| Wieruszeski J et al., 1985, France | Glycomics | FAB-MS and LC-MS. | Not reported | Not reported | Identified two novel oligosaccharides (lacto-N-sialylated fucopentaose I and II), likely reflecting mammary glycosyltransferase activity during lactation. |
| Grönberg G et al., 1990, Sweden | Glycomics | SEC-IEC-HPLC-NMR. | Not reported | Not reported | Identified three novel disialylated oligosaccharides in human milk. |
| Finke B et al., 1999, Germany | Glycomics | MALDI-MS. | Not reported | Not reported | Detected acidic and neutral oligosaccharides, including complex neutral structures of up to 35 monosaccharide units. |
| Chaturvedi P et al., 2001, USA | Glycomics | rpHPLC. | Not reported | Transitional and mature milk from healthy mothers | Oligosaccharides varied in quality and quantity during lactation, with higher fucosylated and sialylated forms early on, decreasing after 26 weeks postpartum; low concentrations may inhibit pathogen binding. |
| Niñonuevo M et al., 2008, USA | Glycomics | HPLC-Chip/TOF-MS. | Not reported | Colostrum, transitional and mature milk from healthy mothers | LNT, LNnT and LNFP I/V were most abundant and stable throughout lactation, with higher fucosylated vs. sialylated HMOs from day 1 to 71, potentially influenced by maternal or infant factors. |
| Albrecht S et al., 2010, Netherlands | Glycomics | Off-line CE-LIF, Online CE-LIF-ESI-MS. | Not reported | Not reported | Detected major peaks of SL, DS-LNT, S-LNT, FL, LNDFH, LNT, LNFP I/III, LNFP II, and DF-L. |
| Dallas D et al., 2011, USA | Glycomics | HPLC-Chip/TOF-MS | In-house Postgres relational database | Mature milk in healthy mothers. | Identified 52 N-linked glycans (84% fucosylated, 47% sialylated); breast milk provides Neu5Ac, important for neonatal brain development. |
| Xu G et al., 2017, USA | Glycomics | HPLC y UPLC/QqQ-MS. | Not reported | Transitional and mature milk from healthy mothers | Most oligosaccharides decreased over lactation, while fucosylation increased; secretor mothers had higher total and fucosylated HMOs. |
| Ma L et al., 2018, China | Glycomics | LC−MRM−MS | Not reported | Mature milk from healthy mothers. | Observed high variability in BMH concentrations, influenced by genetic and ethnic factors and secretor/blood group status |
| Nijman et al., 2018, USA | Glycomics | nano-LC-chip/Q-TOF MS | In-house HMOS database | Colostrum and mature milk from healthy mothers | Identified key health-related oligosaccharides (sialylated, α1,2-fucosylated, LNT), which declined from day 3 to 42. |
| Zhang W et al., 2019, China | Glycomics | LC–MS/MS MRM | Not reported | Mature milk from healthy mothers | Identified 12 oligosaccharides (including isomeric pairs); variations linked to donor ethnicity and timing of collection. |
| Yan J et al., 2019, China | Glycomics | ERLIC−MS/MS | Not reported | Transitional and mature milk from healthy mothers | Oligosaccharides declined during lactation, with neutral forms decreasing faster than sialylated ones. |
| Gao X et al., 2019, China | Glycomics | MALDI-TOF-MS | Not reported | Mature milk from healthy mothers | Sialylated HMOs (SHMO) reduced leukocyte adhesion; 3′-SL had antiviral effects; 2′-FL and 3′-SL improved memory and learning in infants. |
| Tonon M, 2019, Brazil | Glycomics | LC-MS | Not reported | Transitional and mature milk from healthy mothers and mothers with allergic disease | Higher 2′-FL in mothers of girls, higher LNH in mothers of boys; allergic mothers had higher DFpLNnH; secretor phenotype linked to allergy incidence. |
| Mernie E, 2019, Taiwan | Glycomics | TLC MALDI-MS | Not reported | Colostrum, transitional and mature milk from healthy mothers | Identified 25 neutral HMOs; early milk richer in large oligosaccharides; no sialylated HMOs detected. |
| Wang M et al., 2020, China | Glycomics | HPLC-ESI-MS | Not reported | Colostrum, transitional and mature milk from healthy mothers | Secretor phenotype influenced by ethnicity; multiparity associated with higher LNT and LNnT, lower 3′FL. |
| Ferreira A et al., 2020, Brazil | Glycomics | HPLC-FL | In-house HMOS database | Colostrum, transition milk and mature milk from healthy mothers | Secretor pattern more common in Latin women; multiparity linked to higher LNT and LNnT, lower 3′FL; mechanism unclear. |
