study.","authors":"Paola Quifer-Rada, Laia Aguilar-Camprubí, Sara Samino, Nuria Amigó, Oria Soler, Alba Padró-Arocas","doi":"10.3390/metabo14100566","DOIUrl":"https://doi.org/10.3390/metabo14100566","url":null,"abstract":"<p><p><b>Background and aims</b>: Mastitis is one of the main complications during breastfeeding and contributes to the cessation of breastfeeding. However, the etiopathogenesis and diagnosis of mastitis are complex and not yet well defined. We aimed to identify metabolic and lipidic changes in human milk during acute and subacute mastitis in order to detect potential biomarkers of mastitis. <b>Methods:</b> We conducted a pilot case-control study including 14 breastfeeding women with acute mastitis, 32 with subacute mastitis symptoms, and 19 without any mastitis symptoms (control). Milk samples were collected and analyzed by proton nuclear magnetic resonance (H-NMR) for metabolomics analysis. To assess the association between the significant metabolites and lipids and the development of acute and subacute mastitis, multi-adjusted logistic regression models were developed. <b>Results:</b> The NMR-based metabolomics approach was able to identify and quantify a total of 40 metabolites in breast milk samples. After adjusting for confounding variables, acute mastitis was significantly associated with acetate (OR 3.9 IC 1.4-10.8), total cholesterol (OR 14 CI 3.2-62), esterified cholesterol (OR 3.3 CI 1.9-5.8), and sphingomyelin (OR 2.6 CI 1.2-5.8). The other metabolites presented weak association (OR < 2.5). Subacute mastitis was significantly associated with glutamine, lysophosphatidylcholine, phosphatidylcholine, plasmalogen, and total polyunsaturated fatty acids, but only cholesterol showed a strong association (OR > 2.5) with an OR of 2.6 (IC 1.1-6.6). <b>Conclusions</b>: Metabolic alteration in breast milk occurs during a process of both acute and subacute mastitis. Acetate, esterified cholesterol, lysophostidylcholine, and polyunsaturated fatty acids increased in both acute and subacute mastitis. However, according to the multi-adjusted regression logistic models, the candidate biomarkers for acute and subacute mastitis are cholesterol, lysophosphatidylcoholine, phosphatidylcholine, plasmalogen, and polyunsaturated fatty acids.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Different Photoperiods on Peripheral 5-Hydroxytryptamine Metabolism, Breast Muscle Glucose Metabolism, and Myopathies in Broilers.","authors":"Miao Yu, Mengjie Xu, Guangju Wang, Jinghai Feng, Minhong Zhang","doi":"10.3390/metabo14100567","DOIUrl":"https://doi.org/10.3390/metabo14100567","url":null,"abstract":"<p><p><b>Background</b>: There is a close relationship between breast muscle glucose metabolism, peripheral 5-hydroxytryptamine (5-HT), and myopathies in animals. Here, this study aimed to investigate the effects of different photoperiods on peripheral 5-HT metabolism, white striping (WS), and wooden breast (WB) in broilers. <b>Methods</b>: A total of 216 healthy 5-day-old (d) Arbor Acres (AA) male broilers were randomly assigned to 12L:12D, 18L:6D, and 24L:0D photoperiods for 4 weeks. <b>Results</b>: Compared with the 12L:12D photoperiod, we found the WB score in broilers was significantly increased in the 18L:6D and 24L:0D photoperiod at week 4 (<i>p</i> < 0.05). Muscle glycogen was significantly reduced (<i>p</i> < 0.05) and glycolysis was promoted in the breast muscles of broilers under the 18L:6D and 24L:0D photoperiods at week 2 and 4. Peripheral 5-HT concentrations, the mRNA expression of tryptophan hydroxylase 1 (TPH1) and serotonin transporter (SERT) in the cecal mucosa, and 5-hydroxytryptamine receptor 2A (5-HTR_2A) mRNA expression in the breast muscle of broilers significantly up-regulated in the 18L:6D and 24L:0D photoperiod at week 2 and 4 (<i>p</i> < 0.05). <b>Conclusions</b>: Our findings revealed that extending the photoperiod improved the breast muscle growth rate, but up-regulated 5-HT synthesis and secretion to higher peripheral 5-HT, induced breast muscle glucose metabolism disorder, and increased WB incidence rates in broilers.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Underlying Effect of Urate Levels on Female Infertility.","authors":"Muhammad Naveed, Jennifer W Hill","doi":"10.3390/metabo14100564","DOIUrl":"https://doi.org/10.3390/metabo14100564","url":null,"abstract":"<p><p>Female infertility is a complex and multifaceted condition that affects millions of women globally [...].