Milk fat globule membrane: composition, production and its potential as encapsulant for bioactives and probiotics

Figures & data

Figure 1. The structure of the milk fat globule membrane (MFGM) (A). molecular structure of MFGM phospholipids (B).

Table 1. Healthful properties of MFGM lipids, proteins, and carbohydrates.

Compositions		Healthful properties	References
Lipids	Sphingomyelin (SM)	Involve in regulation of cell growth, differentiation and apoptosis, cholesterol distribution and homeostasis	Fernández-Arroyo et al. (2019)
		Reduce cholesterol absorption	Vors et al. (2020)
		Promote cognitive development	(Ortega-Anaya and Jiménez-Flores (2019)
		Promote infant intestinal maturation	Motouri et al. (2003) and Ortega-Anaya and Jiménez-Flores (2019)
		Promote intestinal lipid metabolism and prevent obesity	Norris et al. (2017) and Weiland et al. (2016)
		Prevent and suppress colon cancer	Hertervig et al. (1997)
		Protect skin cells from ultraviolet radiation	Russell et al. (2010)
	Phosphatidylethanolamine (PE)	Regulate lipid droplet fusion in mammary epithelial cells	Cohen et al. (2017)
		Alter brain phospholipid and metabolism; promote reflex development	Moukarzel et al. (2018)
	Phosphatidylcholine (PC)	Participate in lipoprotein secretion	Lee et al. (2018)
		Anti-obesity	Li et al. (2020)
		Repair toxicity of toxic chemicals to the liver	Kidd (2000)
		Protect gastrointestinal mucosa against toxic attack	Anand et al. (1999)
		Reduce incidence of enterocolitis	Carlson et al. (1998)
		Improve symptoms of leukocyte-mediated acute arthritis	Hartmann et al. (2009)
	Phosphatidylinositol (PI)	Produce free inositol by hydrolysis in vivo	Liu et al. (2016)
		Promote cholesterol transport and excretion	Burgess et al. (2003)
	Phosphatidylserine (PS)	Improve declining memory and have positive impact on Alzheimer patients	Hashioka et al. (2004)
		Regulate apoptosis; DHA carrier	Kimura and Kim (2013) and Vance (2008)
		Improve exercise capacity of exercising humans	Kingsley (2006)
	Cholesterol	Maintain structure of lipid rafts	Hussain et al. (2019)
		Substrate for biles, vitamin D, hormones and oxysterols	Koletzko (2016)
Proteins	MUC 1	Protective effect against SARS-CoV-2	Lai et al. (2021)
		Prevent attachment of microorganisms	Parker et al. (2010)
		Intercellular communication; anti-inflammation and anti-cancer	Dhanisha et al. (2018), Guo et al. (2020), and Lee et al. (2018)
	XDH/XO	Regulate milk fat secretion	Al-Shehri, Duley, and Bansal (2020)
		Immunity; anti-bacterial; anti-inflammatory	Brink and Lönnerdal (2020) and Martin et al. (2004)
		Inhibitory effect and lower the serum uric acid content	Lastra et al. (2017) and Manoni et al. (2020)
	PAS 6/7	Protect the intestine from rotavirus infection	Kvistgaard et al. (2004)
		Role in epithelialization, cell polarization, cell movement and rearrangement, neurite growth and synaptic activity of the central nervous system	Lee et al. (2018)
		Prevent bacterial infection	Bu et al. (2007) and Fong, Norris, and Macgibbon (2007)
	BTN	Regulate MFG secretion; proliferation and metabolism of T-cell	Kvistgaard et al. (2004) and Lee et al. (2018)
		Immunity; intercellular communication	Han et al. (2020) and Lee et al. (2018)
		Prevent or suppress experimental human multiple sclerosis	Dewettinck et al. (2008)
	ADPH	Participate in fatty acids, triglycerides uptake and transport	Kvistgaard et al. (2004) and Lee et al. (2018)
		Regulate accumulation or hydrolysis of fat; anti-bacterial	Bickel, Tansey, and Welte (2009) and Fong, Norris, and Macgibbon (2007)
	FABP	Cell growth inhibitor; regulate lipid metabolism	Kvistgaard et al. (2004) and Lee et al. (2018)
		Anti-breast cancer; anti-bacterial	Bickel, Tansey, and Welte (2009), Fong, Norris, and Macgibbon (2007), Manoni et al. (2020), and Novakovic et al. (2015)
Carbohydrates	Sialic acid	Promote brain development of infants	Harris et al. (2020), Sukhov et al. (2020), and Tang et al. (2021)
	Gangliosides	Bind to cholera virus, protect newborns from infection	Bint E Naser et al. (2021)

Table 2. MFGM Brands and components on the market.

