Abstract
Background:: Current scientific research on breastfeeding provides substantial evidence of its numerous positive impacts, not only for children in both the short and long term but also for mothers who engage in breastfeeding. Summary:: In addition to the gold standard effect of human milk on infant nutrition, breastfeeding is associated with a lower incidence of infections, reduced infant/childhood mortality, necrotizing enterocolitis, and obesity during childhood and later in life, better cognitive performance, and a higher IQ score. For mothers, breastfeeding prolongs lactational amenorrhea, may facilitate postpartum weight loss, and may reduce breast and ovarian cancers and cardiovascular diseases. Breastfeeding can also play a beneficial role in preventing antibiotic resistance, which is a global concern across all age groups. Implementing exclusive breastfeeding for all infants has the potential to enhance child development and decrease healthcare expenses, leading to economic savings for both individual families and society. Human milk is a biologically active food that functions as both prebiotic and probiotic because of its oligosaccharides and the composition of its microbiota, which act as synergistic synbiotics.
Early-life conditioning like breastfeeding, which includes interactions between the mother and infant dyad, influences all aspects of life and can have beneficial effects on the community and future generations.
Nevertheless, conducting more extensive studies is important for validating the direct correlation between breastfeeding, the microbiome, and both short- and long-term infectious and noncommunicable diseases.
Introduction
Human milk (HM) is a unique and constantly changing source of food specifically customized to meet the individual needs of each infant and contains a variety of nutritional and bioactive components [1‒3]. HM is a complex fluid that comprises a diverse array of macro- and micronutrients, and includes bioactive components, such as biotics [1, 3‒5]. HM is not merely a nourishing substance, but rather a complex biological fluid that has profound and extensive impacts on a child’s health, psychology, and social behavior, and promotes physical and neurological development [6‒9]. It also has long-lasting effects on infant health, spanning from infancy to adolescence, and even into adulthood [1, 2, 4, 9‒13]. Current scientific research on breastfeeding (BF) provides substantial evidence of its numerous positive impacts, not only for children in both the short and long term but also for mothers who engage in BF [1, 2, 4, 10‒12]. Furthermore, according to the Barker hypothesis or Developmental Origins of Health and Disease (DOHaD), early-life conditioning, which includes interactions between the mother and infant dyad, influences all aspects of life and can also have beneficial effects on the community and future generations [14]. In this review, the short- and long-term effects of BF for the infant and mother, the microbiota and biotic content of HM, and the relationship between the benefits of HM and microbiota composition are evaluated.
Breastfeeding’s Short- and Long-Term Benefits for Infants and Children
BF is associated with a lower incidence of infections, mainly pneumonia and diarrhea, reduces dental caries, sudden infant death syndrome (SIDS), infant/childhood mortality, necrotizing enterocolitis, obesity, and diabetes during childhood and later in life. It is also linked with better cognitive performance and a higher Intelligence Quotient (IQ) score [1, 2, 4, 11, 12, 15] (Fig. 1).
Infectious Diseases and Antibiotic Resistance
In both developed and lower-middle-income countries (LMICs), BF reduces upper and lower respiratory tract infections, including pneumonia and bronchiolitis, acute otitis media, and diarrhea [1, 2, 4, 11, 12]. BF, and especially its exclusive use during the first 6 months of life, substantially protects against morbidity and mortality from diarrhea, reducing morbidity, hospital admissions, and mortality [12, 16]. BF is also associated with a significantly lower risk for pneumonia and otitis media, reducing the severity, hospitalizations, and morbidity related to these infections [1, 12]. These effects are also associated with exclusive and longer duration of BF.
Efforts to deal with antibiotic resistance should also consider policies that promote continued BF [17, 18]. Continued BF after 6 months conferred protection against children’s incident gut colonization with antibiotic resistant microorganisms [19]. Early BF improves the immune system against pathogens and reduces exposure to contaminated food and water, providing infants with 24 h of clean and personalized nutrition. BF reduces exposure to and infections with antimicrobial-resistant bacteria, reduces diarrhea and diarrhea-related hospitalizations, and reduces antibiotic use. HM microbiota, antimicrobial peptides, HMOs, maternal antibodies, immune cells, extracellular vesicles, and miRNAs all contribute to the protection of antimicrobial resistance [18].
