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Li K, Jin J, Liu Z, Chen C, Huang L, Sun Y. Dysbiosis of infant gut microbiota is related to the altered fatty acid composition of human milk from mothers with gestational diabetes mellitus: a prospective cohort study. Gut Microbes 2025; 17:2455789. [PMID: 39834317 PMCID: PMC11776479 DOI: 10.1080/19490976.2025.2455789] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 10/13/2024] [Accepted: 01/14/2025] [Indexed: 01/22/2025] Open
Abstract
Gestational diabetes mellitus (GDM) is known to be associated with dysbiosis of offspring gut microbiota, but the mechanism remains unclear. The present prospective study explored the role of human milk fatty acid composition in this association. Mothers with GDM and normal controls were recruited at 24-28 gestational weeks. Follow-up was conducted at 1-3 days postpartum and 1 month postpartum to collect human milk and infant feces. A total of 80 mother-infant pairs (40 in the GDM group and 40 in the normal group) were included in the study. The mothers received guidance on diet and exercise but not drug therapy. All infants were exclusively breastfed. We observed significant differences in 8 phyla and 13 genera in the infant between GDM and normal groups at 1-3 days postpartum or 1 month postpartum. Among these bacteria, significant time × group interaction was observed for 7 phyla (such as Acidobacteriota, Gemmatimonadota, and Myxococcota) and 9 genera (such as Sphingomonas, Allorhizobium Neorhizobium Pararhizobium Rhizobium, and TM7a), after adjusting for confounding factors. Changes in these differential infant bacteria were negatively correlated with changes in C18:3n-3 and total n-3 PUFA levels of breast milk. The increases in C18:3n-3 and total n-3 PUFA levels in human milk over time were much greater in the normal group compared to the GDM group. Our findings indicate that altered human milk fatty acid composition is one important reason for GDM-related dysbiosis of offspring gut microbiota.
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Affiliation(s)
- Kelei Li
- School of Public Health, Qingdao University, Qingdao, China
- Institute of Nutrition and Health, Qingdao University, Qingdao, China
| | - Jin Jin
- School of Public Health, Qingdao University, Qingdao, China
| | - Zhizuo Liu
- Department of Obstetrics, Women and Children’s Hospital Affiliated to Qingdao University, Qingdao, China
| | - Chuanjing Chen
- School of Public Health, Qingdao University, Qingdao, China
| | - Ludi Huang
- School of Public Health, Qingdao University, Qingdao, China
| | - Yongye Sun
- School of Public Health, Qingdao University, Qingdao, China
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Nagel EM, Peña A, Dreyfuss JM, Lock EF, Johnson KE, Lu C, Fields DA, Demerath EW, Isganaitis E. Gestational Diabetes, the Human Milk Metabolome, and Infant Growth and Adiposity. JAMA Netw Open 2024; 7:e2450467. [PMID: 39666338 PMCID: PMC11638796 DOI: 10.1001/jamanetworkopen.2024.50467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 10/07/2024] [Indexed: 12/13/2024] Open
Abstract
Importance Gestational diabetes (GD) is linked to health risks for the birthing parent and infant. The outcomes of GD on human milk composition are mostly unknown. Objective To determine associations between GD, the human milk metabolome, and infant growth and body composition. Design, Setting, and Participants Cohort study using data from the Mothers and Infants Linked for Healthy Growth and the Maternal Milk, Metabolism, and the Microbiome studies at the University of Oklahoma and University of Minnesota, large prospective US cohorts with a high proportion of exclusive breastfeeding. Participants were mother-infant dyads recruited between October 2014 and August 2019 who planned to exclusively breastfeed for 3 or more months. Data were analyzed from July 2022 to August 2024. Exposure GD diagnosed via oral glucose tolerance test. Main Outcomes and Measures The milk metabolome was assessed by untargeted liquid chromatography-gas chromatography-mass spectrometry at 1 month post partum. Infant growth (weight for length z score, length for age z score, and rapid weight gain) and body composition (percentage body fat and fat-free mass index) from 0 to 6 months were assessed. Linear regression analyses tested associations between GD and milk metabolites, with adjustment for covariates and potential confounders. Results Among 348 dyads (53 with GD), 27 (51%) of the GD-exposed infants were female and 157 (53%) of nonexposed infants were male; 10 (19%) were Asian, 2 (4%) were Black or African American, and 37 (70%) were White. The mean (SD) age was higher in the GD group (with GD, 34.0 [4.3] years; without GD, 30.7 [4.1] years). In adjusted models, GD was associated with differential levels of 9 metabolites of 458 tested (FDR<0.05); 3 were higher (2-hydroxybutyric acid, 3-methylphenylacetic acid, and pregnanolone sulfate) and 6 were lower in women with GD (4-cresyl sulfate, cresol, glycine, P-cresol sulfate, phenylacetic acid, and stearoylcarnitine). Phenylacetic acid was associated with length for age z score (β = 0.27; SE, 0.13; 95% CI, 0.02 to 0.16), 2-hydroxybutryic acid with percentage body fat (β = -1.50; SE, 0.66; 95% CI, -2.79 to -4.82), and stearoylcarnitine with greater odds of rapid weight gain (odds ratio, 1.66; 95% CI, 1.23 to 2.25). GD was associated with greater length for age z scores (β = 0.48; SE, 0.22; 95% CI, 0.04 to 0.91). Conclusions and Relevance In this observational cohort study, GD was associated with altered concentrations of several human milk metabolites. The associations between these metabolites and infant growth suggest that milk compositional differences in mothers with GD may beneficially moderate the growth and body composition of their infants.
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Affiliation(s)
- Emily M. Nagel
- School of Public Health, University of Minnesota, Twin Cities
- Department of Pediatrics, University of Minnesota, Minneapolis
| | - Armando Peña
- Department of Health and Wellness Design, School of Public Health, Indiana University Bloomington, Bloomington
| | | | - Eric F. Lock
- Division of Biostatistics and Health Data Science, School of Public Health, University of Minnesota-Twin Cities
| | - Kelsey E. Johnson
- Department of Genetics, Cell Biology, and Development, University of Minnesota-Twin Cities
| | - Chang Lu
- Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
- Division of Endocrinology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts
| | - David A. Fields
- Department of Pediatrics, University of Oklahoma College of Medicine
| | | | - Elvira Isganaitis
- Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
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Yao D, Shen C, Zhang X, Tang J, Yu J, Tu M, Panpipat W, Chaijan M, Zhang H, Xu X, Liu Y, Cheong LZ. Untargeted metabolomics study of mature human milk from women with and without gestational diabetes mellitus. Food Chem 2024; 460:140663. [PMID: 39142199 DOI: 10.1016/j.foodchem.2024.140663] [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: 05/20/2024] [Revised: 07/25/2024] [Accepted: 07/25/2024] [Indexed: 08/16/2024]
Abstract
Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder during pregnancy that alters the metabolites in human milk. Integrated Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) were employed for comprehensive identification and comparison of metabolites in mature human milk (MHM) from women with and without GDM. A total of 268 differentially expressed metabolites (DEMs) were identified. Among these, linoleic acid, arachidonic acid, 9R-HODE and L-glutamic acid were significantly elevated and 12,13-DHOME was significantly decreased in MHM of women with GDM. These metabolites are significantly enriched in linoleic acid metabolism, fatty acid biosynthesis, galactose metabolism and ABC transporters pathways. Disorders in these metabolic pathways are associated with insulin resistance and poor glucose metabolism indicating these conditions may persist postpartum.