</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Serum Fibroblast Growth Factor 21 Level and Its Altered Regulation by Thyroid Hormones in Patients with Hashimoto's Thyroiditis on Levothyroxine Substitution.","authors":"Eszter Berta, Sándor Halmi, István Molnár, Dávid Hutkai, Sára Csiha, Harjit Pal Bhattoa, Hajnalka Lőrincz, Sándor Somodi, Mónika Katkó, Mariann Harangi, György Paragh, Endre V Nagy, Miklós Bodor","doi":"10.3390/metabo14100565","DOIUrl":"https://doi.org/10.3390/metabo14100565","url":null,"abstract":"<p><strong>Background/objectives: </strong>Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism exerting protection against atherosclerosis by multiple actions on the blood vessels, liver, and adipose tissues. We aimed to investigate serum FGF21 level and its relation to thyroid hormones and metabolic parameters among patients with Hashimoto's thyroiditis (HT).</p><p><strong>Methods: </strong>Eighty patients with HT on levothyroxine treatment and eighty-two age- and BMI-matched adults without thyroid disease serving as controls were enrolled. Serum FGF21 concentrations were determined with an enzyme-linked immunosorbent assay.</p><p><strong>Results: </strong>Median serum FGF21 level was significantly lower in HT patients compared with controls (74.2 (33.4-148.3) pg/mL vs. 131.9 (44.8-236.3) pg/mL; <i>p</i> = 0.03). We found a positive correlation between FGF21 and age, triglyceride, total cholesterol, and low-density lipoprotein cholesterol in both groups, while thyroid stimulating hormone and C-reactive protein showed a positive correlation, and thyroxine had an inverse correlation with FGF21 only in control subjects. According to multiple regression analyses, thyroid status is the main predictor of FGF21 in healthy controls, while it is not a significant predictor of FGF21 among HT patients on levothyroxine supplementation therapy.</p><p><strong>Conclusions: </strong>Our results indicate that the physiological role of thyroid function in the regulation of FGF21 synthesis is impaired in HT patients, which may contribute to the metabolic alterations characteristic of HT patients.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Evaluation of the Chemical Components and Anti-Inflammatory Potential of Yellow- and Blue-Flowered <i>Meconopsis</i> Species: <i>M. integrifolia</i> and <i>M. betonicifolia</i>.","authors":"Peizhao Cheng, Ruixi Gan, Cong Wang, Qian Xu, Kelsang Norbu, Feng Zhou, Sixin Kong, Zhuoma Jia, Dawa Jiabu, Xin Feng, Junsong Wang","doi":"10.3390/metabo14100563","DOIUrl":"https://doi.org/10.3390/metabo14100563","url":null,"abstract":"<p><p><b>Background/Objectives:</b><i>Meconopsis</i> has long been used in traditional Tibetan medicine to treat various inflammatory and pain-related conditions. However, blue-flowered <i>Meconopsis</i> (<i>M. betonicifolia</i>) is becoming increasingly scarce due to overharvesting. As a potential alternative, yellow-flowered <i>Meconopsis</i> (<i>M. integrifolia</i>) shows promise but requires comprehensive characterization. This study aimed to evaluate and compare the anti-inflammatory potential of yellow- and blue-flowered <i>Meconopsis</i> species. <b>Methods:</b> Liquid chromatography-mass spectrometry (LC-MS) techniques were used to analyze the chemical profiles of yellow- and blue-flowered <i>Meconopsis</i>. Putative targets of shared constituents were subjected to GO and disease enrichment analysis. The LPS-induced RAW264.7 macrophage model was employed to assess anti-inflammatory effects. Metabolomics was applied to gain mechanistic insights. <b>Results:</b> LC-MS revealed over 70% chemical similarity between species. Enrichment analysis associated targets with inflammation-related pathways. In macrophage assays, both species demonstrated dose-dependent antioxidative and anti-inflammatory activities, with yellow <i>Meconopsis</i> exhibiting superior efficacy. Metabolomics showed modulation of key inflammatory metabolic pathways. <b>Conclusions:</b> This integrative study validated yellow-flowered <i>Meconopsis</i> as a credible alternative to its blue-flowered counterpart for anti-inflammatory applications. Metabolic profiling provided initial clues regarding their multi-targeted modes of action, highlighting their potential for sustainable utilization and biodiversity conservation.