Metataxonomic and immunological analysis of milk from ewes with or without a history of mastitis.

Mastitis is a highly prevalent condition that has a great impact on milk production and animal welfare, and often requires substantial management efforts. For this reason, it is generally considered an important threat to the dairy industry. Many microbial, host, and environmental factors can protect against, predispose to, or influence the development of mastitis. The objective of this work was to characterize the milk microbiota of Manchega ewes, and to compare samples from animals with and without a history of mastitis. We analyzed milk samples from 36 ewes belonging to 2 different farms (18 ewes from each farm) using culture-dependent and culture-independent techniques. We also analyzed several immune compounds to investigate associations of mastitis with 3 main variables: farm; history of mastitis or no mastitis; and parity number. Both culture-dependent and culture-independent techniques showed that ewe milk harbored a site-specific complex microbiota and microbiome. Staphylococcus epidermidis was the main species driving the difference between farm A (where it was the dominant species) and B (where it was not). In contrast, samples from farm B were characterized by the presence of a wide spectrum of other coagulase-negative staphylococci. Some of these species have already been associated with subclinical intramammary infections in ruminants. Of the 10 immune compounds assayed in this study, 3 were related to a history of mastitis [IL-8, IFN-γ, and IFN-gamma-induced protein 10 (IP-10)]. Increases in IL-8 concentrations in milk seemed to be a feature of subclinical mastitis in sheep, and in this study, this immune factor was detected only in samples from ewes with some episodes of mastitis and from the group with the highest somatic cell count. We also observed a positive correlation between the samples with the highest somatic cell count and IFN-γ and IP-10 levels. Our results suggest that these 3 compounds could be used as biomarkers for the negative selection of mastitis-prone animals, particularly when somatic cell count is very high.

Prevention of Infectious Mastitis by Oral Administration of Lactobacillus salivarius PS2 During Late Pregnancy.

BACKGROUND: Previous studies have shown that oral administration of lactobacilli can be an efficient approach to treat lactational infectious mastitis. In this trial, we have evaluated the potential of Lactobacillus salivarius PS2 to prevent this condition when orally administered during late pregnancy to women who had experienced infectious mastitis after previous pregnancies. METHODS: In this study, 108 pregnant women were randomly assigned to one of 2 groups. Those in the probiotic group (n = 55) ingested daily 9 log10 colony-forming units of L. salivarius PS2 from approximately week 30 of pregnancy until delivery, whereas those in the placebo group (n = 53) received a placebo. The occurrence of mastitis was evaluated during the first 3 months after delivery. RESULTS: Globally, 44 of 108 women (41%) developed mastitis; however, the percentage of women with mastitis in the probiotic group (25% [n = 14]) was significantly lower than in the control group (57% [n = 30]). When mastitis occurred, the milk bacterial counts in the probiotic group were significantly lower than those obtained in the placebo group. CONCLUSIONS: Oral administration of L. salivarius PS2 during late pregnancy appears to be an efficient method to prevent infectious mastitis in a susceptible population. CLINICAL TRIALS REGISTRATION: NCT01505361.

Early Gut Colonization of Preterm Infants: Effect of Enteral Feeding Tubes.

OBJECTIVE: The aim of the study was to evaluate the potential colonization of nosocomial bacteria in enteral feeding systems and its effect on early gut colonization of preterm neonates. METHODS: Mother's own milk, donor milk, and preterm formula samples obtained after passing through the external part of the enteral feeding tubes were cultured. In addition, meconium and fecal samples from 26 preterm infants collected at different time points until discharge were cultured. Random amplification polymorphism DNA and pulse field gel electrophoresis were performed to confirm the presence of specific bacterial strains in milk and infant fecal samples. RESULTS: Approximately 4000 bacterial isolates were identified at the species level. The dominant species in both feces from preterm infants and milk samples were Staphylococcus epidermidis, S aureus, Enterococcus faecalis, E faecium, Serratia marcescens, Klebsiella pneumoniae, and Escherichia coli. All of them were present at high concentrations independently of the feeding mode. Random amplification polymorphism DNA and pulse field gel electrophoresis techniques showed that several bacteria strains were found in both type of samples. Furthermore, scanning electron microscopy revealed the presence of a dense bacterial biofilm in several parts of the feeding tubes and the tube connectors. CONCLUSIONS: There is a sharing of bacterial strains between the neonates' gastrointestinal microbiota and the feeding tubes used to feed them.