| Siziba L, 2021, Germany | Glycomics | LC-MS2 | Not reported | Mature milk from healthy mothers | Oligosaccharides decreased at 6–12 months; secretor mothers produced more; early FUT-dependent HMO exposure may be beneficial. |
| Siziba L, 2022, Germany | Glycomics | LC-ESI-MS | Not reported | Mature milk from healthy mothers | No association found between HMOs and atopic dermatitis at 1–2 years; identified several key HMOs. |
| Xun Y et al., 2022, China | Glycomics | UPLC-MS | Not reported | Mature milk from healthy mothers | Multiparous mothers had higher LNT and LNnT, lower 3FL, regardless of secretor status; explained by FUT2/FUT3 gene expression. |
| Vinjamuri A, 2022, USA | Glycomics | nano–HPLC–time of flight (TOF)–MS | Not reported | Mature milk in healthy mothers | HMO abundance decreased in first 6 months; α(1,2)-fucosylated species varied most; secretor mothers had higher 2′FL and LDFT, non-secretors had higher α(1,3)/α(1,4)-fucosylated HMOs. |
| Donatella Fortunato et al., 2003, Italy | Proteomics | MALDI-TOF-MS | PROSITE database | Colostrum from healthy mothers | Identified 107 proteins, mainly lactadherin, butyrophilin, lactoferrin, adipophilin, and carbonic anhydrase. |
| Gianluca Picariello et al., 2008, Italy | Proteomics | MALDI-TOF-MS | Databases from the National Center for Biotechnology Information (nrNCBI) | Colostrum from healthy mothers. | Identified 32 glycoproteins with 63 N-glycosylation sites, mainly polymeric Ig receptor, lactoferrin, IgA2 chain, serum albumin, and caseins. |
| Liao et al., 2011, USA | Proteomics | LC-MS/MS | Uniprot database | Colostrum, transition milk and mature milk from healthy mothers | Identified 115 proteins; early lactation showed higher expression of R-1-antitrypsin, carbonic anhydrase, chordin-like protein 2, and galectin-3 binding protein; later lactation showed higher fatty acid-binding protein, lysozyme C, and monocyte differentiation antigen. |
| Liao et al., 2011, USA | Proteomics | LC-MS/MS | Uniprot database | Colostrum, transition milk and mature milk from healthy mothers. | Identified 191 MFGM proteins: 21.5% involved in energy metabolism, 8.4% in growth, 19.9% in immune functions; novel proteins included polymeric immunoglobulin receptor and HLA antigens. |
| Liao et al., 2011, USA | Proteomics | LC-MS/MS | Not reported | Colostrum, transition milk and mature milk from healthy mothers. | Identified 82 proteins (18 specific to casein fraction) grouped into nine functional categories, highlighting immune response (28%), metabolism (22%), and cell communication (18.3%); casein fraction lacked proteins regulating nucleic acid metabolism. |
| Smilowitz et al., 2013, USA | Proteomics | nanoLC-Chip/TOF MS | Not reported | Mature milk from healthy mothers and mothers with gestational diabetes mellitus (GDM) | Compared to controls, GDM milk had 63.6% less sIgA, 45% more lactoferrin N-glycans, 36–72% more fucosylated and sialylated lactoferrin N-glycans, and 32–43% less sIgA and mannose, fucose, and sialic acid N-glycans. |
| Mandal et al., 2014, India | Proteomics | MALDI-TOF-MS | NCBI and SwissProt databases | Mature milk from healthy mothers | Identified 24 peptides with antimicrobial, antioxidant, and growth-stimulating activities; lactoferrin- and casein-derived peptides showed antibacterial, proliferative, and antioxidant effects. |
| Dmitry Grapov et al., 2014, USA | Proteomics | LC/MS/MS | Uniprot and Repository of Adventitious Proteins databases | Colostrum from GDM and non-GDM mothers. | Identified 27 proteins, with 10 differing between GDM and controls; GDM milk had more apolipoprotein A1, heavy chain Ig V–II region, and prostatin. |
| Kasper A. Hettinga et al., 2015, USA | Proteomics | LC/MS/MS | Uniprot database | Mature milk from allergic and non-allergic mothers | Identified 357 proteins in allergic mothers and 355 in non-allergic mothers; 9 were unique to allergic and 7 to non-allergic mothers. |
| Lingli Chen et al., 2018, USA | Proteomics | LC-MS/MS | UniProt database | Colostrum from hypothyroid and non-hypothyroid mothers | Identified 44 proteins; 29 related to energy metabolism and cell structure decreased in hypothyroid mothers, while 15 immune-related proteins increased. |
| Laura Di Francesco et al., 2018, Italy | Proteomics | MALDI-TOF-MS | Not reported | Colostrum and mature milk from healthy mothers | Early milk showed higher signals for peptides, proteins, and vitamins compared to mature milk, with a higher proportion of proteins <10 kDa in colostrum. |
