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Cai P, Zheng Y, Chen L, Fang Q, Lei Y, She Z. Association of serum N,N,N-trimethyl-5-aminovaleric acid, trimethylamine N-oxide, and trimethyllysine levels with gestational diabetes mellitus. J Matern Fetal Neonatal Med 2025; 38:2467999. [PMID: 39972978 DOI: 10.1080/14767058.2025.2467999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 01/27/2025] [Accepted: 02/10/2025] [Indexed: 02/21/2025]
Abstract
OBJECTIVE To investigate the association of serum N,N,N-trimethyl-5-aminovaleric acid (TMAVA), trimethylamine N-oxide (TMAO), and trimethyllysine (TML) levels with gestational diabetes mellitus (GDM). METHODS Seventy pregnant women from the Hunan Provincial Maternal and Child Health Care Hospital (March 2021 to October 2023) were enrolled in this study. Forty GDM patients with GDM were included in the GDM group (GDM), and 30 healthy controls were included (Con). Participants were further categorized into adverse and good outcome groups based on pregnancy outcomes. Serum TMAVA, TMAO, and TML levels were quantified using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Correlations between biomarker levels and clinical indicators were assessed using Pearson and Spearman analyses. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate risk factors and predictive value. RESULTS Serum TMAVA, TMAO, and TML levels were significantly higher in the GDM group. TMAVA levels were positively correlated with fasting plasma glucose (FPG), fasting insulin (FINS), creatinine (Cr), TMAO, and TML. TMAO and TML positively correlated with FPG, 2-h postprandial glucose (2h PG), FINS, Cr, and uric acid (UA) levels, while TMAO negatively correlated with triglyceride (TG). Combined TMAVA, TMAO, and TML predicted GDM with an area under the curve (AUC) of 0.940 (95% CI: 0.883-0.997). Elevated TMAVA levels were associated with adverse pregnancy outcomes in GDM, with an AUC of 0.757 (95% CI: 0.612-0.902). CONCLUSIONS Elevated serum levels of TMAVA, TMAO, and TML were significantly associated with the occurrence of GDM and adverse pregnancy outcomes. The combined detection of these three biomarkers demonstrated superior accuracy in predicting GDM. Among them, TMAVA demonstrated the highest predictive efficiency for adverse pregnancy outcomes in women with GDM. These findings provide new biomarkers for early screening and risk assessment of GDM, offering promising applications in clinical practice.
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Affiliation(s)
- Pei Cai
- Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China
| | - Yi Zheng
- Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China
| | - Lulu Chen
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, China
- Changsha Duxact Biotech Co., Ltd., Changsha, China
| | - Qing Fang
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, China
- Changsha Duxact Biotech Co., Ltd., Changsha, China
| | - Yingjuan Lei
- Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China
| | - Zhihua She
- Hunan Provincial Maternal and Child Health Care Hospital, Changsha, China
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Fang Q, Lei Y, Wu H, Li C, Jiang J, Wang S, Wu Y, Chen L, Ouyang D, Li X, Li Y. Plasma reference interval of Trimethylamine-N-oxide in healthy adults: A multicenter study using Trimethylamine-N-oxide assay kit for analysis and validation. Clin Chim Acta 2025; 571:120223. [PMID: 40032200 DOI: 10.1016/j.cca.2025.120223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 02/17/2025] [Accepted: 02/27/2025] [Indexed: 03/05/2025]
Abstract
BACKGROUND Trimethylamine-N-oxide (TMAO) is a potential cardiovascular biomarker in Chinese people without a defined plasma reference range. Its clinical application is restricted due to incomplete knowledge of pre-analytical factors' impact on measurement. METHODS Assess the effects of standard anticoagulants and pre-analytical factors on TMAO test outcomes to determine optimal conditions. Plasma TMAO levels in 649 healthy Chinese individuals were analyzed using a non-parametric approach to set a 95% reference interval. Examine how age, gender, region, and BMI affect TMAO levels and their correlation with clinical metrics like blood pressure, glucose, lipemia, and liver-kidney function. RESULTS Anticoagulants had minimal effect on TMAO assay results. TMAO concentrations remain stable during sample storage at 4 °C for 24 h, 25 °C for 12 h, or 35 °C for six h before centrifugation -prolonged storage at 25 °C or 35 °C results in changes below the acceptable limit. The 95 % reference interval for plasma TMAO is 5.72 µM, with a median of 1.70 µM and an interquartile range of 1.09-2.53 µM. Age, sex, region, and BMI do not affect TMAO levels. SBP, FPG, TC, and BUN positively correlate, while HDL-C, ALT, AST, and TBIL negatively correlate with TMAO. CONCLUSIONS This guides for selecting blood collection tubes for TMAO detection and optimal pre- centrifugation storage conditions. We set a 95% reference interval for plasma TMAO in healthy adults in China and examined the correlation between TMAO levels and demographic and biochemical markers.
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Affiliation(s)
- Qing Fang
- Changsha Duxact Biotech Co., Ltd., Changsha, China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, China
| | - Yuyan Lei
- Department of Pharmacology, Xiangya School of Pharmaceutical Science, Central South University, Changsha, China; The Second Nanning People's Hospital, Nanning, China
| | - Hao Wu
- Department of Health Management, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Chao Li
- Changsha Duxact Biotech Co., Ltd., Changsha, China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, China
| | - Junyi Jiang
- Department of Clinical Pharmacology, Xiangya Hospital, Central South University and Institute of Clinical Pharmacology, Changsha, China
| | - Shiyun Wang
- The Affiliated Hospital of Xiangnan University, Chenzhou, Changsha, China
| | - Yu Wu
- The Second Nanning People's Hospital, Nanning, China
| | - Lulu Chen
- Changsha Duxact Biotech Co., Ltd., Changsha, China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, China.
| | - Dongsheng Ouyang
- Changsha Duxact Biotech Co., Ltd., Changsha, China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, China.
| | - Xiaohui Li
- Changsha Duxact Biotech Co., Ltd., Changsha, China; Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, China; Department of Pharmacology, Xiangya School of Pharmaceutical Science, Central South University, Changsha, China.
| | - Ying Li
- Department of Health Management, The Third Xiangya Hospital, Central South University, Changsha, China.
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Nikparast A, Mirzaei P, Tadayoni ZS, Asghari G. The Association Between Overall, Healthy, and Unhealthy Plant-Based Diet Index and Risk of Prediabetes and Type 2 Diabetes Mellitus: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies. Nutr Rev 2025; 83:e157-e177. [PMID: 38796844 DOI: 10.1093/nutrit/nuae049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/29/2024] Open
Abstract
CONTEXT The global incidence of prediabetes and type 2 diabetes mellitus (T2DM) has increased substantially in recent years. Among the established, modifiable lifestyle factors associated with favorable prediabetes and T2DM risk, healthy dietary patterns have attracted considerable attention. OBJECTIVE The association between adherence to plant-based dietary pattern indices (PDIs), including the overall PDI (O-PDI), healthy PDI (H-PDI), and unhealthy PDI (U-PDI), and the risk of prediabetes and T2DM was investigated in this study. DATA SOURCES A literature search was conducted of the PubMed/Medline, Scopus, and Web of Sciences databases from their inception to February 2024. A systematic review and meta-analysis were conducted using random effects models and dose-response analyses. The Cochran Q test and the I2 statistic were used to evaluate heterogeneity between studies. DATA EXTRACTION A total of 16 publications, with data on a total of 721 012 participants, were identified for the meta-analysis. DATA ANALYSIS According to a pooled analysis, compared with the lowest category of O-PDI and H-PDI adherence, the highest category was associated with a 14% and 19% reduction in T2DM risk, respectively, for O-PDI (effect size [ES] = 0.86; 95%CI, 0.82-0.90; I2 = 57.7) and H-PDI (ES = 0.81; 95%CI, 0.75-0.88; I2 = 82.6). Greater adherence to U-PDI was significantly associated with an 10% increase in the risk of T2DM (ES = 1.10; 95%CI, 1.04-1.16). Consistent associations were found within the predetermined subgroups. As well, there was a nonlinear inverse association between O-PDI, H-PDI, and T2DM risk. No significant association was found between adherence to O-PDI (ES = 0.87; 95%CI, 0.75-1.01; I2 = 68%), H-PDI (ES = 0.99; 95%CI, 0.87-1.13; I2 = 0.0%), and U-PDI (ES = 1.09; 95%CI, 0.94-1.21; I2 = 22.9%) and risk of prediabetes. CONCLUSION These findings underscore the importance of dietary selections within the framework of a plant-based dietary pattern, particularly when incorporating healthful, plant-based foods, which may have potential benefits in reducing the T2DM risk. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42023459851.
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Affiliation(s)
- Ali Nikparast
- Pediatric Gastroenterology and Hepatology Research Center, Pediatrics Centre of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Faculty of Nutrition Science and Food Technology, Department of Clinical Nutrition & Dietetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parmis Mirzaei
- Faculty of Nutrition Science and Food Technology, Department of Clinical Nutrition & Dietetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zeinab S Tadayoni
- Faculty of Nutrition Science and Food Technology, Department of Clinical Nutrition & Dietetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Golaleh Asghari
- Faculty of Nutrition Science and Food Technology, Department of Clinical Nutrition & Dietetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Yao M, Xiao Y, Sun Y, Zhang B, Ding Y, Ma Q, Liang F, Yang Z, Ge W, Liu S, Xin L, Yin J, Zhu X. Association of maternal gut microbial metabolites with gestational diabetes mellitus: evidence from an original case-control study, meta-analysis, and Mendelian randomization. Eur J Clin Nutr 2025; 79:33-41. [PMID: 39223299 DOI: 10.1038/s41430-024-01502-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 07/06/2024] [Accepted: 08/22/2024] [Indexed: 09/04/2024]
Abstract
BACKGROUND The associations of gut microbial metabolites, such as trimethylamine N-oxide (TMAO), its precursors, and phenylacetylglutamine (PAGln), with the risk of gestational diabetes mellitus (GDM) remain unclear. METHODS Serum samples of 201 women with GDM and 201 matched controls were collected and then targeted metabolomics was performed to examine the metabolites of interest. Multivariable conditional logistic regression was applied to investigate the relationship between metabolites and GDM. Meta-analysis was performed to combine our results and four similar articles searched from online databases, and Mendelian randomization (MR) analysis was eventually conducted to explore the causalities. RESULTS In the case-control study, after dichotomization and comparing the higher versus the lower group, the adjusted odds ratio and 95% confidence interval of choline and L-carnitine with GDM were 2.124 (1.186-3.803) and 0.293 (0.134-0.638), respectively; but neutral relationships between TMAO, betaine, and PAGln with GDM were observed. The following meta-analysis consistently revealed that L-carnitine was negatively associated with GDM. However, MR analyses showed no evidence of causalities. CONCLUSIONS Maternal levels of L-carnitine were related to the risk of GDM in both the original case-control study and meta-analysis. However, we did not observe any genetic evidence to establish a causal relationship between this metabolite and GDM.
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Affiliation(s)
- Mengxin Yao
- Suzhou Center for Disease Prevention and Control, Suzhou, China
- Department of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, China
| | - Yue Xiao
- Department of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, China
| | - Yanqun Sun
- Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China
| | - Bing Zhang
- Department of Geriatrics, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, China
| | - Yaling Ding
- Department of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, China
| | - Qiuping Ma
- Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, 58 Changsheng Road, Suzhou, China
| | - Fei Liang
- Department of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, China
| | - Zhuoqiao Yang
- Department of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, China
| | - Wenxin Ge
- Department of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, China
| | - Songliang Liu
- Taicang Affiliated Hospital of Soochow University, The First People's Hospital of Taicang, 58 Changsheng Road, Suzhou, China
| | - Lili Xin
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, Medical College of Soochow University, Suzhou, China
| | - Jieyun Yin
- Department of Epidemiology and Health Statistics, Medical College of Soochow University, Suzhou, China.
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, Medical College of Soochow University, Suzhou, China.
| | - Xiaoyan Zhu
- Suzhou Center for Disease Prevention and Control, Suzhou, China.
- School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Li Z, He X, Fang Q, Yin X. Gut Microbe-Generated Metabolite Trimethylamine-N-Oxide and Ischemic Stroke. Biomolecules 2024; 14:1463. [PMID: 39595639 PMCID: PMC11591650 DOI: 10.3390/biom14111463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 11/05/2024] [Accepted: 11/08/2024] [Indexed: 11/28/2024] Open
Abstract
Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO's aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe-TMAO pathway.
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Affiliation(s)
| | | | - Qi Fang
- Department of Neurology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215006, China; (Z.L.); (X.H.)
| | - Xulong Yin
- Department of Neurology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Road, Suzhou 215006, China; (Z.L.); (X.H.)
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Lamkin K, Xu L, Wang K, Liu Y, Yang K, Wu H, Lu L, Shen X, Johnson CM, Jia J, Zhu J. Choline and betaine intakes during pregnancy in relation to risk of gestational diabetes mellitus among Chinese women. Br J Nutr 2024; 132:971-978. [PMID: 39429119 PMCID: PMC11576091 DOI: 10.1017/s0007114524001995] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 06/04/2024] [Accepted: 07/11/2024] [Indexed: 10/22/2024]
Abstract
Previous animal studies found beneficial effects of choline and betaine on maternal glucose metabolism during pregnancy, but few human studies explored the association between choline or betaine intake and incident gestational diabetes mellitus (GDM). We aimed to explore the correlation of dietary choline or betaine intake with GDM risk among Chinese pregnant women. A total of 168 pregnant women with GDM cases and 375 healthy controls were enrolled at the Seventh People's Hospital in Shanghai during their GDM screening at 24-28 gestational weeks. A validated semi-quantitative FFQ was used to estimate choline and betaine consumption through face-to-face interviews. An unconditional logistic regression model was adopted to examine OR and 95 % CI. Compared with the controls, those women with GDM incidence were likely to have higher pre-pregnancy BMI, be older, have more parities and have higher plasma TAG and lower plasma HDL-cholesterol. No significant correlation was observed between the consumption of choline or betaine and incident GDM (adjusted OR (95 % CI), 0·77 (0·41, 1·43) for choline; 0·80 (0·42, 1·52) for betaine). However, there was a significant interaction between betaine intake and parity on the risk of GDM (Pfor interaction = 0·01). Among those women with no parity history, there was a significantly inverse correlation between betaine intake and GDM risk (adjusted OR (95 % CI), 0·25 (0·06, 0·81)). These findings indicated that higher dietary betaine intake during pregnancy might be considered a protective factor for GDM among Chinese women with no parity history.
