Human milk microbiome
The human milk microbiota, also known as human milk probiotics , refers to the microbiota residing in the human mammary glands and breast milk. Human breast milk has been traditionally assumed to be sterile, but more recently both microbial culture and culture-independent techniques have confirmed that human milk contains diverse communities of bacteria which are distinct from other microbial communities inhabiting the human body.
The human milk microbiota which could be source of commensal, mutualistic, and potentially probiotic bacteria to the infant gut microbiota. The World Health Organization defines "probiotics" as "living organisms which when administered in adequate amounts confer a health benefit on the host".
Occurrence
Breast milk is a natural source of lactic acid bacteria for the newborn through breastfeeding, and may be considered a symbiotic food. The normal concentration of bacteria in milk from healthy women was about 103 colony-forming units per milliliter. The milk's bacterial communities were generally complex. Among the hundreds of operational taxonomic units detected in the milk of every woman, only nine were present in every sample from every woman, but an individual's milk bacterial community was generally stable over time. Human milk is a source of live Staphylococci, Streptococci, lactic acid bacteria, Bifidobacteria, Propionibacteria, Corynebacteria, and closely related Gram-positive bacteria for the infant gut.Composition
Breast milk was considered to be free of bacteria until about the early 2000s, when lactic acid bacteria were first described in human milk hygienically collected from healthy women. Several studies have shown that there is a mother-to-infant transfer of bacterial strains belonging, at least, to the genera Lactobacillus, Staphylococcus, Enterococcus, and Bifidobacterium through breastfeeding, thus accounting for the close relationship of bacterial composition of the gut microbiota of breastfed infants with that found in the breast milk of their respective mothers. Research has also found that there are similarities between human milk and infant gut microbial flora, suggesting that dietary exposure, such as human milk probiotics, may have a contribution in supporting infant gut microbiota and immune development.Bacteria commonly isolated in human milk samples include Bifidobacterium, Lactobacillus, Staphylococcus, Streptococcus, Bacteroides, Clostridium, Micrococcus, Enterococcus, and Escherichia. Metagenomic analyses of human milk find it is dominated by Staphylococcus, Pseudomonas, and Edwardsiella. The human milk microbiome likely varies by population and between individual women, however, a study based on a group of U.S. women observed the same nine bacterial taxa in all samples from all of their participants, suggesting a common "core" of the milk microbiome, at least in that population. Bacterial communities of human colostrum have been reported as being more diverse than those found in mature milk.
The three strains of Lactobacilli with probiotic properties that were isolated from breast milk were L. fermentum CECT5716, L. gasseri CECT5714, and L. salivarius CECT5713, with L. fermentum being one of the most abundant strains. Early administration of L. fermentum CECT5716 in infant formula is claimed to be safe and well tolerated for infants one to six months of age, and safe for long term use.
Origin
While the origins of the human milk microbiome are not exactly known, several hypotheses for its establishment have been proposed. Bacteria present in human milk may be derived from the surrounding breast skin flora, or the infant's oral cavity microbiota. Retrograde backflow during nursing or suckling may also lead to bacterial establishment in the mammary ducts, supported by the observation that a certain degree of flowback has been shown to occur during nursing using infrared photography. Alternatively, bacteria may be translocated to the mammary duct from the maternal gastrointestinal tract via an entero-mammary pathway, facilitated by dendritic cells.Environmental factors
Several factors may influence the composition of human milk probiotics, such as maternal body mass index, infant sex, birth modality, and mode of breastfeeding. A study done by Soto et al also revealed that Lactobacilli and Bifidobacteria are more commonly found in the human milk of women who did not receive any antibiotics during pregnancy and lactation.Human milk oligosaccharides, a primary component of human milk, are prebiotics which have been shown to promote growth of beneficial Bifidobacterium and Bacteroides species.
Maternal health
Maternal health status is associated with changes in the bacterial composition of milk. Higher maternal BMI and obesity are associated with changes in the levels of Bifidobacterium and Staphylococcus species and overall lower bacterial diversity. Milk of women with celiac disease is observed to have reduced levels of Bacteroides and Bifidobacterium. Women who are HIV-positive show higher bacterial diversity and increased abundances of Lactobacillus in their milk than do non-HIV-positive women. Mastitis has been linked to changes in human milk microbiota at the phylum level, lower microbial diversity, and decreased abundance of obligate anaerobic taxa.Women delivering term and preterm show differences in their milk microbiome composition, with mothers of term-births showing lower abundances of Enterococcus species and higher amounts of Bifidobacterium species in their milk compared to mothers of preterm births.