Noncommunicable Diseases
Noncommunicable diseases progressively contribute more to the overall burden of disease around the world. Studies have established a connection between extended BF and a reduced likelihood of developing specific chronic conditions in the future, including obesity, diabetes, cardiovascular diseases (CVDs), inflammatory bowel diseases, asthma, and allergies [1, 2, 4, 11, 12].
Obesity
BF confers protection against obesity in both childhood and adulthood and can diminish the probability of being obese or overweight in the future [12]. The duration and exclusivity of BF appear to have a close link to this positive effect [12]. While most of the data originated from high-income countries, a meta-analysis of studies from LMICs found that BF reduced the risk of being overweight or obese by 24% [13]. The ability of infants to regulate their own feeding patterns and the unique composition of HM, particularly its hormonal content, may play a role in reducing the likelihood of obesity from early childhood to adolescence [1]. Additionally, these variables may be linked to the microbiota and other microbiome-related factors, and the benefits of BF may be associated with forming better eating habits beyond childhood [1, 20].
HM transmits the flavors of the mother’s food to the newborn, hence enhancing flavor learning by exposing the infant to a diverse range of flavors on multiple occasions. The early exposure of infants to different flavors has a significant impact on their future dietary preferences and their willingness to consume solid food [20, 21]. De Carvalho et al. [22] showed that exposure to BF is associated with lower consumption of ultra-processed foods and higher consumption of fresh or minimally processed foods in childhood, adolescence, and adulthood. Through the establishment of nutritious eating habits during the early stages of life, BF can play a role in diminishing the likelihood of obesity and associated metabolic problems in both childhood and adulthood [1, 20, 21]. The composition of the gut microbiome throughout early life has been linked to a higher likelihood of becoming obese [1, 23].
Exposure to BF is associated with lower consumption of ultra-processed foods and higher consumption of fresh or minimally processed foods in childhood, adolescence, and adulthood
Diabetes Mellitus
BF decreased the odds of diabetes mellitus [1, 4, 11‒13]. A meta-analysis of available studies suggested that it could provide a 24–32% reduction in type 2 diabetes [11]. Individuals who were mostly breastfed as newborns had a 35% lower likelihood of developing type 2 diabetes in their adult years [13]. There is also a potential method of preventing type 1 diabetes, although the reported findings regarding its effectiveness are contradictory [1].
Cardiovascular Health
Prior research has shown that BF results in a slight decrease in blood pressure levels in adults, as well as lower levels of total cholesterol and low-density lipoprotein cholesterol. Additionally, BF has been found to alter the body mass index of adults [4]. Callanan et al. [24] used the ROLO longitudinal birth cohort study to look at the effects of feeding and dietary habits, such as BF, on cardiometabolic outcomes in preteens. In their study, any HM exposure was associated with a lower body fat percentage (lower preteen adiposity) at 9–11 years, irrespective of duration. In 2024, McNestry et al. [25] reported a prospective 10-year longitudinal cohort study of 168 women and they showed that longer and exclusive BF is associated with favorable body composition, including lower fat mass index, tissue percentage fat, visceral adipose tissue volume, and lower cardiometabolic risk marker like glycoprotein acetyls [25].
Allergic Disorders
Evidence for the protection of BF against food allergies, eczema, and allergic rhinitis is unconvincing [1, 26]. BF has been shown to reduce the incidence of atopic dermatitis, particularly in the early infant period, and has revealed promising benefits in preventing food allergies in children with a positive family history of eczema [4]. Brew et al. [27] found a correlation between greater BF duration and a decreased likelihood of developing asthma in early infancy. Specifically, for every additional 3 months of BF, there was a favorable association with a reduced risk of asthma. Nevertheless, this impact was more pronounced in the group with a longer BF duration [27]. Silvers et al. [28] found that for every additional month of BF, there was a 7–8% decrease in the likelihood of infants developing asthma and wheezing by the time they reached 15 months of age. This study demonstrated that the length of time a child was exclusively breastfed is a more powerful indicator of respiratory disease than the length of time they were breastfed in general [28]. Observational studies have indicated that BF can reduce the negative effects of respiratory infections on the lungs, resulting in better lung function in school-aged children, especially those with a history of allergies [4].