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on Antioxidant Peptides from Fish By-Products: Purification, Identification, and Structure-Activity Relationship.","authors":"Xinru Liu, Qiuyue Hu, Yafang Shen, Yuxin Wu, Lu Gao, Xuechao Xu, Guijie Hao","doi":"10.3390/metabo14100561","DOIUrl":"https://doi.org/10.3390/metabo14100561","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Excessive reactive oxygen species (ROS) can lead to oxidative stress, which has become an urgent problem requiring effective solutions. Due to the drawbacks of chemically synthesized antioxidants, there is a growing interest in natural antioxidants, particularly antioxidant peptides. <b>Methods</b>: By reviewing recent literature on antioxidant peptides, particularly those extracted from various parts of fish, summarize which fish by-products are more conducive to the extraction of antioxidant peptides and elaborate on their characteristics. <b>Results</b>: This article summarizes recent advancements in extracting antioxidant peptides from fish processing by-products, Briefly introduced the purification and identification process of antioxidant peptides, specifically focusing on the extraction of antioxidant peptides from various fish by-products. Additionally, this article comprehensively reviews the relationship between amino acid residues that compose antioxidant peptides and their potential mechanisms of action. It explores the impact of amino acid types, molecular weight, and structure-activity relationships on antioxidant efficacy. <b>Conclusions</b>: Different amino acid residues can contribute to the antioxidant activity of peptides by scavenging free radicals, chelating metal ions, and modulating enzyme activities. The smaller the molecular weight of the antioxidant peptide, the stronger its antioxidant activity. Additionally, the antioxidant activity of peptides is influenced by specific amino acids located at the C-terminus and N-terminus positions. Simultaneously, this review provides a more systematic analysis and a broader perspective based on existing research, concluded that fish viscera are more favorable for the extraction of antioxidant peptides, providing new insights for the practical application of fish by-products. This could increase the utilization of fish viscera and reduce the environmental pollution caused by their waste, offering valuable references for the study and application of antioxidant peptides from fish by-products.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detailed Profiling of 17-Hydroxygeranyllinalool Diterpene Glycosides from <i>Nicotiana</i> Species Reveals Complex Reaction Networks of Conjugation Isomers.","authors":"Alina Ebert, Saleh Alseekh, Lucio D'Andrea, Ute Roessner, Ralph Bock, Joachim Kopka","doi":"10.3390/metabo14100562","DOIUrl":"https://doi.org/10.3390/metabo14100562","url":null,"abstract":"<p><strong>Background: </strong>Specialised anti-herbivory metabolites are abundant in the solanaceous genus <i>Nicotiana</i>. These metabolites include the large family of 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs). Many HGL-DTGs occur exclusively within the <i>Nicotiana</i> genus, but information from the molecular model species <i>N. tabacum</i>, <i>N. benthamiana</i>, and the tree tobacco <i>N. glauca</i> is limited.</p><p><strong>Objectives: </strong>We studied HGL-DTG occurrence and complexity in these species with the aim of providing in-depth reference annotations and comprehensive HGL-DTG inventories.</p><p><strong>Methods: </strong>We analysed polar metabolite extracts in comparison to the previously investigated wild reference species <i>N. attenuata</i> using positive ESI(+) and negative ESI(-) mode electrospray ionisation LC-MS and MS/MS.</p><p><strong>Results: </strong>We provide annotations of 66 HGL-DTGs with in-source and MS/MS fragmentation spectra for selected HGL-DTGs with exemplary fragment interpretations of ESI(+) as well as less studied ESI(-) spectra. We assemble a potential biosynthesis pathway comparing the presence of HGL-DTGs in <i>N. tabacum</i>, <i>N. glauca</i>, and <i>N. benthamiana</i> to <i>N. attenuata</i>. Approximately one-third of HGL-DTGs are chromatographically resolved isomers of hexose, deoxyhexose, or malonate conjugates. The number of isomers is especially high for conjugates with low numbers of deoxyhexose moieties.</p><p><strong>Conclusions: </strong>We extend the number of known HGL-DTGs with a focus on <i>Nicotiana</i> model species and demonstrate that the HGL-DTG family of <i>N. tabacum</i> plants can be surprisingly complex. Our study provides an improved basis with detailed references to previous studies of wild <i>Nicotiana</i> species and enables inference of HGL-DTG pathways with required enzymes for the biosynthesis of this important family of specialised defence metabolites.