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Affiliation(s)
- Dan Yao
- Zhejiang-Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, College of Food Science and Engineering, Ningbo University, Ningbo 315800, China
| | - Cai Shen
- School of Agriculture and Food, Faculty of Science, University of Melbourne, 3010, Australia
| | - Xinghe Zhang
- School of Agriculture and Food, Faculty of Science, University of Melbourne, 3010, Australia
| | - Jiayue Tang
- Zhejiang-Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, College of Food Science and Engineering, Ningbo University, Ningbo 315800, China
| | - Jingwen Yu
- Zhejiang-Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, College of Food Science and Engineering, Ningbo University, Ningbo 315800, China
| | - Maolin Tu
- Zhejiang-Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, College of Food Science and Engineering, Ningbo University, Ningbo 315800, China
| | - Worawan Panpipat
- School of Agricultural Technology and Food Industry, Walailak University, 80161, 222 Thaiburi, Thasala District, Nakhonsrithammarat, Thailand
| | - Manat Chaijan
- School of Agricultural Technology and Food Industry, Walailak University, 80161, 222 Thaiburi, Thasala District, Nakhonsrithammarat, Thailand
| | - Hong Zhang
- Wilmar (Shanghai) Biotechnology Research and Development Center Co Ltd., No.118 Gaodong Rd., Pudong New District, Shanghai 200137, China
| | - Xuebing Xu
- Wilmar (Shanghai) Biotechnology Research and Development Center Co Ltd., No.118 Gaodong Rd., Pudong New District, Shanghai 200137, China
| | - Yanan Liu
- Zhejiang-Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, College of Food Science and Engineering, Ningbo University, Ningbo 315800, China
| | - Ling-Zhi Cheong
- School of Agriculture and Food, Faculty of Science, University of Melbourne, 3010, Australia
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Fu J, Wang Y, Qiao W, Di S, Huang Y, Zhao J, Jing M, Chen L. Research progress on factors affecting the human milk metabolome. Food Res Int 2024; 197:115236. [PMID: 39593319 DOI: 10.1016/j.foodres.2024.115236] [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: 07/12/2024] [Revised: 09/24/2024] [Accepted: 10/18/2024] [Indexed: 11/28/2024]
Abstract
Human milk is the gold standard for infant nutrition and contains macronutrients, micronutrients, and various bioactive substances. The human milk composition and metabolite profiles are complex and dynamic, complicating its specific analysis. Metabolomics, a recently emerging technology, has been used to identify human milk metabolites classes. Applying metabolomics to study the factors affecting human milk metabolites can provide significant insights into the relationship between infant nutrition, health, and development and better meet the nutritional needs of infants during growth. Here, we systematically review the current status of human milk metabolomic research, and related methods, offering an in-depth analysis of the influencing factors and results of human milk metabolomics from a metabolic perspective to provide novel ideas to further advance human milk metabolomics.
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Affiliation(s)
- Jieyu Fu
- Key Laboratory of Dairy Science, Ministry of Education, Food Science College, Northeast Agricultural University, Harbin 150030, China; National Engineering Research Center of Dairy Health for Maternal and Child, Bejing Sanyuan Foods Co. Ltd., Beijing 100163, China; Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd., Beijing 100163, China
| | - Yaling Wang
- National Engineering Research Center of Dairy Health for Maternal and Child, Bejing Sanyuan Foods Co. Ltd., Beijing 100163, China; Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd., Beijing 100163, China
| | - Weicang Qiao
- National Engineering Research Center of Dairy Health for Maternal and Child, Bejing Sanyuan Foods Co. Ltd., Beijing 100163, China; Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd., Beijing 100163, China
| | - Shujuan Di
- Key Laboratory of Dairy Science, Ministry of Education, Food Science College, Northeast Agricultural University, Harbin 150030, China; National Engineering Research Center of Dairy Health for Maternal and Child, Bejing Sanyuan Foods Co. Ltd., Beijing 100163, China; Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd., Beijing 100163, China
| | - Yibo Huang
- Key Laboratory of Dairy Science, Ministry of Education, Food Science College, Northeast Agricultural University, Harbin 150030, China; National Engineering Research Center of Dairy Health for Maternal and Child, Bejing Sanyuan Foods Co. Ltd., Beijing 100163, China; Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd., Beijing 100163, China
| | - Junying Zhao
- National Engineering Research Center of Dairy Health for Maternal and Child, Bejing Sanyuan Foods Co. Ltd., Beijing 100163, China; Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd., Beijing 100163, China
| | - Mengna Jing
- National Engineering Research Center of Dairy Health for Maternal and Child, Bejing Sanyuan Foods Co. Ltd., Beijing 100163, China; Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd., Beijing 100163, China
| | - Lijun Chen
- Key Laboratory of Dairy Science, Ministry of Education, Food Science College, Northeast Agricultural University, Harbin 150030, China; National Engineering Research Center of Dairy Health for Maternal and Child, Bejing Sanyuan Foods Co. Ltd., Beijing 100163, China; Beijing Engineering Research Center of Dairy, Beijing Technical Innovation Center of Human Milk Research, Beijing Sanyuan Foods Co. Ltd., Beijing 100163, China.
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Schulkers Escalante K, Bai-Tong SS, Allard SM, Ecklu-Mensah G, Sanchez C, Song SJ, Gilbert J, Bode L, Dorrestein P, Knight R, Gonzalez DJ, Leibel SA, Leibel SL. The impact of breastfeeding on the preterm infant's microbiome and metabolome: a pilot study. Pediatr Res 2024:10.1038/s41390-024-03440-9. [PMID: 39138352 DOI: 10.1038/s41390-024-03440-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 06/23/2024] [Accepted: 07/10/2024] [Indexed: 08/15/2024]
Abstract
BACKGROUND Human milk is unquestionably beneficial for preterm infants. We investigated how the transition from tube to oral/breastfeeding impacts the preterm infants' oral and gut microbiome and metabolome. METHODS We analyzed stool, saliva, and milk samples collected from a cohort of preterm infants enrolled in the MAP Study, a prospective observational trial. The microbiome and metabolome of the samples were analyzed from 4 longitudinal sample time points, 2 during tube feeds only and 2 after the initiation of oral/breastfeeding. RESULTS We enrolled 11 mother-infant dyads (gestational age = 27.9 (23.4-32.2)) and analyzed a total of 39 stool, 44 saliva, and 43 milk samples over 4 timepoints. In saliva samples, there was a shift towards increased Streptococcus and decreased Staphylococcus after oral feeding/breastfeeding initiation (p < 0.05). Milk sample metabolites were strongly influenced by the route of feeding and milk type (p < 0.05) and represented the pathways of Vitamin E metabolism, Vitamin B12 metabolism, and Tryptophan metabolism. CONCLUSION Our analysis demonstrated that the milk and preterm infant's saliva microbiome and metabolome changed over the course of the first four to 5 months of life, coinciding with the initiation of oral/breastfeeds. IMPACT The microbiome and metabolome is altered in the infant's saliva but not their stool, and in mother's milk when feeds are transitioned from tube to oral/breastfeeding. We assessed the relationship between the gut and oral microbiome/metabolome with the milk microbiome/metabolome over a longitudinal period of time in preterm babies. Metabolites that changed in the infants saliva after the initiation of oral feeds have the potential to be used as biomarkers for disease risk.
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Affiliation(s)
| | - Shiyu S Bai-Tong
- Department of Pediatrics, University of California San Diego, Rady Children's Hospital, La Jolla, CA, USA
| | - Sarah M Allard
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
| | | | - Concepcion Sanchez
- Department of Pharmacology and the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
| | - Se Jin Song
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
| | - Jack Gilbert
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Department of Pediatrics and Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA, USA
| | - Lars Bode
- Department of Pediatrics, Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), and the Human Milk Institute (HMI), University of California San Diego, La Jolla, CA, USA
| | - Pieter Dorrestein
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, USA
| | - Rob Knight
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Collaborative Mass Spectrometry Innovation Center, University of California San Diego, La Jolla, CA, USA
| | - David J Gonzalez
- Department of Pharmacology and the Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
| | - Sydney A Leibel
- Department of Pediatrics, University of California San Diego, Rady Children's Hospital, La Jolla, CA, USA
| | - Sandra L Leibel
- Department of Pediatrics, University of California San Diego, Rady Children's Hospital, La Jolla, CA, USA.
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Yu HT, Xu WH, Gong JY, Chen YF, He Y, Chen ST, Wu YY, Liu GL, Zhang HY, Xie L. Effect of high-fat diet on the fatty acid profiles of brain in offspring mice exposed to maternal gestational diabetes mellitus. Int J Obes (Lond) 2024; 48:849-858. [PMID: 38341506 DOI: 10.1038/s41366-024-01486-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Revised: 01/11/2024] [Accepted: 01/25/2024] [Indexed: 02/12/2024]
Abstract
OBJECTIVE Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/β-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of β-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.
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Affiliation(s)
- Hai-Tao Yu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, Jilin, China
| | - Wen-Hui Xu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, Jilin, China
| | - Jia-Yu Gong
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, Jilin, China
| | - Yi-Fei Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, Jilin, China
| | - Yuan He
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, Jilin, China
| | - Shu-Tong Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, Jilin, China
| | - Yan-Yan Wu
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, Jilin, China
| | - Guo-Liang Liu
- Experimental Teaching Center for Preventive Medicine, School of Public Health, Jilin University, Changchun, 130021, Jilin, China
| | - Hai-Ying Zhang
- Experimental Teaching Center for Radiation Medicine, School of Public Health, Jilin University, Changchun, 130021, Jilin, China
| | - Lin Xie
- Department of Nutrition and Food Hygiene, School of Public Health, Jilin University, Changchun, 130021, Jilin, China.
