The intestinal bacterial colonisation in preterm infants: A review of the literature

Article (PDF Available)inClinical Nutrition 25(3):361-8 · July 2006with195 Reads
DOI: 10.1016/j.clnu.2006.03.002 · Source: PubMed
Abstract
The aim of this study is to review the normal development of the intestinal microflora of preterm infants and the factors influencing its development. Preterm infants have an increased intestinal permeability, which may lead to bacterial translocation to systemic organs and tissues. In combination with immaturity of the immune system the risk to systemic infections might be increased. Especially potential pathogenic bacteria are able to translocate. The intestinal microflora of breast-fed term infants, dominated by bifidobacteria and lactobacilli, is thought to suppress the growth of potentially pathogenic bacteria. Many attemps have been made to stimulate the presence of bifidobacteria and lactobacilli with changes in the diet and ingredients-like prebiotics and probiotics. After selection, six studies were included reviewing the intestinal bacterial colonisation of preterm infants. In general, these studies show that the intestinal bacterial colonisation with beneficial bacteria is delayed in preterm infants. The number of potentially pathogenic bacteria is high. Antibiotics influence the intestinal colonisation. Many preterm infants receive prophylactic antibiotics at birth. As antibiotics delay the normal intestinal colonisation, caution should be given to the treatment with broadspectrum antibiotics in preterm infants at birth and every attempt has to be made to restrict the period of treatment.
Clinical Nutrition (2006) 25, 361 368
REVIEW
The intestinal bacterial colonisation in preterm
infants: A review of the literature
Elisabeth A.M. Westerbeek
a
, Anemone van den Berg
a
, Harrie N. Lafeber
a
,
Jan Knol
b
, Willem P.F. Fetter
a
, Ruurd M. van Elburg
a,
a
Department of Pediatrics, Subdivision of Neonatology, VU University Medical Center, De Boelelaan 1117,
1081 HV Amsterdam, The Netherlands
b
Biomedical Research Department, Numico Research BV, Wageningen, The Netherlands
Received 10 January 2006; accepted 3 March 2006
KEYWORDS
Intestinal bacterial
colonisation;
Preterm infant;
Infant, very low birth
weight;
Enteral nutrition
Summary The aim of this study is to review the normal development of the
intestinal microflora of preterm infants and the factors influencing its development.
Preterm infants have an increased intestinal permeability, which may lead to
bacterial translocation to systemic organs and tissues. In combination with
immaturity of the immune system the risk to systemic infections might be increased.
Especially potential pathogenic bacteria are able to translocate. The intestinal
microflora of breast-fed term infants, dominated by bifidobacteria and lactobacilli,
is thought to suppress the growth of potentially pathogenic bacteria. Many attemps
have been made to stimulate the presence of bifidobacteria and lactobacilli with
changes in the diet and ingredients-like prebiotics and probiotics.
After selection, six studies were included reviewing the intestinal bacterial
colonisation of preterm infants. In general, these studies show that the intestinal
bacterial colonisation with beneficial bacteria is delayed in preterm infants. The
number of potentially pathogenic bacteria is high. Antibiotics influence the
intestinal colonisation. Many preterm infants receive prophylactic antibiotics at
birth. As antibiotics delay the normal intestinal colonisation, caution should be given
to the treatment with broadspectrum antibiotics in preterm infants at birth and
every attempt has to be made to restrict the period of treatment.
& 2006 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All
rights reserved.
ARTICLE IN PRESS
http://intl.elsevierhealth.com/journals/clnu
0261-5614/$ - see front matter & 2006 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
doi:10.1016/j.clnu.2006.03.002
Corresponding author. Tel.: +31 204442413; fax: +31 204443045.
E-mail address: rm.vanelburg@vumc.nl (R.M. van Elburg).