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Impact of Catechins on Bone Metabolism: A Comprehensive Review of Current Research and Future Directions.","authors":"Iris Jasmin Santos German, Sandra Maria Barbalho, Jesus Carlos Andreo, Tereza Lais Menegucci Zutin, Lucas Fornari Laurindo, Victória Dogani Rodrigues, Adriano Cressoni Araújo, Elen Landgraf Guiguer, Rosa Direito, Karina Torres Pomini, André Luis Shinohara","doi":"10.3390/metabo14100560","DOIUrl":"https://doi.org/10.3390/metabo14100560","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Degenerative musculoskeletal diseases represent a global health problem due to the progressive deterioration of affected individuals. As a bioactive compound, catechins have shown osteoprotective properties by stimulating osteoblastic cells and inhibiting bone resorption. Thus, this review aimed to address the mechanism of action of catechins on bone tissue. <b>Methods:</b> The search was applied to PubMed without limitations in date, language, or article type. Fifteen articles matched the topic and objective of this review. <b>Results:</b> EGCG (epigallocatechin gallate) and epicatechin demonstrated action on the osteogenic markers RANKL, TRAP, and NF-κβ and expression of BMPs and ALP, thus improving the bone microarchitecture. Studies on animals showed the action of EGCG in increasing calcium and osteoprotegerin levels, in addition to regulating the transcription factor NF-ATc1 associated with osteoclastogenesis. However, it did not show any effect on osteocalcin and RANK. Regarding human studies, EGCG reduced the risk of fracture in a dose-dependent manner. In periodontal tissue, EGCG reduced IL-6, TNF, and RANKL in vitro and in vivo. Human studies showed a reduction in periodontal pockets, gingival index, and clinical attachment level. The action of EGCG on membranes and hydrogels showed biocompatible and osteoinductive properties on the microenvironment of bone tissue by stimulating the expression of osteogenic growth factors and increasing osteocalcin and alkaline phosphate levels, thus promoting new bone formation. <b>Conclusions:</b> EGCG stimulates cytokines related to osteogenes, increasing bone mineral density, reducing osteoclastogenesis factors, and showing great potential as a therapeutic strategy for reducing the risk of bone fractures.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal Metabolomic and Lipidomic Analysis of Circulating Plasma Metabolites in Autism: A Comprehensive Mendelian Randomization Study with Independent Cohort Validation.","authors":"Zhifan Li, Yanrong Li, Xinrong Tang, Abao Xing, Jianlin Lin, Junrong Li, Junjun Ji, Tiantian Cai, Ke Zheng, Sai Sachin Lingampelly, Kefeng Li","doi":"10.3390/metabo14100557","DOIUrl":"https://doi.org/10.3390/metabo14100557","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of autism spectrum disorder (ASD) highlights the need for objective diagnostic markers and a better understanding of its pathogenesis. Metabolic differences have been observed between individuals with and without ASD, but their causal relevance remains unclear.</p><p><strong>Methods: </strong>Bidirectional two-sample Mendelian randomization (MR) was used to assess causal associations between circulating plasma metabolites and ASD using large-scale genome-wide association study (GWAS) datasets-comprising 1091 metabolites, 309 ratios, and 179 lipids-and three European autism datasets (PGC 2015: <i>n</i> = 10,610 and 10,263; 2017: <i>n</i> = 46,351). Inverse-variance weighted (IVW) and weighted median methods were employed, along with robust sensitivity and power analyses followed by independent cohort validation.</p><p><strong>Results: </strong>Higher genetically predicted levels of sphingomyelin (SM) (d17:1/16:0) (OR, 1.129; 95% CI, 1.024-1.245; <i>p</i> = 0.015) were causally linked to increased ASD risk. Additionally, ASD children had higher plasma creatine/carnitine ratios. These MR findings were validated in an independent US autism cohort using machine learning analysis.</p><p><strong>Conclusion: </strong>Utilizing large datasets, two MR approaches, robust sensitivity analyses, and independent validation, our novel findings provide evidence for the potential roles of metabolomics and circulating metabolites in ASD diagnosis and etiology.</p>","PeriodicalId":18496,"journal":{"name":"Metabolites","volume":"14 10","pages":""},"PeriodicalIF":3.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11509474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}