The role of human milk fats in shaping neonatal development and the early life gut microbiota
Abstract
Human breast milk (HBM) is the main source of nutrition for neonates across the critical early-life developmental period. The highest demand for energy is due to rapid neurophysiological expansion post-delivery, which is largely met by human milk lipids (HMLs). These HMLs also play a prebiotic role and potentially promote the growth of certain commensal bacteria, which, via HML digestion, supports the additional transfer of energy to the infant. In tandem, HMLs can also exert bactericidal effects against a variety of opportunistic pathogens, which contributes to overall colonisation resistance. Such interactions are pivotal for sustaining homeostatic relationships between microorganisms and their hosts. However, the underlying molecular mechanisms governing these interactions remain poorly understood. This review will explore the current research landscape with respect to HMLs, including compositional considerations and impact on the early life gut microbiota. Recent papers in this field will also be discussed, including a final perspective on current knowledge gaps and potential next research steps for these important but understudied breast milk components.
Keywords
INTRODUCTION
Human breast milk (HBM) is pivotal for nutrition, immunological priming, neurodevelopmental support, and gut microbiome establishment in newborn infants. The mechanisms by which HBM impacts these key host responses are varied and include hormones for the regulation of digestion[1], infant appetite[2], and multiple pro- and anti-inflammatory cytokines to support and train the largely naive infant immune system[3]. HBM is considered the gold standard in infant nutrition, which is highly variable between lactating individuals[4] and generally seems temporally and conditionally suited to match the respective infants’ needs[5]. One of the most studied nutritional substrates are human milk oligosaccharides (HMOs), which pass undigested into the infant colon where they can act as prebiotic (i.e., selective) nutrient sources for certain microbial genera such as Bifidobacterium. Fermentation of these HMOs then provides key metabolites to the growing infant and the wider microbiota[6]. Another key nutritional component of HBM are human milk lipids (HMLs), which are a major source of energy for infants, with an average content of ~40 g/L breast milk during the initial semester post-delivery[7]. HMLs also include several compounds that are essential for infant development. For example, phosphorylated lipids, glycosylated lipids, short- and long-chain fatty acids, polyunsaturated fatty acids[8], and several fat-soluble vitamins[9], which are all important for cognitive and immune system development[10], bone growth[11], anti-oxidation[12], and establishment of gastrointestinal tract (GIT) mucus[13]. It is becoming increasingly clear that the GIT microbiota also participates in the degradation of HMLs, which like HMOs, may influence the initial assembly of specific microbial members and communities. Thus, HMLs may indirectly affect infant health via interactions between the host, bacteria, and their shared diet. However, in comparison to HMOs, our understanding concerning the microbial utilisation of HMLs is limited.
The milk fat globule: core and membrane
Milk fat globules (MFGs) are functionally versatile droplets that are secreted into human milk via secretory cells of the mammary gland alveoli during lactation[14]. Their main nutritional purpose is to passage a triglyceride-rich core through the infants’ digestive tract. Although there is already a significant microbial ecosystem in the initial days post-birth[15], and many colonisers are reportedly capable of incorporating dietary lipids[16], the nutrient-rich core remains available for the infant as the milk fat globule membranes (MFGMs) protect the fat droplet from microbial digestion. MFGMs are heterogeneous and change throughout lactation, both regarding overall quantity and composition[17]. In general, MFGs are coated by two such membranes: a monolayer coating the triglyceride-rich core, and an overlying bi-layer membrane. Both membranes include proteins, phospholipids, sphingolipids, gangliosides, choline, sialic acid, and cholesterol, whereby the outer layer contains most of the glycolipids found in human milk (HM)[8]. Most of these glycolipids can be classified as gangliosides with a ceramide lipid chain anchoring respective combinations of oligosaccharides and sialic acids to the MFGM[18]. Notably, gangliosides have been shown to be highly important for both cerebral[19] and enteral[20] development, growth, communication, and differentiation of colonocytes[21], and gut-associated immune cells[22]. The most abundant gangliosides in human milk are monosialoganglioside-3 (GM-3) and disialoganglioside-3 (GD-3)[23]. GD-3 is very abundant in colostrum, while GM-3 increases in abundance at later time points[24]. Gangliosides, in particular, have been shown in many cases to protect against gastrointestinal pathogens via inhibition of various toxins[25], and GM-3 and GD-3 can act as decoy receptors for rotavirus[26] and influenza viruses[27], respectively. Indirectly, gangliosides exert anti-inflammatory effects on the developing immune system via influencing dendritic cell maturation[28] and downstream stimulation of the hosts’ own intestinal IgA production[22]. However, gangliosides are not antagonistic to all gastrointestinal microorganisms. Previous work has indicated that the dominant and keystone early-life bacterial gut microbiota member Bifidobacterium can grow in the presence of GM-3 and GD-3 while simultaneously lowering ganglioside levels in vitro, which is suggestive of possible incorporation or conversion. Notably, different bifidobacterial species have different preferences. Bifidobacterium bifidum is very efficient in removing GD-3 by employing extracellular mechanisms, while Bifidobacterium longum subsp. infantis degrades GM-3 intracellularly, with overall lower glycosidase activity[29]. These observations indicate that gangliosides support the establishment of commensal microbiota during early-life.
The MFGM is equipped with many other compounds that, such as gangliosides, are interpretable as bioactive, as summarised in Table 1. Phosphatidylethanolamines (PEs) are integral to the outer MFG bilayer membrane, and while they are important for human cell proliferation during early life, some bacteria of the Clostridium and Enterococcus genera were shown to use ethanolamine as a source of carbon and nitrogen[30]. Furthermore, phosphatidylserine has implications for brain development in infants[31] and was shown to induce major shifts in Bacillota (Firmicutes): Bacteroidota (Bacteroidetes) ratio in human gut microbiomes[32]. For strictly anaerobic representatives of the Clostridia and Veillonella genera, it was shown that they can use phosphatidylserine as a substrate to catalyse phosphatidylethanolamine and plasmenylethanolamine, both by employing respective phospholipid decarboxylase activities[33], a function that is commonly found among many lactic acid bacteria found in the human gut[34]. Furthermore, phosphatidylcholine is a major membrane-forming phospholipid in eukaryotes, with an estimated presence of 15% in the bacterial kingdom[35]. As a provided substrate, it can exert a prebiotic function on B. longum subsp. infantis, which, by translating the compound to 1,2-sn-diacylglycerols, affects the regulation of colonic mucus production. However, conflicting evidence from in vitro studies indicates that Clostridia and Enterobacteriaceae could also be involved in phosphatidylcholine metabolism, which decreases the abundance of Bifidobacterium spp. due to competition for the substrate[36]. The outer MFG membrane also contains most of the sphingomyelins, for which many bactericidal activities against human opportunistic pathogens are described[37], thereby greatly increasing colonisation resistance. Sphingomyelins were observed to increase gut barrier function, thereby decreasing the chances of translocation of intestinal bacteria during inflammation[38]. Dietary sphingomyelins were also observed to significantly reduce inflammatory cytokine levels in the circulation of mice[39]. However, sphingomyelins have also been observed to act as binding sites for toxins of the enteropathogen Helicobacter pylori[40]. However, sphingosine, a hydrolytic product of sphingomyelin, reportedly showed general bactericidal activity in the GIT[41].