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Zhang F, Shan S, Fu C, Guo S, Liu C, Wang S. Advanced Mass Spectrometry-Based Biomarker Identification for Metabolomics of Diabetes Mellitus and Its Complications. Molecules 2024; 29:2530. [PMID: 38893405 PMCID: PMC11173766 DOI: 10.3390/molecules29112530] [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: 02/08/2024] [Revised: 04/15/2024] [Accepted: 04/16/2024] [Indexed: 06/21/2024] Open
Abstract
Over the years, there has been notable progress in understanding the pathogenesis and treatment modalities of diabetes and its complications, including the application of metabolomics in the study of diabetes, capturing attention from researchers worldwide. Advanced mass spectrometry, including gas chromatography-tandem mass spectrometry (GC-MS/MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and ultra-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS), etc., has significantly broadened the spectrum of detectable metabolites, even at lower concentrations. Advanced mass spectrometry has emerged as a powerful tool in diabetes research, particularly in the context of metabolomics. By leveraging the precision and sensitivity of advanced mass spectrometry techniques, researchers have unlocked a wealth of information within the metabolome. This technology has enabled the identification and quantification of potential biomarkers associated with diabetes and its complications, providing new ideas and methods for clinical diagnostics and metabolic studies. Moreover, it offers a less invasive, or even non-invasive, means of tracking disease progression, evaluating treatment efficacy, and understanding the underlying metabolic alterations in diabetes. This paper summarizes advanced mass spectrometry for the application of metabolomics in diabetes mellitus, gestational diabetes mellitus, diabetic peripheral neuropathy, diabetic retinopathy, diabetic nephropathy, diabetic encephalopathy, diabetic cardiomyopathy, and diabetic foot ulcers and organizes some of the potential biomarkers of the different complications with the aim of providing ideas and methods for subsequent in-depth metabolic research and searching for new ways of treating the disease.
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Affiliation(s)
- Feixue Zhang
- Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Medical College, Hubei University of Science and Technology, Xianning 437100, China; (F.Z.); (C.F.); (S.G.)
| | - Shan Shan
- College of Life Science, National R&D Center for Freshwater Fish Processing, Jiangxi Normal University, Nanchang 330022, China;
| | - Chenlu Fu
- Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Medical College, Hubei University of Science and Technology, Xianning 437100, China; (F.Z.); (C.F.); (S.G.)
- School of Pharmacy, Medical College, Hubei University of Science and Technology, Xianning 437100, China
| | - Shuang Guo
- Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Medical College, Hubei University of Science and Technology, Xianning 437100, China; (F.Z.); (C.F.); (S.G.)
| | - Chao Liu
- Hubei Key Laboratory of Diabetes and Angiopathy, Medicine Research Institute, Medical College, Hubei University of Science and Technology, Xianning 437100, China; (F.Z.); (C.F.); (S.G.)
| | - Shuanglong Wang
- Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang 330013, China
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Scime NV, Turner S, Miliku K, Simons E, Moraes TJ, Field CJ, Turvey SE, Subbarao P, Mandhane PJ, Azad MB. Association of Human Milk Fatty Acid Composition with Maternal Cardiometabolic Diseases: An Exploratory Prospective Cohort Study. Breastfeed Med 2024; 19:357-367. [PMID: 38501380 PMCID: PMC11250837 DOI: 10.1089/bfm.2024.0019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/20/2024]
Abstract
Background: Human milk fatty acids derive from maternal diet, body stores, and mammary synthesis and may reflect women's underlying cardiometabolic health. We explored whether human milk fatty acid composition was associated with maternal cardiometabolic disease (CMD) during pregnancy and up to 5 years postpartum. Materials and Methods: We analyzed data from the prospective CHILD Cohort Study on 1,018 women with no preexisting CMD who provided breast milk samples at 3-4 months postpartum. Milk fatty acid composition was measured using gas-liquid chromatography. Maternal CMD (diabetes or hypertension) was classified using questionnaires and birth records as no CMD (reference outcome group; 81.1%), perinatal CMD (developed and resolved during the perinatal period; 14.9%), persistent CMD (developed during, and persisted beyond, the perinatal period; 2.9%), and incident CMD (developed after the perinatal period; 1.1%). Multinomial logistic regression was used to model associations between milk fatty acid composition (individual, summary, ratios, and patterns identified using principal component analysis) and maternal CMD, adjusting for pre-pregnancy anthropometry and race/ethnicity. Results: Medium-chain saturated fatty acids (MC-SFA), lauric (C12:0; odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.60-0.89) and myristic acid (C14:0; OR = 0.80, 95% CI = 0.66-0.97), and the high MC-SFA principal component pattern (OR = 0.86, 95% CI = 0.76-0.96) were inversely associated with perinatal CMD. Long-chain polyunsaturated fatty acids adrenic acid (C22:4n-6) was positively associated with perinatal (OR = 1.21, 95% CI = 1.01-1.44) and persistent CMD (OR = 1.56, 95% CI = 1.08-2.25). The arachidonic (C20:4n-6)-to-docosahexaenoic acid (C22:6n-3) ratio was inversely associated with incident CMD (OR = 0.52, 95% CI = 0.28-0.96). Conclusions: These exploratory findings highlight a potential novel utility of breast milk for understanding women's cardiometabolic health.
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Affiliation(s)
- Natalie V. Scime
- Department of Health & Society, University of Toronto Scarborough, Toronto, Ontario, Canada
| | - Sarah Turner
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Kozeta Miliku
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
| | - Elinor Simons
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Theo J. Moraes
- Division of Respiratory Medicine, Department of Pediatrics, SickKids Research Institute, Toronto, Ontario, Canada
| | - Catherine J. Field
- Department of Agricultural Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada
| | - Stuart E. Turvey
- BC Children’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada
- Division of Allergy and Immunology, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Padmaja Subbarao
- Division of Respiratory Medicine, Department of Pediatrics, SickKids Research Institute, Toronto, Ontario, Canada
- Department of Physiology, University of Toronto, Toronto, Ontario, Canada
| | - Piushkumar J. Mandhane
- Department of Pediatrics, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
| | - Meghan B. Azad
- Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
- Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada
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de Souza HMR, Pereira TTP, de Sá HC, Alves MA, Garrett R, Canuto GAB. Critical Factors in Sample Collection and Preparation for Clinical Metabolomics of Underexplored Biological Specimens. Metabolites 2024; 14:36. [PMID: 38248839 PMCID: PMC10819689 DOI: 10.3390/metabo14010036] [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: 11/24/2023] [Revised: 01/02/2024] [Accepted: 01/03/2024] [Indexed: 01/23/2024] Open
Abstract
This review article compiles critical pre-analytical factors for sample collection and extraction of eight uncommon or underexplored biological specimens (human breast milk, ocular fluids, sebum, seminal plasma, sweat, hair, saliva, and cerebrospinal fluid) under the perspective of clinical metabolomics. These samples are interesting for metabolomics studies as they reflect the status of living organisms and can be applied for diagnostic purposes and biomarker discovery. Pre-collection and collection procedures are critical, requiring protocols to be standardized to avoid contamination and bias. Such procedures must consider cleaning the collection area, sample stimulation, diet, and food and drug intake, among other factors that impact the lack of homogeneity of the sample group. Precipitation of proteins and removal of salts and cell debris are the most used sample preparation procedures. This review intends to provide a global view of the practical aspects that most impact results, serving as a starting point for the designing of metabolomic experiments.
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Affiliation(s)
- Hygor M. R. de Souza
- Instituto de Química, Universidade Federal do Rio de Janeiro, LabMeta—LADETEC, Rio de Janeiro 21941-598, Brazil;
| | - Tássia T. P. Pereira
- Departamento de Genética, Ecologia e Evolucao, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil;
- Departamento de Biodiversidade, Evolução e Meio Ambiente, Universidade Federal de Ouro Preto, Ouro Preto 35400-000, Brazil
| | - Hanna C. de Sá
- Departamento de Química Analítica, Instituto de Química, Universidade Federal da Bahia, Salvador 40170-115, Brazil;
| | - Marina A. Alves
- Instituto de Pesquisa de Produtos Naturais Walter Mors, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-599, Brazil;
| | - Rafael Garrett
- Instituto de Química, Universidade Federal do Rio de Janeiro, LabMeta—LADETEC, Rio de Janeiro 21941-598, Brazil;
- Department of Laboratory Medicine, Boston Children’s Hospital—Harvard Medical School, Boston, MA 02115, USA
| | - Gisele A. B. Canuto
- Departamento de Química Analítica, Instituto de Química, Universidade Federal da Bahia, Salvador 40170-115, Brazil;
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10
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Li W, Zeng W, Zhang Y, Ma Z, Fang X, Han Y, Sun Y, Jin X, Ma L. A comparative metabolomics analysis of domestic yak ( Bos grunniens) milk with human breast milk. Front Vet Sci 2023; 10:1207950. [PMID: 37841471 PMCID: PMC10570732 DOI: 10.3389/fvets.2023.1207950] [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: 04/18/2023] [Accepted: 09/08/2023] [Indexed: 10/17/2023] Open
Abstract
Yaks are tough animals living in Tibet's hypoxic stress environment. However, the metabolite composition of yak milk and its role in hypoxic stress tolerance remains largely unexplored. The similarities and differences between yak and human milk in hypoxic stress tolerance are also unclear. This study explored yak colostrum (YC) and yak mature milk (YMM) using GC-MS, and 354 metabolites were identified in yak milk. A comparative metabolomic analysis of yak and human milk metabolites showed that over 70% of metabolites were species-specific. Yak milk relies mainly on essential amino acids- arginine and essential branched-chain amino acids (BCAAs): L-isoleucine, L-leucine, and L-valine tolerate hypoxic stress. To slow hypoxic stress, human breast milk relies primarily on the neuroprotective effects of non-essential amino acids or derivates, such as citrulline, sarcosine, and creatine. In addition, metabolites related to hypoxic stress were significantly enriched in YC than in YMM. These results reveal the unique metabolite composition of yak and human milk and provide practical information for applying yak and human milk to hypoxic stress tolerance.
