Livestock Production Science 66 2000 95–107 www.elsevier.com locate livprodsci
Postnatal adaptation of the gastrointestinal tract in neonatal pigs: a possible role of milk-borne growth factors
a , a
b
R.J. Xu , F. Wang , S.H. Zhang
a
Department of Zoology , The University of Hong Kong, Pokfulam Road, Hong Kong, China
b
Department of Human Physiology , Flinders University of South Australia, Bedford Park, SA, Australia
Abstract
During the postnatal period the gastrointestinal GI tract of the neonatal pig encounters numerous challenges and severe stress, particularly at the time of birth and weaning. In response to such challenges, the GI tract undergoes marked changes,
including accelerated tissue growth and functional maturation during the immediate postnatal period, and intestinal villus atrophy and damage following weaning. The changes are apparently related to the onset of colostrum ingestion at the time of
birth and the withdrawal of milk ingestion at the time of weaning. Porcine colostrum and milk contain not only highly digestible nutrients but also numerous bioactive compounds, including various types of growth factors, including epidermal
growth factor, insulin-like growth factor-I IGF-I, IGF-II, insulin and transforming growth factor-b. Experimental evidence summarized in the review indicates a regulatory role of these milk-borne growth factors in stimulating GI tissue growth and
function maturation, and in enhancing repair of damaged GI mucosa in the suckling young. The findings imply that milk-borne growth factors may be used to enhance GI maturation in neonatal animals and be used to treat GI mucosal
damages. Potential therapeutic applications of milk-borne growth factors in both agricultural animals and human infants warrant further investigation.
2000 Elsevier Science B.V. All rights reserved.
Keywords : Milk, Pig; Growth Factor; EGF; IGF; TGF-b
1. Introduction tract switches from handling a liquid nutritious diet,
milk, to solid food, often of plant origin. In response The gastrointestinal GI tract in neonatal animals
to these challenges, the GI tract in healthy animals encounters numerous challenges and severe physio-
undergoes marked changes in structure and function logical stresses during the postnatal period, particu-
Xu, 1996; Pluske et al., 1997. However, some larly at the times of birth and weaning. At the time
animals fail to adapt to these challenges, often of birth, the GI tract is exposed, for the first time, to
resulting in reduced growth, diarrhoea or death Odle nutrient dense colostrum as well as to various types
et al., 1996. of microorganisms. At the time of weaning, the GI
The mechanisms involved in postnatal adaptation of the GI tract are complex. Maternal milk apparent-
ly plays an important role in facilitating postnatal
Corresponding author. Tel.: 1 852-2859-7014; fax: 1 852-
adaptation of the GI tract in neonates. It has long
2559-9114. E-mail address
: xuruojunhkucc.hku.hk R.J. Xu.
been known that milk not only contains easily
0301-6226 00 – see front matter
2000 Elsevier Science B.V. All rights reserved. P I I : S 0 3 0 1 - 6 2 2 6 0 0 0 0 2 1 7 - 7
96 R
.J. Xu et al. Livestock Production Science 66 2000 95 –107 Table 1
digestible nutrients but also bioactive compounds,
Changes in body weight BW, stomach tissue weight SW,
such as immunoglobulins and lysozymes, which
parietal cell volume density in the gastric glands PCVD,
protect the GI tract from pathogenic microorganisms
maximal acid output per unit gastric tissue mass MAO, gastric
Xanthou, 1998. More recently, a number of growth
acid secretory capacity GASC, concentration of gastrin in antral
factors have been detected in maternal milk of
tissue TG, concentration of gastrin in plasma PG, maximal proteolytic enzyme output per unit gastric tissue mass MPO and
various species Xu, 1998. There is increasing
gastric proteolytic enzyme secretory capacity GPSC in neonatal
evidence showing that milk-borne growth factors can
a
pigs during the immediate postnatal period
survive in the GI lumen of the suckling young, and
Birth Day 1
Day 3 Day 7
exogenous growth factors administered orally stimu- late GI maturation in neonates Odle et al., 1996; Xu,
BW kg 1.34
1.44 1.65
2.10 SW g
5.7 7.2
8.7 11.1
1996. The biological significance of milk-borne
PCVD 4.2
5.7 10.7
–
growth factors, however, remains to be fully eluci-
MAO mM g per h 35
59 107
–
dated. Understanding the role of milk-borne growth
GASC mM h 198
422 932
–
factors in postnatal GI adaptation and their mecha-
TG pmol g 106
– –
459
nisms of action may help us to prevent and treat
PG fmol ml 44
– –
108 MPO mg g per h
3.9 –
– 29
many GI disorders in neonatal animals. This review
GPSC mg h 22
– –
322
discusses the recent progress in the area of milk-
a
Data derived from Sangild et al. 1991, Xu and Cranwell
borne growth factors and regulation of postnatal
1990, 1991 and Xu et al. 1992a.