| Jing Zhu et al., 2019, Netherlands | Proteomics | LC-MS/MS | UniProt database | Mature milk from healthy mothers | Identified 109 non-human peptides grouped into 36 proteins, mainly bovine caseins and β-lactoglobulin, likely from maternal diet. |
| Lina Zhang et al., 2019, China | Proteomics | LC-MS/MS | UniProt database | Mature milk from healthy mothers | Identified 693 proteins, most abundant were lactoferrin, serum albumin, polymeric Ig receptor, macrophage mannose receptor 1, and bile salt-activated lipase; 34 proteins varied by geography and ethnicity. |
| Jing Zhu et al., 2020, Netherlands | Proteomics | LC/MS/MS | Uniprot Swiss-Prot database | Colostrum, transition milk and mature milk from healthy mothers. | Identified 1,320 proteins and 2,096 peptides, adding 60 novel proteins to the human milk peptidome; 65% of peptides belonged to caseins, followed by osteopontin. |
| Kelly A. Dingess et al., 2021, Netherlands | Proteomics | LC-MS/MS | UniProt database, Byonic database | Transitional and mature milk from healthy mothers | Observed decreased phosphosite occupancy and O-glycosylation of β-casein during lactation, which may influence calcium binding; O-glycans localized to the β-casein C-terminal. |
| Vaksha Patel et al., 2021, England | Proteomics | LC-MS/MS | UniProt database | Mature milk from healthy mothers | Identified 136 previously unreported proteins, 21 linked to calcium metabolism; main proteins included serum albumin, lysozyme, lactotransferrin, and lactalbumin; FAM20A detected in all samples. |
| Juanjuan Guo et al., 2022, China | Proteomics | LC-MS/MS | Uniprot Swiss-Prot database, Byonic database | Colostrum and mature milk from healthy mothers and mothers with COVID-19 | COVID-19 colostrum had 4.1× higher total protein, 3.9× lower caseins, and 7.2× higher whey proteins compared to controls; differences diminished by 1 month postpartum. |
| Marincola et al., 2012, Italy | Metabolomics | H-NRM and GC-MS | Human Metabolome Database | Transitional and mature milk from healthy mothers with preterm newborn | Observed transient changes in carbohydrate composition (increased lactose) during the first 3 weeks of life; fatty acid profile was dominated by oleic and linoleic acids; no differences between late and extreme preterm infants. |
| Villaseñor A, 2014, United Kingdom | Metabolomics | LC-MS and GC-MS | KEGG, METLIN, and LipidMAPS databases | Colostrum, transitional and mature milk from healthy mothers | Identified previously undescribed metabolites, including fatty esters, aldehydes, ceramides, PG and PA; also detected amino acids, organic acids, fatty acids, sugars, TCA intermediates, cholesterol, and disaccharides across lactation. |
| Li K et al., 2018, China | Metabolomics | UPLC-Q-TOF-MS | 2002 Chinese food composition database | Colostrum, transitional milk and mature milk from healthy mothers | Identified 84 metabolites, including glycerolipids, glycerophospholipids, sphingolipids, vitamins, nucleotides, amino acids, dipeptides, steroid hormones, and others; tryptophan, histidine, and glycerolipids increased over lactation. |
| Gaitan A et al., 2018, USA | Metabolomics | LC-MS | Not reported | Transitional milk and mature milk from healthy mothers | Identified ARA as main metabolite; DHA, a DHEA precursor, may support infant brain and cognitive development; OEA predominated over PEA in mature milk; glycerol group accounted for > 90% of PG glycerols. |
| Wen L et al., 2019, China | Metabolomics | GC-MS-NMR | HMDB and NIST database | Colostrum, transitional milk and mature milk from healthy mothers and women with gestational diabetes mellitus. | Demonstrated dynamic milk metabolome over early lactation; colostrum enriched in fatty amino acids, mature milk enriched in saturated/unsaturated fatty acids and TCA intermediates; 28 metabolites differed in GDM mothers. |
| Isganaitis E et al., 2019, USA | Metabolomics | LC-GC-MS | Kyoto Encyclopedia of Genes and Genomes | Mature milk, from obese and healthy mothers. | Found 20 metabolites that were elevated in obese mothers’ milk; adenine positively correlated with maternal BMI and infant adiposity; suggested potential milk-mediated mechanisms for obesity transmission. |
| Arias-Borrego A, 2021, Spain | Metabolomics | UHPLC-MS | METLIN and HMDB database | Colostrum, from iodine-deficient mothers. | Identified 31 altered metabolites (e.g., glycerophospholipids) in iodine-deficient mothers, distinguishing them from normal, even with normal urine iodine levels; alterations may impact neurodevelopment. |
| Wu Y et al., 2021, China | Metabolomics | LC-MS/MS | Human Metabolome Database | Colostrum, transitional and mature milk from healthy mothers and mothers with diabetes mellitus | Identified 620 components — including keto acids, carboxylated acids, glycerophospholipids, fatty acids, organic compounds, nucleotides, and benzenoids — in healthy and diabetic mothers over the course of lactation. |
| Li M, 2022, China | Metabolomics | GC-TOF-MS | LECO-Fiehn Rtx5 database | Colostrum and mature milk from healthy mothers | Characterised 159 metabolites in colostrum and mature milk; 17 up-regulated and 55 down-regulated in colostrum; observed pathway differences in amino acid, lipid, inositol phosphate, glutathione, and galactose metabolism. |
| Zhang W, 2022, China | Metabolomics | HPLC-MS/MS | In-house MS2 database | Mature milk from healthy mothers | Identified two metabolites; PC1 associated with linoleic and α-linolenic acid derivatives; PC2 associated with phospholipids including glycerophospholipids and sphingomyelins, which may facilitate allergen absorption. |
| Koulman A, 2019, England | Lipidomics | LESA-MS and CID | Not reported | Transitional milk and mature milk of healthy mothers | LESA-MS revealed that mammary glands within an individual can produce distinct triacylglycerol (TG) profiles; also identified very long-chain fatty acids (C26:0 and C26:1), not previously reported in human milk. |
| George A et al., 2020, Australia | Lipidomics | LC-IM-MS | LIPID MAPS structure database, Australian Food Composition Database | Mature milk from healthy mothers with preterm newborn | Identified 205 TAGs, including 98 novel species; observed high levels of odd-chain fatty acids likely from diet; TAGs varied across the day, lactation stage, and between breasts; fish intake linked to DHA levels. |
| Xu L et al., 2020, China | Lipidomics | LC-MS/MS | Not reported | Colostrum from healthy mothers with term newborn and preterm newborn | Found significant differences in 16 lipid subclasses between term and preterm milk; preterm milk had higher phosphatidylethanolamine and phosphatidylcholine but lower diacylglycerol and ceramide; dysregulated lipids were related to metabolism, neuronal signaling, and LXR/RXR pathways. |
| Hewelt-Belka W et al., 2020, Poland | Lipidomics | RPLC-Q-TOF-MS | LIPID MAPS Structure Database (LMSD) | Colostrum, transitional milk and mature milk from healthy mothers | Mature milk contained 76 lipids at higher levels compared to colostrum, which had 40 lipids elevated; colostrum was richer in TGs with > 20 carbons, ether glycerophospholipids, and LC-PUFAs like eicosatetraenoic acid. |
| Song S et al., 2021, China | Lipidomics | LC-MS-MS | LIPID MAPS Structure Database | Colostrum, transitional milk and mature milk from healthy mothers | Phosphatidylcholine was the most abundant lipid; plasmalogens and polyunsaturated phospholipids decreased over lactation; early changes included declines in phosphatidylcholines and phosphatidylglycerols and increases in lysophosphatidylethanolamines and lysophosphatidylcholines; lipid profile stabilized after ~200 days. |
| Alexandre-Gouabau M et al., 2019, France | Glycomics, lipidomics, metabolomics, proteomics | LC-HR-MS | LIPID Metabolites and Pathways Strategy Database (LipidMaps), Human Metabolite Data base (HMDB), Biofluid Metabolites Database (MetLin), Milk Metabolome Database (MCDB) | Mature milk from healthy mothers | Identified biomarkers (arginine, tyrosine, hydroxybutyrate, niacinamide, choline, and lacto-N-fucopentaose I) predictive of infant weight gain; arginine, tyrosine, medium-chain fatty acids, triglycerides, and phospholipids were associated with faster growth, whereas oleic acid, plasmalogens, ceramide, and very long-chain TGs were associated with slower growth. Non-secretor mothers had very low 2′-FL, while secretors had high 2′-FL levels. |
| McJarrow P et al., 2019, New Zealand | Glycomic, lipidomic | HPLC-MS | Not reported | Transitional milk and mature milk from healthy mothers | Found higher concentrations of HMOs and ganglioside GD3 in transitional milk compared to mature milk, except for 3-fucosyllactose and GM3, which were higher in mature milk. |