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Affiliation(s)
- Wenhao Li
- Institute of Animal Husbandry and Veterinary Science, Qinghai University, Xining, China
| | - Weike Zeng
- Center for Genomics, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Fujian Agriculture and Forestry University, Fuzhou, China
- College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Yanping Zhang
- Institute of Animal Husbandry and Veterinary Science, Qinghai University, Xining, China
| | - Zhijie Ma
- Institute of Animal Husbandry and Veterinary Science, Qinghai University, Xining, China
| | - Xingyan Fang
- Center for Genomics, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Fujian Agriculture and Forestry University, Fuzhou, China
- College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Yingcang Han
- Institute of Animal Husbandry and Veterinary Science, Qinghai University, Xining, China
| | - Yonggang Sun
- Institute of Animal Husbandry and Veterinary Science, Qinghai University, Xining, China
| | - Xiayang Jin
- Institute of Animal Husbandry and Veterinary Science, Qinghai University, Xining, China
| | - Liuyin Ma
- Center for Genomics, Fujian Provincial Key Laboratory of Haixia Applied Plant Systems Biology, Fujian Agriculture and Forestry University, Fuzhou, China
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11
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Martín-Carrasco I, Carbonero-Aguilar P, Dahiri B, Moreno IM, Hinojosa M. Comparison between pollutants found in breast milk and infant formula in the last decade: A review. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 875:162461. [PMID: 36868281 DOI: 10.1016/j.scitotenv.2023.162461] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2022] [Revised: 02/03/2023] [Accepted: 02/21/2023] [Indexed: 06/18/2023]
Abstract
Since ancient times, breastfeeding has been the fundamental way of nurturing the newborn. The benefits of breast milk are widely known, as it is a source of essential nutrients and provides immunological protection, as well as developmental benefits, among others. However, when breastfeeding is not possible, infant formula is the most appropriate alternative. Its composition meets the nutritional requirements of the infant, and its quality is subject to strict control by the authorities. Nonetheless, the presence of different pollutants has been detected in both matrices. Thus, the aim of the present review is to make a comparison between the findings in both breast milk and infant formula in terms of contaminants in the last decade, in order to choose the most convenient option depending on the environmental conditions. For that, the emerging pollutants including metals, chemical compounds derived from heat treatment, pharmaceutical drugs, mycotoxins, pesticides, packaging materials, and other contaminants were described. While in breast milk the most concerning contaminants found were metals and pesticides, in infant formula pollutants such as metals, mycotoxins, and packaging materials were the most outstanding. In conclusion, the convenience of using a feeding diet based on breast milk or either infant formula depends on the maternal environmental circumstances. However, it is important to take into account the immunological benefits of the breast milk compared to the infant formula, and the possibility of using breast milk in combination with infant formula when the nutritional requirements are not fulfilled only with the intake of breast milk. Therefore, more attention should be paid in terms of analyzing these conditions in each case to be able to make a proper decision, as it will vary depending on the maternal and newborn environment.
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Affiliation(s)
- I Martín-Carrasco
- Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C/ Profesor García González 2, 41012 Seville, Spain
| | - P Carbonero-Aguilar
- Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C/ Profesor García González 2, 41012 Seville, Spain
| | - B Dahiri
- Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C/ Profesor García González 2, 41012 Seville, Spain
| | - I M Moreno
- Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C/ Profesor García González 2, 41012 Seville, Spain.
| | - M Hinojosa
- Area of Toxicology, Faculty of Pharmacy, University of Sevilla, C/ Profesor García González 2, 41012 Seville, Spain; Department of Biochemistry and Biophysics, Stockholm University, Institutionen för biokemi och biofysik, 106 91 Stockholm, Sweden
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12
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Elbeltagi R, Al-Beltagi M, Saeed NK, Bediwy AS. Cardiometabolic effects of breastfeeding on infants of diabetic mothers. World J Diabetes 2023; 14:617-631. [PMID: 37273257 PMCID: PMC10236993 DOI: 10.4239/wjd.v14.i5.617] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 03/01/2023] [Accepted: 04/07/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Breast milk is the best and principal nutritional source for neonates and infants. It may protect infants against many metabolic diseases, predominantly obesity and type 2 diabetes. Diabetes mellitus (DM) is a chronic metabolic and microvascular disease that affects all the body systems and all ages from intrauterine life to late adulthood. Breastfeeding protects against infant mortality and diseases, such as necrotizing enterocolitis, diarrhoea, respiratory infections, viral and bacterial infection, eczema, allergic rhinitis, asthma, food allergies, malocclusion, dental caries, Crohn's disease, and ulcerative colitis. It also protects against obesity and insulin resistance and increases intelligence and mental development. Gestational diabetes has short and long-term impacts on infants of diabetic mothers (IDM). Breast milk composition changes in mothers with gestational diabetes. AIM To investigate the beneficial or detrimental effects of breastfeeding on the cardiometabolic health of IDM and their mothers. METHODS We performed a database search on different engines and a thorough literature review and included 121 research published in English between January 2000 and December 15, 2022, in this review. RESULTS Most of the literature agreed on the beneficial effects of breast milk for both the mother and the infant in the short and long terms. Breastfeeding protects mothers with gestational diabetes against obesity and type 2 DM. Despite some evidence of the protective effects of breastfeeding on IDM in the short and long term, the evidence is not strong enough due to the presence of many confounding factors and a lack of sufficient studies. CONCLUSION We need more comprehensive research to prove these effects. Despite many obstacles that may enface mothers with gestational diabetes to start and maintain breastfeeding, every effort should be made to encourage them to breastfeed.
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Affiliation(s)
- Reem Elbeltagi
- Department of Medicine, Irish Royal College of Surgeon, Busaiteen 15503, Bahrain
| | - Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Bahrain
- Department of Microbiology, Irish Royal College of Surgeon, Bahrain, Busaiteen 15503, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Diseases, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
- Department of Pulmonology, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
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13
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Baumgartel K, Stevens M, Vijayakumar N, Saint Fleur A, Prescott S, Groer M. The Human Milk Metabolome: A Scoping Literature Review. J Hum Lact 2023; 39:255-277. [PMID: 36924445 DOI: 10.1177/08903344231156449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
BACKGROUND Human milk is a complex source of nutrition and other bioactives that protects infants from disease, holding a lifetime of beneficial effects. The field of metabolomics provides a robust platform through which we can better understand human milk at a level rarely examined. RESEARCH AIM To Identify, describe, synthesize, and critically analyze the literature within the past 5 years related to the human milk metabolome. METHODS We conducted a scoping literature review and quality analysis of the recent science reflecting untargeted metabolomic approaches to examining human milk. We searched six databases using the terms "breast milk," "metabolome," "metabolite," and "human milk," Out of more than 1,069 abstracts, we screened and identified 22 articles that met our inclusion criteria. RESULTS We extracted data related to the study author, geographic location, research design, analyses, platform used, and results. We also extracted data related to human milk research activities, including collection protocol, infant/maternal considerations, and time. Selected studies focused on a variety of phenotypes, including maternal and infant disease. Investigators used varying approaches to evaluate the metabolome, and differing milk collection protocols were observed. CONCLUSION The human milk metabolome is informed by many factors-which may contribute to infant health outcomes-that have resulted in disparate milk metabolomic profiles. Standardized milk collection and storage procedures should be implemented to minimize degradation. Investigators may use our findings to develop research questions that test a targeted metabolomic approach.
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Affiliation(s)
| | - Monica Stevens
- College of Medicine, University of South Florida, Tampa, FL, USA
| | - Nisha Vijayakumar
- School of Public Health, University of South Florida, Tampa, FL, USA
| | | | | | - Maureen Groer
- College of Nursing, University of Tennessee, Knoxville, TN, USA
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14
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Pintus R, Dessì A, Mussap M, Fanos V. Metabolomics can provide new insights into perinatal nutrition. Acta Paediatr 2023; 112:233-241. [PMID: 34487568 PMCID: PMC10078676 DOI: 10.1111/apa.16096] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/01/2021] [Accepted: 09/03/2021] [Indexed: 01/13/2023]
Abstract
Perinatal nutrition is a key factor related to the Developmental Origin of Health and Disease hypothesis, which states that each and every event that happens during the periconceptional period and pregnancy can affect the health status of an individual. Metabolomics can be a very useful tool for gathering information about the effect of perinatal nutrition on both mothers and newborn infants. This non-systematic review focuses on the main metabolites detected by this technique, with regard to gestational diabetes, intrauterine growth restriction and breast milk. Conclusion. Nutrition, metabolome and microbiome interactions are gaining interest in the scientific community.