Summary of bioactive MFGM components
| Lipid | Description | Role for Microbiome | Citation |
| Phosphatidylethanolamine | Inner membrane lipid, important for cell proliferation and differentiation by regulation of immunological pathways. Degraded by phosphodiesterases to yield glycerol and ethanolamine | Certain intestinal bacteria including several pathogenic species such as Clostridium, Enterococcus, Escherichia and Salmonella catabolise ethanolamine as a major carbon and/or N source with the aid of ethanolamine utilisation proteins | [30,110,111] |
| Phosphatidylserine | Inner membrane lipid, responsible for the induction of apoptosis, carrier of Docosahexaenoic acid | Phosphatidylserine was observed to decrease the ratio of Bacillota (Firmicutes) to Bacteroidota (Bacteroidetes) | [32,112,113] |
| Phosphatidylinositol | Inner membrane lipid, important for cell signalling and activation of immunological pathways. Cell signalling, activation of Akt (1) | Phosphatidylinositol was shown to exert active bursting action on the protoplasts of Bacillus megaterium | [114,115] |
| Cholesterol | Found in inner and outer membrane, responsible for the structural maintenance of membranes, compartmentalization of membrane proteins, and serves as a substrate for bile acids, vitamin D, hormones and oxysterols | Several studies on germ-free animal models showed evidence of microbial involvement in cholesterol and bile metabolism | [8,116-118] |
| Phosphatidylcholine | Outer membrane lipid, important for membrane structure, lipoprotein assembly, and secretion | Bifidobacterium longum subsp. infantis was observed to utilize phosphatidylcholine to produce 1,2-sn-Diacylglycerols (DAG), which are involved in the regulation of colonic mucosal proliferation | [36,112] |
| Sphingomyelin | Metabolized to ceramide and sphingosine. Important for vascular development and immunological modifications | General bactericidal activities | [37,119-121] |
| Cerebrosides | Cerebrosides are major glycosphingolipids of human milk. These are glycolipids with a Galactose/Glucose moiety | Protect the procedure of digestion and gut-mucus integrity | [122,123] |
| Gangliosides | Gangliosides are glycosphingolipids consisting of a hydrophobic ceramide and a hydrophilic oligosaccharide chain. Seminal involvement for cognitive development and immunological modulation | Often described as putative decoys that enhance colonisation resistance against opportunistic pathogens | [19-22] |
| Monoacylglycerols | Hydrolysis of dietary triacylglycerols by endogenous lipases produces sn-2 monoacylglycerols | General bactericidal activities | [37,124] |
| Saturated fatty acids | Some dietary fatty acids are converted to biologically active metabolites by enzymes not only by the host but also by gastrointestinal bacteria | Bacteria can incorporate extracellular fatty acids into membrane lipids | [125,126] |
| Triacylglycerols | Diverse set of lipids found in the core of the MFG. Mainly consists of stearic, palmitic, oleic, linoleic, myristic and lauric acid | Some metabolic products of the acids (Monoglycerides) can have an inactivating effect on bacteria | [8,127] |
| Stearic acid | The high concentration of stearic acid in brain grey matter suggests that this fatty acid has an important role in neural function | General modulatory effects on gut microbiota | [43,128,129] |
| Palmitic acid | Used for energy metabolism and the synthesis of bioactive lipids | Higher proportions of palmitic acid in infant formula were observed to increase faecal Lactobacillus and Bifidobacterium levels | [45,124] |
| Oleic acid | Used for energy storage and metabolism, can alter cell membrane fluidity | Was observed as beneficial for growth of several Lactobacillus species | [46,130] |
| Linoleic acid | Involved in functions for skin barrier maintenance, a precursor to Arachidonic acid, and competes with n-3 fatty acid metabolism. Described as one of the most abundant and active fatty acids in protection from infections | Microbial conversion of linoleic acid into conjugated linoleic acids reportedly contributes to gut health | [131-134] |
| Myristic acid | Myristic acid is directly involved in post-translational protein changes and mechanisms that control important metabolic processes in the human body | Abundance of myristic acid was associated with Bacteroides, Enterobacteriaceae, Veillonella, Streptococcus, and Clostridium abundances in infant gut microbiota | [85,135] |
| Lauric acid | One of the most active fatty acids in protection from infections, makes up 5% of milk fatty acids | Lauric acid has significant antimicrobial activity against Gram-positive bacteria | [133,136] |
The core of MFGs consists of a pool of triacylglycerols (TAGs) that is composed of several saturated fatty acids, including stearic, palmitic, oleic, linoleic, myristic, and lauric acids[8]. These by themselves interact with colonising microbiota, but especially during their initial hydrolysis, monoacylglycerols are generated, constituting prominent bactericidal bi-products [42]. Stearic acid was found in high concentrations in infant brain grey matter, suggesting important implications for neurogenesis[43]. Furthermore, stearic acid, similar to palmitic acid, forms crystallite surfaces that display bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus[44], both relevant pathogens during human early life. Greater proportions of palmitic acid in the pool of triacylglycerides, for instance, were associated with higher levels of fecal Lactobacillus and Bifidobacterium in neonates[45]. Similarly, oleic acid was observed as beneficial for Lactobacillus spp.[46], while lauric acid was shown to exert antimicrobial activity against Cutibacterium acnes[47]. Lastly, freely-available myristic acid is involved in the post-translational folding of proteins in humans[48] and can inhibit the activity of some bacterial ATP-binding cassette (ABC) transporters, for instance, observed for bacillus multidrug-resistance ATP (BmrA) of Bacillus subtilis (B. subtilis). The bmrA gene encodes an ABC half-transporter which, besides many different substrates, also transports cervimycin out of the cell, thereby rendering B. subtilis resistant to the antibiotic. In this case, freely-available myristic acid was observed to have an inhibitory effect on the respective ATPase and BmrA transport activity, thereby rendering the B. subtilis unviable[49]. Whether this is the case for other bacterial ABC transporters, such as LmrA or MsbA, remains to be elucidated. Furthermore, the accessibility of TAGs for hydrolysis is highly dependent on the structural integrity of the MFG during digestion[50]. Cholesterols are mainly responsible for the structural maintenance of both membranes but also serve as the substrate for bile acids, vitamin D, hormones, and oxysterols[8]. Recently, it was shown that Clostridia can metabolise cholesterol to coprostanol[51], which escapes hepatic recirculation as it is not reabsorbed by colonocytes. Since cholesterol forms the backbone of bile-acid production, this has massive consequences for downstream absorption of lipids emulsions and implied interactions with gut microbiota during stabilisation and digestion of TAG-cores.