Brand	Product	Protein (%)	Lipid (%)	Phospholipid (%)	Ash (%)	Carbohydrate (%)	Moisture (%)	Cholesterol (mg/100g)	PE (%)	PC (%)	PI (%)	PS (%)	S M (%)	Gangliosides (%)	Sialic acid (%)	Ceramides (%)
HILMAR	Hilmar^TM 7500 Milk Fat Globule Membrane Enriched Whey Protein Concentrate	72.0	15.0	6.5	3.0	3.0 ∼ 6.0	4.5	660	39.9	25.7	5.4	1.1	16.7	—	—	—
LECICO	LIPAMINE M 20 Milk Phospholipid Concentrate	40.0 ∼ 60.0	—	16.0 ∼ 21.0	—	—	5.0	—	3.0 ∼ 5.5	4.0 ∼ 5.5	0.5 ∼ 1.8	1.0 ∼ 2.5	3.0 ∼ 5.0	0.3 ∼ 0.6	—	1.5 ∼ 2.5
Arla	LACPRODAN^® MFGM-10 Whey Protein Concentrate	73 ± 3	16 ± 2	7 ± 1	3.0	3.0	6.0	—	1.9	1.9	0.5	0.9	1.8	—	2	—
nzmp	SureStart^TM Lipid 100	31.0	19.8	7.6	6.2	39.8	3.2	118	31.8	26.9	8.3	11.8	21.0	0.35	—	—
	SureStart^TM Lipid 70	72	20	5	—	3	—	—	—	—	—	—	—	—	—	—
	WHEY PROREIN CONCENTRATE 392	80.0	7.5	—	3.5	12.0	5.0	—	—	—	—	—	—	—	—	—

Figure 2. Isolation and purification methods of MFGM.

Figure 3. Liposomal structures for encapsulation of bioactive substances (A). TEM analysis of strains grown in AOAC medium (B). (a) L. rhamnosus GG wild-type (LGG WT); (b) welE mutant CMPG5351 (Lebeer et al. 2009). TEM analysis of LGG grown after 3 h of incubation (C). (a) in MRS broth; (b) MRS broth with 5 g/L MFGM-10; (c) 0.5% bile in MRS broth; (d) 0.5% bile in MRS broth with 5 g/L of MFGM-10 (Zhang et al. 2020). TEM analysis of the effect of MFGM phospholipids in the cell morphology (D). (b) and (d) have MFGM phospholipids adhered to L. delbrueckii and L. plantarum obviously (the arrows indicate accumulation of MFGM phospholipids on the cell wall) (Ortega-Anaya, Marciniak, and Jiménez-Flores 2021).

Table 3. Use of MFGM for encapsulation of bioactive substances.

