In an article published by Olmstead, Snodgrass, Meiss and Ralston, we learn that colonization of an infant's gastro-intestinal tract begins at birth. They tell us that acquisition and normal development of the neonatal microflora is vital for the healthy maturation of the immune system. It is through a process called 'micrometabolic imprinting' that intestinal microflora progression has profound effects on health.
An infant's gastro-intestinal microflora may be disrupted by many factors like cesarean section and formula feeding. Infants born by cesarean section are usually colonized by hospital microorganisms and are at increased risk for asthma, allergies, and gastroenteritis. Breastfed infants have a microflora dominated by Bifidobacterium species. On the other hand, it has been found that formula fed babies have low numbers of Bifidobacterium and a haphazard microflora.
For this reason, breastfeeding reduces the risk of allergies, obesity, inflammatory bowel disease, celiac disease, diabetes mellitus, and childhood cancer. The gastrointestinal microbiota that are introduced by breastfeeding may be responsible in part for these benefits.
Neonatal probiotics can supply Lactobacillus species essential for normal immunological development and establish a Bifidobacterium dominance in babies born by cesarean section or formula fed. It is well documented that there is altered intestinal microflora in atopic eczema and other allergies in infancy and childhood.
Selected probiotics such as Lactobacillus Rhamnosus and Bifidus lactis have been shown to reduce the risk of allergic eczema in infants and, when present, reduce its clinical severity. The authors suggest that probiotics selected for infants should ideally be dairy free and produce only the L(+) form of lactic acid. An optimal infant probiotic should contain age appropriate Bifidobacterium species, Lactobacillus species important for immune system maturation, and Lactobacillus species normally found in breast milk.
Humans live in beneficial symbiosis with the vast numbers of microorganisms colonizing the gastrointestinal tract. The intestinal microflora thrives in a nutrient-rich, sheltered, anaerobic environment. In return, a balanced microbial community protects against infection, promotes normal bowel function, provides energy and nutrition, and maintains normal immune function.
Sterile before birth, an infant's gastrointestinal tract is rapidly colonized in a progression that begins with delivery. This microbial colonization is vital for normal neonatal gastrointestinal and immune system development. Through a process of micro-metabolic imprinting, normal intestinal microflora progression has profound implications not only for well-being during infancy, but for long-term health.
Many factors may disrupt the infant acquiring and maintaining a healthy, balanced gastro-intestinal micro-community. These factors include maternal microflora, maternal diet and medications, the manner of birth delivery, breast-feeding versus formula-feeding, antibiotic use, and exposure to toxin. Disruption of the normal intestinal microflora, known as dysbiosis, leads to proliferation of pathogenic microorganisms and impaired immune system development.
Intestinal dysbiosis predisposes the infant to infections and allergies. Long-term consequences of neonatal intestinal dysbiosis is thought to include allergies, asthma, increased susceptibility to infections, inflammatory bowel diseases, diabetes mellitus, obesity, and colon cancer.
Giving probiotics during infancy and childhood offers a means of correcting intestinal microflora imbalances and favorably modulating immune and gastro-intestinal system maturation. Health benefits of comsuming probiotics during infancy and childhood has been established. It may support long-term well-being as well.
GUT MICROFLORA & IMMUNE SYSTEM MATURATION
Infants are born with an immature immune defense system. The gastrointestinal tract is the largest bodily surface to come in contact with the outside world. The gastrointestinal mucosal immune system must learn to distinguish foe from friend; combat pathogenic microorganisms and accept the multitude of commensal bacteria.
It must also recognize and defend against toxins and allergens while simultaneously becoming tolerant of the large number of ingested dietary antigens. The gastrointestinal mucosal immune system is linked to mucosal immune systems in the mouth, nasopharynx, lung, breast, and genitourinary tract in a common mucosa-associated lymphoid tissue.