Evaluation of technological properties of Enterococcus faecium CECT 8849, a strain isolated from human milk, for the dairy industry.

In this work, a variety of biochemical properties of Enterococcus faecium CECT 8849, which had been isolated from breast milk, were analyzed. Its acidifying capacity and proteolytic activity were low but, in contrast, remarkable peptidase and esterase activities were observed. Ethanol and 3-hydroxy-2-butanone were the most abundant volatile compounds found in experimental model cheese manufactured with E. faecium CECT 8849. This strain inhibited the growth of several Listeria monocytogenes and Listeria innocua strains in vitro. Enterocin A and B structural genes were detected in E. faecium CECT 8849. Model fermented milk and cheeses were manufactured from milk inoculated or not with L. innocua CECT 8848 (2.5-3 log10 colony forming units mL(-1)) using E. faecium CECT 8849 or Lactococcus lactis ESI 153 as starter cultures. Although E. faecium CECT 8849 controlled Listeria growth in both dairy models, it led to lower reduction in Listeria counts when compared with L. lactis ESI 153.

Risk Factors Predicting Infectious Lactational Mastitis: Decision Tree Approach versus Logistic Regression Analysis.

Objectives Lactational mastitis frequently leads to a premature abandonment of breastfeeding; its development has been associated with several risk factors. This study aims to use a decision tree (DT) approach to establish the main risk factors involved in mastitis and to compare its performance for predicting this condition with a stepwise logistic regression (LR) model. Methods Data from 368 cases (breastfeeding women with mastitis) and 148 controls were collected by a questionnaire about risk factors related to medical history of mother and infant, pregnancy, delivery, postpartum, and breastfeeding practices. The performance of the DT and LR analyses was compared using the area under the receiver operating characteristic (ROC) curve. Sensitivity, specificity and accuracy of both models were calculated. Results Cracked nipples, antibiotics and antifungal drugs during breastfeeding, infant age, breast pumps, familial history of mastitis and throat infection were significant risk factors associated with mastitis in both analyses. Bottle-feeding and milk supply were related to mastitis for certain subgroups in the DT model. The areas under the ROC curves were similar for LR and DT models (0.870 and 0.835, respectively). The LR model had better classification accuracy and sensitivity than the DT model, but the last one presented better specificity at the optimal threshold of each curve. Conclusions The DT and LR models constitute useful and complementary analytical tools to assess the risk of lactational infectious mastitis. The DT approach identifies high-risk subpopulations that need specific mastitis prevention programs and, therefore, it could be used to make the most of public health resources.

Bacteriological, biochemical, and immunological properties of colostrum and mature milk from mothers of extremely preterm infants.

OBJECTIVES: The objective of this work was to elucidate the influence of extremely premature birth (gestational age 24-27 weeks) on the microbiological, biochemical, and immunological composition of colostrum and mature milk. METHODS: A total of 17 colostrum and 34 mature milk samples were provided by the 22 mothers of extremely preterms who participated in this study. Bacterial diversity was assessed by culture-based methods, whereas the concentration of lactose, glucose, and myo-inositol was determined by a gas chromatography procedure. Finally, the concentrations of a wide spectrum of cytokines, chemokines, growth factors, and immunoglobulins were measured using a multiplex system. RESULTS: Bacteria were present in a small percentage of the colostrum and milk samples. Staphylococci, streptococci, and lactobacilli were the main bacterial groups isolated from colostrum, and they could be also isolated, together with enterococci and enterobacteria, from some mature milk samples. The colostrum concentrations of lactose and glucose were significantly lower than those found in mature milk, whereas the contrary was observed in relation to myo-inositol. The concentrations of most cytokines and immunoglobulins in colostrum were higher than in mature milk, and the differences were significant for immunoglobulin G3, immunoglobulin G4, interleukin (IL)-6, interferon-γ, interleukin-4 (IL-4), IL-13, IL-17, macrophage-monocyte chemoattractant protein-1 and macrophage inflammatory protein-1ß. CONCLUSIONS: The bacteriological, biochemical, and immunological content of colostrum and mature milk from mothers of extremely preterm infants is particularly valuable for such infants. Efforts have to be made to try that preterm neonates receive milk from their own mothers or from donors matching, as much as possible, the gestational age of the preterm.