Cancer
A meta-analysis conducted in 2015 revealed that BF for a duration of 6 months or more may lead to a 14–20% decrease in the occurrence of childhood leukemia. Additionally, there is a 9% reduced likelihood of leukemia in children who have been breastfed compared to those who have never been breastfed [29]. Rudant et al. [30] conducted a retrospective analysis in France and discovered that BF for over a year was linked to a 40% reduced risk of acute lymphoblastic leukemia when compared to no BF at all. Among a cohort of 300 pediatric patients diagnosed with various types of cancer, it was shown that the control group had a considerably longer BF duration compared to the patient group [31].
Intelligence and Cognitive Development
Several studies conducted throughout the years have focused on analyzing the relationship between BF and developmental outcomes, including IQ test scores [8, 9, 32‒34]. Research primarily conducted in wealthy nations indicated that the length of time a child is breastfed is linked to higher scores on intelligence tests and improved cognitive development [9]. Extended BF may be linked to enhancements in cognitive function and academic achievement lasting from childhood to adulthood [15]. The Belarus experiment, which involved 17,046 newborns, showed strong evidence that prolonged and exclusive BF has a positive impact on children’s cognitive development until they reach 6.5 years of age. The children assigned to a BF-supported group achieved a verbal IQ test score 7.5 points higher compared to the control group [35]. Based on a meta-analysis of 18 research studies, children and adolescents who were breastfed scored an average of 3.44 points higher than those who were not [9]. The correlation between BF and higher IQ in children provides additional evidence for the beneficial effects of this practice on the neurodevelopment of both full- and preterm children [1]. Although most of the research was conducted in high socioeconomic status environments and did not assess maternal IQ, the studies that did account for maternal IQ demonstrated a lesser advantage of BF, with an increase of only 2.62 points [1, 9]. The increase in IQ resulting from BF has a lasting effect, as individuals who were breastfed demonstrate enhanced performance in academic assessments into adolescence and maturity [9]. Infants who are breastfed exhibit elevated levels of vigor, which includes aspects such as social approach, activity level, and the strength of their reactions. BF also enhances language development compared to children who were not breastfed [36]. Furthermore, there are studies indicating a reduced likelihood of developing attention-deficit/hyperactivity disorder and autistic spectrum disorder among breastfed children [37, 38]. The components of HM (mainly human milk oligosaccharides and LCPUFAs) may work together in a synergistic manner to improve neurodevelopment [1, 4].
Premature and Small for Gestational Age Neonates
HM has been linked to a decreased occurrence of necrotizing enterocolitis and late-onset sepsis in premature newborns [2]. Premature infants who were given HM exhibited a greater IQ, while Zhang et al. [39] showed that BF leads to an increase in gray matter volume in specific brain regions, such as the right temporal lobe, left caudate nucleus, and bilateral frontal lobe, when compared to babies who were fed formula. Pagano et al. [40] discovered that the existing evidence about the long-term advantages of exclusive HM in small for gestational age and intrauterine growth retardation indicates a favorable impact on IQ, cognitive measures, physical measurements, heart-related metabolic parameters, growth, and bone strength [40].
Childhood Mortality
Infants and children who are breastfed have a lower risk of mortality from any cause and from infections. This link is shown up to the age of 2 years, and there is a direct relationship between the duration of BF and the decrease in mortality [1, 41]. A meta-analysis of over 130,000 infants revealed that infants who were exclusively breastfed and delayed BF initiation until 2–24 h after birth had a 33% higher risk of neonatal death compared to those who commenced BF within an hour of birth [42]. A meta-analysis of data from LMICs revealed that exclusive BF during the first 6 months of life significantly decreases mortality caused by infections by 88% compared to infants who were not breastfed at all [41]. Advocating for BF practices is also seen as a cost-efficient measure to reduce the occurrence of hospitalization and fatalities caused by respiratory infections [11].