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Affiliation(s)
- Roberta Pintus
- Neonatal Intensive Care Unit, AOU Cagliari Department of Surgery, University of Cagliari, Cagliari, Italy
| | - Angelica Dessì
- Neonatal Intensive Care Unit, AOU Cagliari Department of Surgery, University of Cagliari, Cagliari, Italy
| | - Michele Mussap
- Neonatal Intensive Care Unit, AOU Cagliari Department of Surgery, University of Cagliari, Cagliari, Italy
| | - Vassilios Fanos
- Neonatal Intensive Care Unit, AOU Cagliari Department of Surgery, University of Cagliari, Cagliari, Italy
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15
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Melnik BC, Schmitz G. Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life. Int J Mol Sci 2022; 23:ijms231911503. [PMID: 36232796 PMCID: PMC9569743 DOI: 10.3390/ijms231911503] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Revised: 09/15/2022] [Accepted: 09/20/2022] [Indexed: 11/16/2022] Open
Abstract
Pancreatic β cell expansion and functional maturation during the birth-to-weaning period is driven by epigenetic programs primarily triggered by growth factors, hormones, and nutrients provided by human milk. As shown recently, exosomes derived from various origins interact with β cells. This review elucidates the potential role of milk-derived exosomes (MEX) and their microRNAs (miRs) on pancreatic β cell programming during the postnatal period of lactation as well as during continuous cow milk exposure of adult humans to bovine MEX. Mechanistic evidence suggests that MEX miRs stimulate mTORC1/c-MYC-dependent postnatal β cell proliferation and glycolysis, but attenuate β cell differentiation, mitochondrial function, and insulin synthesis and secretion. MEX miR content is negatively affected by maternal obesity, gestational diabetes, psychological stress, caesarean delivery, and is completely absent in infant formula. Weaning-related disappearance of MEX miRs may be the critical event switching β cells from proliferation to TGF-β/AMPK-mediated cell differentiation, whereas continued exposure of adult humans to bovine MEX miRs via intake of pasteurized cow milk may reverse β cell differentiation, promoting β cell de-differentiation. Whereas MEX miR signaling supports postnatal β cell proliferation (diabetes prevention), persistent bovine MEX exposure after the lactation period may de-differentiate β cells back to the postnatal phenotype (diabetes induction).
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Affiliation(s)
- Bodo C. Melnik
- Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, D-49076 Osnabrück, Germany
- Correspondence: ; Tel.: +49-52-4198-8060
| | - Gerd Schmitz
- Institute for Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, University of Regensburg, D-93053 Regensburg, Germany
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16
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Nutritional Parameters in Colostrum of Different Mammalian Species. BEVERAGES 2022. [DOI: 10.3390/beverages8030054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Colostrum (or first milk) is the food produced by all the mothers in all specific mammalian species, ruminants, monogastric and marine mammalians for their newborns during the first 24–48 h post-partum. Colostrum provides to the neonate all essential nutrients necessary for the first week of life, but the effect of colostrum shows a long-term effect not limited to these first days. Colostrum is considered to be a safe and essential food for human consumption. Some young children can show at the beginning of their colostrum-based diet some side effects, such as nausea and flatulence, but they disappear quickly. In human colostrum, the immunoglobulins and lactoferrin determined show the ability to create natural immunity in newborns, reducing greatly the mortality rate in children. Recent studies suggest that bovine colostrum (BC) may be an interesting nutraceutical food, due to its ability in preventing and/or mitigating several diseases in newborns and adults. This review aims to show the nutraceutical and functional properties of colostrum produced by several mammalian species, describing the different colostrum bio-active molecules and reporting the clinical trials aimed to determine colostrum nutraceutical and therapeutic characteristics in human nutrition.
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17
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Ong YY, Pang WW, Huang JY, Aris IM, Sadananthan SA, Tint MT, Yuan WL, Chen LW, Chan YH, Karnani N, Velan SS, Fortier MV, Choo J, Ling LH, Shek L, Tan KH, Gluckman PD, Yap F, Chong YS, Godfrey KM, Chong MFF, Chan SY, Eriksson JG, Wlodek ME, Lee YS, Michael N. Breastfeeding may benefit cardiometabolic health of children exposed to increased gestational glycemia in utero. Eur J Nutr 2022; 61:2383-2395. [PMID: 35124728 PMCID: PMC7613060 DOI: 10.1007/s00394-022-02800-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Accepted: 01/06/2022] [Indexed: 02/03/2023]
Abstract
PURPOSE There is altered breastmilk composition among mothers with gestational diabetes and conflicting evidence on whether breastfeeding is beneficial or detrimental to their offspring's cardiometabolic health. We aimed to investigate associations between breastfeeding and offspring's cardiometabolic health across the range of gestational glycemia. METHODS We included 827 naturally conceived, term singletons from a prospective mother-child cohort. We measured gestational (26-28 weeks) fasting plasma glucose (FPG) and 2-h plasma glucose (2 hPG) after an oral glucose tolerance test as continuous variables. Participants were classified into 2 breastfeeding categories (high/intermediate vs. low) according to their breastfeeding duration and exclusivity. Main outcome measures included magnetic resonance imaging (MRI)-measured abdominal fat, intramyocellular lipids (IMCL), and liver fat, quantitative magnetic resonance (QMR)-measured body fat mass, blood pressure, blood lipids, and insulin resistance at 6 years old (all continuous variables). We evaluated if gestational glycemia (FPG and 2 hPG) modified the association of breastfeeding with offspring outcomes after adjusting for confounders using a multiple linear regression model that included a 'gestational glycemia × breastfeeding' interaction term. RESULTS With increasing gestational FPG, high/intermediate (vs. low) breastfeeding was associated with lower levels of IMCL (p-interaction = 0.047), liver fat (p-interaction = 0.033), and triglycerides (p-interaction = 0.007), after adjusting for confounders. Specifically, at 2 standard deviations above the mean gestational FPG level, high/intermediate (vs. low) breastfeeding was linked to lower adjusted mean IMCL [0.39% of water signal (0.29, 0.50) vs. 0.54% of water signal (0.46, 0.62)], liver fat [0.39% by weight (0.20, 0.58) vs. 0.72% by weight (0.59, 0.85)], and triglycerides [0.62 mmol/L (0.51, 0.72) vs. 0.86 mmol/L (0.75, 0.97)]. 2 hPG did not significantly modify the association between breastfeeding and childhood cardiometabolic risk. CONCLUSION Our findings suggest breastfeeding may confer protection against adverse fat partitioning and higher triglyceride concentration among children exposed to increased glycemia in utero.
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Affiliation(s)
- Yi Ying Ong
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Wei Wei Pang
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Jonathan Y Huang
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
| | - Izzuddin M Aris
- Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
| | - Suresh Anand Sadananthan
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
| | - Mya-Thway Tint
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
| | - Wen Lun Yuan
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ling-Wei Chen
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
| | - Yiong Huak Chan
- Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Neerja Karnani
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
| | - S Sendhil Velan
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
- Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore, Singapore
| | - Marielle V Fortier
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
- Department of Diagnostic and Interventional Imaging, KK Women's and Children's Hospital, Singapore, Singapore
| | - Jonathan Choo
- Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Singapore
| | - Lieng Hsi Ling
- Department of Cardiology, National University Heart Centre, Singapore, Singapore
| | - Lynette Shek
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
- Division of Paediatric Endocrinology, Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore
| | - Kok Hian Tan
- Duke-NUS Medical School, Singapore, Singapore
- Department of Maternal Fetal Medicine, KK Women's and Children's Hospital, Singapore, Singapore
| | - Peter D Gluckman
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
- Liggins Institute, University of Auckland, Auckland, New Zealand
| | - Fabian Yap
- Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Yap-Seng Chong
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
| | - Keith M Godfrey
- MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK
| | - Mary F-F Chong
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - Shiao-Yng Chan
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
| | - Johan G Eriksson
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
- Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland
- Folkhälsan Research Center, Helsinki, Finland
| | - Mary E Wlodek
- Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore
- Department of Physiology, University of Melbourne, Melbourne, Australia
| | - Yung Seng Lee
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore.
- Division of Paediatric Endocrinology, Department of Paediatrics, Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore.
| | - Navin Michael
- Brenner Centre for Molecular Medicine, Singapore Institute for Clinical Science, Agency for Science, Technology, and Research, 30 Medical Drive, Singapore, 117609, Singapore.