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Affiliation(s)
- Kallie Lamkin
- Nutrition and Foods Program, School of Family and Consumer Sciences, Texas State University, San Marcos, TX78666, USA
| | - Lan Xu
- Department of Epidemiology, School of Medicine, Shanghai Jiao Tong University, Shanghai200025, People’s Republic of China
| | - Kaipeng Wang
- Graduate School of Social Work, University of Denver, Denver, CO80208, USA
| | - Yuhong Liu
- Department of Gynecology and Obstetrics, Shanghai Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai200137, People’s Republic of China
| | - Kefeng Yang
- Department of Clinical Nutrition, College of Heath Science and Technology, School of Medicine, Shanghai Jiao Tong University, Shanghai200025, People’s Republic of China
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200092, People’s Republic of China
| | - Hui Wu
- Department of Clinical Nutrition, Shanghai Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai200137, People’s Republic of China
| | - Lingpeng Lu
- Department of Clinical Laboratory, Shanghai Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai200137, People’s Republic of China
| | - Xiaoxi Shen
- Department of Mathematics, Texas State University, San Marcos, TX78666, USA
| | - Cassandra M. Johnson
- Nutrition and Foods Program, School of Family and Consumer Sciences, Texas State University, San Marcos, TX78666, USA
| | - Jie Jia
- Department of Clinical Nutrition, College of Heath Science and Technology, School of Medicine, Shanghai Jiao Tong University, Shanghai200025, People’s Republic of China
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai200092, People’s Republic of China
| | - Jie Zhu
- Nutrition and Foods Program, School of Family and Consumer Sciences, Texas State University, San Marcos, TX78666, USA
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Sugino KY, Hernandez TL, Barbour LA, Kofonow JM, Frank DN, Friedman JE. Distinct Plasma Metabolomic and Gut Microbiome Profiles after Gestational Diabetes Mellitus Diet Treatment: Implications for Personalized Dietary Interventions. Microorganisms 2024; 12:1369. [PMID: 39065137 PMCID: PMC11278888 DOI: 10.3390/microorganisms12071369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 06/24/2024] [Accepted: 06/29/2024] [Indexed: 07/28/2024] Open
Abstract
Gestational diabetes mellitus (GDM) triggers alterations in the maternal microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. We investigated maternal microbiome-metabolomic changes, including over 600 metabolites from a subset of the "Choosing Healthy Options in Carbohydrate Energy" (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n = 18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n = 16, 40% carbohydrate/45% fat/15% protein). All meals were provided. Diets were eucaloric, and fiber content was similar. CHOICE was associated with increases in trimethylamine N-oxide, indoxyl sulfate, and several triglycerides, while CONV was associated with hippuric acid, betaine, and indole propionic acid, suggestive of a healthier metabolome. Conversely, the microbiome of CHOICE participants was enriched with carbohydrate metabolizing genes and beneficial taxa such as Bifidobacterium adolescentis, while CONV was associated with inflammatory pathways including antimicrobial resistance and lipopolysaccharide biosynthesis. We also identified latent metabolic groups not associated with diet: a metabolome associated with less of a decrease in fasting glucose, and another associated with relatively higher fasting triglycerides. Our results suggest that GDM diets produce specific microbial and metabolic responses during pregnancy, while host factors also play a role in triglycerides and glucose metabolism.
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Affiliation(s)
- Kameron Y. Sugino
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA;
| | - Teri L. Hernandez
- Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA; (T.L.H.); (L.A.B.)
- College of Nursing, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA
| | - Linda A. Barbour
- Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA; (T.L.H.); (L.A.B.)
- Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA
| | - Jennifer M. Kofonow
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA; (J.M.K.); (D.N.F.)
| | - Daniel N. Frank
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA; (J.M.K.); (D.N.F.)
| | - Jacob E. Friedman
- Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA;
- Department of Biochemistry & Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
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Li X, Wang C, Yanagita T, Xue C, Zhang T, Wang Y. Trimethylamine N-Oxide in Aquatic Foods. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:14498-14520. [PMID: 38885200 DOI: 10.1021/acs.jafc.4c01974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/20/2024]
Abstract
Trimethylamine N-oxide (TMAO), a characteristic nonprotein nitrogen compound, is widely present in seafood, which exhibits osmoregulatory effects for marine organisms in vivo and plays an important role in aquaculture and aquatic product preservation. However, much attention has been focused on the negative effect of TMAO since it has recently emerged as a putative promoter of chronic diseases. To get full knowledge and maximize our ability to balance the positive and negative aspects of TMAO, in this review, we comprehensively discuss the TMAO in aquatic products from the aspects of physiological functions for marine organisms, flavor, quality, the conversion of precursors, the influences on human health, and the seafood ingredients interaction consideration. Though the circulating TMAO level is inevitably enhanced after seafood consumption, dietary seafood still exhibits beneficial health effects and may provide nutraceuticals to balance the possible adverse effects of TMAO.
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Affiliation(s)
- Xiaoyue Li
- SKL of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China
| | - Chengcheng Wang
- SKL of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China
| | - Teruyoshi Yanagita
- Laboratory of Nutrition Biochemistry, Department of Applied Biochemistry and Food Science, Saga University, Saga 840-8502, Japan
| | - Changhu Xue
- SKL of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China
| | - Tiantian Zhang
- SKL of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China
| | - Yuming Wang
- SKL of Marine Food Processing & Safety Control, College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China
- Sanya Institute of Oceanography, Ocean University of China, Sanya 572024, China
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9
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Dymek A, Oleksy Ł, Stolarczyk A, Bartosiewicz A. Choline-An Underappreciated Component of a Mother-to-Be's Diet. Nutrients 2024; 16:1767. [PMID: 38892700 PMCID: PMC11174651 DOI: 10.3390/nu16111767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 05/27/2024] [Accepted: 06/02/2024] [Indexed: 06/21/2024] Open
Abstract
The nutritional status of the mother-to-be has a key impact on the proper development of the fetus. Although all nutrients are important for the developing baby, recent research indicates the importance of adequate choline intake during the periconceptional period, pregnancy, and lactation. Choline plays a key role in the biosynthesis of cell membranes, supporting liver function, neurotransmission, brain development, and DNA and histone methylation. Choline participates in the formation of a child's nervous system, supports its cognitive development, and reduces the risk of neural tube defects. The human body is incapable of producing sufficient choline to meet its needs; therefore, it must be obtained from the diet. Current data indicate that most women in their reproductive years do not achieve the recommended daily intake of choline. The presented narrative review indicates the importance of educating mothers-to-be and thereby increasing their awareness of the effects of choline on maternal and child health, which can lead to a more aware and healthy pregnancy and proper child development.
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Affiliation(s)
- Agnieszka Dymek
- Students Scientific Club of Dietetics, Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
| | - Łukasz Oleksy
- Department of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, 31-008 Kraków, Poland
| | - Artur Stolarczyk
- Department of Orthopedics and Rehabilitation, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Anna Bartosiewicz
- Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
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Wierzchowska-Opoka M, Grunwald A, Rekowska AK, Łomża A, Mekler J, Santiago M, Kabała Z, Kimber-Trojnar Ż, Leszczyńska-Gorzelak B. Impact of Obesity and Diabetes in Pregnant Women on Their Immunity and Vaccination. Vaccines (Basel) 2023; 11:1247. [PMID: 37515062 PMCID: PMC10385489 DOI: 10.3390/vaccines11071247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 07/14/2023] [Accepted: 07/15/2023] [Indexed: 07/30/2023] Open
Abstract
Pregnant women with obesity and diabetes are at increased risk of developing infections and other complications during pregnancy. Several mechanisms are involved in the immunological mechanisms that contribute to reduced immunity in these populations. Both obesity and diabetes are associated with chronic low-grade inflammation that can lead to an overactive immune response. Pregnant women with obesity and diabetes often have an increase in pro-inflammatory cytokines and adipokines, such as TNF-α, IL-6, IL-1β, leptin, and resistin, which are involved in the inflammatory response. Insulin resistance can also affect the functioning of immune cells. Furthermore, both conditions alter the composition of the gut microbiome, which produces a variety of biomolecules, including short-chain fatty acids, lipopolysaccharides, and other metabolites. These substances may contribute to immune dysfunction. In addition to increasing the risk of infections, obesity and diabetes can also affect the efficacy of vaccinations in pregnant women. Pregnant women with obesity and diabetes are at increased risk of developing severe illness and complications from COVID-19, but COVID-19 vaccination may help protect them and their fetuses from infection and its associated risks. Since both obesity and diabetes classify a pregnancy as high risk, it is important to elucidate the impact of these diseases on immunity and vaccination during pregnancy. Research examining the efficacy of the COVID-19 vaccine in a high-risk pregnant population should be of particular value to obstetricians whose patients are hesitant to vaccinate during pregnancy. Further research is needed to better understand these mechanisms and to develop effective interventions to improve immune function in these populations.
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Affiliation(s)
| | - Arkadiusz Grunwald
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Anna K Rekowska
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Aleksandra Łomża
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Julia Mekler
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Miracle Santiago
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Zuzanna Kabała
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
| | - Żaneta Kimber-Trojnar
- Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-059 Lublin, Poland
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11
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Singh P, Elhaj DAI, Ibrahim I, Abdullahi H, Al Khodor S. Maternal microbiota and gestational diabetes: impact on infant health. J Transl Med 2023; 21:364. [PMID: 37280680 PMCID: PMC10246335 DOI: 10.1186/s12967-023-04230-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2023] [Accepted: 05/26/2023] [Indexed: 06/08/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is a common complication of pregnancy that has been associated with an increased risk of obesity and diabetes in the offspring. Pregnancy is accompanied by tightly regulated changes in the endocrine, metabolic, immune, and microbial systems, and deviations from these changes can alter the mother's metabolism resulting in adverse pregnancy outcomes and a negative impact on the health of her infant. Maternal microbiomes are significant drivers of mother and child health outcomes, and many microbial metabolites are likely to influence the host health. This review discusses the current understanding of how the microbiota and microbial metabolites may contribute to the development of GDM and how GDM-associated changes in the maternal microbiome can affect infant's health. We also describe microbiota-based interventions that aim to improve metabolic health and outline future directions for precision medicine research in this emerging field.
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Affiliation(s)
- Parul Singh
- College of Health & Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar
- Research Department, Sidra Medicine, Doha, Qatar
| | | | - Ibrahim Ibrahim
- Women's Department, Sidra Medicine, Weill Cornell Medical College-Qatar, Doha, Qatar
| | - Hala Abdullahi
- Women's Department, Sidra Medicine, Weill Cornell Medical College-Qatar, Doha, Qatar
| | - Souhaila Al Khodor
- College of Health & Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
- Research Department, Sidra Medicine, Doha, Qatar.
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12
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Safari-Alighiarloo N, Emami Z, Rezaei-Tavirani M, Alaei-Shahmiri F, Razavi S. Gut Microbiota and Their Associated Metabolites in Diabetes: A Cross Talk Between Host and Microbes-A Review. Metab Syndr Relat Disord 2023; 21:3-15. [PMID: 36301254 DOI: 10.1089/met.2022.0049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Dysbiosis of the gut microbiota's composition and function is important in developing insulin resistance and diabetes. Diabetes has also been linked to changes in the circulating and fecal metabolites. Evidence suggests the associations between the gut microbiota and the aberrant diabetes-related metabolome. Metabolites play a crucial role in the host-microbiota interactions. Researchers have used a combination of metagenomic and metabolomic approaches to investigate the relationships between gut microbial dysbiosis and metabolic abnormalities in diabetes. We summarized current discoveries on the associations between the gut microbiota and metabolites in type 1 diabetes, type 2 diabetes, and gestational diabetes mellitus in the scoping review. According to research, the gut microbiota changes might involve in the development of diabetes through modulating the host's metabolic pathways such as immunity, energy metabolism, lipid metabolism, and amino acid metabolism. These results add to our understanding of the interplay between the host and gut microbiota metabolism.
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Affiliation(s)
- Nahid Safari-Alighiarloo
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Emami
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fariba Alaei-Shahmiri
- Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
| | - Shabnam Razavi
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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13
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Zeng J, Yang K, Nie H, Yuan L, Wang S, Zeng L, Ge A, Ge J. The mechanism of intestinal microbiota regulating immunity and inflammation in ischemic stroke and the role of natural botanical active ingredients in regulating intestinal microbiota: A review. Biomed Pharmacother 2023; 157:114026. [PMID: 36436491 DOI: 10.1016/j.biopha.2022.114026] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2022] [Revised: 11/07/2022] [Accepted: 11/17/2022] [Indexed: 11/27/2022] Open
Abstract
Intestinal microbiota is a unique ecosystem, known as the "second genome" of human beings. With the widespread application of next generation sequencing (NGS), especially 16 S rRNA and shotgun sequencing, numerous studies have shown that dysregulation of intestinal microbiota is associated with many central nervous system diseases. Ischemic stroke (IS) is a cerebrovascular disease with high morbidity and mortality. Brain damage in IS affects intestinal function, and intestinal dysfunction further aggravates brain damage, forming a vicious circle of mutual interference in pathology. The microbiota-gut-brain axis study based on the intestinal microbiota has opened up broader ideas for exploring its pathogenesis and risk factors, and also provided more possibilities for the selection of therapeutic targets for this type of drug. This review discussed the application of NGS technology in the study of intestinal microbiota and the research progress of microbiota-gut-brain axis in recent years, and systematically sorts out the literature on the relationship between ischemic stroke and intestinal microbiota. It starts with the characteristics of microbiota-gut-brain axis' bidirectional regulation, respectively discusses the high risk factors of IS under intestinal microbiota imbalance and the physiological and pathological changes of intestinal microbiota after IS, and summarizes the related targets, in order to provide reliable reference for the treatment of IS from intestinal microbiota. In addition, natural botanical active ingredients have achieved good results in the treatment of IS based on regulating the homeostasis of gut microbiota, providing new evidence for studying the potential targets and therapies of IS based on the microbiota-gut-brain axis.