Infants and children who are breastfed have a lower risk of mortality from any cause and from infections
HM also has advantageous effects in the prevention of SIDS, and the impact is more pronounced when BF is extended, although the underlying processes remain unknown [2]. A meta-analysis of six research studies indicated that newborns who were breastfed at any point experienced a 36% decrease in the occurrence of SIDS [12]. Breastfed infants exhibit a more consistent sleep pattern and demonstrate an enhanced capacity to rouse from deep sleep, which may explain their reduced susceptibility to SIDS [1].
The Benefits of Breastfeeding for Mothers
In addition to positively impacting the child’s health, BF may also reduce the mother’s susceptibility to several ailments. The immediate advantages of lactation for women’s health include decreased occurrence of infectious symptoms, less stress response, lower blood pressure, weight reduction, enhanced good moods, and improved reproductive control. Studies have found a strong connection between BF and long-term health outcomes [1, 11, 12, 15, 43] (Fig. 1).
Postpartum Beneficial Effects of Breastfeeding
Engaging in BF and practicing skin-to-skin contact immediately after giving birth aid in the process of postpartum healing by stimulating the production of oxytocin in the mother [1]. Lactating mothers report less anxiety, negative moods, and stress, as well as increased sleep duration and reduced sleep disturbances [44]. Research has shown that BF might reduce postpartum depression and stress, exhibiting a dose-response effect [1, 45]. The era of unregulated online forums, social media posts, and print media exacerbates this issue by subjecting moms to criticism for not BF or promoting unfavorable social attitudes toward BF [1, 46]. Various research studies conducted over several decades have consistently demonstrated that BF induces a phase of lactational amenorrhea, which assists in regulating the timing between births [12].
Lactating mothers report less anxiety, negative moods, and stress, as well as increased sleep duration and reduced sleep disturbances
Breast Cancer
Research has demonstrated a positive association between BF and a decreased relative likelihood of developing breast cancer [4, 10]. Victora et al. [10] examined a sample of 50,000 cancer patients from 30 different countries, revealing that for every 12 months of BF, there was a 4.3% decrease in breast cancer risk. Moreover, women who have given birth and breastfed at any time in their life have a 14% reduced likelihood of having breast cancer compared to those who have never breastfed [47]. Each year, approximately 20,000 deaths caused by breast cancer are averted [15]. In addition, mothers who test positive for the BRCA1 gene and breastfeed for a minimum of 1 year see a 37% reduction in their chance of developing breast cancer compared to carriers of the mutation who do not breastfeed [48].
Ovarian Cancer
Early and exclusive BF throughout the first months of an infant’s life may have a stronger effect on reducing the incidence of ovarian cancer [49, 50]. Comprehensive and robust meta-analyses have indicated that BF at any point in time, compared to never BF, as well as BF for longer durations, compared to shorter durations, has a quantifiable preventive impact on ovarian malignancies [4, 49]. BF for a duration of 1–3 months resulted in an 18% reduction in the likelihood of developing ovarian cancer, while BF for 12 months was linked to a 34% lower risk, and this risk reduction remains significant for many years [50]. Research has shown that women who have given birth to several children and breastfed them for long periods of time have a reduced likelihood of developing ovarian cancer compared to women who have never given birth or have less experience with BF [49, 50].
Cardiovascular Health
Maternal CVD risk is decreased by BF [2, 12]. Lactation can modify the balance of sugar and lipid levels in the mother’s body and impact the management of blood pressure, leading to decreased triglyceride levels and increased levels of HDL cholesterol [2]. Tschiderer et al. [43] conducted a comprehensive analysis of eight studies that included over 1.2 million women who had given birth. Their findings indicated that lactation provides protection against CVD (11%), future stroke (12%), coronary heart disease (14%), and fatal CVD (17%). They also discovered a gradual decrease in the risk of CVD with BF durations of up to 12 months over the course of a mother’s lifetime [43]. An analysis combining data from six cohort studies has shown that there is a 32% decrease in the chances of getting type 2 diabetes [51]. A study involving middle-aged and elderly women who breastfed for over 12 months in their lifetime showed a lower chance of experiencing a heart attack compared to women who had given birth but never breastfed. Furthermore, BF seemed to decrease mortality rates associated with ischemic heart disease [4]. Ajmera et al. [52] have shown that BF for a longer period, particularly beyond 6 months, is linked to a decreased likelihood of developing nonalcoholic fatty liver disease in middle age.
Societal and Economic Benefits of Breastfeeding
The advantages of BF extend beyond providing nourishment, as it is a very effective worldwide public health strategy that enhances child health, increases survival rates, and positively impacts adulthood [11, 15]. It facilitates the process of bonding between a mother and her newborn, promoting emotional connections and offering the baby a sense of warmth and security. Beneficial impact of BF on cognitive abilities may be attributed to familial context rather than nutritional factors [9]. There was a favorable correlation between BF and IQ, better education, and income in adulthood [34].
Implementing exclusive BF for all infants has the potential to enhance child development and decrease healthcare expenses, leading to economic savings for both individual families and nations [40]. Victora et al. [10] found that if all infants were breastfed within an hour of birth, exclusively for 6 months, and continuing until 2 years of age, BF might avert 823,000 deaths per year in children under the age of five. The occurrence of 20,000 maternal deaths caused by breast cancer might also be prevented with BF [10]. Furthermore, the overall impact on saving maternal lives would be much greater when considering the effects on ovarian cancer, hypertension, myocardial infarction, and type 2 diabetes [11].
Implementing exclusive BF for all infants has the potential to enhance child development and decrease healthcare expenses, leading to economic savings for both individual families and nations
Walters et al. [53] assessed the “Cost of Not Breastfeeding” tool to evaluate the economic consequences of not adhering to BF recommendations at country, regional, and global scales, demonstrating that there were 595,379 fatalities in children aged 6–59 months due to diarrhea and pneumonia. The lack of BF is also responsible for 974,956 cases of childhood obesity each year. Estimations indicate that BF for mothers has the ability to annually avert 98,243 fatalities caused by breast and ovarian malignancies, as well as type II diabetes. The yearly treatment expenditures for the global health system due to this preventable morbidity and mortality amount to USD 1.1 billion, and the overwhelming portion of economic losses can be attributed to cognitive impairments [53]. North et al. [11] utilized the Lives Saved Tool to show that by gradually increasing the rates of early, exclusive, and sustained BF from present levels to achieve the WHO’s 2030 targets of 60–80% coverage, it would be possible to save around 200,000 lives of children under the age of 5 years by 2030. Each dollar invested in BF assistance is projected to generate USD 35 in economic returns, which can be attributed to reduced child mortality rates and higher cognitive results [11].
Microbiome and Human Milk Microbiome
New-generation sequencing methods for microbiota analysis have detected microbiota elements, especially bacteria, in many body fluids, including HM, which was once thought to be sterile [54]. HM was considered sterile until Martin et al. [55] showed that endogenous lactic acid bacteria were present in HM and that HM lactic acid bacteria were the most important source of infants’ intestinal microbiota. Previous studies on the composition of the HM core microbiota revealed that Streptococcus and Staphylococcus species dominated, while Pseudomonas and Lactobacillus strains were common in many studies [56]. There are differences between colostrum, transient, and mature HM samples. Compared to mature milk samples, colostrum samples had greater percentages of Bifidobacterium or Lactobacillus (76.9% and 48.6%, respectively) [56].