Bioactive substances	Materials	Preparation of liposomes	Encapsulation Efficiency (EE%)	Key findings	References
Vitamin C /Vitamin E	MFGM (source: buttermilk powder)	phospholipids, cholesterol and vitamin E were mixed in 5:1:1 (w/w/w) at 45 °C, and 0.125M vitamin C were prepared with Tris-buffer solution (pH = 7.4). Liposomes were prepared by using the SC-CO2 assisted Vent-RESS system. Due to the Bernoulli effect, Vitamin C solution enters the educator and collides with the CO2 stream. After stabilization, phospholipid molecules were assembled into bilayer liposomes.	Vitamin E: 77% Vitamin C: 65%	MFGM phospholipids mostly produced ULV-type morphology that are more suitable to encapsulate water-soluble compounds. The heat stability of MFGM liposomes was higher than that of SFPC liposomes, that can be attributed toward the presence of saturated phospholipids with high Tm.	Jash, Ubeyitogullari, and Rizvi (2020)
β-carotene/Potassium chromate	MFGM-derived phospholipid (Fonterra)	β-carotene and potassium chromate were added to the mixture with ethanol and MFGM phospholipid (1, 5, 10 (%, w/w)), solvent evaporation (80 °C), and hydrated. The dispersions were cycled through Microfluidizer (75 μm, 5 times, 103 MPa).	Ratio of EE (soya liposome/MFGM liposome) 1(%, w/w) phospholipid = 0.23, 5(%, w/w) phospholipid = 0.64, 10(%, w/w) phospholipid = 0.79.	Increasing the phospholipids concentration increased the hydrophilic EE. Higher entrapment efficiencies have been obtained with the MFGM-derived phospholipid dispersions than with the soya dispersions because of the larger particle size.	Thompson, Couchoud, and Singh (2009)
Lactoferrin	MFGM-derived phospholipid (Fonterra)	MFGM-derived phospholipid, cholesterol, Tween-80, and vitamin E were mixed at a mass ratio of 6:1:1.8: 0.12 and dissolved in absolute ethanol and then evaporated under vacuum in a rotary evaporator (60 °C), rehydrated with PBS containing 2 mg/mL lactoferrin (pH 7.4, 0.05 M) and ultrasound (10 min).	46.4 ± 8.7%	The lactoferrin entrapped in the liposomal membrane was not hydrolyzed by pepsin under simulated gastric fluid (SGF) conditions, independent of the concentration of enzyme. The liposomal membrane was obviously damaged in simulated intestinal fluid (SIF), with some of the inner membranes also appearing to be broken.	Liu et al. (2013)
Curcumin	MFGM phospholipids (prepare)	MFGM phospholipids and curcumin were dissolved in chloroform and anhydrous ethanol, respectively. The mixture solution was evaporated at 35 °C until formed thin film, and then washed (PBS), hydrated (2 h) and sonicated (4 min).	74%	The optimal conditions for curcumin liposomes prepared with MFGM phospholipids are ratio of curcumin to phospholipids 1:40, ultrasonic time 3 min, PBS pH 5.5, concentration of PBS 0.020 mol/L, volume of PBS 15 mL. MFGM liposomes could effectively protect curcumin from degradation at the conditions of light, high temperature, oxygen and high relative humidity.	Jin, Lu, and Jiang (2016)
Salmon protein hydrolysates (SPH)	MFGM phospholipid Phosphlac 700^® (Fonterra)	MFGM and SPH were hydrated and heated (60 − 80 °C). The pH of the mixture was adjusted to 7.3, heated (60 °C), shaked (60 min) and homogenized. Chitosan-coated solution was added into liposomal suspension.	71%	Chitosan coating greatly improved the stability of liposomes. The physical stability were achieved with 10% MFGM phospholipid and 0.4% chitosan.	Li, Paulson, and Gill (2015)
Tea polyphenols (containing 94% epigallocatechin-3-gallate (EGCG))	Milk phospholipid (PC-700) (Fonterra)	Milk phospholipids (10%) were dispersed in buffer (20 mM imidazole, 50 mM NaCl in Milli-Q water, pH 7.0) using a magnetic stirrer (1 h). Added tea polyphenols, sheared (30 000 rpm, 1 min) and homogenized (690 bar, two times)	58%	The extent of encapsulation increased with tea polyphenol concentration up to 4 mg·mL^−1, and at the concentrations ≥ 6 mg·mL^−1, liposome dispersions were unstable. Milk phospholipid liposomes showed higher EE than soy liposomes at pH 3, 5, 7. The presence of sucrose caused a release of EGCG from liposomes.	Gülseren and Corredig (2013)
Tea polyphenol (containing 94% EGCG) /β-carotene	Milk phospholipids (PC-700) (Fonterra)	Milk phospholipids were dispersed in buffer (20 mM imidazole, 50 mM NaCl in Milli-Q water, pH 7.0) using a magnetic stirrer (2 h). Added tea polyphenols or β-carotene, stirred and homogenized.	EGCG: 52% β-carotene: 36%	Milk liposomes had good stability under broad pH ranges and more stable than soy liposomes under environmental and in vitro digestive condition. Mucus layer covering cocultures of Caco-2/HT29-MTX was associated with the lower recoveries of EGCG and β-carotene of the liposomes.	Li et al. (2017)
Curcumin	Bovine milk phospholipids (Fonterra)	Phospholipid and curcumin were dissolved in chloroform (8 µg/mL) and absolute ethanol (4 µg/mL) respectively. After mixing, the film was formed by rotary evaporation at 35 °C, washed the film with PBS, hydrated for 2 h and sonicated to obtain curcumin liposomes.	76%	Curcumin liposomes showed high storage stability under harsh storage conditions (alkaline conditions, oxygen, high temperature and relative humidity). The saturated fatty acids enrich in milk phospholipids reduce the sensitivity to oxygen and improve the antioxidant capacity of liposomes. Curcumin liposomes had the highest EE under the following conditions: the ratios of curcumin to bovine milk phospholipids: 1:20, ultrasound time: 2 min, pH 6.0 and 0.01 M PBS.	Yw et al. (2020)
Curcumin	Bovine milk phospholipids (Fonterra)	Curcumin was dissolved in absolute ethanol, and bovine milk phospholipids and cholesterol (5:1 or 1:1, w / w) were dissolved in chloroform. After mixing of phospholipid-cholesterol solution and curcumin solution, the film was formed by rotary evaporation at 35 °C, washed the film with PBS (0.01 M, pH 6.0), hydrated for 2 h, sonicated for 2 min and centrifuged (6793 × g, 30 min) to obtain curcumin liposomes.	85%	Cholesterol can effectively improve the EE and storage stability of curcumin liposomes under harsh storage conditions (alkaline, heat-resistant and sunlight resistant). Curcumin nanoliposomes prepared by bovine milk phospholipids and cholesterol can target infectious Staphylococcus aureus and lead to cell death by the lysis of the bacterial cell wall, showing antibacterial effect.	Yw et al. (2021)