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
Methods of literature review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363
Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
Results of the literature search. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
Characteristics of included studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
Bacterial intestinal colonisation of preterm infants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Beneficial bacteria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Bifidobacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Lactobacilli. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Potentially pathogenic bacteria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Enterobacteria, E. coli .................................................... 365
Bacteroides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Enterococci, Streptococci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Pathogenic bacteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Clostridia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Staphylococci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Pseudomonas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Klebsiella . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365
Conditions that modify intestinal bacterial microflora . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Preterm versus term infants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Breast-fed versus formula-fed infants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Antibiotic versus no antibiotic treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Vaginal delivery versus caesarean section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Molecular techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Introduction
The gastrointestinal tract is one of the largest
organs of the body serving as an important barrier
between ingested elements from the external
environment and the internal milieu of the body.
In children and adults, the intestine is able to
discriminate between pathogenic microorganisms
and the commensal intestinal microflora.
1
More-
over, it is able to select the beneficial nutrients
from the ingested food. In the preterm infant,
these functions are not completed yet.
2,3
The
development of the intestinal microflora starts at
birth and is influenced by various factors such as
gestational age, mode of delivery, local environ-
ment, type of feeding, and antibiotic treatment.
48
In breast-f ed term infants, bifidobacteria become
the predominant bacteria in the intestinal micro-
flora, whereas in formula-fed term infants the
intestinal micr oflora becomes more diverse with,
apart from bifidobacteria, also bacteroides, clos-
tridia, enterobacteria and streptococci.
911
There-
fore, therapies have focussed on the development
of a bifidogenic intestinal flora, e.g. with prebiotics
and probiotics. Although recent studies with pre-
biotics and probiotics show promising results, more
studies are needed to determine the role of
prebiotics and probiotics in preterm infants.
1216
Bacteria in the lumen of the intestine can be
grouped according to their degree of pathogeni-
city.
17
Three groups of bacteria can be recognised:
(1) beneficial, (2) potentially pathogenic and (3)
pathogenic bacteri a. Beneficial effects are inhibi-
tion of growth of pathogenic bacteria, production
of vitamins, degrading and fermentation of food
ingredients, stimulation of feeding tolerance and
stimulation of immune functions. Pathogenic ef-
fects of bacteria include feeding intolerance,
inflammation, infections and especially in preterm
infants this can lead to necrotising enterocolitis.
Potentially pathogenic bacteria belong to the
normal microflora of the intestine, but may become
pathogenic if present in high numbers: enterobac-
teria, enterococci, Escheria coli, streptococci and
bacteroides. Potentially pathogenic bacteria-like
proteus, staphylococci, clostridia and klebsiella,
may become pathogenic, even if present in low
numbers.
2,17
Due to the immaturity of the gastrointestinal
tract, bacteria may translocate to systemic organs
and tissues and, in combination with immaturity of
the immune system, increase the risk for systemic
infections.
18
Especially potentially pathogenic bac-
teria have the potention to translocate.
19
An
intestinal microflora of anaerobic bacteria-like
bifidobacteria and lactobacilli favours protection,
ARTICLE IN PRESS
E.A.M. Westerbeek et al.362
because it may suppress the growth of pathogenic
bacteria.
20,21
Few studies have determined the developmental
aspects of the intesti nal bacterial colonisation of
preterm infants. As preterm infants often require
intensive care treatment with an increased risk for
serious infections, insight in the development of
the intestinal bacterial colonisation of (preterm)
infants is important. In addition, the various
potential factors influencing the intestinal bacter-
ial colonisation of these infants need to be studied.
It is not known whether prematurity itself may
influence the intestinal bacterial colonisation, but
preterm infants experience intensive care treat-
ment in their first days of life and it is likely that
this influences the intestinal bacterial colonisation.
Preterm infants often need parenteral feeding, due
to the immaturity of their intestine and they often
need respiratory support, they are vulnerable for
infections and often require antibiotic treatment.
Increasing insight in the development of the
intestinal bacterial colonisation and the factors
involved might help to establish conditions in order
to alter a possibly pathogenic developmental micro-
flora to that seen in healthy term infants. The aim of
this study is to review the normal development of
the intestinal microflora of preterm infants and the
factors influencing its development.