- , 1E Kent Ridge Road, NUHS Tower Block Level 12, Singapore, 119228, Singapore.
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18
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Poulsen KO, Meng F, Lanfranchi E, Young JF, Stanton C, Ryan CA, Kelly AL, Sundekilde UK. Dynamic Changes in the Human Milk Metabolome Over 25 Weeks of Lactation. Front Nutr 2022; 9:917659. [PMID: 35911093 PMCID: PMC9331903 DOI: 10.3389/fnut.2022.917659] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Accepted: 06/13/2022] [Indexed: 12/11/2022] Open
Abstract
Human milk (HM) provides essential nutrition for ensuring optimal infant growth and development postpartum. Metabolomics offers insight into the dynamic composition of HM. Studies have reported the impact of lactation stage, maternal genotype, and gestational age on HM metabolome. However, the majority of the studies have considered changes within the first month of lactation or sampled with large intervals. This leaves a gap in the knowledge of progressing variation in HM composition beyond the first month of lactation. The objective of this study was to investigate whether the HM metabolome from mothers with term deliveries varies beyond 1 month of lactation, during the period in which HM is considered fully mature. Human milk samples (n = 101) from 59 mothers were collected at weeks 1-2, 3-5, 7-9, and 20-25 postpartum and analyzed using 1H nuclear magnetic resonance spectroscopy. Several metabolites varied over lactation and exhibited dynamic changes between multiple time points. Higher levels of HM oligosaccharides, cis-aconitate, O-phosphocholine, O-acetylcarnitine, gluconate, and citric acid were observed in early lactation, whereas later in lactation, levels of lactose, 3-fucosyllactose, glutamine, glutamate, and short- and medium-chain fatty acids were increased. Notably, we demonstrate that the HM metabolome is dynamic during the period of maturity.
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Affiliation(s)
- Katrine Overgaard Poulsen
- Department of Food Science, Aarhus University, Aarhus, Denmark
- Sino-Danish Center for Education and Research, Aarhus, Denmark
| | - Fanyu Meng
- School of Food and Nutritional Sciences, University College Cork, Cork, Ireland
| | - Elisa Lanfranchi
- School of Food and Nutritional Sciences, University College Cork, Cork, Ireland
- ACIB – Austrian Centre of Industrial Biotechnology, Graz, Austria
| | | | | | - C. Anthony Ryan
- Brookfield School of Medicine and Health, University College Cork, Cork, Ireland
| | - Alan L. Kelly
- School of Food and Nutritional Sciences, University College Cork, Cork, Ireland
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Liu T, Wen L, Huang S, Han TL, Zhang L, Fu H, Li J, Tong C, Qi H, Saffery R, Baker PN, Kilby MD. Comprehensive Metabolomic Profiling of Cord Blood and Placental Tissue in Surviving Monochorionic Twins Complicated by Twin-Twin Transfusion Syndrome With or Without Fetoscopic Laser Coagulation Surgery: A Retrospective Cohort Study. Front Bioeng Biotechnol 2022; 10:786755. [PMID: 35528207 PMCID: PMC9070302 DOI: 10.3389/fbioe.2022.786755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 03/16/2022] [Indexed: 11/23/2022] Open
Abstract
Objectives: To investigate metabolomic perturbations caused by twin-twin transfusion syndrome, metabolic changes associated with fetoscopic laser coagulation in both placental tissue and cord plasma, and to investigate differential metabolites pertinent to varying fetal outcomes, including hemodynamic status, birth weight, and cardiac function, of live-born babies. Methods: Placental tissue and cord plasma samples from normal term or uncomplicated preterm-born monochorionic twins and those complicated by twin-twin transfusion syndrome treated with or without fetoscopic laser coagulation were analyzed by high-performance liquid chromatography metabolomic profiling. Sixteen comparisons of different co-twin groups were performed. Partial least squares–discriminant analysis, metabolic pathway analysis, biomarker analysis, and Spearman’s correlation analysis were conducted based on differential metabolites used to determine potential biomarkers in different comparisons and metabolites that are pertinent to neonatal birth weight and left ventricular ejection fraction. Results: These metabolomic investigations showed that the cord plasma metabolome has a better performance in discriminating fetuses among different hemodynamic groups than placental tissue. The metabolic alteration of twin-twin transfusion syndrome in these two types of samples centers on fatty acid and lipid metabolism. The fetoscopic laser coagulation procedure improves the metabolomic change brought by this syndrome, making the metabolomes of the treated group less distinguishable from those of the control and preterm birth groups. Certain compounds, especially lipids and lipid-like molecules, are noted to be potential biomarkers of this morbid disease and pertinent to neonatal birth weight and ejection fraction. Conclusions: Fetoscopic laser coagulation can ameliorate the metabolomic alteration caused by twin-twin transfusion syndrome in placental tissue and cord plasma, which are involved mainly in fatty acid and lipid-like molecule metabolism. Certain lipids and lipid-like molecules are helpful in differentiating co-twins of different hemodynamic statuses and are significantly correlated with neonatal birth weight or ejection fraction.
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Affiliation(s)
- Tianjiao Liu
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Laboratory of Reproduction and Development, Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Li Wen
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Laboratory of Reproduction and Development, Ministry of Education, Chongqing Medical University, Chongqing, China
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shuai Huang
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Laboratory of Reproduction and Development, Ministry of Education, Chongqing Medical University, Chongqing, China
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ting-li Han
- International Collaborative Laboratory of Reproduction and Development, Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Lan Zhang
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Laboratory of Reproduction and Development, Ministry of Education, Chongqing Medical University, Chongqing, China
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huijia Fu
- Department of Reproduction Health and Infertility, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Junnan Li
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Laboratory of Reproduction and Development, Ministry of Education, Chongqing Medical University, Chongqing, China
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chao Tong
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- International Collaborative Laboratory of Reproduction and Development, Ministry of Education, Chongqing Medical University, Chongqing, China
- *Correspondence: Chao Tong, ; Hongbo Qi,
| | - Hongbo Qi
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Chongqing Women and Children’s Health Center, Chongqing, China
- *Correspondence: Chao Tong, ; Hongbo Qi,
| | - Richard Saffery
- Cancer, Disease and Developmental Epigenetics, Murdoch Children’s Research Institute, Parkville, VIC, Australia
- Department of Pediatrics, University of Melbourne, Parkville, VIC, Australia
| | - Philip N. Baker
- College of Life Sciences, University of Leicester, Leicester, United Kingdom
| | - Mark D. Kilby
- Institute of Metabolism and System Research, University of Birmingham, Birmingham, United Kingdom
- Fetal Medicine Centre, Birmingham Women’s and Children’s Foundation Trust, Birmingham, United Kingdom
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Peila C, Sottemano S, Cesare Marincola F, Stocchero M, Pusceddu NG, Dessì A, Baraldi E, Fanos V, Bertino E. NMR Metabonomic Profile of Preterm Human Milk in the First Month of Lactation: From Extreme to Moderate Prematurity. Foods 2022; 11:foods11030345. [PMID: 35159496 PMCID: PMC8834565 DOI: 10.3390/foods11030345] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/20/2022] [Accepted: 01/21/2022] [Indexed: 02/06/2023] Open
Abstract
Understanding the composition of human milk (HM) can provide important insights into the links between infant nutrition, health, and development. In the present work, we have longitudinally investigated the metabolome of milk from 36 women delivering preterm at different gestational ages (GA): extremely (<28 weeks GA), very (29–31 weeks GA) or moderate (32–34 weeks GA) premature. Milk samples were collected at three lactation stages: colostrum (3–6 days post-partum), transitional milk (7–15 days post-partum) and mature milk (16–26 days post-partum). Multivariate and univariate statistical data analyses were performed on the 1H NMR metabolic profiles of specimens in relation to the degree of prematurity and lactation stage. We observed a high impact of both the mother’s phenotype and lactation time on HM metabolome composition. Furthermore, statistically significant differences, although weak, were observed in terms of GA when comparing extremely and moderately preterm milk. Overall, our study provides new insights into preterm HM metabolome composition that may help to optimize feeding of preterm newborns, and thus improve the postnatal growth and later health outcomes of these fragile patients.