Maternal factors include ethnicity, maternal BMI, age, diet, lifestyle, maternal breast disease (including mastitis), maternal health status, disease presence, and medications, while infant factors are gender, birth weight, prematurity, presence of siblings, vaginal delivery BF strategy, and maternal antibiotic and probiotic use. Other factors include HM’s geographical region, season, and biochemical components [57]. The mode of delivery influences both the HM microbiota and the infant’s intestinal microbiota composition [58]. Intrapartum antibiotic use, another significant factor influencing HM microbiota, has demonstrated a negative impact on the microbiota under both normal vaginal and cesarean delivery [59]. A long-term follow-up study with 393 BF mothers and their infants in Canada revealed that maternal body mass index, mode of delivery, and exclusive BF are the most influential factors in HM microbiota [60]. Increased consumption of saturated fat and simple carbohydrates during pregnancy may also influence the composition of HM [61]. There are also distinct mammary gland microbiome populations between Mediterranean and Western diets consumed by mothers [62]. Maternal consumption of nonnutritive sweeteners during pregnancy is associated with an alteration in the colostrum microbiota [63]. Keep in mind that factors such as the time of day and lactation stage, sample collection procedures (including manual or pump expression), and microbiota analysis methods can also influence the composition of the microbiota [60, 64, 65]. Researchers have also observed differences in microbiota composition between colostrum, transitional milk, mature milk, foremilk, and hindmilk [64‒66]. Experts believe that the infant’s needs regulate these differences in HM.
HM contains not only bacterial microbiota but also includes viruses, fungi, and archaea. Studies have demonstrated that the interactions between these diverse microorganisms in HM have a positive impact on infant health [56, 58, 65, 67]. Recent study demonstrated that the composition of HM bacteriome, virome, and mycobiome varies with the mode of delivery, birth weight, and prematurity, as well as differences between transitional and mature HM [66, 68, 69]. In terms of HM’s bacterial microbiota composition, studies have revealed distinct compositions, particularly for the gestational age group. In the LGA group, Pelomonas, Burkholderiaceae UC, and Ralstonia were more common than in other age groups [66]. Studies have demonstrated that bacteriophages, which make up the majority of HM virome content, play a crucial role in determining the intestinal virome composition of infants [56, 58, 65, 70]. Bacteriophages also predominantly maintained the composition of HM virome [68]. Fungi made up a smaller part of HM than bacteria. However, the mycobiota content of HM was different in babies born by cesarean section compared to babies born vaginally and also different between prematurity, small for gestational age, and LGA. There are also differences in mycobiota content between transitional and mature milk [69].
There is uncertainty about the origins of bacteria in HM, with potential sources including maternal skin, the infant oral cavity, the peripheral environment, and the maternal gut [65, 71‒76]. There is a bidirectional transmission between mother and infant. Researchers have identified three potentially effective mechanisms and have proposed the enteromammary transfer and retrograde flow transfer hypotheses to interpret the origin of HM microbiota [58, 71, 72]. Breast biopsies have demonstrated the transport of nonpathogenic bacteria from the maternal gut to other tissues, including the breast and its own microbiota content [72]. Maternal skin and infant oral microbiota are the most influential factors as sources of HM microbiota [74]. However, Ruiz et al. [75] showed that collected precolostrum samples from mothers 3 days before birth revealed that the baby’s oral microbiota does not influence HM, at least not in the early stages.
Effects of Breastfeeding on Infant Microbiota Composition
HM contains a variety of bioactive components, such as biotics, lipids, immunomodulating components like lysozyme, lactoferrin, and secreted IgA, as well as antimicrobials. These components modulate immune system maturation and infant microbiome, potentially contributing to positive health outcomes [1, 3, 5, 77‒80]. While there is variation in the published data regarding demographics, infant age, formula type, sampling, and analytical procedures, most studies have suggested that the variety and richness of the microbiome are lower in breastfed newborns than formula-fed infants [80‒82]. Corona-Cervantes et al. [83] found 25 bacterial taxa shared by both HM and infant microbiota and 67.7% of bacteria found in neonate stool were predicted to originate from HM. Exclusive BF causes the presence of more Bifidobacteria and less Enterobacteriaceae, and less alpha diversity compared to babies who are fed formula [81, 82, 84]. Bifidobacteria have a substantial impact on the development of the immune system, protecting children from infections, decreasing the occurrence of atopic dermatitis and rotavirus infections, reducing lactose intolerance in both children and adults, and improving the immune response to vaccinations, and are linked to a decreased likelihood of obesity and allergic diseases [85, 86].