Methods of literature review
A literature search was performed by a PubMed
search from January 1970 till December 2005 using
the followi ng keywords and limits:
(Intestines[mesh] OR intestin* OR gut OR gastro-
intestin* OR enteric) and (flora OR microbiolog* OR
microbiology[sh] OR microflora OR bacteria OR
bacterial OR ent erobacteria* OR colonisation OR
colonisation OR microbes OR microbial) and (neo-
nat* OR infant*) AND (premature OR preterm OR
pre-term OR low birth weight OR low weight OR
small for gestational age) and (english[la] OR
german[la] OR dutch[la]) NOT (Probiotics[mesh]
OR Oligosaccharides[mesh] OR prebiotic*[ti] OR
necrotising enterocolitis OR necrotic enteric colitis
OR ‘Enterocolitis, Necrotising’’[MeSH]).
Forward citation tracking was performed with
the retrieved publications via the Web of Science.
Related articles in PubMed and in the Web of
Science were reviewed as well as references
described in those publications.
Inclusion criteria:
preterm/very low birth weight (VLBW) infants
intestinal colonisation from birth
ARTICLE IN PRESS
Table 1 Included studies.
Author Year Population
(N)
Gestational age
(weeks)
Birth weight (g) Methods Purpose
Blakey et al.
23
1982 28 30 (2536) 1125 (5601500) Faeces culture first 3
weeks
Identify micro-organisms colonising the gut of preterm
infants admitted to a special care nursery.
Stark and Lee
28
1982 26 33 (3035)
y
1920
y
(14402300)
Faeces culture first 4
weeks
Define the early bacterial colonisation of the large
bowel of preterm infants fed expressed breast milk and
compare it to the colonisation of term infants who have
been breast or formula fed.
Rotimi et al.
25
1984 23 29 (2436) 1728 (7502400) Faeces culture first 6
days
Investigate the development of bacterial colonisation
of preterm infants admitted to the special baby care
unit and whose mothers received antenatal care.
Sakata et al.
26
1985 13 29.5 (25.534.7) 1077 (8101350) Faeces culture first 7
weeks
Investigate the development of the intestinal flora in
VLBW infants in comparison with term infants.
Hall et al.
4
1990 98 32 (2533) 1140 (6202510) Faeces culture & gas
liquid chromatography
day 10 & 30
Determine whether a characteristic pattern of
colonisation with lactobacilli and bifidobacteria can be
identified in term and in preterm infants.
Gewolb et al.
24
1999 29 26 782 Faeces culture day 10, 20
&30
Serially characterise the aerobic and anaerobic stool
microflora in a cohort of preterm infants o1000 g at
birth.
Gestational age and birth weight are given as mean or median
y
(range).
The intestinal bacterial colonisation in preterm infants 363
Exclusion criteria:
necrotising enterocolitis
prebiotica/probiotica
The publications were analysed for:
1. Methods used for collecting and analysing the
faecal samples.
2. Investigation of bacterial intestinal colonisation
over time, collecting the faecal samples at least
once a week with precisely describing the day of
collection.
3. Availability of data on the number of infants (or
percentage) from whom bacteria were isolated.
4. Possible confounding factors, such as gestational
age, type of delivery, type of feeding, initiation
of feeding, antibiotic treatment, length of stay
at a NICU and obstetric diagnosis.
Results
Results of the literature search
With the initial search, 11 relevant publications
were found.
4,68,2228
The selected studies were published between
1979 and 2003. Five studies were excluded from
this review because of:
1. Unclear description of sampling.
8,22
2. Heterogeneity of the study population.
6,7
3. Lack of data on the number of infant s colonised
with tested bacteria.
27
Characteristics of included studies
Of the six selected studies, five studies used culturing
techniques on selective media to perform the
colonisation pattern. One study used culturing tech-
niques on selective media and gasliquid chromato-
graphy. Mean gestational age of the infants varied
from 26 weeks
24
to 33 weeks.
28
Mean birth weight of
the infants varied from 814
24
to 1920 g
28
(Tab le 1).
