PDF
Citation
Print
INTRODUCTION
The human gut is a vast and diverse community of bacteria, fungi, archaea, and viruses collectively known as the gut microbiota.1 The gut microbiota assists with essential nutrient synthesis and absorption,2,3 generates short-chain fatty acids that serve as an energy source for colonocytes,4-6 maintains the intestinal mucosal barrier and protects against pathogenic bacteria and endotoxin translocation, stimulates immune-system maturation,7 provides anti-inflammatory signals to the host,8 during a critical developmental window in early life.9
Markedly, multiple studies of mother-infant have indicated the existence of vertical transmission of microbes from mother to infant that can contribute to colonizing microbiota.10,11 During early life, the gut microbial composition rapidly changes by maternal microbiota composition, delivery mode, infant feeding mode, antibiotic usage, and various environmental factors, such as the presence of pets and siblings.12 Disruption in the gut microbiota (ie, gut dysbiosis) has been linked to necrotizing enterocolitis in infancy, as well as some chronic diseases in later, including obesity, diabetes, inflammatory bowel disease, cancer, allergies, asthma,13 and neurological diseases associated with the gut-brain axis.14 This review will focus on the process of early colonization, understanding the factors influencing microbial colonization of the infant gut.
MAIN BODY
1. Colonization of fetus gut
Basically, the uterus and fetus are considered sterile environments unless clinical infection occurs, such as in chorioamnionitis; however, growing body of evidence indicates that the intrauterine environment is not sterile, but that maternal-fetal transmission of microbiota occurs during pregnancy. Nonpathogenic bacteria are detected in the placenta, umbilical cord,15,16 and the meconium of the healthy newborns, independent of birth mode of delivery,17 and its composition is associated with the gestational age. Intrauterine infection has been reported to be associated with a leaky gut, confirmed by finding maternal gut microbes in the amniotic fluid of women with premature membrane rupture.18 This suggests microbial translocation from a maternal leaky gut to the uterus and placenta. But this hypothesis remains controversial up to this day. Certainly, debate will continue on whether or not microbial colonization occurs in utero and well controlled, large cohort studies are essential to ensure that the data produced is robust and reliable.
2. Maternal obesity and nutrition Influencing early colonization
Obesity is characterized with an imbalance in the Firmicutes-to-Bacteroidetes ratio in the gut.19,20 Birth cohort studies disclose that infants born from overweight or obese mothers were profusely colonized with the bacterial genera belonging to the phyla Firmicutes, mainly of the Lachnospiraceae family, and three times more likely to be overweight by 1 year of age, which increases to 5 times in infants born by cesarean section (C-section).21 Weight gain during pregnancy is a normal physiological response, however, excessive gestational weight gain (defined as 16 kg or above for women with BMI 19.8-25 or above 11.5 for women with BMI >25) has been shown to result in the increased relative expansion of Bacteroides,22 Enterobacteriaceae, and E. coli and a reduction in Bifidobacterium and Akkermansia muciniphila.23 Moreover, metagenomics analysis has shown that gestational weight gain impacts on the function of the infant microbiome24 by significant reduction in the community of bacteria involved in metabolic signaling and energy regulation, including Enterococcus, Acinetobacter, Pseudomonas, and Hydrogenophilus. Infant gut dysbiosis associated with maternal obesity has been shown to increase gut permeability and directly initiate pathways of nonalcoholic fatty liver disease.25 C-section–delivered infants from overweight mothers are at higher risk of becoming overweight later in life than infants born vaginally to overweight or obese mothers.21,26
Maternal weight status also might affect maternal milk composition.27,28 Cabrera-Rubio et al.29 noticed higher total bacterial counts, expansion of Staphylococcus and Lactobacillus, and reduced levels of Bifidobacterium in the milk of obese compared with normal weight women during the first 6 months of lactation. It suggested an additional mechanism explaining the intensified obesity risk in infants born to obese and overweight mothers.
Longitudinal cohort data showed that a maternal high-fat diet altered early bacterial colonization independent of maternal obesity.30 In association with a maternal high-fat diet, the neonatal meconium microbiome varied with a significant relative depletion in Bacteroides immediately, which persisted until 6 weeks of age.30 A maternal high-fat diet rather than just maternal obesity profoundly impact on shaping the gut microbiota early in life.31 A combination of a high-fat/high-sugar diet led to gut dysbiosis in mice32 and dietary intake of refined sugars modulate the gut microbial composition to that of an inflammatory-type microbiota.33 Since maternal milk microbiota is hypothesized to originate from maternal gut microbiota, the gut dysbiosis associated with the maternal diet might be transferred to maternal milk and further exacerbate dysbiosis seen in the early gut microbiome in breastfed infants. However, research investigating long-term impact of maternal lifestyle and health status during gestation and lactation on the infant’s gut microbiota is lacking.