Few studies have been conducted examining the influence of maternal diet on the milk microbiome, but diet is known to influence other aspects of milk composition, such as the lipid profile, which in turn could affect its microbial composition. Variation in the fat and carbohydrate content of the maternal diet may influence the taxonomic composition of the milk microbiome.
Both the taxonomic composition and diversity of bacteria present in human milk likely vary by maternal geographic location, however studies with more geographically diverse participants are needed to better understand variation between populations.
Maternal perinatal antibiotic use is associated with changes in the prevalence of Lactobacillus, Bifidobacterium, Staphylococcus, and Eubacterium in milk.
Social network density of mother-infant dyads was found to be associated with increased bacterial diversity in the milk microbiome of mothers in the Central African Republic.
Delivery method
Mode of delivery may influence composition of the human milk microbiome. Vaginal births is associated with high taxonomic diversity and high prevalence of Bifidobacterium and Lactobacillus, and the opposite trend being seen with birth by caesarean section, however no relationship between delivery mode and the maternal milk microbiome has also been observed.Lactation stage
The human milk microbiome varies across lactation stage, with higher microbial diversity observed in colostrum than in mature milk. Taxonomic composition of human milk also varies across the lactation period, initially dominated by Weissella, Leuconostoc, Staphylococcus, Streptococcus, and Lactococcus species, and later composed primarily of Veillonella, Prevotella, Leptotrichia, Lactobacillus, Streptococcus, Bifidobacterium, and Enterococcus.Influences on health
Breastfeeding is thought to be an important driver of infant gut microbiome establishment. The gut microbiome of breastfed infants is less diverse, contains higher amounts of Bifidobacterium and Lactobacillus species, and fewer potential pathogenic taxa than the gut microbiome of formula-fed infants. Human milk bacteria may reduce risk of infection in breastfed infants by competitively excluding harmful bacteria, and producing antimicrobial compounds which eliminate pathogenic strains. Certain Lactobacilli and Bifidobacteria, the growth of which is stimulated by HMOs, contribute to healthy metabolic and immune-related functioning in the infant gut.Benefits for breastfeeding mother
Research studies showed that L. fermentum could improve mastitis, a common inflammatory disease associated with lactation, by reducing the number of Streptococcus load which is believed to be the causal agent and risk factor of mastitis.Benefit for infants
Breastfed children have a lower incidence of infections than formula-fed children, which could be mediated in part through modulation of the intestinal microflora by breast milk components. Indeed, breast-fed infants seem to develop a gut microflora richer in Lactobacilli and Bifidobacteria with reduced pathogenic bacteria compared with formula-fed infants. Research, by Maldonado et al, found that infants receiving a follow-on formula enriched with L. fermentum demonstrated a reduction in gastrointestinal and respiratory infections, thus the administration of such formula may be useful for the prevention of community-acquired gastrointestinal and upper respiratory infections in infants.Human milk probiotics could also act as pioneering species to increase the colonization of ‘beneficial’ bacteria and support the infant’s immature immune system. It is known that Lactobacilli and Bifidobacteria can suppress the growth of pathogenic microorganisms such as Salmonella typhimurium and Clostridium perfringens by colonization of a child's intestine and competing for nutrients, thus preventing their adhesion. Intestinal colonization by commensal bacteria also plays a vital role in maintaining homeostasis of immune system. These bacteria stimulate the T helper 1 response and counteract the trend towards a T helper 2 response of neonatal immune system, which in turn reducing the incidence of the inflammatory processes such as necrotizing enterocolitis.
Children with colic symptoms possibly have an imbalance in the intestinal microbiota – analyses of faecal samples found higher counts of coliform bacteria and lower counts of Lactobacilli in infants with colic symptoms compared with children not suffering from colic. On the other hand, probiotics have been shown to influence intestinal motility and sensory neurons as well as contractile activity of the intestine and to exert anti-inflammatory effects.