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Affiliation(s)
- Chiara Peila
- Neonatal Unit, University of Turin, City of Health and Science of Turin, 10126 Turin, Italy; (C.P.); (S.S.); (E.B.)
| | - Stefano Sottemano
- Neonatal Unit, University of Turin, City of Health and Science of Turin, 10126 Turin, Italy; (C.P.); (S.S.); (E.B.)
| | - Flaminia Cesare Marincola
- Department of Chemical and Geological Sciences, Cittadella Universitaria di Monserrato, University of Cagliari, Monserrato, 09042 Cagliari, Italy;
- Correspondence: (F.C.M.); (M.S.)
| | - Matteo Stocchero
- Department of Women’s and Children’s Health, University of Padova, 35128 Padova, Italy;
- Institute of Pediatric Research (IRP), Fondazione Città della Speranza, 35128 Padova, Italy
- Correspondence: (F.C.M.); (M.S.)
| | - Nicoletta Grazia Pusceddu
- Department of Chemical and Geological Sciences, Cittadella Universitaria di Monserrato, University of Cagliari, Monserrato, 09042 Cagliari, Italy;
| | - Angelica Dessì
- Neonatal Intensive Care Unit, Neonatal Pathology and Neonatal Section, Azienda University Polyclinic, University of Cagliari, 09042 Cagliari, Italy; (A.D.); (V.F.)
| | - Eugenio Baraldi
- Department of Women’s and Children’s Health, University of Padova, 35128 Padova, Italy;
- Institute of Pediatric Research (IRP), Fondazione Città della Speranza, 35128 Padova, Italy
| | - Vassilios Fanos
- Neonatal Intensive Care Unit, Neonatal Pathology and Neonatal Section, Azienda University Polyclinic, University of Cagliari, 09042 Cagliari, Italy; (A.D.); (V.F.)
| | - Enrico Bertino
- Neonatal Unit, University of Turin, City of Health and Science of Turin, 10126 Turin, Italy; (C.P.); (S.S.); (E.B.)
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21
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Odor-active volatile compounds in preterm breastmilk. Pediatr Res 2022; 91:1493-1504. [PMID: 33963300 PMCID: PMC9197798 DOI: 10.1038/s41390-021-01556-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/01/2021] [Accepted: 03/04/2021] [Indexed: 02/03/2023]
Abstract
BACKGROUND Volatile compounds in breastmilk (BM) likely influence flavor learning and, through the cephalic phase response, metabolism, and digestion. Little is known about the volatile compounds present in preterm BM. We investigated whether maternal or infant characteristics are associated with the profile of volatile compounds in preterm BM. METHODS Using solid-phase microextraction coupled with gas chromatography/mass spectrometry, we analyzed volatile compounds in 400 BM samples collected from 170 mothers of preterm infants. RESULTS Forty volatile compounds were detected, mostly fatty acids and their esters (FA and FAe), volatile organic compounds (VOCs), aldehydes, terpenoids, alcohols, and ketones. The relative concentration of most FA and FAe increased with advancing lactation and were lower in BM of most socially deprived mothers and those with gestational diabetes (p < 0.05), but medium-chain FAs were higher in colostrum compared to transitional BM (p < 0.001). Infant sex, gestational age, and size at birth were not associated with the profile of volatile compounds in preterm BM. CONCLUSIONS Sensory-active volatile FA and FAe are the major contributors to the smell of preterm BM. The associations between lactation stage, maternal characteristics, and volatile compounds, and whether differences in volatile compounds may affect feeding behavior or metabolism, requires further research. IMPACT Sensory-active volatile FAs are major contributors to the smell of preterm BM and are influenced by the lactation stage and maternal characteristics. Longitudinal analysis of volatile compounds in preterm BM found that FAs increased with advancing lactation. Colostrum had a higher concentration of medium-chain FAs compared to transitional BM and the concentration of these is associated with socioeconomic status, gestational diabetes, and ethnicity.
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22
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The Intestinal Dysbiosis of Mothers with Gestational Diabetes Mellitus (GDM) and Its Impact on the Gut Microbiota of Their Newborns. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2021; 2021:3044534. [PMID: 34603565 PMCID: PMC8481071 DOI: 10.1155/2021/3044534] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 09/11/2021] [Indexed: 02/06/2023]
Abstract
Gestational diabetes mellitus (GDM) is defined as “diagnosed as impaired glucose tolerance for the first time during pregnancy,” which can lead to adverse pregnancy outcomes and produces divergent effects on mothers and newborns. In recent years, with the continuous expansion of obese people, GDM shows an upward trend. The abundant and diverse members of the human gut microbiota exert critical roles in the maintenance of human health. Studies have shown that GDM may be associated with disordered gut microbiota in both mothers and newborns. Taking into account the potential effects on maternal and consequently neonatal health, in this review, we analyzed the available data and discussed the current knowledge about the potential relationship between GDM and intestinal dysbiosis in mothers and newborns. In addition, we also discussed the influencing factors derived from GDM mothers on the gut microbiome of their newborns, including the vertical transmission of microbiota from mothers, the alteration of milk components of GDM mothers, and using of probiotics. Hoping that new insights into the role of the gut microbiota in GDM could lead to the development of integrated strategies to prevent and treat these metabolic disorders.
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23
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Wang QY, You LH, Xiang LL, Zhu YT, Zeng Y. Current progress in metabolomics of gestational diabetes mellitus. World J Diabetes 2021; 12:1164-1186. [PMID: 34512885 PMCID: PMC8394228 DOI: 10.4239/wjd.v12.i8.1164] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 05/20/2021] [Accepted: 07/07/2021] [Indexed: 02/06/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders of pregnancy and can cause short- and long-term adverse effects in both pregnant women and their offspring. However, the etiology and pathogenesis of GDM are still unclear. As a metabolic disease, GDM is well suited to metabolomics study, which can monitor the changes in small molecular metabolites induced by maternal stimuli or perturbations in real time. The application of metabolomics in GDM can be used to discover diagnostic biomarkers, evaluate the prognosis of the disease, guide the application of diet or drugs, evaluate the curative effect, and explore the mechanism. This review provides comprehensive documentation of metabolomics research methods and techniques as well as the current progress in GDM research. We anticipate that the review will contribute to identifying gaps in the current knowledge or metabolomics technology, provide evidence-based information, and inform future research directions in GDM.
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Affiliation(s)
- Qian-Yi Wang
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 21000, Jiangsu Province, China
| | - Liang-Hui You
- Nanjing Maternity and Child Health Care Institute, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
| | - Lan-Lan Xiang
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
| | - Yi-Tian Zhu
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
| | - Yu Zeng
- Department of Clinical Laboratory, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing 21000, Jiangsu Province, China
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Boudry G, Charton E, Le Huerou-Luron I, Ferret-Bernard S, Le Gall S, Even S, Blat S. The Relationship Between Breast Milk Components and the Infant Gut Microbiota. Front Nutr 2021; 8:629740. [PMID: 33829032 PMCID: PMC8019723 DOI: 10.3389/fnut.2021.629740] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Accepted: 02/16/2021] [Indexed: 12/12/2022] Open
Abstract
The assembly of the newborn's gut microbiota during the first months of life is an orchestrated process resulting in specialized microbial ecosystems in the different gut compartments. This process is highly dependent upon environmental factors, and many evidences suggest that early bacterial gut colonization has long-term consequences on host digestive and immune homeostasis but also metabolism and behavior. The early life period is therefore a "window of opportunity" to program health through microbiota modulation. However, the implementation of this promising strategy requires an in-depth understanding of the mechanisms governing gut microbiota assembly. Breastfeeding has been associated with a healthy microbiota in infants. Human milk is a complex food matrix, with numerous components that potentially influence the infant microbiota composition, either by enhancing specific bacteria growth or by limiting the growth of others. The objective of this review is to describe human milk composition and to discuss the established or purported roles of human milk components upon gut microbiota establishment. Finally, the impact of maternal diet on human milk composition is reviewed to assess how maternal diet could be a simple and efficient approach to shape the infant gut microbiota.