Figure 4. Schematic diagram of proposed gastrointestinal digestion of MFGM-encapsulated probiotics. Encapsulation of probiotics (e.g., LGG-welE, LGG-spa CBA, L. reuteri, L. delbrueckii, and L. plantarum) by MFGM (e.g., glycoprotein and phospholipid) (A). proposed protection mechanism of probiotics against gastric acid (B). proposed gastrointestinal digestion of MFGM-encapsulated probiotics (C).

Fernández-Arroyo, S., A. Hernández-Aguilera, M. A. de Vries, B. Burggraaf, E. van der Zwan, N. Pouw, J. Joven, and M. Castro Cabezas. 2019. Effect of Vitamin D3 on the postprandial lipid profile in obese patients: A non-targeted lipidomics study. Nutrients 11 (5):1194. doi: 10.3390/nu11051194.

 PubMed Web of Science ®Google Scholar

Vors, C., L. Joumard-Cubizolles, M. Lecomte, E. Combe, L. Ouchchane, J. Drai, K. Raynal, F. Joffre, L. Meiller, M. Le Barz, et al. 2020. Milk polar lipids reduce lipid cardiovascular risk factors in overweight postmenopausal women: Towards a gut sphingomyelin-cholesterol interplay. Gut 69 (3):487–501. doi: 10.1136/gutjnl-2018-318155.

 PubMed Web of Science ®Google Scholar

Ortega-Anaya, J., and R. Jiménez-Flores. 2019. Symposium review: The relevance of bovine milk phospholipids in human nutrition-Evidence of the effect on infant gut and brain development. Journal of Dairy Science 102 (3):2738–48. doi: 10.3168/jds.2018-15342.

 PubMed Web of Science ®Google Scholar

Motouri, M., H. Matsuyama, J. I. Yamamura, M. Tanaka, S. Aoe, T. Iwanaga, and H. Kawakami. 2003. Milk sphingomyelin accelerates enzymatic and morphological maturation of the intestine in artificially reared rats. Journal of Pediatric Gastroenterology and Nutrition 36 (2):241–7. doi: 10.1097/00005176-200302000-00016.

 PubMed Web of Science ®Google Scholar

Norris, G. H., C. M. Porter, C. Jiang, C. L. Millar, and C. N. Blesso. 2017. Dietary sphingomyelin attenuates hepatic steatosis and adipose tissue inflammation in high-fat-diet-induced obese mice. The Journal of Nutritional Biochemistry 40:36–43. doi: 10.1016/j.jnutbio.2016.09.017.

 PubMed Web of Science ®Google Scholar

Weiland, A., A. Bub, S. W. Barth, J. Schrezenmeir, and M. Pfeuffer. 2016. Effects of dietary milk- and soya-phospholipids on lipid-parameters and other risk indicators for cardiovascular diseases in overweight or obese men – two double-blind, randomised, controlled, clinical trials. Journal of Nutritional Science 5: E 21. doi: 10.1017/jns.2016.9.

 Google Scholar

Hertervig, E., A. Nilsson, L. Nyberg, and R. D. Duan. 1997. Alkaline sphingomyelinase activity is decreased in human colorectal carcinoma. Cancer 79 (3):448–53. doi: 10.1016/j.foodres.2018.11.040.

 PubMed Web of Science ®Google Scholar

Russell, A., A. Laubscher, R. Jiménez-Flores, and L. H. Laiho. 2010. Investigating the protective properties of milk phospholipids against ultraviolet light exposure in a skin equivalent model. Proceedings of SPIE – The International Society for Optical Engineering, 7569. doi: 10.1117/12.845803.