Interactions of gut bacteria with the lipid emulsion during digestion
Human breast milk is considered the optimal food for the growth and development of healthy infants, as well as pivotal for the initial establishment of human gut microbiota. However, many infants are not exclusively fed breast milk during the initial months post-delivery, and previous work has indicated that formula-fed infants are more susceptible to diarrhea, pneumonia, and sepsis, which may be due to a lack of immunological support and colonisation resistance against pathogenic microorganisms provided by breast milk[52]. Indeed, receipt of breast milk was shown to be the most significant factor associated with infant gut microbiome composition, leading to an increased abundance and prolonged occurrence of bacteria of the genus Bifidobacterium, while cessation of breast milk was observed to be associated with a premature establishment of Bacillota instead[53]. However, it remains poorly understood how HMLs interact with intestinal microbiota during early-life succession. It is believed that the developing central and peripheral nervous systems account for the largest fraction of energy demand and expenditure during infancy[54]. Approximately half of this energy demand is met by digestible HMLs, such as TAGs[55]. The MFGM passes a TAG-rich core through the digestive tract in the presence of gastrointestinal bacteria. For neurons to receive this energy, homeostasis between the immune system and the microbiome is favourable[56] during the digestion of a TAG emulsion. Questions remain as to where in the gut TAGs and other lipids are preferentially absorbed and under which circumstances colonising bacteria aid in absorption or become opportunistic scavengers of released nutrients.
Digestion of MFGs starts in the stomach, where gastric proteases begin to hydrolyse MFGM-bound proteins at low pH[57]. This partially destabilises the membrane and releases nutritious fat while simultaneously releasing sphingomyelins and cholesterol stabilise the coagulate, enabling adherence of lipases secreted from gastric mucus[58]. Gastric absorption of lipids is of higher relevance shortly post-delivery, as duodenal absorption is deficient due to the initial lack of bile acids and pancreatic lipases in the duodenum and onwards[59]. Bile acids are synthesised from cholesterol in the liver[60], and once their synthesis is steadily established, primary bile acids are secreted from the gallbladder in dependence on ingested cholesterol: phosphatidylcholine ratios[61]. The primary bile acid profile in infants predominantly consists of cholic acid (CA) and chenodeoxycholic acid (CDCA), with a greater proportion of CA and its conjugates than CDCA and its conjugates[62]. These (conjugated) primary bile acids are key for the degradation of MFGs in the small intestine, where they ensure the removal of lipolytic products from the oil-water interface as surface-active molecules, coordinate micellar solubilisation, and stabilise lipid droplets against aggregation[63]. They furthermore stimulate the activity of lipases such as the bile salt-stimulated lipase (BSSL)[64]. Interestingly, BSSL is also produced in mammary glands and seeded via breast-feeding, while other lipases are only produced in the pancreas, such as pancreatic lipase-related proteins (PLRP) and pancreatic triglyceride lipase (PTL)[57]. Around 95% of all bile acids reabsorbed in the distal ileum enter hepatic recirculation[65]. The remaining, however, are subjected to microbial translation into secondary bile acids via microbial deconjugation, oxidation, epimerisation, 7-dehydroxylation, esterification, and desulfation. To do so, GIT microbes employ bile salt hydrolases (BSHs) in the presence of taurine or glycine to deconjugate primary bile acids[66], a process that largely takes place in the small intestine and results in the hydrolysis of amide bonds in primary bile acids and leads to the release of free amino acids[67]. Generally, the microbiome from duodenum to ileum is phylogenetically less diverse and has lower biomass in total compared to the colon[68]. Bacterial genera commonly found in the infant small intestine include Lactobacillus, Clostridium, Staphylococcus, Streptococcus, Bacteroides, and Bifidobacterium[69], many of which reportedly show respective BSH activity[70]. Currently, only a few three-dimensional structures of the BSH enzyme have been reported, including those of bacteria that are prevalent initial colonisers of the infant gut, such as Bifidobacterium longum[71], Enterococcus faecalis[72], and Clostridium perfringens[73]. While each is similar in topology, they display different catalytic efficiencies and substrate preferences[74]. It is well known that some of these bacteria establish as commensals in the human gut, while others may be detrimental to health when overly abundant, with a “disturbed” microbial composition potentially being funnelled via key actions of strain-specific BSH activities. Importantly, secondary bile acids escape hepatic recirculation, which reportedly, in turn, decreases cholesterol absorption and enhances its fecal excretion via modulation of farnesoid X receptor (FXR) signalling[75]. Microbial modulation of bile acid profiles has been linked to inflammatory bowel disease (IBD), with related FXR modifications as an underlying mechanism of gut barrier destabilisation[76]. Furthermore, microbial bile acid deconjugation was shown to involve immunological modifications, whereby ω-muricholic acid (ω-MCA) and 3β-hydroxydeoxycholic acid (isoDCA) in particular have been shown to stimulate dendritic cell recruitment and increase the frequency of Foxp3+ T regulatory cells[77]. However, it remains unclear which species are responsible for the given transformations.