The included studies collected faecal samples at
different postnatal ages. For comparison, four
groups were defined according to postnatal age at
sampling (Table 2):
1. within 48 h after birth;
2. day 59 (week 1);
ARTICLE IN PRESS
Table 2 Intestinal bacterial colonization at different postnatal ages.
o 2d 1wk 2wk 43wk o2d 1wk 2wk 43wk o2d 1wk 2wk 4 3wk
Beneficial
Bifidobacteria Lactobacilli
Blakey ——— 7 8 14 25
Stark 0 55 63 ———
Rotimi 86 96 —— 13 14 ——
Sakata 0 43 100 100 0 0 14 80
Hall ——17 11 ——14 19
Gewolb ——44 ——44
Potentially pathogenic
Enterobacteria/E.coli Enterococci Bacteroides
Blakey 13 44 46 60 7 8 25 20 57 44 79 35
Stark ——— —— 40 64 38
Rotimi 78 100 —— X57 X91 —— X17 X78 ——
Sakata 100 100 100 100 100 100 100 100 14 14 29 43
Hall ——62 95 ——— ——
Gewolb ——14 43 ——X28 X57 ——10 10
Pathogenic
Clostridia Staphylococci Pseudomonas
Blakey X10 X20 X18 X35 X17 X20 X18 X35 0 12 11 0
Stark 20 56 25 ——— ——
Rotimi X44 X50
—— X48 X77 —— 49——
Sakata 0 0 29 57 43 71 86 100 0 29 14 29
Hall ——— —— ——
Gewolb ——— X59 X57 ——47
Data are expressed as percentage of the number of preterm infants with positive culture.
E.A.M. Westerbeek et al.364
3. day 1016 (week 2);
4. day 20 and more (Xweek 3).
Bacterial intestinal colonisation of
preterm infants
Beneficial bacteria
Bifidobacteria
In five studies bifidobacteria were determined in
the faeces.
4,2426,28
In two of three studies,
bifidobacteria were not detected directly after
birth.
26,28
In these two studies, bifidobacteria
increased over time. In two studies, bifidobacteria
were rarely found during the whole study peri-
od.
4,24
In only one study, high numbers of bifido-
bacteria were found also directly after birth.
25
In
conclusion, low numbers of bifidobacteria are
found in faeces of preterm infants.
Lactobacilli
In five studies, lactobacilli were determined in
the faeces.
4,2326
In none of the studies, lacto-
bacilli were found at birth. In the study of Sakata
et al.
26
lactobacilli growth increased after
2 weeks. In the other studies, lactobacilli growth
remained low.
4,23,25
In conc lusion, low numbers of
lactobacilli were found in the faeces of preterm
infants.
In summary, low numbers of beneficial bacteria
are found in the intestinal microflora in preterm
infants.
Potentially pathogenic bacteria
Enterobacteria, E. coli
In five studies, enterobacteria were deter-
mined.
4,2326
In four studies analysing E. coli,
4,2325
E. coli was found in high numbers. In two studies,
enterobacteria were sparsely found.
24,25
In one
study, enterobacteria growth was rarely found
during the whol e study period.
18
The study of
Sakata et al.
26
analysed enterobacteria, without
further culturing of E. coli. Enterobacteria were
found in high numbers in all infants during the
whole study period. In conclusion, high numbers of
enterobacteria , E. coli are found in the faeces of
preterm infants.
Bacteroides
In five studies, Bacteroides was determined.
2325,28
In three studies, Bacteroides was found in high
numbers.
23,25,28
In one study Bacteroides growth
increased during the study period.
26
In one study,
Bacteroides was rarely found during the whole
study period.
24
In conclusion, high numbers of
Bacteroides are found in the faeces of preterm
infants.
Enterococci, Streptococci
In four studies, enterococci were determined.
2326
In two studies, strepto cocci were found in
high numbers during the whole study period.
25,26
In one study enterococci growth increased during
the study period.
24
In one study, enterococci were
not found.
23
In conclusion, high numbers of
enterococci are found in the faeces of preterm
infants.
In summary, high numbers of potentially patho-
genic bacteria are found in the intestinal microflora
of preterm infants.
Pathogenic bacteria
Clostridia
In five studies, clostridia were determined.
2326,28
In two studies clostridia were sparsely found.
