Ingredients
Prebiotics:
Cultivating Essential Infant Gut Flora
Many studies have been
carried out on the effect of
commercial prebiotics,
such as oligofructose and
inulin, on tolerance, gut
health, bowel function,
resistance to infection and
development of the
immune system in infants.
This review will highlight
the role of prebiotics in
optimalizing health in
infants and children.
By Dr Anne Franck
Oligosaccharides, or prebiotics, can now be found in infant cereal
20 FOOD & BEVERAGE ASIA APRIL/MAY 2007
I
NFANT nutrition has long been viewed as important. Optimal infant
nutrition enables infants to grow and develop successfully, and ensures
good physiological programming at early life which favours a lower
disease risk in later life. Much has been said about the impact of programming
on cardiovascular disease, diabetes and metabolic syndrome (1). In contrast,
there has been relatively little discussion on how early diet modulates gut
function. A healthy, functioning gut is crucial in the defence against external
pathogens and in the maturation of the immune system. Infants are vulnerable
to infection because their guts are immature and they are in the early stages of
building up immunity to common pathogens. However, breast-fed infants have
generally lower risk for developing disease because of the presence of prebiotic
oligosaccharides in human milk. This opens new perspectives for food and
beverage innovators aiming to direct their products towards infant health.
Indeed, there is growing evidence that non-digestible oligosaccharides, e.g.
inulin and oligofructose, have a special role to play.
The infant gut
The foetal gut is sterile but birth leads to rapid colonisation by bacteria
present in the immediate environment, e.g. E. coli and streptococci or by
beneficial bacteria, e.g. bifidobacteria and lactobacilli (2). The evolution of
the gut flora depends upon how infants are fed. In breast-fed infants, pathogenic
bacteria are rapidly replaced by Bifidobacterium species (3). In formula-fed
infants, pathogens proliferate alongside more beneficial species resulting in a
more varied and complex flora. Bifidobacteria are normally the most prevalent
organism in the infant gut, although breast-fed
infants have 10 times more than formula-fed
infants. The ability to ferment inulin and
oligofructose is evident from an early age and
improves throughout weaning.
The composition of the microflora of the
infant gut has a major impact on the resistance
to infection. Several properties of
bifidobacteria and lactobacilli contribute to this
effect. Fermentation of prebiotic
oligosaccharides such as inulin and
oligofructose creates metabolites, such as lactic
and acetic acids, which have direct anti-
microbial effects. These also lower the pH of
the gut lumen which deters external pathogens
from taking up residence, as they tend to favour
less acidic conditions. In addition, there exists
a strong cross-talk between the endogenous
microbial flora and the immune system (gut
associated lymphoid tissue) influencing its
development during infancy.

Infant feeding into the future
The golden standard for infant
feeding is, and always will be, human
breast milk. Yet a minority of infants
are breast-fed to the recommended
age of 6 months. With that in mind,
there is a need to determine the key
constituents of breast milk and apply
best practice to formula milk and
weaning foods. While, it may be
impossible to replicate the complex
nature of human breast milk, some
beneficial components can be
mimicked. One important example is
oligosaccharides (prebiotics). These
are non-digestible carbohydrates
which represent the third component
of human milk (12-14 g/l) after
lactose and lipids. Several
investigations have shown that
oligosaccharides are responsible for
the well-known bifidogenic effects of
human milk (4). In comparison, cow’s
milk (used as the basis for infant
formulae) contains very few
oligosaccharides (< 1 g/l) and these
have a different structure from those
present in human milk (5).
In this perspective, supple-
mentation of infant formula with
oligosaccharides as food
ingredient might offer an
interesting approach to support
gut health in infants, children
and also adults who, otherwise,
would not consume sufficient
amounts. While commercial
oligosaccharides are not
identical to those found in
human milk, research shows
that they are very effective at
promoting colonies of
bifidobacteria and lactobacilli
(4,6).
Improving health with
oligosaccharides
The test of a prebiotic is whether
it (a) is resistant to digestion and
absorption in the upper intestine; (b)
can be fermented by colonic bacteria;
(c) selectively stimulates the growth
and metabolic activity of beneficial
Figure 1: Clinical outcomes observed during the
supplementation period (Saavedra & Tschernia, 2002).
bacteria, e.g. bifidobacteria and
lactobacilli. To that end, there are few
‘true’ prebiotics and the properties of
inulin and oligofructose are most
extensively studied and described (7).
Several studies have shown that
supplementation of infant formulae
with inulin, oligofructose, galacto-
oligosaccharides (GOS), or combi-
nations of these selectively promotes
colonic bifidobacteria and lacto-
bacilli. A change in faecal consistency
towards softer stools and a higher
stool frequency is also observed. Two
studies (9,10) compared the
proportion of bifidobacteria in the
stool flora of newborn infants fed with
a standard formula or one sup-
plemented with a mixture of inulin
Ingredients
and GOS. In the prebiotic group,
numbers of gut bifidobacteria
increased from 31% at baseline to
59% at 6 weeks of age, whereas no
significant change was observed in
the standard group. At 6 weeks of age,
the percentage of bifidobacteria in the
prebiotic group was close to levels
reported for breast-fed infants (i.e.
79%).
The gut flora of older
infants can also be modulated
by prebiotics. Knol et al. (10)
introduced a prebiotic-
containing formula (inulin and
GOS) to infants aged 4-12
weeks that had been fed for at
least 4 weeks with a standard
infant formula. After 6 weeks
on the prebiotic formula, the
numbers and species of gut
bifidobacteria were similar to
those typically found in breast-
fed infants. In another study,
Boehm (11) showed a dose-dependent
increase in the numbers of
bifidobacteria and a change of the
faecal pH after giving a prebiotic
formula containing either 0.4 g/dl or
0.8 g/dl of inulin and GOS. In the
group fed the higher dose, numbers
of gut bifidobacteria were similar to
those seen in breast-fed infants. This
FOOD & BEVERAGE ASIA APRIL/MAY 2007 21
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was confirmed in 28-day studies