 Google Scholar

Cohen, B.-C., C. Raz, A. Shamay, and N. Argov-Argaman. 2017. Lipid droplet fusion in mammary epithelial cells is regulated by phosphatidylethanolamine metabolism. Journal of Mammary Gland Biology and Neoplasia 22 (4):235–49. doi: 10.1007/s10911-017-9386-7.

 PubMed Web of Science ®Google Scholar

Moukarzel, S., R. A. Dyer, C. Garcia, A. M. Wiedeman, G. Boyce, J. Weinberg, B. O. Keller, R. Elango, and S. M. Innis. 2018. Milk fat globule membrane supplementation in formula-fed rat pups improves reflex development and may alter brain lipid composition. Scientific Reports 8 (1):15277. doi: 10.1038/s41598-018-33603-8.

 PubMedGoogle Scholar

Lee, H., E. Padhi, Y. Hasegawa, J. Larke, M. Parenti, A. Wang, O. Hernell, B. Lönnerdal, and C. Slupsky. 2018. Compositional dynamics of the milk fat globule and its role in infant development. Frontiers in Pediatrics 6:313. doi: 10.3389/fped.2018.00313.

 PubMed Web of Science ®Google Scholar

Li, T., M. Du, H. Wang, and X. Mao. 2020. Milk fat globule membrane and its component phosphatidylcholine induce adipose browning both in vivo and in vitro. The Journal of Nutritional Biochemistry 81:108372. doi: 10.1016/j.jnutbio.2020.108372.

 PubMed Web of Science ®Google Scholar

Kidd, P. 2000. Dietary phospholipids as anti-aging nutraceuticals. Anti-Aging Medical Therapeutics 4:282–300. doi: 10.1007/0-387-28813-9_4.

 Google Scholar

Anand, B. S., J. J. Romero, S. K. Sanduja, and L. M. Lichtenberger. 1999. Phospholipid association reduces the gastric mucosal toxicity of aspirin in human subjects. The American Journal of Gastroenterology 94 (7):1818–22. doi: 10.1016/S0002-9270(99)00267-1.

 PubMed Web of Science ®Google Scholar

Carlson, S. E., M. B. Montalto, D. L. Ponder, S. H. Werkman, and S. B. Korones. 1998. Lower Incidence of necrotizing enterocolitis in infants fed a preterm formula with egg phospholipids. Pediatric Research 44 (4):491–8. doi: 10.1203/00006450-199810000-00005.

 PubMed Web of Science ®Google Scholar

Hartmann, P., A. Szabó, G. Eros, D. Gurabi, G. Horváth, I. Németh, M. Ghyczy, and M. Boros. 2009. Anti-inflammatory effects of phosphatidylcholine in neutrophil leukocyte-dependent acute arthritis in rats. European Journal of Pharmacology 622 (1-3):58–64. doi: 10.1016/j.ejphar.2009.09.012.

 PubMed Web of Science ®Google Scholar

Liu, Z., B. Cocks, A. Patel, A. Oglobline, G. Richardson, and S. Rochfort. 2016. Identification and quantification of phosphatidylinositol in infant formulas by liquid chromatography–mass spectrometry. Food Chemistry 205:178–86. doi: 10.1016/j.foodchem.2016.02.163.

 PubMed Web of Science ®Google Scholar

Burgess, J. W., J. Boucher, T. A. Neville, P. Rouillard, C. Stamler, S. Zachariah, and D. L. Sparks. 2003. Phosphatidylinositol promotes cholesterol transport and excretion. Journal of Lipid Research 44 (7):1355–63. doi: 10.1194/jlr.M300062-JLR200.

 PubMed Web of Science ®Google Scholar

Hashioka, S., A. Monji, Y. Han, H. Nakanishi, and S. Kanba. 2004. Potentiality of phosphatidylserine (PS)-liposomes for treatment of Alzheimer’s disease. Journal of Neuroimmunology 154:119.

 Web of Science ®Google Scholar

Kimura, A. K., and H.-Y. Kim. 2013. Phosphatidylserine synthase 2: High efficiency for synthesizing phosphatidylserine containing docosahexaenoic acid. Journal of Lipid Research 54 (1):214–22. doi: 10.1194/jlr.M031989.