23,24
In
two studies low numbers of clostridia were found in
the beginning of the study, but increased over
time.
26,28
In the study of Rotimi et al.
25
clostridia
were only found within 48 h. In conclusion, coloni-
sation with clostridia is diverse in the faeces of
preterm infants.
Staphylococci
In four studies, staphylococci were deter-
mined.
2326
In two studies, staphylococci were
sparsely found.
23,24
In the two other studies, high
numbers of staphylococci were found during the
whole study period.
25,26
In conclusion, high num-
bers of staphylococci are found in the faeces of
preterm infants.
Pseudomonas
In four studies, pseudomonas was determined.
2326
In all studies, pseudomonas was sparsely found. In
one study, pseudomonas growth increased slightly
over time.
26
In conclusion, low numbers of pseu-
domonas are found in the faeces of preterm
infants.
Klebsiella
In two studies, klebsiella were determined.
23,25
In
both studies, klebsiella growth increased over
time during the study. In conclusion, high numbers
of klebsiella are found in the faeces in preterm
infants
ARTICLE IN PRESS
The intestinal bacterial colonisation in preterm infants 365
In summary, high numbers of pathogenic bacteria
are found in the intestinal bacterial microflora of
preterm infants.
Conditions that modify intestinal bacterial
microflora
Preterm versus term infants
Three studies determined intestinal bacterial mi-
croflora in preterm and term infants.
4,26,28
In the
study of Sakata et al. enterobacteria and str epto-
cocci were dominant on day 1 in both groups. On
day 4, bifidobacteria became dominant in the term
group, whereas bifidobacteria became dominant on
day 20 in the VLBW infants group. The dominance
was weaker in the preterm group (ratio bifidobac-
teria to enterobacteria remained 10:1 at 7 weeks of
life) than in the term group (ratio 1000:1 on day
7).
26
In preterm infants, Stark and Lee
28
found that
colonisation with bifidobacteria was significant
delayed during the first week of life.
Hall et al.
4
found a significantly lower prevalence
of colonisation with coliforms (Po0.01) and lacto-
bacilli (Po0.005) in the preterm group at 10 days.
At 30 days, there was a significant lower prevalence
of lactobacilli in preterm infants (Po0.01).
Breast-fed versus formula-fed infants
One study compared the intestinal microflora of
breast-fed with formula-fed preterm infants.
24
In
the study of Gewolb et al. breast-fed infants
showed a more diverse bacterial population than
formula-fed infants with lower numbers of patho-
genic micr o-organisms.
Antibiotic versus no antibiotic treatment
Three studies determined the influence of anti-
biotic treatment on the intestinal bacterial coloni-
sation.
4,23,24
In the study of Gewolb et al. all
infants received at least 2 days of antibiotic
treatment during the first month of life. They
found an inverse correlation between the number
of days of antibiotic treatment in the first month of
life and the number of bacterial species (r ¼ 0.491;
P ¼ 0.007) and the to tal number of organisms
(r ¼ 0.482; P ¼ 0.008) in the faecal samples at
day 30. Only in one infant lactobacilli and bifido-
bacteria were found.
24
Blakey et al.
23
found that in
infants receiving antibiotics after birth lactobacilli
were never isolated in the first 20 days of life.
Before 12 days of age, clostridia were reduced in
infants receiving antibiotic treatment. At 10 days
of age, Hall et al.
4
found that infants treated
parenteral antibiotics had significant reduced co-
lonisation rates of lactobacilli (Po0.01).
In summary, colonisation with bacteria, espe-
cially beneficial bacteria like lactobacilli, is de-
layed in infants receiving antibiotics after birth.
Vaginal delivery versus caesarean section
Only one study determined the influence of method
of birth. Rotimi et al.
25
found that colonisation with
Bacteroides and clostridia is delayed in infants
delivered by caesarean section.
Molecular techniques
The studies discussed in this review used conven-
tional cultivating techniques to study the intestinal
microflora. In recent years molecular techniques
are developed for directly detecting different
groups of bacteria in faecal samples without
further cultivation.
29,30
However, only a few studies
used molecular techniques to study the intestinal
microflora in preterm infants.