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Affiliation(s)
- Jinsong Zeng
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Kailin Yang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha City, China..
| | - Huifang Nie
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha City, China
| | - Le Yuan
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha City, China
| | - Shanshan Wang
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha City, China
| | - Liuting Zeng
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha City, China..
| | - Anqi Ge
- The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China
| | - Jinwen Ge
- Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha City, China.; Hunan Academy of Chinese Medicine, Changsha, China..
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14
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Zhen J, Zhou Z, He M, Han HX, Lv EH, Wen PB, Liu X, Wang YT, Cai XC, Tian JQ, Zhang MY, Xiao L, Kang XX. The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases. Front Endocrinol (Lausanne) 2023; 14:1085041. [PMID: 36824355 PMCID: PMC9941174 DOI: 10.3389/fendo.2023.1085041] [Citation(s) in RCA: 56] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 01/26/2023] [Indexed: 02/10/2023] Open
Abstract
Morbidity and mortality of cardiovascular diseases (CVDs) are exceedingly high worldwide. Researchers have found that the occurrence and development of CVDs are closely related to intestinal microecology. Imbalances in intestinal microecology caused by changes in the composition of the intestinal microbiota will eventually alter intestinal metabolites, thus transforming the host physiological state from healthy mode to pathological mode. Trimethylamine N-oxide (TMAO) is produced from the metabolism of dietary choline and L-carnitine by intestinal microbiota, and many studies have shown that this important product inhibits cholesterol metabolism, induces platelet aggregation and thrombosis, and promotes atherosclerosis. TMAO is directly or indirectly involved in the pathogenesis of CVDs and is an important risk factor affecting the occurrence and even prognosis of CVDs. This review presents the biological and chemical characteristics of TMAO, and the process of TMAO produced by gut microbiota. In particular, the review focuses on summarizing how the increase of gut microbial metabolite TMAO affects CVDs including atherosclerosis, heart failure, hypertension, arrhythmia, coronary artery disease, and other CVD-related diseases. Understanding the mechanism of how increases in TMAO promotes CVDs will potentially facilitate the identification and development of targeted therapy for CVDs.
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Affiliation(s)
- Jing Zhen
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
- School of Chemical Engineering and Technology, China University of Mining and Technology, Xuzhou, Jiangsu, China
| | - Zhou Zhou
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Meng He
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Hai-Xiang Han
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - En-Hui Lv
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Peng-Bo Wen
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Xin Liu
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yan-Ting Wang
- Department of Biochemical Pharmacy, School of Pharmacy, Naval Medical University, Shanghai, China
| | - Xun-Chao Cai
- Department of Gastroenterology and Hepatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong, China
| | - Jia-Qi Tian
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Meng-Ying Zhang
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Lei Xiao
- School of Chemical Engineering and Technology, China University of Mining and Technology, Xuzhou, Jiangsu, China
- *Correspondence: Xing-Xing Kang, ; Lei Xiao,
| | - Xing-Xing Kang
- Department of Bioinformatics, School of Medical Informatics, Xuzhou Medical University, Xuzhou, Jiangsu, China
- *Correspondence: Xing-Xing Kang, ; Lei Xiao,
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15
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Bankole T, Winn H, Li Y. Dietary Impacts on Gestational Diabetes: Connection between Gut Microbiome and Epigenetic Mechanisms. Nutrients 2022; 14:nu14245269. [PMID: 36558427 PMCID: PMC9786016 DOI: 10.3390/nu14245269] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 12/05/2022] [Accepted: 12/07/2022] [Indexed: 12/14/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is one of the most common obstetric complications due to an increased level of glucose intolerance during pregnancy. The prevalence of GDM increases due to the obesity epidemic. GDM is also associated with an increased risk of gestational hypertension and preeclampsia resulting in elevated maternal and perinatal morbidity and mortality. Diet is one of the most important environmental factors associated with etiology of GDM. Studies have shown that the consumption of certain bioactive diets and nutrients before and during pregnancy might have preventive effects against GDM leading to a healthy pregnancy outcome as well as beneficial metabolic outcomes later in the offspring's life. Gut microbiome as a biological ecosystem bridges the gap between human health and diseases through diets. Maternal diets affect maternal and fetal gut microbiome and metabolomics profiles, which consequently regulate the host epigenome, thus contributing to later-life metabolic health in both mother and offspring. This review discusses the current knowledge regarding how epigenetic mechanisms mediate the interaction between maternal bioactive diets, the gut microbiome and the metabolome leading to improved metabolic health in both mother and offspring.
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Affiliation(s)
- Taiwo Bankole
- Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA
| | - Hung Winn
- Department of Obstetrics, Gynecology and Women’s Health, University of Missouri, Columbia, MO 65212, USA
| | - Yuanyuan Li
- Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA
- Correspondence:
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16
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A Study of the Metabolic Pathways Affected by Gestational Diabetes Mellitus: Comparison with Type 2 Diabetes. Diagnostics (Basel) 2022; 12:diagnostics12112881. [PMID: 36428943 PMCID: PMC9689375 DOI: 10.3390/diagnostics12112881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/15/2022] [Accepted: 11/17/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) remains incompletely understood and increases the risk of developing Diabetes mellitus type 2 (DM2). Metabolomics provides insights etiology and pathogenesis of disease and discovery biomarkers for accurate detection. Nuclear magnetic resonance (NMR) spectroscopy is a key platform defining metabolic signatures in intact serum/plasma. In the present study, we used NMR-based analysis of macromolecules free-serum to accurately characterize the altered metabolic pathways of GDM and assessing their similarities to DM2. Our findings could contribute to the understanding of the pathophysiology of GDM and help in the identification of metabolomic markers of the disease. METHODS Sixty-two women with GDM matched with seventy-seven women without GDM (control group). 1H NMR serum spectra were acquired on an 11.7 T Bruker Avance DRX NMR spectrometer. RESULTS We identified 55 metabolites in both groups, 25 of which were significantly altered in the GDM group. GDM group showed elevated levels of ketone bodies, 2-hydroxybutyrate and of some metabolic intermediates of branched-chain amino acids (BCAAs) and significantly lower levels of metabolites of one-carbon metabolism, energy production, purine metabolism, certain amino acids, 3-methyl-2-oxovalerate, ornithine, 2-aminobutyrate, taurine and trimethylamine N-oxide. CONCLUSION Metabolic pathways affected in GDM were beta-oxidation, ketone bodies metabolism, one-carbon metabolism, arginine and ornithine metabolism likewise in DM2, whereas BCAAs catabolism and aromatic amino acids metabolism were affected, but otherwise than in DM2.
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17
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Zhong C, Chen R, Zhou X, Zhang Y, Liu C, Huang L, Li Q, Xu S, Chen X, Xiong T, Wang W, Gao Q, Zhang H, Wu Y, Hong M, Wu J, Cui W, Li X, Wang W, Lin L, Wang H, Gao D, Li N, Li D, Zhang G, Wang X, Zhang X, Wu M, Yang S, Cao X, Tan T, Tu M, Guo J, Hu W, Zhu W, Xiao D, Gong L, Zhang H, Liu J, Yang S, Wei S, Xiao M, Sun G, Xiong G, Ni Z, Wang J, Jin Z, Yang X, Hao L, Yang H, Yang N. Cohort Profile: The Tongji Maternal and Child Health Cohort (TMCHC). Int J Epidemiol 2022; 52:e152-e161. [PMID: 36343093 DOI: 10.1093/ije/dyac209] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 10/18/2022] [Indexed: 11/09/2022] Open
Affiliation(s)
- Chunrong Zhong
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Renjuan Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Xuezhen Zhou
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Yu Zhang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Chaoqun Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Li Huang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Qian Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Shangzhi Xu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Xi Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Ting Xiong
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Weiye Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Qin Gao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Hongmin Zhang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Yuanjue Wu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Miao Hong
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Jiangyue Wu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Wenli Cui
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Xiating Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Weiming Wang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Lixia Lin
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Huanzhuo Wang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Duan Gao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Nan Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - De Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Guofu Zhang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Xiaoyi Wang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Xu Zhang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Meng Wu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Sen Yang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Xiyu Cao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Tianqi Tan
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Menghan Tu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Jingrong Guo
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Wenqi Hu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Wenwen Zhu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Daxiang Xiao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Lin Gong
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Huaqi Zhang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Jin Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Siyu Yang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Sheng Wei
- Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Mei Xiao
- Department of Obstetrics, Hubei Maternal and Child Health Hospital , Wuhan, China
- Department of Integrated Traditional and Western Medicine, Hubei Maternal and Child Health Hospital , Wuhan, China
| | - Guoqiang Sun
- Department of Obstetrics, Hubei Maternal and Child Health Hospital , Wuhan, China
- Department of Integrated Traditional and Western Medicine, Hubei Maternal and Child Health Hospital , Wuhan, China
| | - Guoping Xiong
- Department of Obstetrics and Gynecology, The Central Hospital of Wuhan , Wuhan, China
| | - Zemin Ni
- Jiang'an Maternal and Child Health Hospital , Wuhan, China
| | - Jing Wang
- Jiang'an Maternal and Child Health Hospital , Wuhan, China
| | - Zhichun Jin
- Department of Obstetrics, Hubei Maternal and Child Health Hospital , Wuhan, China
| | - Xuefeng Yang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Liping Hao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
| | - Hongying Yang
- Institute of Health Education, Hubei Provincial Center for Disease Control and Prevention , Wuhan, China
| | - Nianhong Yang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China
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18
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Does the Gut Microbial Metabolome Really Matter? The Connection between GUT Metabolome and Neurological Disorders. Nutrients 2022; 14:nu14193967. [PMID: 36235622 PMCID: PMC9571089 DOI: 10.3390/nu14193967] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 09/20/2022] [Accepted: 09/21/2022] [Indexed: 11/30/2022] Open
Abstract
Herein we gathered updated knowledge regarding the alterations of gut microbiota (dysbiosis) and its correlation with human neurodegenerative and brain-related diseases, e.g., Alzheimer’s and Parkinson’s. This review underlines the importance of gut-derived metabolites and gut metabolic status as the main players in gut-brain crosstalk and their implications on the severity of neural conditions. Scientific evidence indicates that the administration of probiotic bacteria exerts beneficial and protective effects as reduced systemic inflammation, neuroinflammation, and inhibited neurodegeneration. The experimental results performed on animals, but also human clinical trials, show the importance of designing a novel microbiota-based probiotic dietary supplementation with the aim to prevent or ease the symptoms of Alzheimer’s and Parkinson’s diseases or other forms of dementia or neurodegeneration.
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Experimental Evidence of Buyang Huanwu Decoction and Related Modern Preparations (Naoxintong Capsule and Yangyin Tongnao Granule) in Treating Cerebral Ischemia: Intestinal Microorganisms and Transcriptomics in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:4016935. [PMID: 36185082 PMCID: PMC9519341 DOI: 10.1155/2022/4016935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 07/02/2022] [Accepted: 07/15/2022] [Indexed: 11/24/2022]
Abstract
Background The traditional Chinese medicines of Buyang Huanwu decoction (BYHW), Naoxintong capsule (NXT), and Yangyin Tongnao granules (YYTN) have excellent effects in preventing and treating cerebrovascular disease and are widely tolerated by patients. However, their effects on middle cerebral artery occlusion (MCAO) remain unknown. Methods We evaluated gut microbiota alterations, the brain transcriptome, and nerve cell responses in rats with MCAO. Results Our results showed that BYHW, NXT, and YYTN not only effectively improved the damaged state of blood vessels in rats and restored nerve function, but also improved survival. Additional experiments showed that treatment with BYHW, NXT, and YYTN regulated the intestinal microflora. Transcriptome analyses showed that BYHW, NXT, and YYTN modulated the transcriptome of rats with MCAO. The common mechanism of the three prescriptions for the treatment of cerebral ischemia may be related to the intestinal flora regulation of 60S ribosomal protein L18 (Rpl18), eukaryotic translation initiation factor 3 subunit, Ras homolog family member C, G protein subunit gamma 13 (Gng13), and Gng10 genes, among which Rpl18 is the most important. In addition, the three prescriptions had great specificity as anticerebral ischemia targets. Moreover, BYHW, NXT, and YYTN mitigated MCAO-induced hyperactivation of microglia and astrocytes. Conclusion This study provides a foundation for further research on the mechanisms and treatment of IS. The results strongly suggest that key gut microbiota can be used to study functional genomics of brain, leading to novel discoveries about key genes involved in important biological processes.
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Kapoor B, Gulati M, Rani P, Gupta R. Psoriasis: Interplay between dysbiosis and host immune system. Clin Exp Rheumatol 2022; 21:103169. [PMID: 35964945 DOI: 10.1016/j.autrev.2022.103169] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 08/07/2022] [Indexed: 11/30/2022]
Abstract
With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of both gut and skin microbiota in the pathogenesis of psoriasis. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts, have been identified as possible triggers for recurrent episodes of psoriasis. Mechanistically, gut dysbiosis leads to "leaky gut syndrome" via disruption of epithelial bilayer, thereby, resulting in translocation of bacteria and other endotoxins to systemic circulation, which in turn, results in inflammatory response. Similarly, skin dysbiosis disrupts the cutaneous homeostasis, leading to invasion of bacteria and other pathogens to deeper layers of skin or even systemic circulation further enhanced by injury caused by pruritus-induced scratching, and elicit innate and adaptive inflammation. The present review explores the correlation of both skin and gut microbiota dysbiosis with psoriasis. Also, the studies highlighting the potential of bacteriotherapeutic approaches including probiotics, prebiotics, metabiotics, and fecal microbiota transplantation for the management of psoriasis have been discussed.