Relationships between the genome and some phenotypical properties of Lactobacillus fermentum CECT 5716, a probiotic strain isolated from human milk.

Lactobacillus fermentum CECT 5716, isolated from human milk, has immunomodulatory, anti-inflammatory, and anti-infectious properties, as revealed by several in vitro and in vivo assays, which suggests a strong potential as a probiotic strain. In this work, some phenotypic properties of L. fermentum CECT 5716 were evaluated, and the genetic basis for the obtained results was searched for in the strain genome. L. fermentum CECT 5716 does not contain plasmids and showed neither bacteriocin nor biogenic amine biosynthesis ability but was able to produce organic acids, glutathione, riboflavin, and folates and to moderately stimulate the maturation of mouse dendritic cells. No prophages could be induced, and the strain was sensitive to all antibiotics proposed by European Food Safety Authority (EFSA) standards, while no transmissible genes potentially involved in antibiotic resistance were detected in its genome. Globally, there was an agreement between the phenotype properties of L. fermentum CECT 5716 and the genetic information contained in its genome.

Lactobacilli and bifidobacteria in human breast milk: influence of antibiotherapy and other host and clinical factors.

OBJECTIVE: The objective of this work was to study the lactobacilli and bifidobacteria population in human milk of healthy women, and to investigate the influence that several factors (including antibioteraphy during pregnancy and lactation, country and date of birth, delivery mode, or infant age) may exert on such population. METHODS: A total of 160 women living in Germany or Austria provided the breast milk samples. Initially, 66 samples were randomly selected and cultured on MRS-Cys agar plates. Then, the presence of DNA from the genera Lactobacillus and Bifidobacterium, and from most of the Lactobacillus and Bifidobacterium species that were isolated, was assessed by qualitative polymerase chain reaction (PCR) using genus- and species-specific primers. RESULTS: Lactobacilli and bifidobacteria could be isolated from the milk of 27 (40.91%) and 7 (10.61%), respectively, of the 66 cultured samples. On the contrary, Lactobacillus and Bifidobacterium sequences were detected by PCR in 108 (67.50%) and 41 (25.62%), respectively, of the 160 samples analyzed. The Lactobacillus species most frequently isolated and detected was L salivarius (35.00%), followed by L fermentum (25.00%) and L gasseri (21.88%), whereas B breve (13.75%) was the bifidobacterial species most commonly recovered and whose DNA was most regularly found. The number of lactobacilli- or bifidobacteria-positive samples was significantly lower in women who had received antibiotherapy during pregnancy or lactation. CONCLUSIONS: Our results suggest that either the presence of lactobacilli and/or bifidobacteria or their DNA may constitute good markers of a healthy human milk microbiota that has not been altered by the use of antibiotics.

Case-control study of risk factors for infectious mastitis in Spanish breastfeeding women.

BACKGROUND: The purpose of this study was to identify potential predisposing factors associated with human infectious mastitis. METHODS: We conducted a case-control study among breastfeeding women, with 368 cases (women with mastitis) and 148 controls. Data were collected by a questionnaire designed to obtain retrospective information about several factors related to medical history of mother and infant, different aspects of pregnancy, delivery and postpartum, and breastfeeding practices that could be involved in mastitis. Bivariate analyses and multivariate logistic regression model were used to examine the relationship between mastitis and these factors. RESULTS: The variables significantly- and independently-associated with mastitis were cracked nipples (P < 0.0001), oral antibiotics during breastfeeding (P < 0.0001), breast pumps (P < 0.0001), topical antifungal medication during breastfeeding (P = 0.0009), mastitis in previous lactations (P = 0.0014), breast milk coming in later than 24 h postpartum (P = 0.0016), history of mastitis in the family (P = 0.0028), mother-infant separation longer than 24 h (P = 0.0027), cream on nipples (P = 0.0228) and throat infection (P = 0.0224). CONCLUSIONS: Valuable factors related to an increased risk of infectious mastitis have been identified. This knowledge will allow practitioners to provide appropriate management advice about modifiable risk factors, such as the use of pumps or inappropriate medication. They also could identify before delivery those women at an increased risk of developing mastitis, such as those having a familial history of mastitis, and thus develop strategies to prevent this condition.

Evaluation of Safety and Beneficial Health Effects of the Human-Milk Strain Bifidobacterium breve DSM32583: An Infant Pilot Trial.