Although the components of the mucosal immune system are in place after full gestation, bacterial colonization of the intestinal tract is important for stimulating full development and mediating maturation of the gut-associated lymphoid tissue i.e.GALT, the largest collection of lymphoid tissue in the human body. The acquisition of a normal, balanced gastro-intestinal microflora is essential for the success of GALT, and in fact, the entire common mucosa-associated lymphoid tissue, in carrying out their vital immune functions.
Studies involving germ-free animals have shown that without an intestinal microbiota, intestinal lymphatic tissue develops poorly, shows fewer numbers of specialized ileal lymphoid follicles called Peyer's patches, and produces intra-epithelial lymphocytes with no lytic activity compared to normal colonized animals.
NORMAL NEONATAL INTESTINAL MICROFLORA ACQUISITION AFTER BIRTH
The gastrointestinal tract of the fetus is completely free of any microbes.
The infant aquires microflora, beginning during birth. The mother's intestinal and genital microflora, maternal diet and medications, manner of delivery, and birthing environment all influence its initial development.
The infant is exposed to microorganisms colonizing the mother's cervix, vagina, and perineum during the passage through the birth canal. It has been found that E- coli serotypes isolated from mothers' feces and infant mouths just after vaginal delivery are identical.
Also, bacterial cultures of gastric contents from 5-10 minute old newborns are similar to the maternal cervical microflora. The nasopharynx of most vaginally delivered newborns contain bacteria similar to those of the mother's vagina immediately before delivery.
However, the maternal vaginal microflora does not usually colonize the baby's digestive tract. The maternal gastrointestinal microbiota is the normal source of the neonatal intestinal microflora development.
E- coli and streptococci are the microbes most frequently cultured from the upper digestive tract immediately after birth. Within hours of delivery, enterococci, staphylococci, steptococci, and enterobacteria are present in the gastrointestinal tract of newborns.
By the second day of life, all infants are usually colonized with E- coli. The early colonizing aerobic microorganisms consume intestinal luminal oxygen and lower intestinal pH and redox potential creating conditions that are favorable for the colonization of anaerobic microbes.
Bifidobacteria may be found in low numbers on the first day after delivery, but generally Bifidobacterium and other anaerobic species, such as Lactobacillus and Bacteroides, do not appear in the infant intestines until several days after birth when a favorable microenvironment has been created.
It is well established that probiotics consumed by pregnant women will colonize the newborn gastrointestinal tract following birth.
Consumption of Lactobacillus rhamnosus strain by pregnant moms and continued by the infants up to 6 months has been shown to decrease the risk of eczema by about 50% in the children at 2 and 4 years of age.
It has been noted that maternal vaginal dysbiosis (bacterial vaginosis), in which normal vaginal lactobacilli have been replaced with pathogens, not only has significant implications for pregnancy and delivery but is also associated with premature rupture of the membranes, preterm delivery, and low infant birth weight.
Oral probiotics have been shown to re-establish and support a normal vaginal microflora.
CESAREAN DELIVERY AND NEONATAL INTESTINAL MICROFLORA ACQUISITION
Cesarean delivery significantly alters aquisition of neonatal microflora. The infant does not pass into the world through the birth canal and is thus deprived of the initial exposure to maternal vaginal and fecal microflora. Infants born by cesarean section are not usually colonized by maternal microorganisms, but rather by microbes from the hospital environment.
Prophylactic antibiotics administered to mothers prior to cesarean section may further compromise the acquisition of a normal neonatal intestinal microflora.
In a study of neonatal E. coli colonization when first maternal-infant contact after delivery ranged from 8 to 72 hours, only 14% of hospitalized infants shared E. coli or other Enterobacteriaceae strains with their mothers. Normal mothers and infants share identical E. coli strains. Hospital strains were the majority of acquired E. coli including a strain carrying the Kl capsular antigen virulence factor that led to hospital acquired urinary tract infections in two babies.