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Affiliation(s)
- Bhupinder Kapoor
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India.
| | - Monica Gulati
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, NSW 2007, Australia.
| | - Pooja Rani
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Reena Gupta
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
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21
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Kant R, Chandra L, Verma V, Nain P, Bello D, Patel S, Ala S, Chandra R, Antony MA. Gut microbiota interactions with anti-diabetic medications and pathogenesis of type 2 diabetes mellitus. World J Methodol 2022; 12:246-257. [PMID: 36159100 PMCID: PMC9350729 DOI: 10.5662/wjm.v12.i4.246] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 05/03/2022] [Accepted: 06/18/2022] [Indexed: 02/06/2023] Open
Abstract
Microorganisms including bacteria, viruses, protozoa, and fungi living in the gastrointestinal tract are collectively known as the gut microbiota. Dysbiosis is the imbalance in microbial composition on or inside the body relative to healthy state. Altered Firmicutes to Bacteroidetes ratio and decreased abundance of Akkermansia muciniphila are the predominant gut dysbiosis associated with the pathogenesis of type 2 diabetes mellitus (T2DM) and metabolic syndrome. Pathophysiological mechanisms linking gut dysbiosis, and metabolic diseases and their complications include altered metabolism of short-chain fatty acids and bile acids, interaction with gut hormones, increased gut microbial metabolite trimethylamine-N-oxide, bacterial translocation/Leaky gut syndrome, and endotoxin production such as lipopolysaccharides. The association between the gut microbiota and glycemic agents, however, is much less understood and is the growing focus of research and conversation. Recent studies suggest that the gut microbiota and anti-diabetic medications are interdependent on each other, meaning that while anti-diabetic medications alter the gut microbiota, the gut microbiota also alters the efficacy of anti-diabetic medications. With increasing evidence regarding the significance of gut microbiota, it is imperative to review the role of gut microbiota in the pathogenesis of T2DM. This review also discusses the interaction between gut microbiota and the various medications used in the treatment of T2DM.
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Affiliation(s)
- Ravi Kant
- Department of Endocrinology, Diabetes and Metabolism, Medical University of South Carolina, Anderson, SC 29621, United States
- Department of Endocrinology, Diabetes and Metabolism, AnMed Health, Anderson, SC 29621, United States
| | - Lakshya Chandra
- Department of Internal Medicine, St Francis Hospital, Greenville, SC 29601, United States
| | - Vipin Verma
- Department of Internal Medicine, Medical University of South Carolina, Anderson, SC 29621, United States
- Department of Internal Medicine, AnMed Health, Anderson, SC 29621, United States
| | - Priyanshu Nain
- Department of Graduate Medical Education, Maulana Azad Medical College, Delhi 110002, India
| | - Diego Bello
- Department of Surgery, AnMed Health, Anderson, SC 29621, United States
| | - Siddharth Patel
- Department of Internal Medicine, Decatur Morgan Hospital, Decatur, AL 35601, United States
| | - Subash Ala
- Department of Internal Medicine, St Francis Hospital, Greenville, SC 29601, United States
| | - Rashmi Chandra
- Department of Internal Medicine, Medical University of South Carolina, Anderson, SC 29621, United States
| | - Mc Anto Antony
- Department of Endocrinology, Diabetes and Metabolism, Medical University of South Carolina, Anderson, SC 29621, United States
- Department of Endocrinology, Diabetes and Metabolism, AnMed Health, Anderson, SC 29621, United States
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22
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Li D, Lu Y, Yuan S, Cai X, He Y, Chen J, Wu Q, He D, Fang A, Bo Y, Song P, Bogaert D, Tsilidis K, Larsson SC, Yu H, Zhu H, Theodoratou E, Zhu Y, Li X. Gut microbiota-derived metabolite trimethylamine-N-oxide and multiple health outcomes: an umbrella review and updated meta-analysis. Am J Clin Nutr 2022; 116:230-243. [PMID: 35348578 PMCID: PMC9257469 DOI: 10.1093/ajcn/nqac074] [Citation(s) in RCA: 59] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 03/24/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced from dietary nutrients. Many studies have discovered that circulating TMAO concentrations are linked to a wide range of health outcomes. OBJECTIVES This study aimed to summarize health outcomes related to circulating TMAO concentrations. METHODS We searched the Embase, Medline, Web of Science, and Scopus databases from inception to 15 February, 2022 to identify and update meta-analyses examining the associations between TMAO and multiple health outcomes. For each health outcome, we estimated the summary effect size, 95% prediction CI, between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate the evidence credibility of the identified associations. RESULTS This umbrella review identified 24 meta-analyses that investigated the association between circulating TMAO concentrations and health outcomes including all-cause mortality, cardiovascular diseases (CVDs), diabetes mellitus (DM), cancer, and renal function. We updated these meta-analyses by including a total of 82 individual studies on 18 unique health outcomes. Among them, 14 associations were nominally significant. After evidence credibility assessment, we found 6 (33%) associations (i.e., all-cause mortality, CVD mortality, major adverse cardiovascular events, hypertension, DM, and glomerular filtration rate) to present highly suggestive evidence. CONCLUSIONS TMAO might be a novel biomarker related to human health conditions including all-cause mortality, hypertension, CVD, DM, cancer, and kidney function. Further studies are needed to investigate whether circulating TMAO concentrations could be an intervention target for chronic disease.This review was registered at www.crd.york.ac.uk/prospero/ as CRD42021284730.
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Affiliation(s)
- Doudou Li
- Department of Big Data in Health Science, School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Ying Lu
- Department of Big Data in Health Science, School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shuai Yuan
- Department of Big Data in Health Science, School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
| | - Xiaxia Cai
- Department of Nutrition and Food Hygiene, Beijing Key Laboratory of Environmental Toxicology, School of Public Health, Capital Medical University, Beijing, China
| | - Yuan He
- National Research Institute for Health and Family Planning, Beijing, China
| | - Jie Chen
- Department of Big Data in Health Science, School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Qiong Wu
- Department of Epidemiology & Biostatistics, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Di He
- Department of Epidemiology & Biostatistics, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Aiping Fang
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Yacong Bo
- Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China
| | - Peige Song
- School of Public Health and Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Debby Bogaert
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom
| | - Kostas Tsilidis
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Susanna C Larsson
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden
- Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Huanling Yu
- Department of Nutrition and Food Hygiene, Beijing Key Laboratory of Environmental Toxicology, School of Public Health, Capital Medical University, Beijing, China
| | - Huilian Zhu
- Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Evropi Theodoratou
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom
- Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom
| | - Yimin Zhu
- Department of Epidemiology & Biostatistics, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Xue Li
- Department of Big Data in Health Science, School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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McArthur KL, Zhang M, Hong X, Wang G, Buckley JP, Wang X, Mueller NT. Trimethylamine N-Oxide and Its Precursors Are Associated with Gestational Diabetes Mellitus and Pre-Eclampsia in the Boston Birth Cohort. Curr Dev Nutr 2022; 6:nzac108. [PMID: 35949367 PMCID: PMC9356535 DOI: 10.1093/cdn/nzac108] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 03/14/2022] [Accepted: 06/08/2022] [Indexed: 12/01/2022] Open
Abstract
Background Trimethylamine N-oxide (TMAO) and its precursors choline, betaine, and carnitine have been associated with cardiometabolic disease in nonpregnant adults. However, studies examining TMAO and its precursors in relation to cardiometabolic conditions during pregnancy are lacking. Objectives The primary objective was to estimate the association of TMAO and its precursors in maternal and cord plasma with gestational diabetes mellitus (GDM) and pre-eclampsia (PE) among women in the Boston Birth Cohort. A secondary objective was to determine whether associations vary by race/ethnicity. Methods ORs for each outcome according to tertiles and to an SD increment of TMAO, choline, betaine, and carnitine were estimated using logistic regression. Final models were adjusted for covariates. Results Among 1496 women, 115 women had GDM and 159 had PE during the index pregnancy. Intermetabolite correlations of TMAO and its precursors were stronger within cord plasma (r = 0.38-0.87) than within maternal plasma (r = 0.08-0.62). Maternal TMAO was associated with higher odds of GDM (third compared with first tertile OR: 1.75; 95% CI: 1.04, 2.94), whereas maternal choline, betaine, and carnitine were not associated with GDM. Maternal TMAO and choline were not associated with PE, whereas carnitine was associated with higher (OR: 1.86; 95% CI: 1.18, 2.94) and betaine with lower odds of PE (OR: 0.37; 95% CI: 0.23, 0.59). In cord plasma, TMAO was not associated with GDM or PE, but choline, betaine, and carnitine were associated with higher odds of PE (OR: 3.11; 95% CI: 1.62, 5.96; OR: 2.65; 95% CI: 1.42, 4.93; OR: 2.56; 95% CI: 1.39, 4.69, respectively). Cord choline was associated with lower odds of GDM (OR: 0.52; 95% CI: 0.27, 0.99), whereas other cord metabolites were not significantly associated with GDM. Associations did not vary by race/ethnicity. Conclusions TMAO and its precursors were associated with GDM and PE, but the associations differed based on the metabolite medium (maternal compared with cord plasma).This trial was registered at clinicaltrials.gov as NCT03228875.
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Affiliation(s)
- Kristen L McArthur
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Mingyu Zhang
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
| | - Xiumei Hong
- Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Guoying Wang
- Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Jessie P Buckley
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Xiaobin Wang
- Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Noel T Mueller
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
- Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
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24
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Sources of Variation in Food-Related Metabolites during Pregnancy. Nutrients 2022; 14:nu14122503. [PMID: 35745237 PMCID: PMC9227758 DOI: 10.3390/nu14122503] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/10/2022] [Accepted: 06/14/2022] [Indexed: 12/04/2022] Open
Abstract
The extent to which variation in food-related metabolites are attributable to non-dietary factors remains unclear, which may explain inconsistent food-metabolite associations observed in population studies. This study examined the association between non-dietary factors and the serum concentrations of food-related biomarkers and quantified the amount of variability in metabolite concentrations explained by non-dietary factors. Pregnant women (n = 600) from two Canadian birth cohorts completed a validated semi-quantitative food frequency questionnaire, and serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry. Hierarchical linear modelling and principal component partial R-square (PC-PR2) were used for data analysis. For proline betaine and DHA (mainly exogenous), citrus foods and fish/fish oil intake, respectively, explained the highest proportion of variability relative to non-dietary factors. The unique contribution of dietary factors was similar (15:0, 17:0, hippuric acid, TMAO) or lower (14:0, tryptophan betaine, 3-methylhistidine, carnitine) compared to non-dietary factors (i.e., ethnicity, maternal age, gestational age, pre-pregnancy BMI, physical activity, and smoking) for metabolites that can either be produced endogenously, biotransformed by gut microbiota, and/or derived from multiple food sources. The results emphasize the importance of adjusting for non-dietary factors in future analyses to improve the accuracy and precision of the measures of food intake and their associations with health and disease.
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25
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Gao Y, Chen H, Li J, Ren S, Yang Z, Zhou Y, Xuan R. Alterations of gut microbiota-derived metabolites in gestational diabetes mellitus and clinical significance. J Clin Lab Anal 2022; 36:e24333. [PMID: 35285096 PMCID: PMC8993618 DOI: 10.1002/jcla.24333] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/18/2022] [Accepted: 02/25/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The change in the characteristics of the gut microbiota is linked to gestational diabetes mellitus (GDM). However, whether and how the gut microbiota-derived metabolites change in GDM is uncertain. Here, we aimed to determine associations between the gut microbiota-derived metabolites and GDM. METHODS Using targeted metabolomics approaches, 7 types of short-chain fatty acids (SCFAs), 38 types of bile acids (BAs), and 5 types of trimethylamine N-oxide (TMAO), and its derivatives of serum samples were obtained from pregnant women with GDM (n = 24), and healthy pregnant controls (HC, n = 28) were detected to identify the metabolic signature of GDM to investigate the potential biomarkers. Moreover, we assessed the associations between gut microbiota-derived metabolites and clinical parameters. RESULTS In our study, the gut microbiota-derived metabolites signatures were significantly different between GDM and HC. Quantitative results showed the levels of isobutyric acid, isovaleric acid, valeric acid, caproic acid, GUDCA, THDCA + TUDCA, and LCA-3S were significantly higher in GDM, but the level of TMAO and its derivatives did not change significantly. Some altered gut microbiota-derived metabolites were significantly correlated with glucose and lipid levels. Receiver-operating characteristic (ROC) analysis of generalized linear models showed that gut microbiota-derived metabolites may be potential biomarkers of GDM. CONCLUSION This study highlights gut microbiota-derived metabolites alterations in GDM and correlation of the clinical indicators, which provides a new direction for future studies aiming to novel serum biomarker for early detection or target of drug therapy of GDM.
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Affiliation(s)
- Yajie Gao
- Department of Obstetrics and GynecologyThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
| | - Haimin Chen
- Key Laboratory of Applied Marine Biotechnology of Ministry of EducationNingbo UniversityNingboChina
| | - Jialin Li
- School of MedicineNingbo UniversityNingboChina
| | | | | | - Yuping Zhou
- Department of GastroenterologyThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
- Institute of Digestive Disease of Ningbo UniversityNingboChina
| | - Rongrong Xuan
- Department of Obstetrics and GynecologyThe Affiliated Hospital of Medical School of Ningbo UniversityNingboChina
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26
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Loo RL, Chan Q, Nicholson JK, Holmes E. Balancing the Equation: A Natural History of Trimethylamine and Trimethylamine- N-oxide. J Proteome Res 2022; 21:560-589. [PMID: 35142516 DOI: 10.1021/acs.jproteome.1c00851] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Trimethylamine (TMA) and its N-oxide (TMAO) are ubiquitous in prokaryote and eukaryote organisms as well as in the environment, reflecting their fundamental importance in evolutionary biology, and their diverse biochemical functions. Both metabolites have multiple biological roles including cell-signaling. Much attention has focused on the significance of serum and urinary TMAO in cardiovascular disease risk, yet this is only one of the many facets of a deeper TMA-TMAO partnership that reflects the significance of these metabolites in multiple biological processes spanning animals, plants, bacteria, and fungi. We report on analytical methods for measuring TMA and TMAO and attempt to critically synthesize and map the global functions of TMA and TMAO in a systems biology framework.