Human milk promotes the growth of bifidobacteria in the infant gut. Adding bifidobacterial species to infant formula may contribute to increasing their presence in the gut of formula-fed infants. Therefore, the safety and anti-infectious effects of Bifidobacterium breve DSM32583, a breast milk isolate, were assessed in a pilot trial involving 3-month-old infants. The infants were randomly assigned to either the probiotic (PG) or the control (CG) groups. All the infants consumed the same formula, although it was supplemented with the strain (1 × 107 cfu/g of formula) in the PG. Overall, 160 infants (80 per group) finished the intervention. Infants in CG gained more weight compared to PG (p < 0.05), but the weights for age Z-scores at 6 months were within the normal distribution for this age group. The rates of infections affecting the gastrointestinal and respiratory tracts and antibiotic therapy were significantly lower in the PG. The bifidobacterial population and the level of short-chain fatty acids were higher (p < 0.05) in the fecal samples of PG infants. No adverse events related to formula consumption were observed. In conclusion, the administration of an infant formula with B. breve DSM32583 was safe and exerted potential beneficial effects on gut health.

Antibiotic resistance, virulence determinants and production of biogenic amines among enterococci from ovine, feline, canine, porcine and human milk.

BACKGROUND: Recent studies have shown that mammalian milk represents a continuous supply of commensal bacteria, including enterococci. The objectives of this study were to evaluate the presence of enterococci in milk of different species and to screen them for several genetic and phenotypic traits of clinical significance among enterococci. RESULTS: Samples were obtained from, at least, nine porcine, canine, ovine, feline and human healthy hosts. Enterococci could be isolated, at a concentration of 1.00 × 10(2) -1.16 × 10(3) CFU/ml, from all the porcine samples and, also from 85, 50, 25 and 25% of the human, canine, feline and ovine ones, respectively. They were identified as Enterococcus faecalis, Enterococcus faecium, Enterococcus hirae, Enterococcus casseliflavus and Enterococcus durans. Among the 120 initial enterococcal isolates, 36 were selected on the basis of their different PFGE profiles and further characterized. MLST analysis revealed a wide diversity of STs among the E. faecalis and E. faecium strains, including some frequently associated to hospital infections and novel STs. All the E. faecalis strains possessed some of the potential virulence determinants (cad, ccf, cob, cpd, efaA(fs), agg2, gelE, cylA, esp(fs)) assayed while the E. faecium ones only harboured the efaA(fm) gene. All the tested strains were susceptible to tigecycline, linezolid and vancomycin, and produced tyramine. Their susceptibility to the rest of the antimicrobials and their ability to produce other biogenic amines varied depending on the strain. Enterococci strains isolated from porcine samples showed the widest spectrum of antibiotic resistance. CONCLUSIONS: Enterococci isolated from milk of different mammals showed a great genetic diversity. The wide distribution of virulence genes and/or antibiotic resistance among the E. faecalis and E. faecium isolates indicates that they can constitute a reservoir of such traits and a risk to animal and human health.

The human milk microbiota: origin and potential roles in health and disease.

Human milk has been traditionally considered sterile; however, recent studies have shown that it represents a continuous supply of commensal, mutualistic and/or potentially probiotic bacteria to the infant gut. Culture-dependent and -independent techniques have revealed the dominance of staphylococci, streptococci, lactic acid bacteria and bifidobacteria in this biological fluid, and their role on the colonization of the infant gut. These bacteria could protect the infant against infections and contribute to the maturation of the immune system, among other functions. Different studies suggest that some bacteria present in the maternal gut could reach the mammary gland during late pregnancy and lactation through a mechanism involving gut monocytes. Thus, modulation of maternal gut microbiota during pregnancy and lactation could have a direct effect on infant health. On the other hand, mammary dysbiosis may lead to mastitis, a condition that represents the first medical cause for undesired weaning. Selected strains isolated from breast milk can be good candidates for use as probiotics. In this review, their potential uses for the treatment of mastitis and to inhibit mother-to-infant transfer of HIV are discussed.

Immunomodulation of the Vaginal Ecosystem by Ligilactobacillus salivarius CECT 30632 Improves Pregnancy Rates among Women with Infertility of Unknown Origin or Habitual Abortions.