Bifidobacteria have a substantial impact on the development of the immune system
HM studies have detected all four groups of biotics (prebiotic, probiotic, postbiotic, and symbiotic). For this reason, HM appears to be panbiotic, including all defined biotics as well as those not yet detected. The prebiotic oligosaccharide content of HM is an important determinant of its microbiota content and, thus, infant microbiota composition [87‒89]. HMOs are complex sugars indigestible to infants, constituting the third-biggest solid component of HM. Several studies have shown that HMOs change the gut microbiota composition by creating bifidobacterium-rich microbiome and killing pathogens. They may also interact with the gut epithelium to change how microbes and their hosts physically interact and directly affect the immune system [90]. HMOs serve multiple physiological roles, such as potentially aiding the immune system, promoting brain growth, and enhancing cognitive performance [87‒90]. The quantity and distribution of individual HMOs in mothers might vary significantly due to various factors, including geography, race, maternal diet, weight and secretor status, delivery mode, and gestational age [90]. The composition of the human microbiome is significantly influenced by genetic factors [90]. Numerous HMOs found in colostrum play a crucial role in fostering the growth and establishment of Bifidobacterium spp. populations in the digestive tracts of breastfed babies, ensuring their well-being [90]. Not all HMOs cause the same changes in the composition and/or activity of the gut microbiota. Furthermore, certain members within the Bifidobacterium genus possess the ability to metabolize HMOs, although this capability is not uniform across all members of the genus. B. longum subsp. infantis is the most efficient consumer of HMOs, whereas Bifidobacterium bifidum and Bifidobacterium breve can also partially metabolize HMOs [90]. Others, like Bacteroides spp., are also known to use HMOs [78]. Reports say that Bacteroides are more common when bifidobacteria are not present, and when HMOs are low, they may start to exclude each other [91]. Bacteroides thetaiotaomicron, found in a healthy mature gut, provides metabolic and immune support and is an effective HMO degrader. Bacteria ferment HMOs to produce SCFAs, which, in turn, create a low-pH environment in the colon that promotes the growth of beneficial bacteria and inhibits pathogens [90]. Selma-Royo et al. [92] evaluated the mother-infant dyad and collected samples including HM, and mothers’ and infants’ feces, performed microbiome composition and transmission analysis, and followed up on the infants for 1 year. Overall, their findings indicated that the duration of BF significantly influences the strain replacement of B. longum in the infant’s gut over time. This replacement often shifts from the maternal strain, B. longum ssp. longum, to either B. longum ssp. infantis or one of the other subspecies groups due to their superior ability to degrade HMOs [92].
In addition to HMOs, HM serves as a continuous source of bacteria for breastfed infants, facilitating mother-to-infant bacterial transfer. HM functions as both prebiotic and probiotic because of its oligosaccharides and the composition of its microbiota, which act as synergistic synbiotics. The distinct microbial composition of each mother’s HM may contribute to the variability observed in the gut microbiota of breastfed infants [93]. The microbiota present in HM is believed to possess biotic qualities that can impact the newborn’s short- and long-term health [94]. BF is a significant factor affecting the infant’s early microbiota composition. The Environmental Determinants of Diabetes in the Young (TEDDY) study revealed that HM consumption plays a critical role in shaping the composition of the infant gut microbiome during the first 3 years of life [95]. BF exclusivity and duration undoubtedly have a significant impact on an infant’s gut microbiota. BF, particularly for longer durations, is associated with a more stable bacterial composition, as well as a lower microbiota age [93].