Temporal & incidental variability of human milk lipid composition
The size of the MFG and its lipid composition varies across the lactation period and is reflective of the needs of the infant[78]. Generally, a slight increase in the size of MFGs as well as total milk fat content was observed with the time of lactation[79], likely to meet the increased caloric needs. However, MFG size has been shown to be surprisingly large in colostrum during the first two days post-delivery[80], presumably as an adaption to the immature digestive tract and enteric immune system of the newborn. Phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin contribute up to 40% of all MFGM phospholipids, which are subject to intra-individual variation, especially during early lactation, with concentrations ranging from 140 mg/L to 410 mg/L[81], reflective of the plasticity of the MFGM during early life. Lactobacillus species have been shown to either incorporate or coat themselves with milk-derived phospholipids in a species-dependent manner, whereby they increase their surface electronegativity, which results in increased adherence to epithelial cells[82]. Species of the genus Lactobacillus are well-known commensals of the small intestine with many anti-inflammatory properties, and their successful establishment in the GIT is believed to contribute to the colonisation resistance against enteric pathogens[83]. Furthermore, phospholipids, as reviewed in detail elsewhere[84], are important metabolites for intestinal cell integrity and maturation, and disruptions in sphingolipid metabolism were previously implied in the pathogenesis of preterm necrotising enterocolitis[85]. Interestingly, cholesterol concentrations appear to decrease during lactation as well[86], which may have implications for bile acid production. Alongside changes in lipid composition, researchers repeatedly find reoccurring patterns of microbial succession during early life. In general, these include a transition of dominance from facultative anaerobic bacteria to a fully anaerobic lifestyle in the late phases of colonisation[87]. Under anaerobic conditions, intestinal bacteria ferment dietary carbohydrates and produce short-chain fatty acid (SCFA) end-products such as acetate, butyrate, and lactate, the composition of which varies depending on underlying microbial fingerprints[88]. SCFAs have many important interactions with the human host, including the importance of differentiation of dendritic cells[89], as well as the promotion of mucus secretion and epithelial barrier integrity[90]. Interestingly, SCFAs are found in HM[91], presumably to compensate for the initial lack of intestinal SCFA production in infant microbiota.
Infant sex and socioeconomic status are involved in HM composition and early life microbiome establishment
Collective evidence suggests that the composite of HBM is personalised in order to secure optimal developmental conditions for the infant[92]. This highlights the necessity of future research to study mother-infant pairs in order to gain a better understanding of infant nutrition, including the role of HMLs, and early-life gut microbiome establishment. However, non-stochastic sources of variability, such as the difference of sex, provide partial explanations for the observed variance, as metabolic requirements between male and female newborns diverge[93], implying disparities for BM absorption[94] and microbiome establishment[95], which should not be overlooked in future research planning. It was recently highlighted that human milk provides sex-specific growth advantages, even implying the existence of sex-specific micronutrients[96]. Indeed, there are several observations of sexual dimorphism and its obvious connection to nutrition. Overall, male and female growth rates differ[97], and given that the majority of energy is delivered via HMLs, it is implied that HML composition and absorption may differ according to infant sex, while indeed, mothers of male infants produce BM with a higher energy content that mothers of female infants[98]. However, little is known whether microbiome-affecting lipids of the MFGM differ in dependency on infant sex, while several studies indicate there are potential sex-dependent differences in gut microbiota at different stages post-delivery. For example, it was reported that male premature infants have less rich microbiota with higher numbers of Enterobacteriales, as compared to female premature infants who show higher numbers of Clostridiales[99], while another study reported on elevated abundances of Bacteroides spp. in female infants[100]. Also, there is strong evidence indicating that male infants are at higher risk for morbidities when challenged by perinatal complications[101], but the underlying causes are not well-researched and practical guidelines for differential nutritional strategies are lacking. Maternal diet has furthermore been linked to BML contents and related growth of offspring[102]. Socioeconomic status furthermore is linked to the human diet[103] and, therefore, partially underlies the HM content of lactating mothers. While the relationship is complex, obesity as well as malnourishment manifest in association with poverty[104]. It was shown that overall milk lipid contents are negatively associated with the BMI of Congolese mothers[105], and HM fatty acid composition, especially levels of long-chain polyunsaturated fatty acids, were related to the socioeconomic status of Iraqi mothers[106]. Furthermore, it is well known that infant sex and socioeconomic status interactively define milk fat concentrations, given that mothers of sufficient socioeconomic status produce milk richer in fat for male offspring, while mothers of lower socioeconomic status produce milk richer in fat for female offspring[107]. However, it is not well understood how this affects the content of MFGMs and related downstream effects on microbiome establishment.
Conclusion and future prospects of HML research
A balanced establishment of early-life gut microbiota is seminal for health throughout life. Diet heavily influences this succession, and the MFGM represents a largely overlooked interface for cross-communication between establishing microbiota and the developing infant. The MFGM contains a selective repertoire of molecules to strengthen colonisation success for human commensal bacteria and colonisation resistance against opportunistic pathogens, while simultaneously delivering a major fraction of energy supply through the digestive tract. In order to understand the various effects of HMLs on early life microbiome establishment, constituent parts of the MFGM and their effects on particular microorganisms during digestion of human milk is a key area for future research. For example, stable-isotope probing (SIP) techniques are extensively discussed for general application in the inquiry of human microbiomes[108] and could be employed for the detection of utilisation of respective MFGM components by particular microorganisms of the establishing infant gut microbiome. Thereby, mechanisms underlying pathogenicity or colonisation resistance could be identified, described, and attributed to respective microorganisms. Diarrhea remains a major cause of child mortality[109], and neurophysiological impairments following premature birth have been linked to aberrant development of the enteric microbiota[88]. Therefore, globally many infants and their families would benefit from such additional research to improve colonisation resistance against pathogenic microorganisms and to improve outcomes against serious infections with novel therapeutic options while concurrently reducing antibiotic usage, which is also linked to the antimicrobial resistance crisis. Furthermore, our understanding of early-life microbiota is biased, as most sequencing efforts have focused on samples from high-income countries. Therefore, future microbiota profiling and dietary mechanistic studies should be broadened to capture a more global and true perspective on infant gut microbial communities and the diversity and impact of HMLs.
DECLARATIONS
Authors’ contributionsConceived, planned, drafted, and finalised the review article: Hall LJ, Seki D
Reviewed the associated literature: Seki D
Sourced and reviewed the current literature and final draft: Errerd T
Availability of data and materialsNot applicable.
Financial support and sponsorshipLindsay J. Hall is supported by Wellcome Trust Investigator Awards (100974/C/13/Z) and (220876/Z/20/Z); and a BBSRC Institute Strategic Programme, Gut Microbes and Health (BB/R012490/1), and its constituent projects (BBS/E/F/000PR10353) and (BBS/E/F/000PR10356).
Conflicts of interestAll authors declared that there are no conflicts of interest.
Ethical approval and consent to participateNot applicable.
Consent for publicationNot applicable.
Copyright© The Author (s) 2023.
REFERENCES
1. Khaldi N, Vijayakumar V, Dallas DC, et al. Predicting the important enzymes in human breast milk digestion. J Agric Food Chem 2014;62:7225-32.
2. Neville MC, Anderson SM, McManaman JL, et al. Lactation and neonatal nutrition: defining and refining the critical questions. J Mammary Gland Biol Neoplasia 2012;17:167-88.
3. Böttcher MF, Jenmalm MC, Garofalo RP, Björkstén B. Cytokines in breast milk from allergic and nonallergic mothers. Pediatr Res 2000;47:157-62.
4. Valverde R, Dinerstein N, Vain N. Mother’s own milk and donor milk. In: Koletzko B, Cheah F, Domellöf M, Poindexter BB, Vain N, van Goudoever JB, editors. Nutritional Care of Preterm Infants. S. Karger AG; 2021. pp. 212-24.
5. Grote V, Verduci E, Scaglioni S, et al. Breast milk composition and infant nutrient intakes during the first 12 months of life. Eur J Clin Nutr 2016;70:250-6.
6. Sela DA, Mills DA. Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides. Trends Microbiol 2010;18:298-307.
7. Kent JC, Mitoulas LR, Cregan MD, Ramsay DT, Doherty DA, Hartmann PE. Volume and frequency of breastfeedings and fat content of breast milk throughout the day. Pediatrics 2006;117:e387-95.
9. Kamao M, Tsugawa N, Suhara Y, et al. Quantification of fat-soluble vitamins in human breast milk by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2007;859:192-200.
10. Garwolińska D, Namieśnik J, Kot-Wasik A, Hewelt-Belka W. Chemistry of human breast milk-a comprehensive review of the composition and role of milk metabolites in child development. J Agric Food Chem 2018;66:11881-96.
11. Kalkwarf HJ, Zemel BS, Yolton K, Heubi JE. Bone mineral content and density of the lumbar spine of infants and toddlers: influence of age, sex, race, growth, and human milk feeding. J Bone Miner Res 2013;28:206-12.
12. Yuksel S, Yigit AA, Cinar M, Atmaca N, Onaran Y. Oxidant and antioxidant status of human breast milk during lactation period. Dairy Sci Technol 2015;95:295-302.
13. Miyake H, Lee C, Chusilp S, et al. Human breast milk exosomes attenuate intestinal damage. Pediatr Surg Int 2020;36:155-63.
14. Cavaletto M, Giuffrida MG, Conti A. Milk fat globule membrane components-a proteomic approach. In: Bösze Z, editor. Bioactive Components of Milk. New York: Springer; 2008. pp. 129-41.
15. Seki D, Schauberger C, Hausmann B, Berger A, Wisgrill L, Berry D. Individuality of the extremely premature infant gut microbiota is driven by ecological drift. mSystems 2022;7:e0016322.
16. Martinez-Guryn K, Hubert N, Frazier K, et al. Small intestine microbiota regulate host digestive and absorptive adaptive responses to dietary lipids. Cell Host Microbe 2018;23:458-469.e5.
17. Thum C, Wall C, Day L, et al. Changes in human milk fat globule composition throughout lactation: a review. Front Nutr 2022;9:835856.
18. Brink LR, Lönnerdal B. Milk fat globule membrane: the role of its various components in infant health and development. J Nutr Biochem 2020;85:108465.
19. Gurnida DA, Rowan AM, Idjradinata P, Muchtadi D, Sekarwana N. Association of complex lipids containing gangliosides with cognitive development of 6-month-old infants. Early Hum Dev 2012;88:595-601.
20. Park EJ, Suh M, Ramanujam K, Steiner K, Begg D, Clandinin MT. Diet-induced changes in membrane gangliosides in rat intestinal mucosa, plasma and brain. J Pediatr Gastroenterol Nutr 2005;40:487-95.
21. Yu RK, Tsai YT, Ariga T, Yanagisawa M. Structures, biosynthesis, and functions of gangliosides - an overview. J Oleo Sci 2011;60:537-44.
22. Rueda R. The role of dietary gangliosides on immunity and the prevention of infection. Br J Nutr 2007;98 Suppl 1:S68-73.
23. Bode L, Beermann C, Mank M, Kohn G, Boehm G. human and bovine milk gangliosides differ in their fatty acid composition. J Nutr 2004;134:3016-20.
24. Ma L, Macgibbon AK, Jan Mohamed HJB, et al. Determination of ganglioside concentrations in breast milk and serum from Malaysian mothers using a high performance liquid chromatography-mass spectrometry-multiple reaction monitoring method. Int Dairy J 2015;49:62-71.
25. Salcedo J, Barbera R, Matencio E, Alegría A, Lagarda MJ. Gangliosides and sialic acid effects upon newborn pathogenic bacteria adhesion: an in vitro study. Food Chem 2013;136:726-34.
26. Bergner DW, Kuhlenschmidt TB, Hanafin WP, Firkins LD, Kuhlenschmidt MS. Inhibition of rotavirus infectivity by a neoglycolipid receptor mimetic. Nutrients 2011;3:228-44.
27. Terabayashi T, Morita M, Ueno M, Nakamura T, Urashima T. Inhibition of influenza-virus-induced cytopathy by sialylglycoconjugates. Carbohydr Res 2006;341:2246-53.
28. Wölfl M, Batten WY, Posovszky C, Bernhard H, Berthold F. Gangliosides inhibit the development from monocytes to dendritic cells. Clin Exp Immunol 2002;130:441-8.
29. Lee H, Garrido D, Mills DA, Barile D. Hydrolysis of milk gangliosides by infant-gut associated bifidobacteria determined by microfluidic chips and high-resolution mass spectrometry. Electrophoresis 2014;35:1742-50.
30. Zhou J, Xiong X, Wang KX, Zou LJ, Ji P, Yin YL. Ethanolamine enhances intestinal functions by altering gut microbiome and mucosal anti-stress capacity in weaned rats. Br J Nutr 2018;120:241-9.
31. Buddington RK, Chizhikov VV, Iskusnykh IY, et al. A phosphatidylserine source of docosahexanoic acid improves neurodevelopment and survival of preterm pigs. Nutrients 2018;10:637.
32. Hu S, Du M, Su L, Yang H. Phosphatidylserine from portunus trituberculatus eggs alleviates insulin resistance and alters the gut microbiota in high-fat-diet-fed mice. Mar Drugs 2020;18:483.
33. Silber P, Borie RP, Mikowski EJ, Goldfine H. Phospholipid biosynthesis in some anaerobic bacteria. J Bacteriol 1981;147:57-61.
34. Rocha-Mendoza D, Kosmerl E, Miyagusuku-Cruzado G, Giusti MM, Jiménez-Flores R, García-Cano I. Growth of lactic acid bacteria in milk phospholipids enhances their adhesion to Caco-2 cells. J Dairy Sci 2020;103:7707-18.
35. Geiger O, López-Lara IM, Sohlenkamp C. Phosphatidylcholine biosynthesis and function in bacteria. Biochim Biophys Acta 2013;1831:503-13.
36. Vulevic J, Gibson GR. In vitro effects of phosphatidylcholine and transgalactooligosaccharides on the production of 1,2-sn-diacylglycerol by Bifidobacterium longum biovar infantis. J Appl Microbiol 2008;105:1678-85.
37. Sprong RC, Hulstein MF, Van der Meer R. Bactericidal activities of milk lipids. Antimicrob Agents Chemother 2001;45:1298-301.
38. Norris G, Porter C, Jiang C, Blesso C. Dietary milk sphingomyelin reduces systemic inflammation in diet-induced obese mice and inhibits LPS activity in macrophages. Beverages 2017;3:37.
39. Norris GH, Jiang C, Ryan J, Porter CM, Blesso CN. Milk sphingomyelin improves lipid metabolism and alters gut microbiota in high fat diet-fed mice. J Nutr Biochem 2016;30:93-101.
40. Gupta VR, Patel HK, Kostolansky SS, Ballivian RA, Eichberg J, Blanke SR. Sphingomyelin functions as a novel receptor for Helicobacter pylori VacA. PLoS Pathog 2008;4:e1000073.
41. Possemiers S, Van Camp J, Bolca S, Verstraete W. Characterization of the bactericidal effect of dietary sphingosine and its activity under intestinal conditions. Int J Food Microbiol 2005;105:59-70.
42. Ham Y, Kim TJ. Inhibitory activity of monoacylglycerols on biofilm formation in Aeromonas hydrophila, Streptococcus mutans, Xanthomonas oryzae, and Yersinia enterocolitica. Springerplus 2016;5:1526.
43. Wang ZJ, Liang CL, Li GM, Yu CY, Yin M. Stearic acid protects primary cultured cortical neurons against oxidative stress. Acta Pharmacol Sin 2007;28:315-26.
44. Ivanova EP, Nguyen SH, Guo Y, et al. Bactericidal activity of self-assembled palmitic and stearic fatty acid crystals on highly ordered pyrolytic graphite. Acta Biomater 2017;59:148-57.
45. Yaron S, Shachar D, Abramas L, et al. Effect of high β-palmitate content in infant formula on the intestinal microbiota of term infants. J Pediatr Gastroenterol Nutr 2013;56:376-81.
46. Williams VR, Fieger E. Oleic acid as a growth stimulant for lactobacillus Casei. J Biol Chem 1946;166:335-43.
47. Huang WC, Tsai TH, Chuang LT, Li YY, Zouboulis CC, Tsai PJ. Anti-bacterial and anti-inflammatory properties of capric acid against Propionibacterium acnes: a comparative study with lauric acid. J Dermatol Sci 2014;73:232-40.
48. Wright MH, Heal WP, Mann DJ, Tate EW. Protein myristoylation in health and disease. J Chem Biol 2010;3:19-35.
49. Oepen K, Özbek H, Schüffler A, Liermann JC, Thines E, Schneider D. Myristic acid inhibits the activity of the bacterial ABC transporter BmrA. Int J Mol Sci 2021;22:13565.
50. Le TT, Van de Wiele T, Do TN, et al. Stability of milk fat globule membrane proteins toward human enzymatic gastrointestinal digestion. J Dairy Sci 2012;95:2307-18.
51. Kenny DJ, Plichta DR, Shungin D, et al. Cholesterol metabolism by uncultured human gut bacteria influences host cholesterol level. Cell Host Microbe 2020;28:245-257.e6.
53. Stewart CJ, Ajami NJ, O'Brien JL, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature 2018;562:583-8.
54. Cunnane SC, Crawford MA. Energetic and nutritional constraints on infant brain development: implications for brain expansion during human evolution. J Hum Evol 2014;77:88-98.
55. Demmelmair H, Koletzko B. Lipids in human milk. Best Pract Res Clin Endocrinol Metab 2018;32:57-68.
56. Sharon G, Sampson TR, Geschwind DH, Mazmanian SK. The central nervous system and the gut microbiome. Cell 2016;167:915-32.
57. He X, McClorry S, Hernell O, Lönnerdal B, Slupsky CM. Digestion of human milk fat in healthy infants. Nutr Res 2020;83:15-29.
58. Moreau H, Bernadac A, Gargouri Y, Benkouka F, Laugier R, Verger R. Immunocytolocalization of human gastric lipase in chief cells of the fundic mucosa. Histochemistry 1989;91:419-23.
60. Javitt NB. Bile acid synthesis from cholesterol: regulatory and auxiliary pathways. FASEB J 1994;8:1308-11.
61. Reshetnyak VI. Physiological and molecular biochemical mechanisms of bile formation. World J Gastroenterol 2013;19:7341-60.
62. ENCRANTZ JC, SJOVALL J. On the bile acids in duodenal contents of infants and children. Bile acids and steroids 72. Clin Chim Acta 1959;4:793-9.
63. Reis P, Holmberg K, Watzke H, Leser ME, Miller R. Lipases at interfaces: a review. Adv Colloid Interf Sci 2009;147-148:237-50.
64. Hernell O, Bläckberg L. Human milk bile salt-stimulated lipase: functional and molecular aspects. J Pediatr 1994;125:S56-61.
65. Chen ML, Takeda K, Sundrud MS. Emerging roles of bile acids in mucosal immunity and inflammation. Mucosal Immunol 2019;12:851-61.
66. Bourgin M, Kriaa A, Mkaouar H, et al. Bile salt hydrolases: at the crossroads of microbiota and human health. Microorganisms 2021;9:1122.
67. Ridlon JM, Kang DJ, Hylemon PB. Bile salt biotransformations by human intestinal bacteria. J Lipid Res 2006;47:241-59.
68. Hayashi H, Takahashi R, Nishi T, Sakamoto M, Benno Y. Molecular analysis of jejunal, ileal, caecal and recto-sigmoidal human colonic microbiota using 16S rRNA gene libraries and terminal restriction fragment length polymorphism. J Med Microbiol 2005;54:1093-101.
69. Kastl AJ Jr, Terry NA, Wu GD, Albenberg LG. The structure and function of the human small intestinal microbiota: current understanding and future directions. Cell Mol Gastroenterol Hepatol 2020;9:33-45.
70. Núñez-Sánchez MA, Herisson FM, Keane JM, et al. Microbial bile salt hydrolase activity influences gene expression profiles and gastrointestinal maturation in infant mice. Gut Microbes 2022;14:2149023.
71. Kumar RS, Brannigan JA, Prabhune AA, et al. Structural and functional analysis of a conjugated bile salt hydrolase from Bifidobacterium longum reveals an evolutionary relationship with penicillin V acylase. J Biol Chem 2006;281:32516-25.
72. Chand D, Panigrahi P, Varshney N, Ramasamy S, Suresh CG. Structure and function of a highly active Bile Salt Hydrolase (BSH) from Enterococcus faecalis and post-translational processing of BSH enzymes. Biochim Biophys Acta Proteins Proteom 2018;1866:507-18.
73. Rossocha M, Schultz-Heienbrok R, von Moeller H, Coleman JP, Saenger W. Conjugated bile acid hydrolase is a tetrameric N-terminal thiol hydrolase with specific recognition of its cholyl but not of its tauryl product. Biochemistry 2005;44:5739-48.
74. Parasar B, Zhou H, Xiao X, Shi Q, Brito IL, Chang PV. Chemoproteomic profiling of gut microbiota-associated bile salt hydrolase activity. ACS Cent Sci 2019;5:867-73.
75. Thomas C, Pellicciari R, Pruzanski M, Auwerx J, Schoonjans K. Targeting bile-acid signalling for metabolic diseases. Nat Rev Drug Discov 2008;7:678-93.
76. Ogilvie LA, Jones BV. Dysbiosis modulates capacity for bile acid modification in the gut microbiomes of patients with inflammatory bowel disease: a mechanism and marker of disease? Gut 2012;61:1642-3.
77. Campbell C, McKenney PT, Konstantinovsky D, et al. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature 2020;581:475-9.
78. Lee H, Padhi E, Hasegawa Y, et al. Compositional dynamics of the milk fat globule and its role in infant development. Front Pediatr 2018;6:313.
79. Mizuno K, Nishida Y, Taki M, et al. Is increased fat content of hindmilk due to the size or the number of milk fat globules? Int Breastfeed J 2009;4:7.
80. Michalski MC, Briard V, Michel F, Tasson F, Poulain P. Size distribution of fat globules in human colostrum, breast milk, and infant formula. J Dairy Sci 2005;88:1927-40.
81. Cilla A, Diego Quintaes K, Barberá R, Alegría A. Phospholipids in human milk and infant formulas: benefits and needs for correct infant nutrition. Crit Rev Food Sci Nutr 2016;56:1880-92.
82. Ortega-Anaya J, Marciniak A, Jiménez-Flores R. Milk fat globule membrane phospholipids modify adhesion of Lactobacillus to mucus-producing Caco-2/Goblet cells by altering the cell envelope. Food Res Int 2021;146:110471.
83. Tien MT, Girardin SE, Regnault B, et al. Anti-inflammatory effect of Lactobacillus casei on Shigella-infected human intestinal epithelial cells. J Immunol 2006;176:1228-37.
84. Norris GH, Milard M, Michalski MC, Blesso CN. Protective properties of milk sphingomyelin against dysfunctional lipid metabolism, gut dysbiosis, and inflammation. J Nutr Biochem 2019;73:108224.
85. Rusconi B, Jiang X, Sidhu R, Ory DS, Warner BB, Tarr PI. Gut sphingolipid composition as a prelude to necrotizing enterocolitis. Sci Rep 2018;8:10984.
86. Kamelska AM, Pietrzak-fiećko R, Bryl K. Variation of the cholesterol content in breast milk during 10 days collection at early stages of lactation. Acta Biochim Pol 2012:59.
87. Guittar J, Shade A, Litchman E. Trait-based community assembly and succession of the infant gut microbiome. Nat Commun 2019;10:512.
88. Seki D, Mayer M, Hausmann B, et al. Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage. Cell Host Microbe 2021;29:1558-1572.e6.
89. Benakis C, Brea D, Caballero S, et al. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells. Nat Med 2016;22:516-23.
90. Pérez-Reytor D, Puebla C, Karahanian E, García K. Use of short-chain fatty acids for the recovery of the intestinal epithelial barrier affected by bacterial toxins. Front Physiol 2021;12:650313.
91. Jiang Z, Liu Y, Zhu Y, et al. Characteristic chromatographic fingerprint study of short-chain fatty acids in human milk, infant formula, pure milk and fermented milk by gas chromatography-mass spectrometry. Int J Food Sci Nutr 2016;67:632-40.
92. Cacho NT, Harrison NA, Parker LA, et al. Personalization of the microbiota of donor human milk with mother’s own milk. Front Microbiol 2017;8:1470.
93. Alur P. Sex differences in nutrition, growth, and metabolism in preterm infants. Front Pediatr 2019;7:22.
94. Isaacs EB, Fischl BR, Quinn BT, Chong WK, Gadian DG, Lucas A. Impact of breast milk on intelligence quotient, brain size, and white matter development. Pediatr Res 2010;67:357-62.
95. Jašarević E, Morrison KE, Bale TL. Sex differences in the gut microbiome-brain axis across the lifespan. Philos Trans R Soc Lond B Biol Sci 2016;371:20150122.
96. Alur P, Ramarao S. Sex differences in preterm nutrition and growth: the evidence from human milk associated studies. J Perinatol 2022;42:987-92.
97. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 2013;13:59.
98. Powe CE, Knott CD, Conklin-Brittain N. Infant sex predicts breast milk energy content. Am J Hum Biol 2010;22:50-4.
99. Cong X, Xu W, Janton S, et al. Gut microbiome developmental patterns in early life of preterm infants: impacts of feeding and gender. PloS One 2016;11:e0152751.
100. Kozyrskyj AL, Kalu R, Koleva PT, Bridgman SL. Fetal programming of overweight through the microbiome: boys are disproportionately affected. J Dev Orig Health Dis 2016;7:25-34.
101. Jašarević E, Howard CD, Misic AM, Beiting DP, Bale TL. Stress during pregnancy alters temporal and spatial dynamics of the maternal and offspring microbiome in a sex-specific manner. Sci Rep 2017;7:44182.
102. Calvo-Lerma J, Selma-Royo M, Hervas D, et al. Breast milk lipidome is associated with maternal diet and infants’ growth. Front Nutr 2022;9:854786.
103. Bhurosy T, Jeewon R. Overweight and obesity epidemic in developing countries: a problem with diet, physical activity, or socioeconomic status? ScientificWorldJournal 2014;2014:964236.
104. Stunkard AJ, Sørensen TI. Obesity and socioeconomic status - a complex relation. N Engl J Med 1993;329:1036-7.
105. Rocquelin G, Tapsoba S, Dop MC, Mbemba F, Traissac P, Martin-Prével Y. Lipid content and essential fatty acid (EFA) composition of mature Congolese breast milk are influenced by mothers' nutritional status: impact on infants’ EFA supply. Eur J Clin Nutr 1998;52:164-71.
106. Al-Tamer YY, Mahmood AA. The influence of Iraqi mothers’ socioeconomic status on their milk-lipid content. Eur J Clin Nutr 2006;60:1400-5.