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Affiliation(s)
- Ruey Leng Loo
- Centre for Computational and Systems Medicine, Health Futures Institute, Murdoch University, 5 Robin Warren Drive, Perth, Western Australia 6150, Australia.,The Australian National Phenome Centre, Health Futures Institute, Murdoch University, 5 Robin Warren Drive, Perth, Western Australia 6150, Australia
| | - Queenie Chan
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London W2 1PG, United Kingdom.,MRC Centre for Environment and Health, School of Public Health, Imperial College London, London W2 1PG, United Kingdom
| | - Jeremy K Nicholson
- Centre for Computational and Systems Medicine, Health Futures Institute, Murdoch University, 5 Robin Warren Drive, Perth, Western Australia 6150, Australia.,The Australian National Phenome Centre, Health Futures Institute, Murdoch University, 5 Robin Warren Drive, Perth, Western Australia 6150, Australia.,Institute of Global Health Innovation, Imperial College London, Level 1, Faculty Building, South Kensington Campus, London SW7 2NA, United Kingdom
| | - Elaine Holmes
- Centre for Computational and Systems Medicine, Health Futures Institute, Murdoch University, 5 Robin Warren Drive, Perth, Western Australia 6150, Australia.,The Australian National Phenome Centre, Health Futures Institute, Murdoch University, 5 Robin Warren Drive, Perth, Western Australia 6150, Australia.,Nutrition Research, Department of Metabolism, Nutrition and Reproduction, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, London SW7 2AZ, United Kingdom
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27
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Portincasa P, Bonfrate L, Khalil M, Angelis MD, Calabrese FM, D’Amato M, Wang DQH, Di Ciaula A. Intestinal Barrier and Permeability in Health, Obesity and NAFLD. Biomedicines 2021; 10:83. [PMID: 35052763 PMCID: PMC8773010 DOI: 10.3390/biomedicines10010083] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/20/2021] [Accepted: 12/28/2021] [Indexed: 02/07/2023] Open
Abstract
The largest surface of the human body exposed to the external environment is the gut. At this level, the intestinal barrier includes luminal microbes, the mucin layer, gastrointestinal motility and secretion, enterocytes, immune cells, gut vascular barrier, and liver barrier. A healthy intestinal barrier is characterized by the selective permeability of nutrients, metabolites, water, and bacterial products, and processes are governed by cellular, neural, immune, and hormonal factors. Disrupted gut permeability (leaky gut syndrome) can represent a predisposing or aggravating condition in obesity and the metabolically associated liver steatosis (nonalcoholic fatty liver disease, NAFLD). In what follows, we describe the morphological-functional features of the intestinal barrier, the role of major modifiers of the intestinal barrier, and discuss the recent evidence pointing to the key role of intestinal permeability in obesity/NAFLD.
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Affiliation(s)
- Piero Portincasa
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (L.B.); (M.K.); (A.D.C.)
| | - Leonilde Bonfrate
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (L.B.); (M.K.); (A.D.C.)
| | - Mohamad Khalil
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (L.B.); (M.K.); (A.D.C.)
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/a, 70126 Bari, Italy; (M.D.A.); (F.M.C.)
| | - Maria De Angelis
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/a, 70126 Bari, Italy; (M.D.A.); (F.M.C.)
| | - Francesco Maria Calabrese
- Department of Soil, Plant and Food Sciences, University of Bari Aldo Moro, Via Amendola 165/a, 70126 Bari, Italy; (M.D.A.); (F.M.C.)
| | - Mauro D’Amato
- Gastrointestinal Genetics Lab, CIC bioGUNE-BRTA, 48160 Derio, Spain;
- Ikerbasque, Basque Foundation for Science, 48009 Bilbao, Spain
| | - David Q.-H. Wang
- Department of Medicine and Genetics, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Einstein-Mount Sinai Diabetes Research Center, Albert Einstein College of Medicine, New York, NY 10461, USA;
| | - Agostino Di Ciaula
- Clinica Medica “A. Murri”, Department of Biomedical Sciences & Human Oncology, University of Bari Medical School, 70124 Bari, Italy; (L.B.); (M.K.); (A.D.C.)
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Liu J, Li J, Li W, Li N, Huo X, Wang H, Leng J, Yu Z, Ma RCW, Hu G, Fang Z, Yang X. Predictive values of serum metabolites in early pregnancy and their possible pathways for gestational diabetes: A nested case-control study in Tianjin, China. J Diabetes Complications 2021; 35:108048. [PMID: 34563440 DOI: 10.1016/j.jdiacomp.2021.108048] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 09/13/2021] [Accepted: 09/14/2021] [Indexed: 11/26/2022]
Abstract
AIMS To investigate the associations and predictive values of serum metabolites in early pregnancy for later development of gestational diabetes mellitus (GDM), and further explore their metabolic pathways to GDM. METHODS We conducted a 1:1 nested case-control study including 486 pregnant women from Tianjin, China, and collected blood samples at their first registration (median at 10th gestational week). Liquid chromatography-tandem mass spectrometry was used to measure serum metabolites. Orthogonal partial least squares discriminant analysis was used to select specific metabolites associated with GDM, and pathway analysis was used to identify the metabolic pathways related to GDM. RESULTS A total of 64 serum metabolites were included in this analysis, 17 of which were identified as specific metabolites associated with GDM. Ten metabolites increased and seven metabolites decreased GDM risk. Inclusion of these specific metabolites to the model of traditional risk factors greatly increased the predictive value from 0.69 (95% confidence interval: 0.64-0.74) to 0.92 (0.90-0.95). In addition, we found that glycerophospholipid metabolism, sphingolipid metabolism and primary bile acid biosynthesis were main metabolic pathways related to GDM. CONCLUSION We identified a set of serum metabolites and their metabolic pathways in early pregnancy associated with GDM, which provided a theoretical basis for further research on the molecular pathways to GDM and early identification of GDM.
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Affiliation(s)
- Jinnan Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University & Tianjin Key Laboratory of Environment, Nutrition and Population Health, Tianjin 300070, China
| | - Jing Li
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University & Tianjin Key Laboratory of Environment, Nutrition and Population Health, Tianjin 300070, China
| | - Weiqin Li
- Project Office, Tianjin Women and Children's Health Center, Tianjin 300070, China
| | - Ninghua Li
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University & Tianjin Key Laboratory of Environment, Nutrition and Population Health, Tianjin 300070, China
| | - Xiaoxu Huo
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University & Tianjin Key Laboratory of Environment, Nutrition and Population Health, Tianjin 300070, China
| | - Hui Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University & Tianjin Key Laboratory of Environment, Nutrition and Population Health, Tianjin 300070, China
| | - Junhong Leng
- Project Office, Tianjin Women and Children's Health Center, Tianjin 300070, China
| | - Zhijie Yu
- Population Cancer Research Program and Department of Pediatrics, Dalhousie University, Halifax 15000, Canada
| | - Ronald C W Ma
- Department of Medicine and Therapeutics and Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong 999077, China
| | - Gang Hu
- Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA
| | - Zhongze Fang
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University & Tianjin Key Laboratory of Environment, Nutrition and Population Health, Tianjin 300070, China.
| | - Xilin Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University & Tianjin Key Laboratory of Environment, Nutrition and Population Health, Tianjin 300070, China.
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Li Y, Cao H, Wang X, Guo L, Ding X, Zhao W, Zhang F. Diet-mediated metaorganismal relay biotransformation: health effects and pathways. Crit Rev Food Sci Nutr 2021:1-19. [PMID: 34802351 DOI: 10.1080/10408398.2021.2004993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
In recent years, the concept of metaorganism expands our insight into how diet-microbe-host interactions contribute to human health and diseases. We realized that many biological metabolic processes in the host can be summarized into metaorganismal relay pathways, in which metabolites such as trimethylamine-N‑oxide, short-chain fatty acids and bile acids act as double-edged swords (beneficial or harmful effects) in the initiation and progression of diseases. Pleiotropic effects of metabolites are derived from several influencing factors including dose level, targeted organ of effect, action duration and species of these metabolites. Based on the pleiotropic effects of metabolites, personalized therapeutic approaches including microecological agents, enzymatic regulators and changes in dietary habits to govern related metabolite production may provide a new insight in promoting human health. In this review, we summarize our current knowledge of metaorganismal relay pathways and elaborate on the pleiotropic effects of metabolites in these pathways, with special emphasis on related therapeutic nutritional interventions.
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Affiliation(s)
- Yanmin Li
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Hong Cao
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Xiaoqian Wang
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Lichun Guo
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Xiaoying Ding
- Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Zhao
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Feng Zhang
- Department of Nutrition, Affiliated Hospital of Jiangnan University, Wuxi, China
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30
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Tsarna E, Christopoulos P. The role of gut microbiome in prevention, diagnosis and treatment of gestational diabetes mellitus. J OBSTET GYNAECOL 2021; 42:719-725. [PMID: 34693846 DOI: 10.1080/01443615.2021.1959534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Gestational diabetes mellitus (GDM) is a common metabolic disease associated with maternal and foetal complications; gut microbiome might participate in GDM pathogenesis. Possible biological links include short chain fatty acids, incretin hormones, bile acids homeostasis and peroxisome proliferator-activated receptor gamma deficiency. Gut microbiome differs in patients with GDM even in early pregnancy, but no differences are observed five years postpartum. Patients have enriched Verrucomicrobia phylum, Christensenellaceae and Lachnospiraceae families, Haemophilus, Prevotella, Actinomyces, Collinsella and Ruminococcus genera during pregnancy. Clostridiales order, Alistipes, Faecalibacterium, Blautia, Eubacterium and Roseburia genera are depleted. However, there is great heterogeneity in the reviewed studies and scientific data on the use of gut microbiome characteristics and related biomarkers in GDM risk stratification and diagnosis are scarce. Probiotics and synbiotics have been tested for prevention and treatment for GDM with limited efficacy. Future studies should explore the effect of probiotics administration at first trimester of pregnancy and their value as adjuvant therapy.
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Affiliation(s)
- Ermioni Tsarna
- 2nd Department of Obstetrics and Gynecology, Aretaieion University Hospital, Athens Medical School, Athens, Greece
| | - Panagiotis Christopoulos
- 2nd Department of Obstetrics and Gynecology, Aretaieion University Hospital, Athens Medical School, Athens, Greece
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31
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Di Filippo D, Wanniarachchi T, Wei D, Yang JJ, Mc Sweeney A, Havard A, Henry A, Welsh A. The diagnostic indicators of gestational diabetes mellitus from second trimester to birth: a systematic review. Clin Diabetes Endocrinol 2021; 7:19. [PMID: 34635186 PMCID: PMC8504031 DOI: 10.1186/s40842-021-00126-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 06/16/2021] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is glucose intolerance first recognised during pregnancy. Both modalities and thresholds of the GDM diagnostic test, the Oral Glucose Tolerance Test (OGTT), have varied widely over time and among countries. Additionally, OGTT limitations include inconsistency, poor patient tolerability, and questionable diagnostic reliability. Many biological parameters have been reported to be modified by GDM and could potentially be used as diagnostic indicators. This study aimed to 1) systematically explore biomarkers reported in the literature as differentiating GDM from healthy pregnancies 2) screen those indicators assessed against OGTT to propose OGTT alternatives. MAIN BODY A systematic review of GDM diagnostic indicators was performed according to PRISMA guidelines (PROSPERO registration CRD42020145499). Inclusion criteria were full-text, comprehensible English-language articles published January 2009-January 2021, where a biomarker (from blood, ultrasound, amniotic fluid, placenta) was compared between GDM and normal glucose tolerance (NGT) women from the second trimester onward to immediately postpartum. GDM diagnostic method had to be clearly specified, and the number of patients per study higher than 30 in total or 15 per group. Results were synthesised by biomarkers. RESULTS Of 13,133 studies identified in initial screening, 174 studies (135,801 participants) were included. One hundred and twenty-nine studies described blood analytes, one amniotic fluid analytes, 27 ultrasound features, 17 post-natal features. Among the biomarkers evaluated in exploratory studies, Adiponectin, AFABP, Betatrophin, CRP, Cystatin-C, Delta-Neutrophil Index, GGT, TNF-A were those demonstrating statistically and clinically significant differences in substantial cohorts of patients (> 500). Regarding biomarkers assessed versus OGTT (i.e. potential OGTT alternatives) most promising were Leptin > 48.5 ng/ml, Ficolin3/adiponectin ratio ≥ 1.06, Chemerin/FABP > 0.71, and Ultrasound Gestational Diabetes Score > 4. These all demonstrated sensitivity and specificity > 80% in adequate sample sizes (> / = 100). CONCLUSIONS Numerous biomarkers may differentiate GDM from normoglycaemic pregnancy. Given the limitations of the OGTT and the lack of a gold standard for GDM diagnosis, advanced phase studies are needed to triangulate the most promising biomarkers. Further studies are also recommended to assess the sensitivity and specificity of promising biomarkers not yet assessed against OGTT. TRIAL REGISTRATION PROSPERO registration number CRD42020145499.
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Affiliation(s)
- Daria Di Filippo
- School, of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia
| | | | - Daniel Wei
- Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Jennifer J Yang
- Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Aoife Mc Sweeney
- Department of Women's and Children's Health, St George Hospital, Sydney, NSW, Australia
| | - Alys Havard
- National Drug and Alcohol Research Centre - Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
- Centre for Big Data Research in Health - Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
| | - Amanda Henry
- School, of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia
- Department of Women's and Children's Health, St George Hospital, Sydney, NSW, Australia
| | - Alec Welsh
- School, of Women's and Children's Health, University of New South Wales, Sydney, NSW, Australia.
- Department of Maternal-Fetal Medicine, Royal Hospital for Women, Locked Bag 2000, Barker Street, Randwick, NSW, 2031, Australia.
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32
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Lin X, Zhang Y, He X, Chen Y, Chen N, Liu J, Wang M, Li Y, Yang H, Fan L, Hou Y, Li J, Wu C, Qi H, Zhang H, Xiao X. The Choline Metabolite TMAO Inhibits NETosis and Promotes Placental Development in GDM of Humans and Mice. Diabetes 2021; 70:2250-2263. [PMID: 34315726 DOI: 10.2337/db21-0188] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 07/23/2021] [Indexed: 11/13/2022]
Abstract
Choline metabolite trimethylamine N-oxide (TMAO) has been recognized as a risk factor of gestational diabetes mellitus (GDM), but its exact role in GDM has not been reported. In this study, we focused on the placenta development to reveal the role of TMAO in GDM. We found that the TMAO levels in peripheral and cord plasma were increased in women with GDM and that TMAO levels were positively correlated with newborn weight and placental thickness. Neutrophil extracellular traps (NETs) in the peripheral and cord plasma and the myeloperoxidase expression in the placenta of women with GDM also increased. NETs could inhibit the proliferation, migration, invasion, and angiogenesis of HTR-8/Svneo cells. However, TMAO not only could inhibit the formation of NETs but also could enhance the biological function of HTR-8/Svneo cells. With induction of GDM in NETs-deficient PAD4-/- and wild-type mice, the placental weight of PAD4-/- mice increased significantly. TMAO feeding also inhibited the formation of NETs and further increased the weight of the placenta and fetuses, and this increase did not affect the placental structure. Our data indicate that higher TMAO levels and the formation of abnormal NETs were associated with GDM. TMAO not only could promote the development of the placenta and fetuses but also could inhibit the formation of NETs.