BF modulates not only the bacterial microbiome but also the virome composition. Healthy infants lack gut virome at birth, and BF plays an important role in viral colonization. Human virome composition and maintenance are crucial for health, and alterations are associated with diarrheal diseases in children, inadequate nutrition, and autoimmune and inflammatory bowel diseases. After the first month of life, HM promotes the formation of phages from pioneering bacteria [96, 97]. HM components, including HMOs, lactoferrin, and milk antibodies, prevent pathogenic phages from colonizing [98]. HMOs act as decoy receptors for viruses (e.g., norovirus, rotavirus, and influenza), preventing their binding to the epithelium. Lactoferrin prevents entry and internalization of the virus (e.g., norovirus, rotavirus, and coronavirus) into the host cell. HM antibodies provide passive immunity against a multitude of viruses, including rubella, dengue, measles, varicella zoster virus, respiratory syncytial virus, and influenza [99]. BF might have beneficial effects on zika virus, chikungunya, and dengue. Recent reports from the COVID-19 pandemic have suggested that BF inhibits SARS-CoV-2 [100]. An infant’s microbiota composition also relates to the composition of BF and HM mycobiota. Geographical location and environments, antibiotics, maternal diets, delivery mode, and BF primarily influence the composition of gut mycobiota in infants [101, 102]. Children with allergy disorders, autism spectrum disorders, obesity, and inflammatory bowel disease have reported alterations in their gut mycobiota [102]. BF and the composition of HM may have beneficial effects on the virome and mycobiota composition of infants and later-aged individuals. Further well-organized studies will help in understanding the trans-kingdom interaction among the bacteriome, virome, and mycobiome.
Recent reports from the COVID-19 pandemic have suggested that BF inhibits SARS-CoV-2
In addition to the HMOs and microbiota of HM (prebiotic, probiotic, and synergistic synbiotic effect), several bacterial metabolites, such as butyrate and other short-chain fatty acids, can also naturally transfer into HM [103]. HM contains some genera like Coprococcus, Faecalibacterium, and Roseburia, which can produce short-chain fatty acids [87]. Although a widely accepted definition has not yet been established, these substances are commonly referred to as “natural postbiotics.” They consist of both inactive bacterial cells and metabolites and are expected to promote the composition and function of the gut microbiota, as well as immune functioning and development [103]. Further studies about the HM postbiotic (natural) will highlight the additional interactions about beneficial effects of BF.
Conclusion
The gut microbiota becomes established during the first 1,000 days of life, and any disruptions or changes in colonization during this early period could potentially affect health outcomes in the future. The initial stages of an infant’s life entail the participation of the microbial community in shaping the development of the immune system and metabolism. BF is a crucial indicator of the maintenance and composition of the infant’s gut microbiota and is linked to a healthy status through the composition of the HM microbiome and other bioactive components. HM microbiomes are postulated to serve the following purposes: establishing a presence in the gut microbiota of infants, shielding the child from colonization by harmful microorganisms, educating the infant’s immune system, prevention of the diseases, and aiding in early nutrition and metabolism. Biotic components refer to bioactive chemicals that provide protection to neonates and decrease the likelihood of several noncommunicable diseases during childhood, including obesity, diabetes, and allergy disorders. Gut microbiota plays a role in influencing behavior, such as cognition and social skills. It also affects the development of the nervous system during the first year of life, hence decreasing the likelihood of neurodevelopmental disorders, and BF continues to form a cornerstone for the prevention of many short- and long-term health risks in the infant and mother dyad, providing protection against childhood infections, enhancing intelligence and cognitive development, lowering the risk of being overweight and diabetes, and reducing infectious morbidity and mortality overall. For mothers, BF aids in postpartum recovery and is associated with a decreased risk of certain cancers, such as breast and ovarian cancer, and a reduction of the risk of CVD. The avoidable costs of morbidity and mortality from a lack of exposure to HM affect not only infants and mothers but also wider society. However, conducting more extensive studies is required to validate the direct correlation between feeding with HM, the microbiota, and the development of the immune system and prevention of the diseases. In conclusion, investing in initiatives to enhance BF rates will provide positive impacts on the health outcomes of women and their infants, as well as the broader global economy. To optimize the health of present and future generations, it is crucial to boost BF rates worldwide. This is a critical public health approach that offers advantages to both infants and mothers and has significant public health benefits. Therefore, there is a need for greater advocacy and action to promote BF.
Acknowledgments
Figure 1 was prepared by BioRender.
Conflict of Interest Statement
Ener Cagri Dinleyici has participated as a clinical investigator, advisory board member, consultant, and speaker for BioGaia, Biocodex, Nestle Health Science, Nestle Nutrition Institute, and Nutricia.
Funding Sources
Nestle Nutrition Institute supports this publication for open access. The funder had no role in the design, data collection, data analysis, and reporting of this study.
Author Contributions
E.C.D. is the sole author of this manuscript preparation.