27
Schwiertz et al.
27
used PCR-denaturing gradient gel electrophoresis
to study the intestinal microflora of preterm
infants. They found an increase in similarity of
bacterial communities in hospitalised preterm
infants in contrast to breast-fed, term infant s on
the environment.
Discussion
Our review has shown that colonisation of bifido-
bacteria and lactobacillus is delayed in preterm
infants, whereas colonisation with potentially
pathogenic bacteria (especially E. coli) is in-
creased. The type of feeding did not influence the
bacterial colonisation in preterm infants, but the
longer time to full enteral feeding may explain this
finding.
26
Early introduction of enteral feedings is thought
to stimulate the intestine of preterm infants. This
might maximise the immune functions of the
intestine, reduce the risk of infection and improve
the outcome of preterm infants. Prebiotics and
probiotics are thought to stimulate the presence of
a bifidogenic microflora and thus have a positive
effect on health.
1216
The intestinal micr oflora is difficult to study. Only
a limited number of bac teria may be detecte d using
conventional cultivation techniques. Several stu-
dies show that fluorescent in situ hybridisation
(FISH) analyses may provide quantitative data on
the relative amount of the different bacterial
groups, while cultivating techniques are insuffi-
ciently select ive and unsuitable for quantitative
analysis.
9,29,30
ARTICLE IN PRESS
E.A.M. Westerbeek et al.366
In this review, emphasis is put on studies using
conventional cultivation techniques and possibly
intestinal colonisation may differ from that in
studies using molecular techniques. Cultivation
techniques have a high sensitivity for E. coli,so
these studies may find relatively high numbers of
E. coli. In this review, data are expressed as the
number of infants colonised with the specific
bacteria. This is not a sensitive metho d, because
every infant will be colonised with at least one
bacteria of every type of bacteria. Quantitat ive
data would be more reliable, but unfortuna tely
most studies in this review did not show these data.
The intestinal microflora has been implicated in
the pathogenesis of necrotising enterocolitis, which
is a significant cau se of morbidity and mortality in
preterm infants. In this review, studies of patients
with necrotising enterocolitis were excluded, be-
cause pathoge nesis is multifactorial and specific
unrecognised bacteria might be involved, which are
not normally found in the intestine.
3133
It is concluded that the intestinal bacterial
colonisation with beneficial bacteria is dela yed in
preterm infants, while the number of potentially
pathogenic bacteria is high. This review shows that
antibiotics may delay the normal intestinal coloni-
sation, caution should be given to the treatment
with broad spectrum antibiotics in preterm infants
at birth and every attempt has to be made to
restrict the period of treatment to a minimum.
References
1. Adlerberth I. Establishment of a normal intestinal microflora
in the newborn. In: Hanson LA, Yolken RH, editors.
Probiotics, other nutritional factors and intestinal micro-
flora, vol. 42. Nestle´ Nutrition Workshop Series, 1999.
p. 6378.
2. Dai D, Walker WA. Protective nutrients and bacterial
colonization in the immature human gut. Adv Pediatr 1999;
46:35382.
3. Mackie RI, Sghir A, Gaskins HR. Developmental microbial
ecology of the neonatal gastrointestinal tract. Am J Clin
Nutr 1999;69:1035S10345S.
4. Hall MA, Cole CB, Smith SL, Fuller R, Rolles CJ. Factors
influencing the presence of faecal lactobacilli in early
infancy. Arch Dis Child 1990;65:1858.
5. Gro¨nlund MM, Lehtonen OP, Eerola E, Kero P. Fecal
microflora in healthy infants born by different methods of
delivery: permanent changes in intestinal flora after
cesarean delivery. J Pediatr Gastroenterol Nutr 1999;28:
1925.
6. Bennet R, Eriksson M, Nord CE, Zetterstrom. Fecal bacterial
microflora of newborn infants during intensive care manage-
ment and treatment with five antibiotic regimens. Pediatr
Infect Dis 1986;5:5339.
7. Bennet R, Nord CE. Development of the faecal anaerobic
microflora after caesarean section and treatment with
antibiotics in newborn infants. Infection 1987;15:3326.