In another report, at 7 years of age, children delivered by cesarean section had fewer gastrointestinal Clostridium species than did children delivered vaginally.This was associated with an increased incidence of asthma. Children born by cesarean section, especially a repeat cesarean section, are well-established to have an increased risk of asthma, allergic rhino-conjunctivitis, allergies, and gastroenteritis requiring hospitalization from 1 year of age up to age 10.
It is becoming increasingly clear that the neonatal period of intestinal microflora acquisition represents a time of vulnerability.
Disruptions of microbial colonization and the associated micro-metabolic imprinting carry long-term health consequences.
Probiotics have been clearly shown to decrease allergic inflammation in infants and to favorably modulate extra-intestinal immune responses resulting in a reduced allergic symptoms.
BREASTFEEDING AND THE TRANSFER OF MATERNAL INTERNAL MICROFLORA
Neonatal intestinal microflora development is profoundly influenced by the infant's diet. There are significant differences in the composition of microflora depending on whether a baby is breastfed or formula fed.
Besides unparalleled nourishment, breast milk provides the newborn with factors that protect against disease as the neonatal immune system begins to mature.
These factors include large amounts of secretory immunoglobulin A (sIgA), white cells, antimicrobial enzymes, lactoferrin, immune-enhancing nucleotides, and oligosaccharides that impart immunologic and antimicrobial protection to the infant.
Lesser known, but equally important components of breast milk are commensal bacteria from the maternal gut microflora Maternal commensal bacteria in breast milk are important for infant immune system development.
Among the lactic acid bacteria normally found in breast milk are probiotic species Lactobacillus gasseri, Lactobacillus fermentum, and Enterococcus faecium.
BREASTFEEDING AND NEONATAL INTESTINAL MICROFLORA DEVELOPMENT
Within the first week after vaginal birth, breastfed infants develop a gastro-intestinal microflora dominated by bifidobacteria. This is mainly due to prebiotic factors like galacto-oligosaccharides in breast milk that stimulate bifidobacterial growth. A smaller number of species found in a nursing infant's gut include Bacteroides, Lactobacillus, and Streptococcus.
During this same period, formula-fed infants have no predominant gut microbial population. Instead, they possess a more haphazard microbiota that includes Bacteroides, staphylococci, E. coli, clostridia, and bifidobacteria.
The intestinal bifidobacteria population in formula-fed infants is approximately one-tenth that of breastfed infants. The stools of breastfed infants have a significantly lower pH than formula-fed infants.42
One month after birth, breastfed babies show a stable flora clearly dominated by bifidobacteria.
Populations of enterococci, enterobacteria, clostridia, and Bacteroides are suppressed and can only be isolated in relatively low numbers.
After 3 months there is a slight reduction in bifidobacterial populations.
At 1 and 3 months of age, no microorganism predominates in the formula-fed infant intestine. Also, formula-fed infants have higher numbers of facultative and obligate anaerobic bacteria compared to breastfed infants.
BREASTFEEDING HEALTH BENEFITS AND THE INFANT INTESTINAL MICROFLORA
Breastfeeding is associated with numerous benefits for the infant.
Perhaps the most widely appreciated benefit is protection against infection:
Breastfeeding not only protects against gastro-intestinal infections and diarrheal diseases, but has been clearly shown to reduce the incidence of extra-intestinal infections such as otitis media, acute lower respiratory diseases, urinary tract infections, and septicemia.
The protective effects persist for months and even years after weaning.
Breastfeeding provides many other health benefits beyond protection from infection:
- reduction in the risks of allergies and atopic diseases, obesity, inflammatory bowel disease, celiac disease,and diabetes mellitus.
- reduction in the risk of childhood cancers.
PROBIOTICS AND INFANCY
When the normal neonatal microflora does not develop properly or an infant's microflora is disrupted by antibiotics or other toxin exposures, probiotics become important tools to restore intestinal microbial balance.
Probiotic supplements containing bifidobacteria may increase gastrointestinal bifidobacteria populations and reduce anaerobic bacteria in formula-fed infants, creating a microflora more similar to healthy breastfed infants.
Probiotics can also supply essential Lactobacillus species such as L. casei, critical for proper dendritic cell differentiation, and L. rhamnosus, shown to enhance bifidobacteria diversity in infants and increase populations of Bifidobacterium breve.
The use of probiotics in infancy to address a disorder associated with altered intestinal microflora has been best studied in children with allergies and atopic eczema. Atopic eczema is often the first appearance of allergies in infants. The incidence of atopic eczema, as well as other allergic diseases, has been increasing dramatically in industrialized countries over the past forty years.
Probiotic formulations have also been shown to be effective in treating viral diarrhea and antibiotic-associated diarrhea in infancy as well as in reducing the risk of necrotizing entero-colitis in premature and low birth weight infants.
PROBIOTIC SELECTION FOR INFANTS
Probiotic selection for infants should be premised on data that support efficacy at creating an intestinal microflora similar to that of a healthy, vaginally delivered, breastfed baby. It is disruptions of this normal neonatal microbiota that lead to acute, short-term disorders such as diarrhea and allergies and may well be a significant causative factor in long-term chronic diseases such as obesity, inflammatory bowel disease, and diabetes.
Many of the Lactobacillus species normally found in breastfed babies cannot be cultured without the use of dairy products which may limit probiotic options in dairy sensitive infants.
Fortunately, the important Bifidobacterium species B. breve, B. infantis, B. lactis, and B. longum can be cultured dairy-free as can the highly important L. casei and L. rhamnosus.
Probiotic dosing is important.
Low doses may be ineffective as illustrated by two studies of probiotics for the prevention of necrotizing enterocolitis.
One study, which used a dose of 60 million CFU of L. rhamnosus GG, failed to find a benefit while the second study, which used a formulation containing 10 billion CFU per capsule administered with breast milk, found that the probiotic formulation significantly reduced the incidence and severity of necrotizing entero-colitis.
The L. rhamnosus may not have been beneficial in the first study because too low of a dose was used.
Underdosing is a recurrent problem in probiotic research design. In terms of how much probiotic can be safely tolerated by infants, one study that assessed the efficacy of B. lactis to restore microbial balance in infants with atopic eczema established that doses up to 110 billion CFU per kilogram of body weight were safely tolerated by the babies.
A rational probiotic formulation for infants would include the age-appropriate bifidobacteria, lactobacilli important for antigen processing and dendritic cell differentiation, and lactobacilli normally found in the healthy infant intestines.
Sterile before birth, an infant's gastro-intestinal tract begins to be colonized during passage through the birth canal.
The normal populations of enteric microflora are acquired primarily from contact with the mother and during breastfeeding. An infant should have a microflora characterized by a predominance of particular Bifidobacterium species, the presence of specific lactobacilli, and low numbers of Bacteroides, clostridia, staphylococci, and enterobacteria.
The normal microbial population patterns in infants appear to be crucial to the healthy maturation of the gastro-intestinal and immune systems.
The composition of the infant's microflora is so important that mothers have specific immunological mechanisms to ensure the transfer of their own enteric bacteria to their babies through breast milk. Breast milk also contains numerous factors such as prebiotic galacto-oligosaccharides that stimulate the growth of bifidobacteria.
Because of the micro-metabolic imprinting of the normal infant microflora on the immune system, disruptions of the microbiota during infancy may relate to the risk of chronic diseases in later childhood and adulthood.
Select probiotics have been shown to restore balance in the infant microflora.
This restoration appears to effectively reduce the incidence of viral and antibiotic-associated diarrhea and to prevent and treat atopic diseases in infancy.
Probiotics have been shown to be safe and well tolerated by infants.
A basis for probiotic formulations for infants provides species that restore the intestinal microflora of a healthy, vaginally delivered, breast fed baby.
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Micrometabolic Imprinting in Infancy:
Microflora, Probiotics & Chronic Disease
Stephen Olmstead, MD, Ryan Snodgrass, MS, Dennis Meiss, PhD, and Janet Ralston, BS