conducted in term infants (12, 13)
with a favourable impact on faecal
flora and stool characteristics (i.e.
frequency, pH and consistency).
Modulating the gut bacteria of
infants is one stage, however the real
test of prebiotics is whether they can
impact favourably on human health.
Some aspects are now discussed.

Resistance to infection
Infants are susceptible to infection
both from the introduction of new
pathogens, e.g. lack of sterilization of
bottles, but also from overgrow of
pathogens normally residing in the
infant gut, e.g. harmful clostridia
species. Breast-fed infants experience
significantly fewer gastrointestinal,
respiratory and urinary infections than
formula-fed infants (5). Part of the
reason may be the presence of
oligosaccharides in human milk.
Animal studies have shown
conclusively that prebiotics can protect
against introduced pathogens. A
number of studies have been done on
germ-free quails inoculated with the
faecal flora of healthy or sick premature
neonates (14; 15). These showed that
oligofructose promoted the growth of
naturally-present bifidobacteria at the
expense of innate pathogenic bacteria.
Oligofructose also appears to act as an
anti-infective agent and can reduce the
occurrence or severity of gut lesions
caused by pathogens (16, 17). Studies
on rat models have confirmed these
findings. Montesi et al. (18)
supplemented rats with 3 types of infant
formulae: a standard formula, a
prebiotic formula enriched with
oligofructose or a probiotic infant
formula. Colonic bifidobacteria levels
rose significantly following the
prebiotic formula, whereas the
probiotic formula was no better than
the standard version. Both the pre-
and probiotic formulae reduced total
numbers of pathogenic bacteria, but
the prebiotic formula was much more
effective.
Figure 2: Day-care absenteeism observed during the
supplementation period (Saavedra & Tschernia, 2002).
The protective effect of inulin and
oligofructose supplemention extends
to infants and children. Saavedra et
al. (19) and Tschernia et al. (20)
examined the impact of oligofructose
supplementation in 123 non-breast-
fed infants (aged 4 to 24 months)
attending day-care centres. One group
received a standard weaning cereal for
six months, while the second group
received the same cereal supplemented
with 0.55g of oligofructose per 15g of
cereal. The consumption of the
prebiotic cereal was associated with a
decrease in severity of diarrhoeal
disease. General gut status was seen to
improve with decreases in bowel
movement discomfort, vomiting and
regurgitation. Furthermore, con-
sumption of the prebiotic cereal
resulted in adequate growth and was
associated with a significant reduction
in febrile events and cold symptoms,
antibiotic prescription (associated
with respiratory illness) and day-care
absenteeism. Figure 1 and 2 show that
infants taking the prebiotic oligo-
fructose supplement had improved
resistance and experienced better
clinical outcomes than controls.
Fisberg et al. (21) evaluated the
incidence and duration of sickness in
626 mild to moderately malnourished
children who received a nutritional
supplement with and without a
synbiotic (a combination of oligo-
fructose and probiotics). Children from
four countries, aged 1-6 years,
participated in the study. The number
of sick days decreased significantly
in both feeding groups, but in children
aged 3-5 years, sick days was fewer
in the synbiotic group as were days
of constipation.
A randomised placebo-controlled
trial (22) in Indonesia involved 118
children aged 1-14 years with acute
diarrhoea. An oligofructose supple-
ment was given to 93 children with
the dose linked to age (range 2.5 to 5
g/day). A further 25 children received
a placebo. The duration of diarrhoea
was shorter in children who consumed
oligofructose (2.6 days versus 4.2
days). A similar result was found in a
study of 8 infants aged 3-12 months
with acute diarrhoea who received a
low-lactose formula supplemented
with oligofructose and a probiotic
(23). The 5 infants receiving the