In this study, the probiotic potential of Ligilactobacillus salivarius CECT 30632 was assessed, including properties specifically related with gynecological targets. This strain displayed co-aggregative and antimicrobial activity against a wide spectrum of vaginal pathogens while being respectful with the growth of vaginal lactobacilli. The strain produced a high concentration of lactic acid and displayed α-amylase activity when assayed in vitro. It showed a noticeable survival rate after exposition to conditions similar to those present in the human digestive tract and was adhesive to both vaginal and intestinal cells. Subsequently, their capacity to increase pregnancy rates among women with habitual abortion or infertility of unknown origin was studied. Administration of L. salivarius CECT 30632 (~9 log10 CFU) daily for a maximum of six months to these women was safe and led to a successful pregnancy rate of 67.5% (80% and 55% for women with repetitive abortion and infertile women, respectively). Significant differences in Nugent score, vaginal pH, and vaginal concentrations of lactobacilli, TGF-ß, and VEFG were observed when the samples collected before the intervention were compared with those collected after the treatment among those women who got pregnant. Therefore, this strain can modulate the vaginal ecosystem and lead to better fertility outcomes.

A randomized pilot trial assessing the reduction of gout episodes in hyperuricemic patients by oral administration of Ligilactobacillus salivarius CECT 30632, a strain with the ability to degrade purines.

Introduction: Hyperuricemia and gout are receiving an increasing scientific and medical attention because of their relatively high prevalence and their association with relevant co-morbidities. Recently, it has been suggested that gout patients have an altered gut microbiota. The first objective of this study was to investigate the potential of some Ligilactobacillus salivarius strains to metabolize purine-related metabolites. The second objective was to evaluate the effect of administering a selected potential probiotic strain in individuals with a history of hyperuricemia. Methods: Inosine, guanosine, hypoxanthine, guanine, xanthine, and uric acid were identified and quantified by high-performance liquid chromatography analysis. The uptake and biotransformation of these compounds by a selection of L. salivarius strains were assessed using bacterial whole cells and cell-free extracts, respectively. The efficacy of L. salivarius CECT 30632 to prevent gout was assessed in a pilot randomized controlled clinical trial involving 30 patients with hyperuricemia and a history of recurrent gout episodes. Half of the patients consumed L. salivarius CECT 30632 (9 log10 CFU/day; probiotic group; n = 15) for 6 months while the remaining patients consumed allopurinol (100-300 mg/daily; control group; n = 15) for the same period. The clinical evolution and medical treatment received by the participants were followed, as well as the changes in several blood biochemical parameters. Results: L. salivarius CECT 30632 was the most efficient strain for inosine (100%), guanosine (100%) and uric acid (50%) conversion and, therefore, it was selected for the pilot clinical trial. In comparison with the control group, administration of L. salivarius CECT 30632 resulted in a significant reduction in the number of gout episodes and in the use of gout-related drugs as well as an improvement in some blood parameters related to oxidative stress, liver damage or metabolic syndrome. Conclusion: Regular administration of L. salivarius CECT 30632 reduced serum urate levels, the number of gout episodes and the pharmacological therapy required to control both hyperuricemia and gout episodes in individuals with a history of hyperuricemia and suffering from repeated episodes of gout.

Complete genome sequence of Streptococcus salivarius PS4, a strain isolated from human milk.

Streptococcus salivarius is a commensal species commonly found in the human oropharyngeal tract. Some strains of this species have been developed for use as oral probiotics, while others have been associated with a variety of opportunistic human infections. Here, we report the complete sequence of strain PS4, which was isolated from breast milk of a healthy woman.

Complete genome sequence of Bifidobacterium breve CECT 7263, a strain isolated from human milk.

Bifidobacterium breve is an actinobacterium frequently isolated from colonic microbiota of breastfeeding babies. Here, we report the complete and annotated genome sequence of a B. breve strain isolated from human milk, B. breve CECT 7263. The genome sequence will provide new insights into the biology of this potential probiotic organism and will allow the characterization of genes related to beneficial properties.

Heating-induced bacteriological and biochemical modifications in human donor milk after holder pasteurisation.