8. Goldmann DA, Leclair J, Macone A. Bacteriel colonization
of neonates admitted to an intensive care environment.
J Pediatr 1978;93:28893.
9. Harmsen HJ, Wildeboer-Veloo AC, Raangs GC, Wagendorp
AA, Klijn N, Bindels JG. Analysis of intestinal flora develop-
ment in breast-fed and formula-fed infants by using
molecular identification and detection methods. J Pediatr
Gastroenterol Nutr 2000;30:617.
10. Yoshioka H, Iseki K, Fujita K. Development and differences
of intestinal flora in the neonatal period in breast-fed and
bottle-fed infants. Pediatrics 1983;72:31721.
11. Long SS, Swenson RM. Development of anaerobic fecal
flora in healthy newborn infants. J Pediatr 1977;91:
298301.
12. Magne F, Suau A, Pochart P, Desjeux JF. Fecal microbial
community in preterm infants. J Pediatr Gastroenterol Nutr
2005;41
:38692.
13. Millar M, Wilks M, Costeloe K. Probiotics for preterm infants.
Arch Dis Child Fetal Neonatal Ed 2003;88:F3548.
14. Caicedo RA, Schanler RJ, LI N, Neu J. The developmental
intestinal ecosystem: implications for the infant. Pediatr
Res 2005;58:6258.
15. Neu J, Caicedo RA. Probiotics: protecting the intestinal
ecosystem? J Pediatr 2005;147:1436.
16. Forchielli ML, Walker WA. The effect of protective nutrients
on mucosal defense in the immature intestine. Acta
Paediatr Suppl 2005;94:7483.
17. Waaij van der D. Microbial ecology of the intestinal
microflora: influence of interactions with the host organism.
In: Hanson LA, Yolken RH, editors. Probiotics, other
nutritional factors and intestinal microflora, vol. 42. Nestle
Nutrition Workshop Series, 1999. p. 115.
18. Duffy LC. Interactions mediating bacterial translocation in
the immature intestine. J Nutr 2000;130:4326.
19. Lichtman SM. Bacterial translocation in humans. J Pediatr
Gastroenterol Nutr 2001;33:110.
20. Camp JM, Tomaselli V, Coran AG. Bacterial translocation in
the neonate. Curr Opin Pediatr 1994;6:32733.
21. Wold AE, Adlerberth I. Breast feeding and the intestinal
microflora of the infant-impications for protection
against infectious diseases. Adv Exp Med Biol 2000;478:
7793.
22. Bell MJ, Rudinsky M, Brotherton T, Schroeder K, Boxerman
SB. Gastrointestinal microecology in the critically ill
neonate. J Pediatr Surg 1984;19:74551.
23. Blakey JL, Lubitz L, Barnes GL, Bishop RF, Cambell NT,
Gilliam GL. Development of gut colonisation in pre-term
neonates. J Med Microbiol 1982;15:51929.
24. Gewolb IH, Schwalbe RS, Taciak VL, Harrison TS,
Panigrahi P. Stool microflora in extremely low birth-
weight infants. Arch Dis Child Fetal Neonatal Ed 1999;
80:F16773.
25. Rotimi VO, Olowe SA, Ahmed I. The development of
bacterial flora of premature neonates. J Hyg (London) 1985;
94:30918.
26. Sakata H, Yosioka H, Fujita K. Development of the
intestinal flora in very low birth weight infants compared
to normal full-term newborns. Eur J Pediatr 1985;144:
18690.
27. Schwiertz A, Gruhl B, Lo¨bnitz M, Michel P, Radke M, Blaut M.
Development of the intestinal bacterial composition in
hospitalized preterm infants in comparison with breast-
fed, full-term infants. Pediatr Res 2003;54:3939.
28. Stark PL, Lee A. The bacterial colonization of the large
bowel of pre-term low birth weight neonates. J Hyg
(London) 1982;89:5967.