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Affiliation(s)
- Xiaojing Lin
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Joint Laboratory of Reproduction and Development of Ministry of Education of P.R.C., Chongqing Medical University, Chongqing, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yunqi Zhang
- The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Joint Laboratory of Reproduction and Development of Ministry of Education of P.R.C., Chongqing Medical University, Chongqing, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
| | - Xiaoling He
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Joint Laboratory of Reproduction and Development of Ministry of Education of P.R.C., Chongqing Medical University, Chongqing, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yan Chen
- The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Endocrinology and Nephrology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, China
| | - Nan Chen
- The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Juncheng Liu
- The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Miaoran Wang
- Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing, China
| | - Yue Li
- Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing, China
| | - Hong Yang
- The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lei Fan
- The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yi Hou
- The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Laboratory of Traditional Chinese Medicine, Experimental Teaching & Management Center, Chongqing Medical University, Chongqing, China
| | - Jibin Li
- Department of Nutrition and Food Hygiene, School of Public Health and Management, Chongqing Medical University, Chongqing, China
| | - Chaodong Wu
- Department of Nutrition and Food Science, Texas A&M University, College Station, TX
| | - Hongbo Qi
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Joint Laboratory of Reproduction and Development of Ministry of Education of P.R.C., Chongqing Medical University, Chongqing, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hua Zhang
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Joint Laboratory of Reproduction and Development of Ministry of Education of P.R.C., Chongqing Medical University, Chongqing, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaoqiu Xiao
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Joint Laboratory of Reproduction and Development of Ministry of Education of P.R.C., Chongqing Medical University, Chongqing, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
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33
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Bekhit AEDA, Giteru SG, Holman BWB, Hopkins DL. Total volatile basic nitrogen and trimethylamine in muscle foods: Potential formation pathways and effects on human health. Compr Rev Food Sci Food Saf 2021; 20:3620-3666. [PMID: 34056832 DOI: 10.1111/1541-4337.12764] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 03/30/2021] [Accepted: 04/02/2021] [Indexed: 12/18/2022]
Abstract
The use of total volatile basic nitrogen (TVB-N) as a quality parameter for fish is rapidly growing to include other types of meat. Investigations of meat quality have recently focused on TVB-N as an index of freshness, but little is known on the biochemical pathways involved in its generation. Furthermore, TVB-N and methylated amines have been reported to exert deterimental health effects, but the relationship between these compounds and human health has not been critically reviewed. Here, literature on the formative pathways of TVB-N has been reviewed in depth. The association of methylated amines and human health has been critically evaluated. Interventions to mitigate the effects of TVB-N on human health are discussed. TVB-N levels in meat can be influenced by the diet of an animal, which calls for careful consideration when using TVB-N thresholds for regulatory purposes. Bacterial contamination and temperature abuse contribute to significant levels of post-mortem TVB-N increases. Therefore, controlling spoilage factors through a good level of hygiene during processing and preservation techniques may contribute to a substantial reduction of TVB-N. Trimethylamine (TMA) constitutes a significant part of TVB-N. TMA and trimethylamine oxide (TMA-N-O) have been related to the pathogenesis of noncommunicable diseases, including atherosclerosis, cancers, and diabetes. Proposed methods for mitigation of TMA and TMA-N-O accumulation are discussed, which include a reduction in their daily dietary intake, control of internal production pathways by targeting gut microbiota, and inhibition of flavin monooxygenase 3 enzymes. The levels of TMA and TMA-N-O have significant health effects, and this should, therefore, be considered when evaluating meat quality and acceptability. Agreed international values for TVB-N and TMA in meat products are required. The role of feed, gut microbiota, and translocation of methylated amines to muscles in farmed animals requires further investigation.
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Affiliation(s)
| | - Stephen G Giteru
- Department of Food Science, University of Otago, Dunedin, New Zealand.,Food & Bio-based Products, AgResearch Limited, Tennent Drive, Palmerston North, 4410, New Zealand
| | - Benjamin W B Holman
- Centre for Red Meat and Sheep Development, NSW Department of Primary Industries, Cowra, New South Wales, Australia
| | - David L Hopkins
- Centre for Red Meat and Sheep Development, NSW Department of Primary Industries, Cowra, New South Wales, Australia
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34
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Liu W, Guo P, Dai T, Shi X, Shen G, Feng J. Metabolic Interactions and Differences between Coronary Heart Disease and Diabetes Mellitus: A Pilot Study on Biomarker Determination and Pathogenesis. J Proteome Res 2021; 20:2364-2373. [PMID: 33751888 DOI: 10.1021/acs.jproteome.0c00879] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Comprehensive understanding of plasma metabotype of diabetes mellitus (DM), coronary heart disease (CHD), and especially diabetes mellitus with coronary heart disease (CHDDM) is still lacking. In this work, the plasma metabolic differences and links of DM, CHD, and CHDDM patients were investigated by the strategy of comparative metabolomics based on 1H NMR spectroscopy combined with network analysis for revealing their metabolic differences. A total of 17 metabolites are related to three diseases, among which valine, alanine, leucine, isoleucine, and N-acetyl-glycoprotein are positively correlated with CHD and CHDDM (odds ratios (OR) > 1). The trimethylamine oxide, glycerol, lactose, indoleacetate, and scyllo-inositol are closely related to the development of DM to CHDDM (OR > 1), and indoleactate (OR: 1.06, 95% confidence interval (CI): 1.01-1.12) and lactose (OR: 2.46, 95% CI: 1.67-3.25) are particularly prominent in CHDDM. We identified three multi-biomarkers types that were significantly associated with glycosylated hemoglobin (HbA1C) at baseline. All diseases demonstrated dysregulated glycolysis/gluconeogenesis and amino acid biosynthesis pathway. In addition, enrichment in tryptophan metabolism observed in CHDDM, enrichment in inositol phosphate metabolism observed in DM, and the metabolites related to microbiota metabolism were dysregulated in both DM and CHDDM. The comparative metabolomics strategy of multi-diseases offers a new perspective in disease-specific markers and pathogenic pathways.
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Affiliation(s)
- Wuping Liu
- Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005, China
| | - Pengfei Guo
- Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005, China
| | - Tao Dai
- Third Affiliated Hospital, Henan University of Science and Technology, Luoyang 471003, China
| | - Xiulin Shi
- The Xiamen Diabetes Institute and Department of Endocrinology and Diabetes, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Guiping Shen
- Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005, China
| | - Jianghua Feng
- Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005, China
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35
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Coutinho-Wolino KS, de F Cardozo LFM, de Oliveira Leal V, Mafra D, Stockler-Pinto MB. Can diet modulate trimethylamine N-oxide (TMAO) production? What do we know so far? Eur J Nutr 2021; 60:3567-3584. [PMID: 33533968 DOI: 10.1007/s00394-021-02491-6] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Accepted: 01/08/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Trimethylamine N-oxide (TMAO) is a metabolite that has attracted attention due to its positive association with several chronic non-communicable diseases such as insulin resistance, atherosclerotic plaque formation, diabetes, cancer, heart failure, hypertension, chronic kidney disease, liver steatosis, cardiac fibrosis, endothelial injury, neural degeneration and Alzheimer's disease. TMAO production results from the fermentation by the gut microbiota of dietary nutrients such as choline and carnitine, which are transformed to trimethylamine (TMA) and converted into TMAO in the liver by flavin-containing monooxygenase 1 and 3 (FMO1 and FMO3). Considering that TMAO is involved in the development of many chronic diseases, strategies have been found to enhance a healthy gut microbiota. In this context, some studies have shown that nutrients and bioactive compounds from food can modulate the gut microbiota and possibly reduce TMAO production. OBJECTIVE This review has as main objective to discuss the studies that demonstrated the effects of food on the reduction of this harmful metabolite. METHODS All relevant articles until November 2020 were included. The articles were searched in Medline through PubMed. RESULTS Both the food is eaten acutely and chronically, by altering the nature of the gut microbiota, influencing colonic TMA production. Furthermore, hepatic production of TMAO by the flavin monooxygenases in the liver may also be influenced by phenolic compounds present in foods. CONCLUSION The evidence presented in this review shows that TMAO levels can be reduced by some bioactive compounds. However, it is crucial to notice that there is significant variation among the studies. Further clinical studies should be conducted to evaluate these dietary components' effectiveness, dose, and intervention time on TMAO levels and its precursors.
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Affiliation(s)
| | - Ludmila F M de F Cardozo
- Postgraduate Program in Cardiovascular Sciences, Faculty of Medicine, Fluminense Federal University, Niterói, Brazil
| | - Viviane de Oliveira Leal
- Division of Nutrition, Pedro Ernesto University Hospital, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | - Denise Mafra
- Postgraduate Program in Nutrition Sciences, Fluminense Federal University (UFF), Niterói, RJ, Brazil.,Postgraduate Program in Cardiovascular Sciences, Faculty of Medicine, Fluminense Federal University, Niterói, Brazil.,Postgraduate Program in Medical Sciences, Faculty of Medicine, Fluminense Federal University, Niterói, Brazil
| | - Milena Barcza Stockler-Pinto
- Postgraduate Program in Nutrition Sciences, Fluminense Federal University (UFF), Niterói, RJ, Brazil.,Postgraduate Program in Cardiovascular Sciences, Faculty of Medicine, Fluminense Federal University, Niterói, Brazil
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36
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Gong X, Du Y, Li X, Yang J, Zhang X, Wei Y, Zhao Y. Maternal Plasma Betaine in Middle Pregnancy Was Associated with Decreased Risk of GDM in Twin Pregnancy: A Cohort Study. Diabetes Metab Syndr Obes 2021; 14:2495-2504. [PMID: 34113141 PMCID: PMC8184138 DOI: 10.2147/dmso.s312334] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 05/08/2021] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Although previous studies have shown that choline-related metabolites in one carbon metabolism (OCM) were related to gestational diabetes mellitus (GDM) risk in singleton pregnancy, their role in twin gestations remains unclear. We aimed to investigate the associations between choline, betaine, methionine, dimethylglycine (DMG), trimethylamine N-oxide (TMAO) and GDM risk among women with twin gestations. PATIENTS AND METHODS This hospital-based cohort study included 187 women with dichorionic twin gestations. Blood samples were collected during pregnancy at a median of 16.1 weeks of gestation (IQR: 13.9 -17.9). Concentrations of plasma metabolites were measured by HPLC-triple quadrupole MS. Log-binomial regression models were applied to estimate the associations between plasma metabolites and the risk of GDM. RESULTS A total of 57 (30.5%) GDM cases were diagnosed over the study follow-up. Eighty-seven percent of women conceived through ART. Plasma betaine had an inverse association with GDM risk, and the adjusted RR of GDM comparing the highest tertile with the lowest tertile was 0.41 (95% CI: 0.19-0.86, P trend=0.015). Women with a high betaine/choline ratio or a low DMG/betaine ratio were at decreased GDM risk (P trend=0.031 or 0.001, respectively). Plasma choline, methionine, DMG and TMAO were not associated with GDM risk. CONCLUSION Among women with dichorionic twin gestations, higher plasma level of betaine in the second trimester was associated with lower risk of GDM. This finding needs further confirmation.
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Affiliation(s)
- Xiaoli Gong
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, National Center for Healthcare Quality Management in Obstetrics, Peking University Third Hospital, Beijing, 100191, People’s Republic of China
| | - Yufeng Du
- Department of Epidemiology and Statistics, School of Public Health, Lanzhou University, Lanzhou, 730000, People’s Republic of China
| | - Xiaona Li
- Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, People’s Republic of China
| | - Jing Yang
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, National Center for Healthcare Quality Management in Obstetrics, Peking University Third Hospital, Beijing, 100191, People’s Republic of China
| | - Xinyuan Zhang
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, National Center for Healthcare Quality Management in Obstetrics, Peking University Third Hospital, Beijing, 100191, People’s Republic of China
| | - Yuan Wei
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, National Center for Healthcare Quality Management in Obstetrics, Peking University Third Hospital, Beijing, 100191, People’s Republic of China
| | - Yangyu Zhao
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, National Center for Healthcare Quality Management in Obstetrics, Peking University Third Hospital, Beijing, 100191, People’s Republic of China
- Correspondence: Yangyu Zhao; Yuan Wei Email ;
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Chang QX, Chen X, Ming-Xin Yang, Zang NL, Li LQ, Zhong N, Xia LX, Huang QT, Zhong M. Trimethylamine N-Oxide increases soluble fms-like tyrosine Kinase-1 in human placenta via NADPH oxidase dependent ROS accumulation. Placenta 2020; 103:134-140. [PMID: 33120049 DOI: 10.1016/j.placenta.2020.10.021] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 10/11/2020] [Accepted: 10/19/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUNDS Preeclampsia (PE) is characterized as placental vascular disturbance and excessive secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) into the maternal circulation. Trimethylamine N-oxide (TMAO, a gut microbe-derived metabolite) is strongly associated with various cardiovascular and cerebrovascular diseases. Recently, we observe that higher maternal circulating TMAO and sFlt-1 in patients with PE. The aims of the present study are to explore the effects of TMAO on placental sFlt-1 production and the underlying mechanism in human placenta. METHODS Human placental explants, human placental primary trophoblasts and the extravillous trophoblasts (EVT) cell line (HRT-8/SVneo) were exposured to various concentrations of TMAO (100, 150, 300, and 600 μM). The mRNA expression and protein secretion of sFlt-1 in placental explants, primary trophoblasts and HRT-8/SVneo cells were determined with qPCR and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS) production in primary trophoblasts and HRT-8/SVneo cells were measured by peroxide-sensitive fluorescent probe dichlorofluorescein diacetate. RESULTS Exposure of placental explants, primary trophoblasts and HRT-8/SVneo cells to TMAO significantly enhanced sFlt-1 at both mRNA and protein levels in a dose dependent manner. Moreover, inhibition of NADPH oxidase with apocynin significantly attenuated TMAO-induced ROS production in primary trophoblasts and HRT-8/SVneo, and suppressed sFlt-1 secretion in placental explants, primary trophoblasts and HRT-8/SVneo. CONCLUSIONS Our findings indicated the NADPH oxidase dependent ROS pathway played a critical role in mediating TMAO-induced sFlt-1 generation in human placenta. TMAO may become a potential novel target for pharmacological or dietary interventions to reduce the risk of developing PE.