OBJECTIVES: The objectives of the present study were to enumerate and characterize the pathogenic potential of the Bacillus population that may survive holder pasteurisation of human milk and to evaluate the nutritional damage of this treatment using the furosine and lactulose indexes. MATERIALS AND METHODS: Milk samples from 21 donors were heated at 62.5°C for 30 minutes. Bacterial counts, lactose, glucose, myoinositol, lactulose, and furosine were determined before and after the heat treatment. Some B cereus isolates that survived after pasteurisation were evaluated for toxigenic potential. RESULTS: Nonpasteurised milk samples showed bacterial growth in most of the agar media tested. Bacterial survival after pasteurisation was observed in only 3 samples and, in these cases, the microorganisms isolated belonged to the species B cereus. Furosine could not be detected in any of the samples, whereas changes in lactose, glucose, and myoinositol concentrations after holder pasteurisation were not relevant. Lactulose was below the detection limit of the analytical method in nonpasteurised samples, whereas it was found at low levels in 62% of the samples after holder pasteurisation. The lactation period influenced myoinositol content because its concentration was significantly higher in transition milk than in mature or late lactation milk samples. CONCLUSIONS: Holder pasteurisation led to the destruction of bacteria present initially in donor milk samples, except for some B cereus that did not display a high virulence potential and did not modify significantly the concentration of the compounds analyzed in the present study.

Interspecies relationships between nosocomial pathogens associated to preterm infants and lactic acid bacteria in dual-species biofilms.

The nasogastric enteral feeding tubes (NEFTs) used to feed preterm infants are commonly colonized by bacteria with the ability to form complex biofilms in their inner surfaces. Among them, staphylococci (mainly Staphylococcus epidermidis and Staphylococcus aureus) and some species belonging to the Family Enterobacteriaceae are of special concern since they can cause nosocomial infections in this population. NETF-associated biofilms can also include lactic acid bacteria (LAB), with the ability to compete with pathogenic species for nutrients and space. Ecological interactions among the main colonizers of these devices have not been explored yet; however, such approach could guide future strategies involving the pre-coating of the inner surfaces of NEFTs with well adapted LAB strains in order to reduce the rates of nosocomial infections in neonatal intensive care units (NICUs). In this context, this work implied the formation of dual-species biofilms involving one LAB strain (either Ligilactobacillus salivarius 20SNG2 or Limosilactobacillus reuteri 7SNG3) and one nosocomial strain (either Klebsiella pneumoniae 9SNG3, Serratia marcescens 10SNG3, Staphylococcus aureus 45SNG3 or Staphylococcus epidermidis 46SNG3). The six strains used in this study had been isolated from the inner surface of NEFTs. Changes in adhesion ability of the pathogens were characterized using a culturomic approach. Species interactions and structural changes of the resulting biofilms were analyzed using scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). No aggregation was observed in dual-species biofilms between any of the two LAB strains and either K. pneumoniae 9SNG3 or S. marcescens 10SNG3. In addition, biofilm thickness and volume were reduced, suggesting that both LAB strains can control the capacity to form biofilms of these enterobacteria. In contrast, a positive ecological relationship was observed in the combination L. reuteri 7SNG3-S. aureus 45SNG3. This relationship was accompanied by a stimulation of S. aureus matrix production when compared with its respective monospecies biofilm. The knowledge provided by this study may guide the selection of potentially probiotic strains that share the same niche with nosocomial pathogens, enabling the establishment of a healthier microbial community inside NEFTs.

Interactions between human milk oligosaccharides, microbiota and immune factors in milk of women with and without mastitis.

Lactational mastitis is an excellent target to study possible interactions between HMOs, immune factors and milk microbiota due to the infectious and inflammatory nature of this condition. In this work, microbiological, immunological and HMO profiles of milk samples from women with (MW) or without (HW) mastitis were compared. Secretor status in women (based on HMO profile) was not associated to mastitis. DFLNH, LNFP II and LSTb concentrations in milk were higher in samples from HW than from MW among Secretor women. Milk from HW was characterized by a low bacterial load (dominated by Staphylococcus epidermidis and streptococci), high prevalence of IL10 and IL13, and low sialylated HMO concentration. In contrast, high levels of staphylococci, streptococci, IFNγ and IL12 characterized milk from MW. A comparison between subacute (SAM) and acute (AM) mastitis cases revealed differences related to the etiological agent (S. epidermidis in SAM; Staphylococcus aureus in AM), milk immunological profile (high content of IL10 and IL13 in SAM and IL2 in AM) and milk HMOs profile (high content of 3FL in SAM and of LNT, LNnT, and LSTc in AM). These results suggest that microbiological, immunological and HMOs profiles of milk are related to mammary health of women.

The Gut‒Breast Axis: Programming Health for Life.

The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma.