1
Prebiotics Supplementation in Infant Nutrition
Sarah Quon
FSN 310
2
I. Introduction
As infants are born with a sterile gastrointestinal tract, it is essential for quick bacterial
colonization and development. Within 48 hours, vaginally born, breast-fed, and formula-fed
infants are exposed to bacterial colonization. Establishing the foundation of the microbiome is
key as the intestinal microflora does not change much after infancy. In order to create this
foundation, probiotics, or microorgansims that are responsible for making metabolic byproducts,
are needed to create the basis of good gut bacteria. However, in order for probiotic bacteria to
grow, prebiotics are needed. Prebiotics are essential in developing the microflora for infants
because they stimulate the growth of the probiotic bacteria. Conveniently the greatest source of
probiotics, specifically oligosaccharides, is human milk. However, sometimes human milk is
also insufficient in providing an adequate amount of human milk oligosaccharides (HOM). With
variables such as insufficient human milk, formula fed infants, and preterm infants, many
questions rise as to how to incorporate an adequate amount of prebiotics into the infant’s
nutrition in order to stimulate the growth of bacterial colonization. This paper will review the
relevance of prebiotics for infant nutrition and adding a prebiotic supplementation to infants’
diets.
II. Prebiotics Overview
Prebiotics work to stimulate colonization of probiotic bacteria by being the preferred
source of energy for the probiotic intestinal bacteria. With more prebiotics readily available, it
will increase the rate of beneficial bacteria colonization in infants. Moreover, it can help prevent
pathogen adherence, influence what the intestinal epithelial cells attach to and absorb, reduce
leukocyte adhesion, and change how pathogen attachment sites are expressed (Mueller, Bakacs,
Combellick, Grigoryan, & Dominguez-Bello, 2015). Prebiotics also play a role in
3
immunomodulatory properties for T-cells. Oligosaccharides become the trigger molecule for Tcells recognizing and responding to dietary and bacterial breakdown in the intestinal tract.
Prebiotics also may be beneficial for reducing common infections in healthy children.
Although indigestible to the infant, human milk is the largest source of prebiotic
oligosaccharides with over 100 different structures which all stimulate different strains of
probiotic bacteria (Mueller et al., 2015). Human milk oligosaccharides have been found to not
only have prebiotic activity, but it also is pathogen binding and it helps with neural development.
The World Health Organization also supports the addition of prebiotic products to infant
formulas because it is more likely to have mature immune response and established intestinal
colonization (Mueller et al., 2015).
III. Safety of Supplementation
There have been several ways that have been studied to incorporate prebiotics into
infants’ nutrition. Because there are numerous structures of oligosaccharides, much of the
clinical trials focus on the addition of different types of oligosaccharides. As HMOs cannot be
replicated the exact same way, there are commercial prebiotics that are derived from plants,
lactose, and more (Berg, Westerbeek, Van Der Klis, Berbers, & Lafeber, 2013). However, these
prebiotics do not have the same structural complexity and specific bacteria targeting that HMOs
have. The closest and most used prebiotics that are used as supplementations are fructose
polymers, inulin and fructo-oligosaccharides (FOS), and galactose polymers (GOS) (Thomas &
Greer, 2010). As for incorporating HMO, one clinical study focused on the idea of an “all
human” diet where concentration of prebiotics in donor human milk was added to the mother’s
human milk as a supplement and also bovine milk supplementation. This study concluded that an
4
“all human” diet was not detrimental, but also it was not able to increase the amount of intestinal
bacteria significantly (Underwood, Kalanetra, Bokulich, Mirmiran, & Barile, 2014).
In all clinical studies, the effectiveness of the prebiotics, with variables such as type of
oligosaccharide used, condition of the infant, and dosage, were determined through the infant’s
stool. Most studies found that with a prebiotic supplementation, there is an increase in frequency
of stool and softer stools. This shows that infants’ stools are studied for their consistency and
presence of bifidobacteria and used to identify whether or not the type of oligosaccharide
provided and dosage is appropriate and beneficial for infants.