 PubMed Web of Science ®Google Scholar

Vance, J. E. 2008. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: Two metabolically related aminophospholipids. Journal of Lipid Research 49 (7):1377–87. doi: 10.1194/jlr.R700020-JLR200.

 PubMed Web of Science ®Google Scholar

Kingsley, D. M. 2006. Effects of phosphatidylserine supplementation on exercising humans. Sports Medicine (Auckland, N.Z.) 36 (8):657–69. doi: 10.2165/00007256-200636080-00003.

 PubMed Web of Science ®Google Scholar

Hussain, G., J. Wang, A. Rasul, H. Anwar, A. Imran, M. Qasim, S. Zafar, S. K. S. Kamran, A. Razzaq, N. Aziz, et al. 2019. Role of cholesterol and sphingolipids in brain development and neurological diseases. Lipids in Health and Disease 18 (1):26. doi: 10.1186/s12944-019-0965-z.

 PubMedGoogle Scholar

Koletzko, B. 2016. Human milk lipids. Annals of Nutrition & Metabolism 69 (Suppl. 2):28–40. doi: 10.1159/000452819.

 PubMedGoogle Scholar

Lai, X., Y. Yu, W. Xian, F. Ye, X. Ju, Y. Luo, H. Dong, Y. Zhou, W. Tan, and H. Zhuang. 2021. Inhibition of SAR S-CoV-2 infection and replication by lactoferrin, MUC1 and α-lactalbumin identified in human breastmilk. bioRxiv doi: 10.1101/2021.10.29.466402.

 Google Scholar

Parker, P., L. Sando, R. Pearson, K. Kongsuwan, R. L. Tellam, and S. Smith. 2010. Bovine Muc1 inhibits binding of enteric bacteria to Caco-2 cells. Glycoconjugate Journal 27 (1):89–97. doi: 10.1007/s10719-009-9269-2.

 PubMed Web of Science ®Google Scholar

Dhanisha, S. S., C. Guruvayoorappan, S. Drishya, and P. Abeesh. 2018. Mucins: Structural diversity, biosynthesis, its role in pathogenesis and as possible therapeutic targets. Critical Reviews in Oncology/Hematology 122:98–122. doi: 10.1016/j.critrevonc.2017.12.006.

 PubMed Web of Science ®Google Scholar

Guo, Y., J. Tao, Y. Li, Y. Feng, H. Ju, Z. Wang, and L. Ding. 2020. Quantitative localized analysis reveals distinct exosomal protein-specific glycosignatures: Implications in cancer cell subtyping, exosome biogenesis, and function. Journal of the American Chemical Society 142 (16):7404–12. doi: 10.1021/jacs.9b12182.

 PubMed Web of Science ®Google Scholar

Al-Shehri, S. S., J. A. Duley, and N. Bansal. 2020. Xanthine oxidase-lactoperoxidase system and innate immunity: Biochemical actions and physiological roles. Redox Biology 34:101524. doi: 10.1016/j.redox.2020.101524.

 PubMed Web of Science ®Google Scholar

Brink, L. R., and B. Lönnerdal. 2020. Milk fat globule membrane: The role of its various components in infant health and development. The Journal of Nutritional Biochemistry 85:108465. doi: 10.1016/j.jnutbio.2020.108465.

 PubMed Web of Science ®Google Scholar

Martin, H. M., K. P. Moore, E. Bosmans, S. Davies, A. K. Burroughs, A. P. Dhillon, D. Tosh, and R. Harrison. 2004. Xanthine oxidoreductase is present in bile ducts of normal and cirrhotic liver. Free Radical Biology & Medicine 37 (8):1214–23. doi: 10.1016/j.freeradbiomed.2004.06.045.

 PubMed Web of Science ®Google Scholar

Lastra, G., C. Manrique, G. Jia, A. R. Aroor, M. R. Hayden, B. J. Barron, B. Niles, J. Padilla, and J. R. Sowers. 2017. Xanthine oxidase inhibition protects against Western diet-induced aortic stiffness and impaired vasorelaxation in female mice. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 313 (2):R67–R77. doi: 10.1152/ajpregu.00483.2016.

 PubMed Web of Science ®Google Scholar

Manoni, M., C. Di Lorenzo, M. Ottoboni, M. Tretola, and L. Pinotti. 2020. Comparative proteomics of milk fat globule membrane (MFGM) proteome across species and lactation stages and the potentials of MFGM fractions in infant formula preparation. Foods (Basel, Switzerland) 9 (9):1251. doi: 10.3390/foods9091251.