22 FOOD & BEVERAGE ASIA APRIL/MAY 2007


synbiotic formula had diarrhoea for a
shorter time than the controls (1.6
versus 2.5 days, respectively). A wider
range of benefits was found in a study
of 35 healthy infants (aged 6-24
months) randomised to receive a
control of 2g/day oligofructose (24).
Infants receiving the oligofructose
supplementation experienced sig-
nificantly less adverse events, e.g.
symptoms of flatulence, diarrhoea,
vomiting and fever, compared to the
controls.
Firmansyah et al. (25) examined
immune response following a measles
vaccination after infants consumed
either a standard weaning food (n=25)
or one supplemented with
oligofructose and inulin (n=24). Post-
vaccination specific IgG antibody
levels were significantly higher in the
supplemented group indicating a
better immune response (96% IgG
positivity rate vs. 88% in controls).
No differences in growth and overall
health status were seen.
Infants are often treated with
antibiotics but these can disrupt
Studies on a formula with a mixture of inulin and galacto-oligosaccharides shows
that prebiotics promote colonic bifidobacteria and lactobacilli
Ingredients
normal gut flora leading to an
increased susceptibility to gut
pathogens. It is likely that prebiotics
could counteract this as shown in a
study of 140 infants treated for acute
bronchitis with amoxicillin (26).
Subjects were randomised to receive
a control or infant formula
supplemented with inulin and
oligofructose (4.5 g/L) for 3 weeks.
Antibiotic therapy lowered overall
bacterial counts as predicted but
bifidobacteria were restored more
rapidly in the group supplemented
with prebiotics (P=0.014).
Allergies
The impact of prebiotics may go
well beyond the gut. Several studies
have suggested that the make-up of
intestinal flora can influence atopia
(susceptibility to allergy) and help
optimise immune function.
Bifidobacteria have been associated
with a better balance between Th1 and
Th2 cells, and can stimulate
appropriate T-helper cell responses.
These encourage normal immune
FOOD & BEVERAGE ASIA APRIL/MAY 2007 23
 Ingredients
responses. Certainly, the guts of atopic
infants have been found to contain
fewer bifidobacteria and more
clostridia than non-atopic infants (8).
In addition, early gut colonisation
with beneficial bacteria accelerates
the maturation of the secretory IgA
response and possibly brings about
earlier innate immunity to microbial
stimulation (2).
Tolerance and safety
Prebiotic oligosaccharides are in
general considered as very safe. In
none of the trials with children were
there any significant signs of
gastrointestinal intolerance such as
flatulence, abdominal discomfort or
increased purge (27). Studies on the
supplementation of a formula for pre-
term and term infants with a mixture
of inulin and GOS did not find any
influence on weight gain or length
increment (28). Euler et al. (29) fed
healthy 2-6 weeks old infants with
oligofructose-supplemented formula
for 5 weeks, finding good tolerance
and improved bowel function (more
frequent and softer stools). Also in
older infants (4-12 months) (n=56)
oligofructose supplementation up to
doses of 3 g/day showed good
tolerance with corresponding
beneficial effects on stool consistency
(soft or loose but not watery) and
stool frequency (30). The infants
participating in both the latter studies
also showed normal growth.
Prebiotic oligosaccharides thus
appear to be well tolerated by infants
and children.
Conclusion
Prebiotics represent a safe, effective
way of increasing the counts of
bifidobacteria and lactobacilli in the
intestinal flora of infants and children.
Increased levels of beneficial bacteria
help infants and children to resist
infection and may help in optimal
development of their immune system
over time. Few oligosaccharides are
true prebiotics and extensive evidence
24 FOOD & BEVERAGE ASIA APRIL/MAY 2007
exists for inulin and oligofructose.
These can be used as ingredients in a
wide variety of food and beverage
products and, thus, offer manufacturers
an innovative means of improving
current infant feeding products.
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Ingredients
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