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Affiliation(s)
- Gaëlle Boudry
- Institut NuMeCan, INRAE, INSERM, Univ Rennes, Saint-Gilles, France
| | - Elise Charton
- Institut NuMeCan, INRAE, INSERM, Univ Rennes, Saint-Gilles, France
- UMR STLO INRAE, Institut Agro, Rennes, France
| | | | | | - Sophie Le Gall
- INRAE, UR BIA, Nantes, France
- INRAE, BIBS facility, Nantes, France
| | | | - Sophie Blat
- Institut NuMeCan, INRAE, INSERM, Univ Rennes, Saint-Gilles, France
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25
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Wu Y, Yu J, Liu X, Wang W, Chen Z, Qiao J, Liu X, Jin H, Li X, Wen L, Tian J, Saffery R, Kilby MD, Qi H, Tong C, Baker PN. Gestational diabetes mellitus-associated changes in the breast milk metabolome alters the neonatal growth trajectory. Clin Nutr 2021; 40:4043-4054. [PMID: 33640207 DOI: 10.1016/j.clnu.2021.02.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 01/22/2021] [Accepted: 02/08/2021] [Indexed: 02/02/2023]
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is the most common metabolic disturbance during pregnancy and leads to an altered metabolic profile of human breast milk (HBM). The association between HBM metabolites and neonatal growth in GDM pregnancies has not been thoroughly investigated. AIMS The primary aim was to quantify differences in the HBM metabolome between normal and GDM pregnancies. The secondary aim was to identify metabolites associated with neonatal growth during the first year postpartum. METHODS In the present study, mothers intending to exclusively breastfeed (BF) and their newborns (mother-infant pairs) were recruited at delivery (n = 129 normal pregnancies and n = 98 GDM pregnancies). HBM samples (colostrum, transition milk, and mature milk) from mothers with normal pregnancies (n = 50) and GDM pregnancies (n = 50) were subjected to metabolomic profiling via liquid chromatography tandem mass spectrometry (LC-MS/MS). Receiver operating characteristic (ROC) analysis revealed the metabolomic fingerprints of GDM-associated mature HBM. Correlations between metabolites and neonatal body weight gain (BWG) were evaluated by Spearman correlation analysis. RESULTS In total, 620 metabolites were identified in each HBM sample; 253 compounds had the same variation patterns, whereas 38 compounds had significantly different pattern transitions between the GDM and normal groups. Moreover, 12, 49 and 28 metabolites exhibited significant differences in the 3 milk types between the 2 groups. Twenty-two metabolites were confirmed by ROC analysis as metabolomic fingerprints in the mature BM of GDM patients. Ten compounds were significantly negatively correlated with neonatal growth, and only 2 unsaturated lipids (eicosatrienoic acid (FA 20:3) and lysophosphatidylcholine (LysoPC) (22:6)) were positively correlated with neonatal BWG. CONCLUSIONS GDM is associated with alterations in the HBM metabolome. Only a small subset of compounds are associated with neonatal body weight (BW). TRIAL REGISTRATION ChiCTR-ROC-17011508. Prospectively registered on 26 May 2017 (http://www.chictr.org.cn/listbycreater.aspx).
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Affiliation(s)
- Yue Wu
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China
| | - Jiaxiao Yu
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China
| | - Xiyao Liu
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China
| | - Wenling Wang
- Department of Obstetrics, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou, Gansu, 730050, China
| | - Zhi Chen
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China
| | - Juan Qiao
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China
| | - Xiaohui Liu
- National Protein Science Technology Center, Tsinghua University, Beijing, 100084, China
| | - Huili Jin
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China
| | - Xin Li
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China
| | - Li Wen
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China
| | - Jing Tian
- Department of Obstetrics and Gynecology, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China
| | - Richard Saffery
- International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China; Cancer, Disease and Developmental Epigenetics, Murdoch Children's Research Institute, Parkville, Victoria, 3052, Australia
| | - Mark D Kilby
- College of Medical & Dental Sciences, University of Birmingham, B15 2TT, UK; Fetal Medicine Centre, Birmingham Women's & Children's Foundation Trust, Edgbaston, Birmingham, B15 2TG, UK
| | - Hongbo Qi
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
| | - Chao Tong
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, China; International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
| | - Philip N Baker
- International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China; College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK
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The Metabolomic Analysis of Human Milk Offers Unique Insights into Potential Child Health Benefits. Curr Nutr Rep 2021; 10:12-29. [PMID: 33555534 DOI: 10.1007/s13668-020-00345-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2020] [Indexed: 10/22/2022]
Abstract
PURPOSE OF REVIEW Human milk is the gold standard of infant nutrition. The milk changes throughout lactation and is tailored for the infant providing the nutrients, minerals and vitamins necessary for supporting healthy infant growth. Human milk also contains low molecular weight compounds (metabolites) possibly eliciting important bioactivity. Metabolomics is the study of these metabolites. The purpose of this review was to examine recent metabolomics studies and cohort studies on human milk to assess the impact of human milk metabolomic analyses combined with investigations of infant growth and development. RECENT FINDINGS The metabolite profile of human milk varies among other factors according to lactation stage, gestation at birth, and maternal genes, diet and disease state. Few studies investigate how these variations impact infant growth and development. Several time-related factors affecting human milk metabolome are potentially ubiquitous among mothers, although maternal-related factors are heavily confounded, which complicates studies of metabolite abundancies and variabilities and further possibilities of observing cause and effect in infants.
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Álvarez D, Muñoz Y, Ortiz M, Maliqueo M, Chouinard-Watkins R, Valenzuela R. Impact of Maternal Obesity on the Metabolism and Bioavailability of Polyunsaturated Fatty Acids during Pregnancy and Breastfeeding. Nutrients 2020; 13:nu13010019. [PMID: 33374585 PMCID: PMC7822469 DOI: 10.3390/nu13010019] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/09/2020] [Accepted: 12/16/2020] [Indexed: 12/13/2022] Open
Abstract
Prenatal and postnatal development are closely related to healthy maternal conditions that allow for the provision of all nutritional requirements to the offspring. In this regard, an appropriate supply of fatty acids (FA), mainly n-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFA), is crucial to ensure a normal development, because they are an integral part of cell membranes and participate in the synthesis of bioactive molecules that regulate multiple signaling pathways. On the other hand, maternal obesity and excessive gestational weight gain affect FA supply to the fetus and neonate, altering placental nutrient transfer, as well as the production and composition of breast milk during lactation. In this regard, maternal obesity modifies FA profile, resulting in low n-3 and elevated n-6 PUFA levels in maternal and fetal circulation during pregnancy, as well as in breast milk during lactation. These modifications are associated with a pro-inflammatory state and oxidative stress with short and long-term consequences in different organs of the fetus and neonate, including in the liver, brain, skeletal muscle, and adipose tissue. Altogether, these changes confer to the offspring a higher risk of developing obesity and its complications, as well as neuropsychiatric disorders, asthma, and cancer. Considering the consequences of an abnormal FA supply to offspring induced by maternal obesity, we aimed to review the effects of obesity on the metabolism and bioavailability of FA during pregnancy and breastfeeding, with an emphasis on LCPUFA homeostasis.
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Affiliation(s)
- Daniela Álvarez
- Endocrinology and Metabolism Laboratory, West Division, Faculty of Medicine, University of Chile, Santiago 8380000, Chile; (D.Á.); (Y.M.); (M.O.); (M.M.)
| | - Yasna Muñoz
- Endocrinology and Metabolism Laboratory, West Division, Faculty of Medicine, University of Chile, Santiago 8380000, Chile; (D.Á.); (Y.M.); (M.O.); (M.M.)
| | - Macarena Ortiz
- Endocrinology and Metabolism Laboratory, West Division, Faculty of Medicine, University of Chile, Santiago 8380000, Chile; (D.Á.); (Y.M.); (M.O.); (M.M.)
| | - Manuel Maliqueo
- Endocrinology and Metabolism Laboratory, West Division, Faculty of Medicine, University of Chile, Santiago 8380000, Chile; (D.Á.); (Y.M.); (M.O.); (M.M.)
| | - Raphaël Chouinard-Watkins
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S1A8, Canada;
| | - Rodrigo Valenzuela
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5S1A8, Canada;
- Nutrition Department, Faculty of Medicine, University of Chile, Santiago 8380000, Chile
- Correspondence: or ; Tel.: +56-2-9786746
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Bardanzellu F, Puddu M, Fanos V. The Human Breast Milk Metabolome in Preeclampsia, Gestational Diabetes, and Intrauterine Growth Restriction: Implications for Child Growth and Development. J Pediatr 2020; 221S:S20-S28. [PMID: 32482230 DOI: 10.1016/j.jpeds.2020.01.049] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 01/16/2020] [Accepted: 01/21/2020] [Indexed: 02/07/2023]
Affiliation(s)
- Flaminia Bardanzellu
- Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU University of Cagliari, Italy.
| | - Melania Puddu
- Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU University of Cagliari, Italy
| | - Vassilios Fanos
- Neonatal Intensive Care Unit, Department of Surgical Sciences, AOU University of Cagliari, Italy
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29
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Influence of Diabetes during Pregnancy on Human Milk Composition. Nutrients 2020; 12:nu12010185. [PMID: 31936574 PMCID: PMC7019231 DOI: 10.3390/nu12010185] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 01/03/2020] [Accepted: 01/07/2020] [Indexed: 12/13/2022] Open
Abstract
Human milk (HM) is a unique nourishment believed to contain biological factors contributing to both short and long-term benefits. Considering that a mother's own milk is often considered the first choice for nutrition of neonates, an aspect of increased interest is the possible effect of diabetes on the mammary gland and therefore on breast milk composition. This article aims to review the published literature on this topic, and to offer additional insights on the role of this disease on the composition of HM. This review was performed by searching the MEDLINE, EMBASE, CINHAL and Cochrane Library databases. A total of 50 articles were selected, focused specifically on one of the two types of diabetes: gestational diabetes mellitus (21 studies) and insulin-dependent diabetes mellitus (8 studies). Overall, the findings from the literature suggest that diabetes can alter the composition of HM. Nevertheless, the studies in this field are scarce, and the related protocols present some limitations, e.g., evaluating the variability of just a few specific milk biochemical markers in association with this syndrome.
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