 PubMed Web of Science ®Google Scholar

Kvistgaard, A., L. Pallesen, C. Arias, S. Lopez, T. Petersen, C. Heegaard, and J. Rasmussen. 2004. Inhibitory effects of human and bovine milk constituents on rotavirus infections. Journal of Dairy Science 87 (12):4088–96. doi: 10.3168/jds.S0022-0302(04)73551-1.

 PubMed Web of Science ®Google Scholar

Bu, H. F., X. L. Zuo, X. Wang, M. A. Ensslin, V. Koti, W. Hsueh, A. S. Raymond, B. D. Shur, and X. D. Tan. 2007. Milk fat globule-EGF factor 8/lactadherin plays a crucial role in maintenance and repair of murine intestinal epithelium. The Journal of Clinical Investigation 117 (12):3673–83. doi: 10.1172/JCI31841.

 PubMed Web of Science ®Google Scholar

Fong, B. Y., C. S. Norris, and A. Macgibbon. 2007. Protein and lipid composition of bovine milk-fat-globule membrane. International Dairy Journal 17 (4):275–88. doi: 10.1016/j.idairyj.2006.05.004.

 Web of Science ®Google Scholar

Han, L., M. Zhang, Z. Xing, D. N. Coleman, Y. Liang, J. J. Loor, and G. Yang. 2020. Knockout of butyrophilin subfamily 1 member A1 (BTN1A1) alters lipid droplet formation and phospholipid composition in bovine mammary epithelial cells. Journal of Animal Science and Biotechnology 11 (1):72. doi: 10.1186/s40104-020-00479-6.

 PubMed Web of Science ®Google Scholar

Dewettinck, K., R. Rombaut, N. Thienpont, T. T. Le, K. Messens, and J. V. Camp. 2008. Nutritional and technological aspects of milk fat globule membrane material. International Dairy Journal 18 (5):436–57. doi: 10.1016/j.idairyj.2007.10.014.

 Web of Science ®Google Scholar

Bickel, P. E., J. T. Tansey, and M. A. Welte. 2009. PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochimica et Biophysica Acta 1791 (6):419–40. doi: 10.1016/j.bbalip.2009.04.002.

 PubMed Web of Science ®Google Scholar

Novakovic, P., Y. Y. Huang, B. Lockerbie, F. Shahriar, J. Kelly, J. R. Gordon, D. M. Middleton, M. E. Loewen, B. A. Kidney, and E. Simko. 2015. Identification of Escherichia coli F4ac-binding proteins in porcine milk fat globule membrane. Canadian Journal of Veterinary Research 79 (2):120–8.

 PubMed Web of Science ®Google Scholar

Harris, A., A. Roseborough, R. Mor, K. K.-C. Yeung, and S. N. Whitehead. 2020. Ganglioside detection from formalin-fixed human brain tissue utilizing MALDI imaging mass spectrometry. Journal of the American Society for Mass Spectrometry 31 (3):479–87. doi: 10.1021/jasms.9b00110.

 PubMed Web of Science ®Google Scholar

Sukhov, I., M. Lebedeva, I. Zakharova, K. Derkach, L. Bayunova, I. Zorina, N. Avrova, and A. Shpakov. 2020. Intranasal administration of insulin and gangliosides improves spatial memory in rats with neonatal type 2 diabetes mellitus. Bulletin of Experimental Biology and Medicine 168 (3):317–20. doi: 10.1007/s10517-020-04699-8.

 PubMed Web of Science ®Google Scholar

Tang, F. L., J. Wang, Y. Itokazu, and R. K. Yu. 2021. Ganglioside GD3 regulates dendritic growth in newborn neurons in adult mouse hippocampus via modulation of mitochondrial dynamics. Journal of Neurochemistry 156 (6):819–33. doi: 10.1111/jnc.15137.

 PubMed Web of Science ®Google Scholar

Bint E Naser, S. F., H. Su, H.-Y. Liu, Z. A. Manzer, Z. Chao, A. Roy, A.-M. Pappa, A. Salleo, R. M. Owens, and S. Daniel. 2021. Detection of ganglioside-specific toxin binding with biomembrane-based bioelectronic sensors. ACS Applied Bio Materials 4 (11):7942–50. doi: 10.1021/acsabm.1c00878.

 PubMedGoogle Scholar

Lebeer, S., T. L. Verhoeven, G. Francius, G. Schoofs, I. Lambrichts, Y. F. Dufrêne, J. Vanderleyden, and S. D. Keersmaecker. 2009. Identification of a gene cluster for the biosynthesis of a long, galactose-rich exopolysaccharide in Lactobacillus rhamnosus GG and functional analysis of the priming glycosyltransferase. Applied and Environmental Microbiology 75 (11):3554–63. doi: 10.1128/AEM.02919-08.

 PubMed Web of Science ®Google Scholar

Zhang, L., M. Chichlowski, G. Gross, M. J. Holle, L. A. Lbarra-Sánchez, S. Wang, and M. J. Miller. 2020. Milk fat globule membrane protects Lactobacillus rhamnosus GG from bile stress by regulating exopolysaccharide production and biofilm formation. Journal of Agricultural and Food Chemistry 68 (24):6646–55. doi: 10.1021/acs.jafc.0c02267.

 PubMed Web of Science ®Google Scholar

Ortega-Anaya, J., A. Marciniak, and R. Jiménez-Flores. 2021. Milk fat globule membrane phospholipids modify adhesion of Lactobacillus to mucus-producing Caco-2/Goblet cells by altering the cell envelope. Food Research International (Ottawa, Ont.) 146:110471. doi: 10.1016/j.foodres.2021.110471.

 PubMed Web of Science ®Google Scholar

Jash, A., A. Ubeyitogullari, and S. S. Rizvi. 2020. Synthesis of multivitamin-loaded heat stable liposomes from milk fat globule membrane phospholipids by using a supercritical-CO2 based system. Green Chemistry 22 (16):5345–56. doi: 10.1039/D0GC01674H.

 Web of Science ®Google Scholar

Thompson, A. K., A. Couchoud, and H. Singh. 2009. Comparison of hydrophobic and hydrophilic encapsulation using liposomes prepared from milk fat globule-derived phospholipids and soya phospholipids. Dairy Science and Technology 89 (1):99–113. doi: 10.1051/dst/2008036.

 Web of Science ®Google Scholar

Liu, W., A. Ye, W. Liu, C. Liu, and H. Singh. 2013. Stability during in vitro digestion of lactoferrin-loaded liposomes prepared from milk fat globule membrane-derived phospholipids. Journal of Dairy Science 96 (4):2061–70. doi: 10.3168/jds.2012-6072.

 PubMed Web of Science ®Google Scholar

Jin, H. H., Q. Lu, and J. G. Jiang. 2016. Curcumin liposomes prepared with milk fat globule membrane phospholipids and soybean lecithin. Journal of Dairy Science 99 (3):1780–90. doi: 10.3168/jds.2015-10391.

 PubMed Web of Science ®Google Scholar

Li, Z., A. T. Paulson, and T. A. Gill. 2015. Encapsulation of bioactive salmon protein hydrolysates with chitosan-coated liposomes. Journal of Functional Foods 19:733–43. doi: 10.1016/j.jff.2015.09.058.

 Web of Science ®Google Scholar

Gülseren, I., and M. Corredig. 2013. Storage stability and physical characteristics of tea-polyphenol-bearing nanoliposomes prepared with milk fat globule membrane phospholipids. Journal of Agricultural and Food Chemistry 61 (13):3242–51. doi: 10.1021/jf3045439.

 PubMed Web of Science ®Google Scholar

Li, Y., E. Arranz, A. Guri, and M. Corredig. 2017. Mucus interactions with liposomes encapsulating bioactives: Interfacial tensiometry and cellular uptake on Caco-2 and cocultures of Caco-2/HT29-MTX. Food Research International (Ottawa, Ont.) 92:128–37. doi: 10.1016/j.foodres.2016.12.010.

 PubMed Web of Science ®Google Scholar

Yw, A., A. Bm, S. B. Shuang, C. Cpt, D. Oml, S. E. Cai, and A. Lzc. 2020. Curcumin-loaded liposomes prepared from bovine milk and krill phospholipids: Effects of chemical composition on storage stability, in-vitro digestibility and anti-hyperglycemic properties. Food Research International 136:109301 doi: 10.1016/j.foodres.2020.109301.

 PubMed Web of Science ®Google Scholar

Yw, A., W. A. Ke, A. Ql, A. Xl, A. Bm, C. Omlb, D. Cpt, and A. Lzc. 2021. Selective antibacterial activities and storage stability of curcumin-loaded nanoliposomes prepared from bovine milk phospholipid and cholesterol. Food Chemistry 367:130700 doi: 10.1016/j.foodchem.2021.130700.

 PubMed Web of Science ®Google Scholar