ARTICLE IN PRESS
The intestinal bacterial colonisation in preterm infants 367
29. Langendijk PS, Schut F, Jansen GJ, et al. Quantitative
fluorescence in situ hybrization of bifidobacterium spp.
with genus-specific 16S rRNA-trageted probes and its
application in fecal samples. Appl Environ Microbiol 1995;
61:306975.
30. Franks AH, Harmsen HJ, Raangs GC, Jansen F,
Schut F, Welling GW. Variations of bacterial popul-
ations in human feces measured by fluorescent in situ
hybridization with group-specific 16S rRNA-targeted oligo-
nucleotide probes. Appl Environ Microbiol 1998;64:
333645.
31. Millar MR, Linton CJ, Cade A, Glancy D, Hall M, Jalal H.
Application of 16S rRNA gene PCR to study bowel flora of
preterm infants with and without necrotizing enterocolitis.
J Clin Microbiol 1996;34:250610.
32. Duffy LC, Zielezny MA, Carrion V, et al. Bacterial toxins and
enteral feeding of premature infants at risk for necrotizing
enterocolitis. Adv Exp Med Biol 2001;501:51927.
33. Hoy C, Millar MR, Mackay P, Godwin PG, Langdale V, Levenne
MI. Quantitative changes in faecal microflora preceding
necrotising enterocolitis in premature neonates. Arch Dis
Child 1990;65:10579.
ARTICLE IN PRESS
E.A.M. Westerbeek et al.368
    • "NEC is a complex process that involves inflammation and bacterial invasion of the immature mucosa. Hypoperfusion of the bowel, the use of antibiotics and delay to commence enteral feeding are factors that act synergistically to promote intestinal atrophy and abnormal bacterial colonization of the bowel (Rodriguez 2015; Westerbeek et al 2006). Late-onset infection (LOI), defined as a blood culture positive microbial infection after 72 hours of life (Stoll 2002), is associated with a high burden of morbidity and mortality in preterm infants. "
    [Show description] [Hide description] DESCRIPTION: A Cochrane Protocol. Published : Cochrane Database of Systematic Reviews 2015, Issue 10
    Full-text · Research · Feb 2016 · Journal of Pharmacy Practice and Research
    • "The gut of preterm infants contains higher levels of C. difficile compared to full term infants (Penders et al., 2006). Moreover, data obtained from short-term stool culture have shown that colonization by Bifidobacterium and Lactobacillus is delayed in preterm infants, whereas colonization by potentially pathogenic bacteria (especially E. coli) is increased (Westerbeek et al., 2006; Butel et al., 2007). During infancy, diet is one of the many contributors to the development of gut microbiome (Koenig et al., 2011). "
    [Show abstract] [Hide abstract] ABSTRACT: Key Points The microbiome has been implicated in the development of obesity. Conventional therapeutic methods have limited effectiveness for the treatment of obesity and prevention of related complications. Gut microbiome transplantation may represent an alternative and effective therapy for the treatment of obesity. Obesity has reached epidemic proportions. Despite a better understanding of the underlying pathophysiology and growing treatment options, a significant proportion of obese patients do not respond to treatment. Recently, microbes residing in the human gastrointestinal tract have been found to act as an “endocrine” organ, whose composition and functionality may contribute to the development of obesity. Therefore, fecal/gut microbiome transplantation (GMT), which involves the transfer of feces from a healthy donor to a recipient, is increasingly drawing attention as a potential treatment for obesity. Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary. Here, we summarize benefits, procedures, and issues associated with GMT, with a special focus on obesity.
    Full-text · Article · Feb 2016
    • "] It has been found that the bifidobacteria and lactobacilli in preterm neonates are less compared with term neonates, while, the amount of potentially pathogenic bacteria in preterm neonates is more than that in term neonates. [3] Furthermore, prescription of antibiotics in preterm infants leads to a serious delay of GI colonization with bacteria. [4] In addition, in premature infants admitted to Neonatal Intensive Care Units (NICUs), the risk of neonatal infection is higher. [3] Although frequently serious infections in preterm infants are caused by coagulase‑negative staphylococci that come from external sources of infants, [3] in many cases, serious infections in newborns can be t"
    Full-text · Article · Feb 2016
Show more