107. Fujita M, Roth E, Lo YJ, Hurst C, Vollner J, Kendell A. In poor families, mothers’ milk is richer for daughters than sons: a test of Trivers-Willard hypothesis in agropastoral settlements in Northern Kenya. Am J Phys Anthropol 2012;149:52-9.
108. Berry D, Loy A. Stable-isotope probing of human and animal microbiome function. Trends Microbiol 2018;26:999-1007.
109. Levine MM, Nasrin D, Acácio S, et al. Diarrhoeal disease and subsequent risk of death in infants and children residing in low-income and middle-income countries: analysis of the GEMS case-control study and 12-month GEMS-1A follow-on study. Lancet Glob Health 2020;8:e204-14.
110. Nakamura S, Kiyohara Y, Jinnai H, et al. Mammalian phospholipase D: phosphatidylethanolamine as an essential component. Proc Natl Acad Sci USA 1996;93:4300-4.
111. Rajkumar K, Nichita A, Anoor PK, Raju S, Singh SS, Burgula S. Understanding perspectives of signalling mechanisms regulating PEBP1 function. Cell Biochem Funct 2016;34:394-403.
112. Vance JE. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids. J Lipid Res 2008;49:1377-87.
113. Kimura AK, Kim HY. Phosphatidylserine synthase 2: high efficiency for synthesizing phosphatidylserine containing docosahexaenoic acid. J Lipid Res 2013;54:214-22.
114. Dohi M, Tamura G, Arima K. Effects of Phosphatidylinositol on Bacterial Protoplasts. Agric Biol Chem 1973;37:1797-807.
115. Zhang X, Majerus PW. Phosphatidylinositol signalling reactions. Semin Cell Dev Biol 1998;9:153-60.
116. . Back Matter. In: Zibadi S, Watson RR, Preedy VR, editors. Handbook of dietary and nutritional aspects of human breast milk. The Netherlands: Wageningen Academic Publishers; 2013. pp. 834-52.
117. Petersen EN, Chung HW, Nayebosadri A, Hansen SB. Kinetic disruption of lipid rafts is a mechanosensor for phospholipase D. Nat Commun 2016;7:13873.
118. Molinero N, Ruiz L, Sánchez B, Margolles A, Delgado S. Intestinal bacteria interplay with bile and cholesterol metabolism: implications on host physiology. Front Physiol 2019;10:185.
119. Paik JH, Chae Ss, Lee MJ, Thangada S, Hla T. Sphingosine 1-phosphate-induced endothelial cell migration requires the expression of EDG-1 and EDG-3 receptors and Rho-dependent activation of alpha vbeta3- and beta1-containing integrins. J Biol Chem 2001;276:11830-7.
120. Spiegel S, Milstien S. Sphingosine 1-phosphate, a key cell signaling molecule. J Biol Chem 2002;277:25851-4.
121. Duan RD, Cheng Y, Jönsson BA, et al. Human meconium contains significant amounts of alkaline sphingomyelinase, neutral ceramidase, and sphingolipid metabolites. Pediatr Res 2007;61:61-6.
123. Basson A, Trotter A, Rodriguez-Palacios A, Cominelli F. Mucosal interactions between genetics, diet, and microbiome in inflammatory bowel disease. Front Immunol 2016;7:290.
124. Innis SM, Dyer R, Nelson CM. Evidence that palmitic acid is absorbed as sn-2 monoacylglycerol from human milk by breast-fed infants. Lipids 1994;29:541-5.
125. Yao J, Rock CO. How bacterial pathogens eat host lipids: implications for the development of fatty acid synthesis therapeutics. J Biol Chem 2015;290:5940-6.
126. Hosomi K, Kiyono H, Kunisawa J. Fatty acid metabolism in the host and commensal bacteria for the control of intestinal immune responses and diseases. Gut Microbes 2020;11:276-84.
127. Isaacs CE. The antimicrobial function of milk lipids. In: Woodward B, Draper HH, editors. Advances in Nutritional Research Volume 10. Boston: Springer US; 2002. pp. 271-85.
128. Senyilmaz-Tiebe D, Pfaff DH, Virtue S, et al. Dietary stearic acid regulates mitochondria in vivo in humans. Nat Commun 2018;9:3129.
129. Nie W, Xu F, Zhou K, Yang X, Zhou H, Xu B. Stearic acid prevent alcohol-induced liver damage by regulating the gut microbiota. Food Res Int 2022;155:111095.
130. Haviv H, Habeck M, Kanai R, Toyoshima C, Karlish SJD. Neutral phospholipids stimulate Na,K-ATPase activity: a specific lipid-protein interaction. J Biol Chem 2013;288:10073-81.
131. Elias PM, Brown BE, Ziboh VA. The permeability barrier in essential fatty acid deficiency: evidence for a direct role for linoleic acid in barrier function. J Invest Dermatol 1980;74:230-3.
132. Clark KJ, Makrides M, Neumann MA, Gibson RA. Determination of the optimal ratio of linoleic acid to alpha-linolenic acid in infant formulas. J Pediatr 1992;120:S151-8.
133. Hamosh M, Peterson JA, Henderson TR, et al. Protective function of human milk: the milk fat globule. Semin Perinatol 1999;23:242-9.
134. Huyan Z, Pellegrini N, Steegenga W, Capuano E. Insights into gut microbiota metabolism of dietary lipids: the case of linoleic acid. Food Funct 2022;13:4513-26.
135. Ruiz-Núñez B, Dijck-Brouwer DA, Muskiet FA. The relation of saturated fatty acids with low-grade inflammation and cardiovascular disease. J Nutr Biochem 2016;36:1-20.
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Seki D, Errerd T, Hall LJ. The role of human milk fats in shaping neonatal development and the early life gut microbiota. Microbiome Res Rep 2023;2:8. http://dx.doi.org/10.20517/mrr.2023.09
AMA Style
Seki D, Errerd T, Hall LJ. The role of human milk fats in shaping neonatal development and the early life gut microbiota. Microbiome Research Reports. 2023; 2(2): 8. http://dx.doi.org/10.20517/mrr.2023.09
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Seki, David, Theresa Errerd, Lindsay J. Hall. 2023. "The role of human milk fats in shaping neonatal development and the early life gut microbiota" Microbiome Research Reports. 2, no.2: 8. http://dx.doi.org/10.20517/mrr.2023.09
ACS Style
Seki, D.; Errerd T.; Hall LJ. The role of human milk fats in shaping neonatal development and the early life gut microbiota. Microbiome. Res. Rep. 2023, 2, 8. http://dx.doi.org/10.20517/mrr.2023.09
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