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Affiliation(s)
- Qing-Xian Chang
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China; First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xia Chen
- Department of Obstetrics and Gynecology, Foshan No.1 People Hospital, Foshan, Guangdong, China
| | - Ming-Xin Yang
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China; First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Nai-Liang Zang
- First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Le-Qian Li
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China; First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Nanbert Zhong
- Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA
| | - Lai-Xin Xia
- Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Qi-Tao Huang
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Obstetrics and Gynecology, Foshan Maternal and Fetal Care Hospital, Foshan, Guangdong, China.
| | - Mei Zhong
- Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Diallo AF, Lockwood MB, Maki KA, Franks AT, Roy A, Jaime-Lara R, Joseph PV, Henderson WA, Chung SY, McGrath J, Green SJ, Fink AM. Metabolic Profiling of Blood and Urine for Exploring the Functional Role of the Microbiota in Human Health. Biol Res Nurs 2020; 22:449-457. [PMID: 32723087 DOI: 10.1177/1099800420941080] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
The quantification of metabolites in blood and urine allows nurses to explore new hypotheses about the microbiome. This review summarizes findings from recent studies with a focus on how the state of the science can influence future nursing research initiatives. Metabolomics can advance nursing research by identifying physiologic/pathophysiologic processes underlying patients' symptoms and can be useful for testing the effects of nursing interventions. To date, metabolomics has been used to study cardiovascular, respiratory, endocrine, autoimmune, and infectious conditions, with research focused on understanding the microbial metabolism of substrates resulting in circulating/excreted biomarkers such as trimethylamine N-oxide. This review provides specific recommendations for the collection of specimens and goals for future studies.
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Affiliation(s)
- Ana F Diallo
- Institute of Inclusion, Inquiry & Innovation (iCubed), Family and Community Health Nursing, School of Nursing, Virginia Commonwealth University, Richmond, VA, USA
| | - Mark B Lockwood
- Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, USA
| | - Katherine A Maki
- Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, USA
| | - Alexis T Franks
- Sensory Science & Metabolism Unit, Biobehavioral Branch, Division of Intramural Research, 2511National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
| | - Abhrarup Roy
- Sensory Science & Metabolism Unit, Biobehavioral Branch, Division of Intramural Research, 2511National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
| | - Rosario Jaime-Lara
- Sensory Science & Metabolism Unit, Biobehavioral Branch, Division of Intramural Research, 2511National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
| | - Paule V Joseph
- Sensory Science & Metabolism Unit, Biobehavioral Branch, Division of Intramural Research, 2511National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
| | - Wendy A Henderson
- Digestive Disorders Unit, Biobehavioral Branch, Division of Intramural Research, 2511National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA
| | - Seon Yoon Chung
- School of Nursing, University of Maryland, Baltimore, MD, USA
| | - Jacqueline McGrath
- School of Nursing, University of Texas Health Science Center, San Antonio, TX, USA
| | - Stefan J Green
- Sequencing Core, Research Resources Center, 14681University of Illinois at Chicago, Chicago, IL, USA
| | - Anne M Fink
- Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, USA
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Sun T, Zhang Y, Yin J, Peng X, Zhou L, Huang S, Wen Y, Cao B, Chen L, Li X, Yang W, Tan A, Cheng J, Liu L. Association of Gut Microbiota-Dependent Metabolite Trimethylamine N-Oxide with First Ischemic Stroke. J Atheroscler Thromb 2020; 28:320-328. [PMID: 32641646 PMCID: PMC8147013 DOI: 10.5551/jat.55962] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
AIM We aimed to investigate the relationship of trimethylamine N-oxide (TMAO) concentrations with ischemic stroke in a large-scale case-control study conducted among the hospital-based general population. METHODS We recruited 953 case-control sex- and age-matched pairs, and cases were confined to first acute ischemic stroke in this study. Fasting plasma TMAO was measured using high-performance liquid chromatography-tandem mass spectroscopy. Conditional logistic regression analysis was conducted to calculate odds ratios (OR) for the association of plasma TMAO with ischemic stroke. RESULTS We found that plasma TMAO concentrations in patients with ischemic stroke were significantly higher than that in the control group (median: 2.85 µmol/L vs. 2.33 µmol/L, P<0.001). In multivariable conditional logistic regression models, higher plasma TMAO concentrations were associated with increased odds of ischemic stroke [fully adjusted OR for highest vs. lowest TMAO quartile: 1.81; 95% confidence interval (CI): 1.27, 2.59; P for trend <0.001]. The multivariable-adjusted OR for ischemic stroke per 1 µmol/L increment of plasma TMAO was 1.05 (95% CI: 1.02, 1.08). Additionally, the positive association also persisted in subgroups stratified by age, sex, body mass index, smoking status, alcohol habits, history of diabetes, and history of hypertension. CONCLUSIONS This study suggested a positive association between plasma TMAO and ischemic stroke. Further studies are required to explore the role of plasma TMAO concentrations in predicting stroke risk.
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Affiliation(s)
- Taoping Sun
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
| | - Yanwei Zhang
- Shenzhen Center for Disease Control and Prevention
| | - Jiawei Yin
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
| | - Xiaobo Peng
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
| | - Li Zhou
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
| | - Suli Huang
- Shenzhen Center for Disease Control and Prevention
| | - Ying Wen
- Shenzhen Center for Disease Control and Prevention
| | - Benfeng Cao
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
| | - Liangkai Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
| | - Xiaoqin Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
| | - Wei Yang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
| | - Aijun Tan
- Zhuhai Center for Disease Control and Prevention
| | | | - Liegang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology.,Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology
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40
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Zheng Y, Tang Z, You L, Wu Y, Liu J, Xue J. Trimethylamine- N-oxide is an independent risk factor for hospitalization events in patients receiving maintenance hemodialysis. Ren Fail 2020; 42:580-586. [PMID: 32576072 PMCID: PMC7946050 DOI: 10.1080/0886022x.2020.1781170] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Background Hospitalization is a significant outcome measurement for maintenance hemodialysis pantients. Trimethylamine-N-oxide (TMAO), created by gut microflora from dietary l-carnitine and choline, cleared by the kidney, has been implicated in the causation of cardiovascular diseases in patients with chronic kidney disease. However, whether it associates with hospitalization risk for these patients is unclear. Methods In this study, 69 patients undergoing outpatient dialysis were enrolled. Enzyme-linked immunosorbent assay was used to quantitate the baseline plasma TMAO levels in patients. The patients were divided into a high TMAO level group (TMAO ≥ 15 μmol/L) and a low TMAO level group (TMAO < 15 μmol/L). During the 1-year follow-up, 1-year dialysis-related data and all-cause hospitalization events were recorded. Results The incidence of hospitalization events was significantly higher in the high TMAO level group than in the low TMAO level group (91 per 100 patient-year vs. 32 per 100 patient-year). The Kaplain–Meier survaial analysis showed that the incidence of hospitalization events in the high TMAO level group was significantly higher than that in the low TMAO level group (log-rank p = 0.0004). After adjustment age, sex, CK-MB and albumin, the results of multivariate Cox proportional hazard analysis showed that high TMAO level was an independent risk factor for hospitalization in maintenance hemodialysis patients. Conclusion TMAO is an independent risk factor for hospitalization events in patients receiving maintenance hemodialysis. It may be a new therapeutic target for improving the outcomes of these patients.
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Affiliation(s)
- Yin Zheng
- Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Zihui Tang
- Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Li You
- Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yuanhao Wu
- Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Junfeng Liu
- Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
| | - Jun Xue
- Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China
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41
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Huang X, Li Z, Gao Z, Wang D, Li X, Li Y, Mi C, Lei J. Association between risk of preeclampsia and maternal plasma trimethylamine-N-oxide in second trimester and at the time of delivery. BMC Pregnancy Childbirth 2020; 20:302. [PMID: 32429856 PMCID: PMC7236207 DOI: 10.1186/s12884-020-02997-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 05/06/2020] [Indexed: 02/07/2023] Open
Abstract
Background The data on the association between the microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) during pregnancy and risk of preeclampsia (PE) is limited. Methods We, therefore, conducted a prospective nested case control study during Sep 2017 to Dec 2018 to examine the association between plasma TMAO measured during pregnancy and the risk of PE. Total of 17 patients diagnosed with early onset PE (EOPE), 49 with late onset PE (LOPE) and 198 healthy controls were enrolled. Blood samples were collected at 15–23 weeks gestation and time at delivery. The Logistic regression model was used to assess the odds ratio (OR) and 95% confidence interval (CI) for TMAO and risk of PE, EOPE, LOPE, mild PE, and severe PE. Results We found that the mean TMAO levels of overall subjects in the second trimester (T2) and at the time of delivery (TD) were 90.39 μg/m3 (standard deviation (SD) =45.91) and 175.01 μg/m3 (SD = 160.97), respectively. No significant spearman correlation was found between the TMAO in those two periods (p > 0.05). T2 TMAO was not significantly associated with risk of PE or risk of any PE subtypes (p > 0.05). However, TD TMAO was significant associated with risk of PE, EOPE and severe PE (adjusted OR and 95%CI were 1.24(1.09, 1.40), 1.62(1.29, 2.03), and 1.41(1.17, 1.70)) per 50 μg/m3 increment, respectively). Conclusion Our study found that plasma TMAO level would alter over the course of pregnancy. The major role of TMAO in PE development might be in the accelerating process not in the initiation.
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Affiliation(s)
- Xin Huang
- Department of Epidemiology, Hunan Normal University School of Medicine, 371 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, Province, China.
| | - Zuodong Li
- Department of Epidemiology, Hunan Normal University School of Medicine, 371 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, Province, China
| | - Zhou Gao
- Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China
| | - Dapeng Wang
- Key Laboratory of Environmental Pollution Monitoring and Disease Control, Guizhou Medical University, Guiyang, 550025, Guizhou, China
| | - Xiaohui Li
- Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha, 411000, Hunan, China.,Department of Pharmacology, Central South University School of Pharmaceutical Sciences, Changsha, 410013, Hunan, China
| | - Ying Li
- Department of Health Management, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China
| | - Chunmei Mi
- Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.
| | - Jun Lei
- Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.
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Papandreou C, Moré M, Bellamine A. Trimethylamine N-Oxide in Relation to Cardiometabolic Health-Cause or Effect? Nutrients 2020; 12:E1330. [PMID: 32392758 PMCID: PMC7284902 DOI: 10.3390/nu12051330] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 04/29/2020] [Accepted: 05/04/2020] [Indexed: 12/19/2022] Open
Abstract
Trimethylamine-N-oxide (TMAO) is generated in a microbial-mammalian co-metabolic pathway mainly from the digestion of meat-containing food and dietary quaternary amines such as phosphatidylcholine, choline, betaine, or L-carnitine. Fish intake provides a direct significant source of TMAO. Human observational studies previously reported a positive relationship between plasma TMAO concentrations and cardiometabolic diseases. Discrepancies and inconsistencies of recent investigations and previous studies questioned the role of TMAO in these diseases. Several animal studies reported neutral or even beneficial effects of TMAO or its precursors in cardiovascular disease model systems, supporting the clinically proven beneficial effects of its precursor, L-carnitine, or a sea-food rich diet (naturally containing TMAO) on cardiometabolic health. In this review, we summarize recent preclinical and epidemiological evidence on the effects of TMAO, in order to shed some light on the role of TMAO in cardiometabolic diseases, particularly as related to the microbiome.
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The gut microbiome in neurological disorders. Lancet Neurol 2020; 19:179-194. [PMID: 31753762 DOI: 10.1016/s1474-4422(19)30356-4] [Citation(s) in RCA: 736] [Impact Index Per Article: 147.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 07/05/2019] [Accepted: 08/16/2019] [Indexed: 12/12/2022]
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Dogan B, Karaer A, Tuncay G, Tecellioglu N, Mumcu A. High-resolution 1H-NMR spectroscopy indicates variations in metabolomics profile of follicular fluid from women with advanced maternal age. J Assist Reprod Genet 2020; 37:321-330. [PMID: 31942667 DOI: 10.1007/s10815-020-01693-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 01/10/2020] [Indexed: 12/31/2022] Open
Abstract
AIM To reveal whether there are differences in follicular fluid metabolomics profile of women with advanced maternal age (AMA). METHOD The group with advanced maternal age includes 23 patients above the age of 40, and the control group includes 31 patients aged between 25 and 35 years and AMH values above 1.1 ng/mL with no low ovarian response history. A single follicular fluid sample from a MII oocyte obtained during the oocyte pick-up procedure was analyzed with high-resolution 1H-NMR (nuclear magnetic resonance) spectroscopy. The results were evaluated using advanced bioinformatics analysis methods. RESULTS Statistical analysis of the NMR spectroscopy data from two groups showed that α-glucose and β-glucose levels of follicular fluid were decreased in the patients with AMA, while in contrast, lactate and trimethylamine N-oxide (TMAO) levels were increased in these patients compared with the controls. In addition to these, there was an increase in alanine levels and a decrease in acetoacetate levels in patients with AMA. However, these changes were not statistically significant. CONCLUSION Obtained results suggest that the follicular cell metabolism of patients with AMA is different from controls. These environmental changes could be associated with the low success rates of IVF treatment seen in these patients.