3. Delivery mode
Mode of delivery is generally accepted as a major factor determining initial colonization.34 Infant born by C-section can have altered immune development and are at a higher risk for numerous non communicable diseases such as obesity, allergy, asthma, and atopy.35 Infants delivered vaginally are colonized with bacteria present in the maternal vagina,34 whereas those delivered by C-section are colonized with bacteria similar to maternal skin and oral cavity.36,37 Although most vaginal and skin bacteria do not seem to take hold in the infant gut, their presence may differentially affect the colonization abilities of other bacteria. Longer period studies that have followed microbiota composition in infants during the first 2 years of life have confirmed an association of C-section with delayed colonization of the Bacteroidetes phylum, and with lower total microbial diversity up to 2 years of age.38 Also, differences between the microbiotas of C-section and vaginally born infants have been detected in analyses performed at 7 years of age.39 C-section delivery impacts on microbiota through several means: 1) the lack of exposure to the vaginal and fecal microbes of the mother will alter the type and diversity of the microbes that colonize the gut at birth; 2) the different starting points in terms of microbial exposure and immune environment will mark the course of microbiota.40 The microbial origin in C-section born infants is distinct between infants born by elective or emergency C-section. The source of the gut microbiota in infants born by emergency C-section is supposed to be the skin and vagina, whereas the skin was thought to be the predominant microbial origin of the gut microbiota in infants born by elective C-section.41 These differences may be due to fetal membrane rupture which commonly occurs before emergency C-section leading to infiltration by vaginal microbe.
4. Feeding
1) Maternal milk―commensal microbes
Recent studies support that human milk is not sterile and is a primary and main factor that drives the acquisition and evolution of the gut microbiota in early life.42,43 Mother-to-child transmission studies support that bacterial transfer from mother to infant occurs via breast milk.44-46 Breast milk contributes significantly to the metabolism, development of gut integrity, and maturation of the immune and neuroendocrine systems.47,48 Breastfeeding confers protection against respiratory and gastrointestinal infections and decreases the risk of sudden infant death syndrome and certain inflammatory diseases such as dermatitis, asthma, obesity, type 1 and 2 diabetes.49,50 Breast milk itself is also a source of commensal bacteria that are naturally present in this secretory fluid. It has been estimated that a breast feeding infant ingests between 1×104 and 1×106 bacteria daily (Table 1).51,52 Streptococci (mitis and salivarius groups) and coagulase negative Staphylococci are potentially able to compete with the establishment of undesired pathogens (eg, Staphylococcus aureus) in the infant gut. Propionibacterium acnes can prevent the growth of S aureus.53 Bifidobacterium and Lactobacillus spp in breast milk are noted to activate IgA-producing plasma cells in the neonatal gut. An association was shown between low levels of intestinal Bifidobacterium microbiota during infancy and an increased risk of atopy later in life.54-56 As with the composition of breast milk itself, its associated microbiome changes during the lactation period. Different factors are thought to be responsible for its composition and diversity, such as gestational age, lactation stage, environmental exposures, geographical location, daily breastfeeding practices, infant gender, and maternal factors (BMI, parity, and delivery mode).57-60 As previously discussed, obesity influences the maternal gut microbiota but it also affects the milk microbiota.29,61 Breast milk microbial alterations might be attributed to the physiological stress and/or hormonal changes that occur with labor or an emergency C-section. Indeed, breast milk dysbiosis was only observed in mothers who underwent an elective C-section not emergency C-section. Vaginal delivery might induce intestinal permeability and enhance the bacterial trans-location from the gut to the mammary gland and breast milk.62 Human milk contains human milk oligosaccharides, a type of prebiotic. Human milk oligosaccharides promote the growth of specific Bifidobacteria, supporting an early Bifidobacteria-dominated gut microbiome.63 Over 200 different oligosaccharides have been identified in human milk.64
5. Antibiotic usage
Antibiotic administration is another major factor that interferes with the composition of the GI microbiome. Especially antibiotic exposure within 1 month of birth alters the balanced development of the microbiome momentarily but also persistently.65 Resistance of some gut microbes to antibiotic agents may also occur, and these resistant genes can possibly be transferred to pathogens. The immune homeostasis will be challenged, disrupting the T-reg/Th balance.66 Therefore, antibiotic administration increases the risk of developing immune-mediated diseases, such as cow milk protein allergy, diabetes, and asthma. The younger, the more frequent, and the larger the spectrum of antibiotic agents administered, the stronger the association with overweight status.67
CONCLUSIONS
The composition and development of infant gut microbiota can be influenced by maternal and infant factors. Microbial colonization primarily occurs after birth but there may be some colonization in utero, although this remains highly controversial. Maternal factors during pregnancy that can affect the infant microbiota include maternal diet, weight, gestational weight gain, and antibiotic usage but overall, their impact is low in comparison to that of birth mode, infant diet, and antibiotic treatment. Microbes are passed from mother to infant during and after birth. Delivery mode, breastfeeding, and intrapartum and early life antibiotic treatment have the largest effects on microbial composition in early life.
The early life gut microbiome plays an important role in the development of the immune system and metabolism. Emerging data demonstrating the importance of early-life gut microbiome development as a protective factor against gut dysbiosis–related diseases later in life support the rationale for targeted therapies to restore early-life gut microbiome.
Therefore, understanding the impact of maternal-to-infant transfer of dysbiotic microbes and then modifying infant early colonization or correcting early-life gut dysbiosis might be a potential strategy to overcome chronic health conditions.
XML Download