Oligosaccharides: Case for/against Infant Formula Supplementation

This report investigates the role of oligosaccharides, specifically fructo-oligosaccharides and galacto-oligosaccharides, in infant formula. It summarizes the benefits of these prebiotics, including increased bifidobacteria and lactobacilli concentrations, which improve gut health, prevent infections, and enhance immunity, stool consistency, and frequency. The report analyzes research supporting and critiquing oligosaccharide supplementation, including dosage and safety considerations. It discusses regulatory policies concerning infant formula in Australia and New Zealand. The report reviews studies demonstrating the positive effects of oligosaccharides on infant gut microbiota, reduced fecal pH, and improved stool consistency, while also acknowledging some contradictory findings and the need for further research to validate allergy and infection prevention claims. The report concludes with a recommendation for further research to solidify the evidence and support the widespread use of oligosaccharides in infant formula.

Running head: OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE
SUPPLEMENTATION OF INFANT FORMULA
OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION OF
INFANT FORMULA
Name of the Student
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Word Count: 2023

1OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION
OF INFANT FORMULA
Executive Summary
This report provides a description about the roles played by oligosaccharides in the health and
well-being of infants, when the infants are fed with infant formula supplemented with these
oligosaccharides. Some of these oligosaccharides used are fructo-oligosaccharides and galacto-
oligosaccharides. These oligosaccharides helped to increase the concentration of bifidobacteria
and lactobacilli, which in turn had a positive impact on the gut health of the infants. It also
helped to prevent infections caused by pathogenic micro-organisms. Moreover, gut immunity,
stool consistency and frequency among infants were also improved. Allergic reactions were also
found to be reduced although significant data is unavailable and further research is needed to
validate the initial findings.

2OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION
OF INFANT FORMULA
Table of Contents
Introduction......................................................................................................................................3
Role of fructo-oligosaccharides and galacto-oligosaccharides in health and well-being of infants3
Dosage and safety issues.................................................................................................................5
Infant supplementation and critique................................................................................................5
Regulatory policies..........................................................................................................................9
Conclusion/Recommendation..........................................................................................................9
Reference List................................................................................................................................11

3OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION
OF INFANT FORMULA
Introduction
Oligosaccharides are short polymers of monosaccharides. Some of the dietary
oligosaccharides are fructo-, galacto- and mannan-oligosaccharides. Fructo-oligosaccharides are
made up of short fructose chains. Galacto-oligosaccharides consist of short chains of galactose
molecules. They are known to support the growth of bifidobacteria in the large intestine.
Bifidobacteria is essential for the maintenance of gut health. Mannan-oligosaccharides are
obtained from Saccharomyces cerevisiae and participate in immunomodulation and agglutination
(Belorkar & Gupta 2016, p.82).
Milk oligosaccharides protect infants by functioning as receptor homologues thereby
preventing the attachment of entero pathogens on the host receptors. Gluco-oligosaccharides and
maltodextrin-oligosaccharides act as dietary fiber and helps to increase the bifidobacteria
concentration in the infant faeces. However, infant food supplemented with oligofructose results
in further increase in the concentration of bifidobacteria. This in turn helps to prevent colonic
epithelial mucosa atrophy (Bode 2012, p.1147).
This report at first describes the role of fructo-oligosaccharide and galacto-
oligosaccharide in the well-being of infants. Next, the report carries out critical analysis of
research based on for and against of oligosaccharides in infant formula.
Role of fructo-oligosaccharides and galacto-oligosaccharides in health and well-being of
infants
Human milk consists of high concentrations of oligosaccharides and other carbohydrates.
Oligosaccharides are the third most abundant constituent present in human milk. Human milk

4OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION
OF INFANT FORMULA
consist of 21 different types of oligosaccharides, some of which are linear, while the others are
branched. Some are composed of fructose and galactose, which are simple sugars, while others
are composed of uronic acids, which are sugar derivatives (Newburg 2013, p.771). The gastro-
intestinal flora of breast milk-fed infants mainly consist of lactobacilli and bifidobacteria. Unlike
the presence of bifidobacteria in breast milk-fed infants, the gastrointestinal flora of formula milk
fed infants generally consist of anaerobic bacteria like bifidobacteria and bacteroides (Turroni et
al. 2012, p.e36957). In order to mimic the gastrointestinal flora of breast-fed infants or to mimic
the breast milk composition, lactobacilli and oligosaccharides are included in the infant milk
formulas. Oligosaccharides addition in infant milk formula, results in bifidobacteria becoming
the predominant flora in the gastrointestinal tract of infants. This also results in significant
increase in the concentration of lactobacilli. Such intestinal flora prevents gastrointestinal
colonization by decreasing the gastrointestinal permeability and providing protection against
translocation. The gastrointestinal flora also participates in stimulation of enterohepatic
circulation. Moreover, Lactobacilli helps to digest lactose and the flora can also carry out the
hydrolysis of complex carbohydrates. The flora also reduces the allergenicity associated with
undigested proteins. Moreover, addition of 90% galactooligosaccharides and fructo-
oligosaccharides in infant formula has been found to be useful in the prevention of eczema
development in infants, who are at high risk of developing this medical condition. Moreover,
oligosaccharides have also been found to increase absorption of minerals in the colon. The by-
products resulting from bacterial fermentation of the oligosaccharides reduces the pH of the
colon, which in turn increases the solubility and subsequent absorption of minerals in the colon
(Holscher et al. 2012, p.95S).

5OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION
OF INFANT FORMULA
Dosage and safety issues
The differences in gastrointestinal flora between infants who are fed breast milk and
formula milk are due to a variety of reasons. This difference is credited to the presence of
carbohydrate, protein, iron and phosphorus in human milk. The gastrointestinal microbiota
contributes in host nutrition, pathogen protection, development of immune response and
regulation of intestinal angiogenesis (Islam 2013, p.20). Infant formula generally consist of
galacto-oligosaccharides, fructo-oligosaccharides and polydextrose. Standard infant formula
consisting of 0.8g/dL of galacto- and fructo-oligosaccharides were close to mimicking the breast-
fed plan. Moreover, galacto-oligosaccharides of 0.24 or 0.44g/100ml in infant starter formula
and 0.5g/100ml in follow on formula was shown to stimulate the growth of both bifidobacteria
and lactobacilli similarly to those observed in the case of breast fed infants (Sierra et al. 2015,
p.89). Supplementation of infant milk with oligosaccharides were not found to have any side-
effects. Moreover, supplementation were also not associated with incidents like vomiting,
regurgitation or crying in the infants. However, some side-effects associated with galacto-
oligosaccharide supplementation but not directly associated with galacto-oligosaccharide intake
was abdominal discomfort, vomiting and increased gas production (Lasekan et al. 2015, p.3022).
Infant supplementation and critique
This part of the report is a critical analysis of some of the research evidences that provide
information about the role and effects of oligosaccharides supplemented in infant milk formula.
The research articles used are titled: “Effects of Pre-biotic containing infant formula on
gastrointestinal tolerance and fecal microbiota in a randomized controlled trial”,
“Oligosaccharides in infant formula: more evidence to validate the role of prebiotics”, “Effect of

6OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION
OF INFANT FORMULA
the specific infant formula mixture of oligosaccharides on local immunity and development of
allergic and infectious disease in young children: randomized study”.
The objective in case of the first study was to evaluate gastrointestinal tolerance, fecal
microbiota, concentration of short chain fatty acids and pH of infants fed with formula milk with
or without the addition of prebiotics like oligosaccharides. In this study, a randomized clinical
study was carried out where formula fed infants were compared with infants fed with breast
milk. The formula fed infants were fed with formula milk containing 4g/L of galacto-
oligosaccharides and fructo-oligosaccharuides in the ratio of 9:1. The concentration of fecal
bacteria, short chain fatty acids and pH were assessed at 0, 3 and 6 weeks intervals. The
concentration and number of bifidobacteria were found to be higher in the case of infants fed
with infant formula containing 4g/L of fructo - and galacto -oligosaccharides than the infants
who were fed the control formula lacking the oligosaccharides. Moreover, the proportion of
intestinal bifidobacteria were more or less the same as in the case of infants fed with breast milk.
Apart from these the concentration of Clostridium difficle was found to be higher in the case of
formula fed infants than those fed with control or breast milk. Additionally, the feces of formula
fed infants had high concentrations of butyrate, acetate, propionate and short chain fatty acids
when compared to those fed with breast milk. Fecal pH of infants fed with formula milk was
lower than those who were fed with control milk. Thus, this study revealed that formula milk
containing oligosaccharides were associated with increased abundance of bifidobacteria, reduced
fecal pH and were well tolerated by the infants (Holscher et al. 2012, p.95S).
The second article is a review that shows the effectiveness of oligosaccharides when
added in infant formula preparations. According to this study, prebiotics when added to infant
formula had a biofidogenic effect on the intestinal gut microbiota of infants. Galacto-

7OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION
OF INFANT FORMULA
oligosaccharides were found to be favorable for the growth of Bifidobacterium but relatively
poor growth was observed in the case of oligosaccharides like inulin, maltodextrin or
polydextrose. Moreover, formulas containing oligofructose and fructose-oligosaccharide as well
as galactose-oligosaccharide and fructose-oligosaccharide were found to have a similar
bifidogenic effect to that of breast milk but was higher when compared to that of standard
formula without oligosaccharides. In pre-term infants, formula supplemented with fructose-
oligosaccharide was found to have positive effects on the growth of Bifidobacterium. This also
resulted in a substantial decrease in the number of Enterococci and Escherichia coli. Moreover,
the impact of the oligosaccharides were found to be much higher when they were administered at
early infancy. Formula milk consisting of 0.24g/100ml and 0.44g/ml of galactose-
oligosaccharide were found to reduce fecal pH to values more or less similar to that of breast
milk. The concentration of short chain fatty acids produced were also similar in the case of
oligosaccharide supplemented infant formula and breast milk. Oligosaccharides were also found
to increase stool frequency and weight, apart from affecting the stool consistency and transit
time. Standard infant milk formula containing 4g/l of galacto-oligosaccharides helped to improve
stool consistency, which were similar to those observed in the case of breast fed infants. The
stool consistency of the infants fed with only a mixture of fructose-oligosaccharide were not
affected, while a mixture of fructo - and galacto -oligosaccharides had a significant effect.
Another study revealed that supplementation with 5g/l of galacto-oligosaccharides resulted in
higher stool frequency and consistency. However, a contradictory result was obtained in another
study, which revealed that 5g/l of galacto-oligosaccharides had no effect on stool frequency and
also decreased the infant stool consistency. The skin fold thickness of infants were found to be
larger in the case of infants fed with breast milk than those fed with supplemented formula milk.

8OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION
OF INFANT FORMULA
Another study revealed no significant differences in the infant growth rates fed with
supplemented or standard infant formula (Sierra et al. 2015, p.89). Oligosaccharides increase the
number of Bifidobacterium, which in turn promotes enhancement of the immune system.
However, according to Scalabrin et al. (2012), no noteworthy differences in the concentration of
secretory IgA were observed in the case of oligosaccharide supplemented formula, when
compared with that of the control groups. However, another study revealed that oligosaccharides
reduced colitis by regulating the trafficking and function of natural killer cells (Gopalakrishnan
et al. 2012, p.1336). Moreover, prebiotic supplementation helped to reduce the atopic dermatitis
development in infants, however, there is no study to validate the atopic dermatitis preventive
effects of oligosaccharides. The beneficial effects associated with the use of oligosaccharides in
infant formula to prevent allergies and infections are not conclusively determined and thus
further research is needed to validate this fact (Vandenplas, Zakharova & Dmitrieva 2015,
p.1339).
The objective of the third article is to determine the efficacy of oligosaccharide enriched
infant formula with respect to standard formula in enhancing the digestive immunity and prevent
allergic diseases and infections. The infants were divided into three groups, which were breast
fed, oligosaccharide formula fed and standard fed. The concentration of Bifidobacteria and
Lactobacilli were found to be similar in the case of infants fed with either breast milk or
supplemented formula milk. Moreover, the infant allergies were also lower in the case of infants
fed with either breast milk or oligosaccharide supplemented formula milk but was higher in the
case of standard formula fed infants. The mixture of short chain galacto-oligosaccharides and
long chain fructo-oligosaccharidesin the ratio 9:1, were found to positively affect the digestive
immunity similar to breast milk compositions (Ivakhnenko & Nyankovskyy 2013, p.398).

9OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION
OF INFANT FORMULA
Regulatory policies
Keeping in mind the health benefits linked with breast feeding, policies have been
generated in Australia and New Zealand, which deals with reducing the barriers to breastfeeding.
These include restrictions to infant formula use. However, some infants require infant formula as
their only source of nutrition and as a result, such infant formula products that are available to
the population are closely regulated products. Infant formula products produced in Australia and
New Zealand are under the standard regulation 2.9.1. According to this standard, an infant
formula is defined as “a product based on milk or other edible food constituents of animal or
plant origin which is nutritional adequate to serve as the principal liquid source of nourishment
for infants”. Moreover, infant formula is regulated in the United States by specific regulations or
legislations that provide a set of nutrients to be added in infant formula. These are managed by
the US food and drug administration. The permitted components to be added to the infant
formula includes oligosaccharides, lutein, polyunsaturated fatty acids like omega 3 and 6,
nucleotides, among others (Ris.pmc.gov.au 2018). According to the FDA, fructo-
oligosaccharidesare permitted to be added to various food products including infant foods. The
maximum intended level of fructose-oligosaccharide in infant starter formulas is permitted by the
FDA to be 400mg/100ml and 500mg/100ml in follow on infant formulas (Fda.gov 2018).
Conclusion/Recommendation
This report gives a description of the roles of oligosaccharides in the health promotion
and well-being of infants. The report also provides a critical analysis of the research that deals
with the effects of these oligosaccharides on the growth and health of infants when compared to
breast milk and standard infant formulas without added oligosaccharides. Supplementation of
formula milk with oligosaccharides were found to result in increased bifidogenic effect, which in

10OLIGOSACCHARIDES: THE CASE FOR AND AGAINST THE SUPPLEMENTATION
OF INFANT FORMULA
turn helps to prevent the attachment of pathogenic microorganisms and in turn prevents the
occurrence of infections. Some studies have reported the role of these oligosaccharides in the
promotion of growth and prevention of allergies, however, with lack of sufficient data, it is
necessary that further research be carried out before successfully claiming such beneficial effects
of oligosaccharides on infant health.

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OF INFANT FORMULA
Reference List
Belorkar, SA & Gupta, AK 2016, ‘Oligosaccharides: a boon from nature’s desk’, AMB
Express, vol.6, no.1, p.82, doi: 10.1186/s13568-016-0253-5
Bode, L 2012, ‘Human milk oligosaccharides: every baby needs a sugar
mama’, Glycobiology, vol. 22, no.9, pp.1147-1162, doi: 10.1093/glycob/cws074
Fda.gov 2018, retrieved 5 January 2018,
<https://www.fda.gov/downloads/Food/IngredientsPackagingLabeling/GRAS/
NoticeInventory/ucm504609.pdf>.
Gopalakrishnan, A, Clinthorne, JF, Rondini, EA, McCaskey, SJ, Gurzell, EA, Langohr, IM,
Gardner, EM & Fenton, JI 2012, ‘Supplementation with galacto-oligosaccharides increases
the percentage of NK cells and reduces colitis severity in Smad3-deficient mice’, The
Journal of nutrition, vol.142, no. 7, pp.1336-1342, doi: 10.3945/jn.111.154732
Holscher, HD, Faust, KL, Czerkies, LA, Litov, R, Ziegler, EE, Lessin, H, Hatch, T, Sun, S &
Tappenden, KA 2012, ‘Effects of prebiotic-containing infant formula on gastrointestinal
tolerance and fecal microbiota in a randomized controlled trial’, Journal of Parenteral and
Enteral Nutrition, vol. 36, no. (1_suppl), pp.95S-105S, doi: 10.1177/0148607111430087
Islam, MR 2013, ‘Bifidogenic Effect and the Immunity Power of Human Breast Milk’, Delta
Medical College Journal, vol.1, no.1, pp.20-24, doi: 10.3329/dmcj.v1i1.14972
Ivakhnenko, OS & Nyankovskyy, SL 2013, ‘Effect of the specific infant formula mixture of
oligosaccharides on local immunity and development of allergic and infectious disease in