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Affiliation(s)
- B Dogan
- Reproductive Sciences & Advanced Bioinformatics Application & Research Center, Inonu University, Malatya, Turkey.,Department of Biomedical Engineering, School of Engineering, Inonu University, Malatya, Turkey
| | - A Karaer
- Reproductive Sciences & Advanced Bioinformatics Application & Research Center, Inonu University, Malatya, Turkey. .,Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Inonu University, School of Medicine, Malatya, Turkey.
| | - G Tuncay
- Reproductive Sciences & Advanced Bioinformatics Application & Research Center, Inonu University, Malatya, Turkey.,Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Inonu University, School of Medicine, Malatya, Turkey
| | - N Tecellioglu
- Reproductive Sciences & Advanced Bioinformatics Application & Research Center, Inonu University, Malatya, Turkey.,Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Inonu University, School of Medicine, Malatya, Turkey
| | - A Mumcu
- Reproductive Sciences & Advanced Bioinformatics Application & Research Center, Inonu University, Malatya, Turkey.,Laboratory of NMR, Scientific and Technological Research Center, Inonu University, Malatya, Turkey
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Eyupoglu ND, Caliskan Guzelce E, Acikgoz A, Uyanik E, Bjørndal B, Berge RK, Svardal A, Yildiz BO. Circulating gut microbiota metabolite trimethylamine N-oxide and oral contraceptive use in polycystic ovary syndrome. Clin Endocrinol (Oxf) 2019; 91:810-815. [PMID: 31556132 DOI: 10.1111/cen.14101] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/02/2019] [Accepted: 09/18/2019] [Indexed: 12/21/2022]
Abstract
OBJECTIVES Polycystic ovary syndrome (PCOS) is associated with an increased cardiometabolic risk that might not necessarily translate into adverse cardiovascular outcome later in life. Recently, alterations in gut microbial composition have been reported in the syndrome. Microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and its precursors are closely linked with development of atherosclerotic cardiovascular disease, independently of traditional risk factors. We aimed to assess whether TMAO and its precursors are altered in PCOS and to determine potential impact of treatment on these metabolites. DESIGN Prospective study. PATIENTS Twenty-seven overweight/obese patients with PCOS and 25 age- and BMI-matched healthy control women. MEASUREMENTS At baseline, fasting serum TMAO and its precursors were measured after a 3-day standardized diet. Patients received 3-month OC therapy along with general dietary advice after which all measurements were repeated. RESULTS Patients had higher total testosterone (T) and free androgen index (FAI) whereas whole-body fat mass, fasting plasma glucose, insulin and lipids were similar between the groups. PCOS group showed significantly higher serum levels of TMAO and its precursors; choline, betaine and carnitine. TMAO and choline showed correlations with T. After 3 months of OC use, TMAO and its precursors significantly decreased along with reductions in BMI, T and FAI. CONCLUSIONS This study reports for the first time that TMAO and its precursors are elevated in PCOS which might contribute to increased cardiometabolic risk of the syndrome and that short-term OC use along with lifestyle intervention is associated with reduction of these microbiome-dependent metabolites.
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Affiliation(s)
- Nesrin Damla Eyupoglu
- Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Ezgi Caliskan Guzelce
- Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Aylin Acikgoz
- Department of Nutrition and Dietetics, Hacettepe University School of Health Sciences, Ankara, Turkey
| | - Esra Uyanik
- Department of Gynecology and Obstetrics, Hacettepe University School of Medicine, Ankara, Turkey
| | - Bodil Bjørndal
- Department of Clinical Sciences, University of Bergen, Bergen, Norway
| | - Rolf K Berge
- Department of Clinical Sciences, University of Bergen, Bergen, Norway
- Department of Heart Disease, Haukeland University Hospital, Bergen, Norway
| | - Asbjørn Svardal
- Department of Clinical Sciences, University of Bergen, Bergen, Norway
| | - Bulent Okan Yildiz
- Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
- Division of Endocrinology and Metabolism, Hacettepe University School of Medicine, Ankara, Turkey
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Huo X, Li J, Cao YF, Li SN, Shao P, Leng J, Li W, Liu J, Yang K, Ma RCW, Hu G, Fang ZZ, Yang X. Trimethylamine N-Oxide Metabolites in Early Pregnancy and Risk of Gestational Diabetes: A Nested Case-Control Study. J Clin Endocrinol Metab 2019; 104:5529-5539. [PMID: 31373635 PMCID: PMC6779108 DOI: 10.1210/jc.2019-00710] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2019] [Accepted: 07/29/2019] [Indexed: 12/16/2022]
Abstract
OBJECTIVES This study aimed to investigate the associations between trimethylamine N-oxide (TMAO) and related metabolites in early pregnancy and the risk of gestational diabetes mellitus (GDM). DESIGN A prospective cohort of 22,302 pregnant women from 2010 to 2012 in Tianjin, China, was used to perform a nested case-control study. A total of 243 women with GDM and 243 women without GDM matched by maternal age (±1 year) were used as cases and controls, respectively. Conditional logistic regression and restricted cubic spline were used to examine the full-range risk associations between individual TMAOs metabolites at the first antenatal care visit with GDM. Trimethylamine conversion ratio (TMAR) was defined as trimethylamine (TMA)/its precursors, and trimethylamine N-oxide conversion ratio (TMAOR) was defined as TMAO/TMA. An additive interaction between high TMAR and low TMAOR indicates a state of TMA accumulation, and a mathematical interaction between high TMAR and high TMAOR indicates accumulation of TMAO. RESULTS TMA was linearly associated with GDM, whereas TMA precursors and TMAO were inversely associated with GDM with clear threshold effects, i.e., 16 nmol/mL for TMAO, 200 nmol/mL for betaine, 112 nmol/mL for l-carnitine, and 110 and 270 nmol/mL for cholinechloride (a U-shaped relationship). Copresence of TMAR >0.35 and TMAOR ≤0.15 was associated with a markedly higher OR (11.16; 95% CI, 5.45 to 22.8), compared with TMAR >0.35 only (OR = 1.71; 95% CI, 0.42 to 6.95) or TMAOR ≤0.15 only (OR = 2.06; 95% CI, 1.09 to 3.90), with a significant additive interaction. However, the mathematical interaction was nonsignificant. CONCLUSIONS TMAO metabolites in the early pregnancy were associated with the risk of GDM, whereas TMA was more likely to play a causal role in GDM.
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Affiliation(s)
- Xiaoxu Huo
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Jing Li
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yun-Feng Cao
- Key Laboratory of Liaoning Tumor Clinical Metabolomics, Jinzhou, Liaoning, China
- RSKT Biopharma Inc, Dalian, Liaoning, China
| | - Sai-Nan Li
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Ping Shao
- Tianjin Women and Children’s Health Center, Tianjin, China
| | - Junhong Leng
- Tianjin Women and Children’s Health Center, Tianjin, China
| | - Weiqin Li
- Tianjin Women and Children’s Health Center, Tianjin, China
| | - Jinnan Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Kai Yang
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Ronald C W Ma
- Department of Medicine and Therapeutics, Prince of Wales Hospital, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Gang Hu
- Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana
| | - Zhong-Ze Fang
- Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
- Correspondence and Reprint Requests: Xilin Yang, PhD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, P.O. Box 154, Tianjin 300070, China. E-mail: or ; or Zhong-Ze Fang, PhD, Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. E-mail:
| | - Xilin Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China
- Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin, China
- Correspondence and Reprint Requests: Xilin Yang, PhD, Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, P.O. Box 154, Tianjin 300070, China. E-mail: or ; or Zhong-Ze Fang, PhD, Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. E-mail:
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Qian F, Liu G, Hu FB, Bhupathiraju SN, Sun Q. Association Between Plant-Based Dietary Patterns and Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis. JAMA Intern Med 2019; 179:1335-1344. [PMID: 31329220 PMCID: PMC6646993 DOI: 10.1001/jamainternmed.2019.2195] [Citation(s) in RCA: 210] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
IMPORTANCE Accumulating epidemiologic evidence has suggested favorable associations between plant-based dietary patterns and risk of type 2 diabetes, although there is a lack of a quantitative summary of evidence substantiating this important association. OBJECTIVE To quantitatively synthesize available prospective observational evidence on the association between plant-based dietary patterns and risk of type 2 diabetes. DATA SOURCES A systematic search of PubMed and MEDLINE, Embase, Web of Science, and reference lists through February 15, 2019, was conducted. Data analysis was conducted between December 2018 and February 2019. STUDY SELECTION All prospective observational studies that examined the association between adherence to plant-based dietary patterns and incidence of type 2 diabetes among adults 18 years or older were identified. DATA EXTRACTION AND SYNTHESIS Meta-analysis of Observational Studies in Epidemiology guidelines for data abstraction and reporting were followed, and a National Heart, Lung, and Blood Institute assessment tool was used to evaluate study quality. Two authors independently conducted full-text assessments and data abstraction. Meta-analysis was conducted using the random-effects method to calculate the overall relative risk (RR) and 95% CI. MAIN OUTCOMES AND MEASURES Level of adherence to a plant-based diet and incidence of type 2 diabetes. RESULTS A total of 9 studies were identified, totaling 307 099 participants with 23 544 cases of incident type 2 diabetes. A significant inverse association was observed between higher adherence to a plant-based dietary pattern and risk of type 2 diabetes (RR, 0.77; 95% CI, 0.71-0.84) in comparison with poorer adherence, with modest heterogeneity across studies (I2 = 44.5%; P = .07 for heterogeneity). Similar findings were obtained when using the fixed-effects model (RR, 0.80; 95% CI, 0.75-0.84). Consistent associations were observed across predefined subgroups. This association was strengthened when healthy plant-based foods, such as fruits, vegetables, whole grains, legumes, and nuts, were included in the definition of plant-based patterns (RR, 0.70; 95% CI, 0.62-0.79). Most studies were deemed to have good quality in terms of dietary assessment, disease outcomes, and statistical adjustment for confounding factors. Using restricted cubic splines, a significant inverse linear dose-response association was identified between plant-based dietary indices and risk of type 2 diabetes. CONCLUSIONS AND RELEVANCE Plant-based dietary patterns, especially when they are enriched with healthful plant-based foods, may be beneficial for the primary prevention of type 2 diabetes.
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Affiliation(s)
- Frank Qian
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Gang Liu
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Frank B Hu
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.,Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Shilpa N Bhupathiraju
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Qi Sun
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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Tilg H, Zmora N, Adolph TE, Elinav E. The intestinal microbiota fuelling metabolic inflammation. Nat Rev Immunol 2019; 20:40-54. [DOI: 10.1038/s41577-019-0198-4] [Citation(s) in RCA: 377] [Impact Index Per Article: 62.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2019] [Indexed: 02/06/2023]
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Ponzo V, Fedele D, Goitre I, Leone F, Lezo A, Monzeglio C, Finocchiaro C, Ghigo E, Bo S. Diet-Gut Microbiota Interactions and Gestational Diabetes Mellitus (GDM). Nutrients 2019; 11:E330. [PMID: 30717458 PMCID: PMC6413040 DOI: 10.3390/nu11020330] [Citation(s) in RCA: 103] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 01/30/2019] [Accepted: 01/31/2019] [Indexed: 02/07/2023] Open
Abstract
Medical nutritional therapy is the first-line approach in managing gestational diabetes mellitus (GDM). Diet is also a powerful modulator of the gut microbiota, whose impact on insulin resistance and the inflammatory response in the host are well known. Changes in the gut microbiota composition have been described in pregnancies either before the onset of GDM or after its diagnosis. The possible modulation of the gut microbiota by dietary interventions in pregnancy is a topic of emerging interest, in consideration of the potential effects on maternal and consequently neonatal health. To date, very few data from observational studies are available about the associations between diet and the gut microbiota in pregnancy complicated by GDM. In this review, we analyzed the available data and discussed the current knowledge about diet manipulation in order to shape the gut microbiota in pregnancy.
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Affiliation(s)
- Valentina Ponzo
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
| | - Debora Fedele
- Dietetic and Clinical Nutrition Unit, S. Giovanni Battista Hospital, Città della Salute e della Scienza, 10126 Turin, Italy.
| | - Ilaria Goitre
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
| | - Filomena Leone
- Clinical Nutrition Unit, S. Anna Hospital, Città della Salute e della Scienza, 10126 Turin, Italy.
| | - Antonela Lezo
- Clinical Nutrition Unit, S. Anna Hospital, Città della Salute e della Scienza, 10126 Turin, Italy.
| | - Clara Monzeglio
- Gynecology and Obstetrics Unit, S. Anna Hospital, Città della Salute e della Scienza, 10126 Turin, Italy.
| | - Concetta Finocchiaro
- Dietetic and Clinical Nutrition Unit, S. Giovanni Battista Hospital, Città della Salute e della Scienza, 10126 Turin, Italy.
| | - Ezio Ghigo
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
| | - Simona Bo
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
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50
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Li P, Yin J, Zhu Y, Li S, Chen S, Sun T, Shan Z, Wang J, Shang Q, Li X, Yang W, Liu L. Association between plasma concentration of copper and gestational diabetes mellitus. Clin Nutr 2019; 38:2922-2927. [PMID: 30661907 DOI: 10.1016/j.clnu.2018.12.032] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 11/26/2018] [Accepted: 12/26/2018] [Indexed: 12/28/2022]
Abstract
BACKGROUND & AIMS Emerging findings have raised concerns about significant associations between excessive copper (Cu) and abnormal glucose metabolism. Nevertheless, related researches on the relationship of Cu concentration and gestational diabetes mellitus (GDM) are limited. The objective of this study was to determine whether plasma Cu concentration is associated with GDM. METHODS A case-control study of 248 cases of GDM and 248 age-, parity- and gestational age-matched controls was conducted in Wuhan, China between August 2012 and April 2015. Fasting blood samples of participants were collected at the time of GDM screening (≥24 weeks of gestation). Plasma Cu concentrations were detected by inductively coupled plasma mass spectrometry. The strength of the association of plasma Cu with GDM odds was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs) from conditional logistic regression. Partial Spearman or Pearson correlation coefficients were calculated to estimate the interrelationship between plasma Cu and the risk factors of GDM. RESULTS Plasma Cu concentrations in the GDM group (mean ± SD: 1960.24 ± 391.98 μg/L) were higher than in the control group (mean ± SD: 1842.43 ± 387.09 μg/L) (P = 0.001). After adjustment for possible confounders, the ORs (95% CIs) of GDM across increasing quartiles of plasma Cu levels were 1.00 (referent), 1.79 (0.90-3.55), 2.72 (1.35-5.48) and 2.91 (1.48-5.75), respectively; the OR (95% CI) of GDM was 1.33 (1.06-1.67) for each standard deviation increment of plasma Cu. Moreover, Cu concentrations were positively associated with fasting plasma glucose, 1-h post-glucose load and 2-h post-glucose load (all P < 0.05). CONCLUSIONS The present study indicated a significantly increased odds of GDM in association with higher concentrations of plasma Cu. Prospective cohort studies in other populations are needed to confirm our findings.
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Affiliation(s)
- Peiyun Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Jiawei Yin
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Yalun Zhu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Shuzhen Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Sijing Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Taoping Sun
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Zhilei Shan
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Jiawei Wang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Qianqian Shang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Xiaoqin Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Wei Yang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
| | - Liegang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
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