While supplementation of prebiotics to infants seems beneficial is every aspect, there is a
wide group of infants that are not able to handle the additional oligosaccharides. Patients that are
at risk include immunocompromised infants, ill preterm infants, and infants who have indwelling
medical devices (Williams, Choe, Price, Katz, & Suarez, 2014). Many infants who are medically
fragile experience sepsis and colic. One of the most at risk categories are preterm babies due to
the fact that mothers who give birth to preterm babies were found to have “premature” human
milk. As a result, the diet of premature infants does not provide an adequate amount of prebiotics
which leads to a small influence on the infants’ intestinal microbiota. In most studies, it shows
that prebiotics benefits healthy children more, but it is still unclear why it is more effective for
healthy children.
The most beneficial amount of supplemented prebiotics has yet to be determined too. In a
clinical study done comparing the stool of infants who were fed human milk, formula with 4
grams GOS/L, formula with 8 grams GOS/L, and just formula, it was concluded that 4 grams
GOS/L was the most tolerated by healthy infants (Underwood et al., 2014). However, in this
data, it showed that the stool that was closest to human milk fed infants was the 8 grams GOS/L
5
(Underwood et al., 2014). The infants that were fed the 8 grams also had a higher tendency to
have watery stool, which is not wanted for an infant. The 4 grams was preferred more due to the
fact that there was not a significant number of watery stool cases and the stool consistency was
generally only a little softer than human milk fed infants’ stool—not the desired consistency. The
conclusions and findings of this study prove that 4 grams of GOS/L despite the 8 grams
matching human milk stool more. Another clinical study that continued to increase the amount of
prebiotic supplementation had conflicting evidence. While some infants were able to tolerate the
increasing amount of prebiotics, other infants had cases of blood streaked stool with mild
abdominal distension (Mueller et al., 2015). This study, along with the others discussed proved
that there is still uncertainty as to how to incorporate prebiotics as a supplement that would be
beneficial to infants.
IV. Conclusion
As an infant is born with a sterile gastrointestinal tract, prebiotics are essential when it
comes to bacterial colonization. Prebiotics are also crucial for other immunomodulatory
properties and development of the intestinal mucosal defense system. While human milk
provides a significant portion of prebiotic oligosaccharides, there are many cases were human
milk is insufficient or formula needs to be used. In these cases, supplementation seems like the
solution. However, supplementation of prebiotics is still being evaluated under many
circumstances. There are several factors and variables when it comes to conducting a study to see
if prebiotics is beneficial or not. These factors include: health of the infant, type of
oligosaccharide, and quantity of dosage. While most clinical studies have proven that prebiotic
supplementation is associated with increased stool frequency and softer stools, the clinical
studies vary in what audience it is applying to. Moreover, some clinical studies have insufficient
6
evidence because their results have some infants benefiting, while others do not. With the known
fact that prebiotics are needed for infants, there still needs to be research done for dosage, the
most beneficial types of prebiotics, and how it can benefit non-healthy infants. If the
circumstance is that the mother’s milk is not sufficient, the addition of prebiotic oligosaccharides
to infant nutrition is an idea that will be beneficial to infants’ health; however, the research
behind it is still underdeveloped.
7
References
Berg, J., Westerbeek, E., Fiona R. M. Van Der Klis, Berbers, G., Lafeber, H., Elburg, R., &
Doherty, T. (2013). Neutral and Acidic Oligosaccharides Supplementation Does Not
Increase the Vaccine Antibody Response in Preterm Infants in a Randomized Clinical
Trial. PLoS ONE, 8(8), E70904-E70904.
Mueller, N., Bakacs, E., Combellick, J., Grigoryan, Z., & Dominguez-Bello, M. (2015). The
infant microbiome development: Mom matters. Trends in Molecular Medicine, 21(2),
109-17.
Thomas, D., & Greer, F. (2010). Clinical Report--Probiotics and Prebiotics in Pediatrics.
American Academy of Pediatrics, 126(6), 1217-31.
Underwood, M., Kalanetra, K., Bokulich, N., Mirmiran, M., Barile, D., Tancredi, D., ... Mills, D.
(2014). Prebiotic Oligosaccharides In Premature Infants. Journal Of Pediatric
Gastroenterology And Nutrition, 58(3), 352-60.
Williams, T., Choe, Y., Price, P., Katz, G., Suarez, F., Paule, C., & Mackey, A. (2014).
Tolerance of Infant Formulas Containing Prebiotics in Healthy, Term Infants. Journal Of
Pediatric Gastroenterology And Nutrition, 59(5), 653-8.