adaptation of the GI tract in neonatal animals with a particular emphasis on neonatal piglets.
1990. The percentage of mucosal volume occupied by parietal cells and the number of parietal cells per
2. Adaptive changes in the GI tract after birth unit volume of gastric mucosa increased significantly
during the same period Xu et al., 1992a. Gastric Before birth, the foetus lives in a sterile environ-
secretory capacity for protease enzymes increased by ment and obtains all the nutrients from the maternal
9-fold during the first 7 postnatal days Sangild et circulation via the placenta. Immediately after birth,
al., 1991. It was also found that the concentration of the GI tract of a newborn has to take over the
gastrin in the gastric antral tissue increased by 3-fold responsibility of absorbing nutrients, and at the same
and the concentration of circulating gastrin increased time the animal is exposed to various types of
by about 1.5-fold in newborn pigs during the post- micro-organisms. To adapt to the functional demands
natal 7 days after birth Xu and Cranwell, 1991. and changes in the environment, the GI tract of a
Table 2
newborn undergoes dramatic tissue growth and
Changes in small intestinal tissue weight IW, length IL and
functional maturation see review by Xu, 1996.
diameter ID, crypt depth, villus height, intestinal total activities
Changes of the GI tract during the immediate
of lactase, sucrase, maltase and aminopeptidase, and intestinal total glucose absorption capacity in neonatal pigs during the
postnatal period in pigs have been examined in a
a
immediate postnatal period
number of recent studies Xu et al., 1992a,b; Zhang et al., 1997 and the results are summarised in Tables
Birth Day 1
Day 3
1 and 2. It was observed that the stomach tissue
IW g 35.7
63.4 61.5
weight in newborn piglets increased 26 and 54,
IL cm 343
426 443
ID mm 3.85
4.44 4.60
respectively, by the first and third day after birth in
Crypt depth mm 82
102 115
comparison with 7.5 and 23 increments in body
Villus height mm 883
1171 1077
weight Xu et al., 1992a. Associated with the tissue
Lactase mM min 257
800 –
weight gain was a dramatic functional maturation.
Sucrase mM min 100
314 –
The gastric acid secretory capacity per unit of gastric
Maltase mM min 103
223 –
Aminopeptidase mM min 137
251 –
tissue mass increased 2-fold during the first 3 days
Glucose mM min 174
158 –
after birth, and the total gastric acid secretory
a
capacity increased by over 3-fold Xu and Cranwell,
Data derived from Xu et al. 1992b and Zhang et al. 1997.
R .J. Xu et al. Livestock Production Science 66 2000 95 –107
97
The small intestine also undergoes a dramatic weaning 940–694 mm, and then continued to
tissue growth and functional change during the decline to approximately 50 of the pre-weaning
immediate postnatal period Table 2. It was reported value 5 days after weaning. Villus height reduction is
that the small intestine in piglets increased up to 70 suspected to be the result of an increased rate of cell
in total tissue weight, 115 in mucosal tissue loss, which subsequently leads to increased crypt cell
weight, 24 in length, 15 in diameter, 24 in production and increased crypt depth Pluske et al.,
crypt depth and 33 in villus height during the first 1997. Associated with the reduction in villus height
postnatal day Xu et al., 1992b. During the same and the increase in crypt depth, the morphology of
period, the intestinal brush border digestive enzyme the villi also change from long finger-like projections
activity increased 80–200, although the specific before weaning to leaf- or tongue-like structures after
activity per unit mucosal tissue mass did not change weaning Cera et al., 1988. The structural changes
significantly Zhang et al., 1997. The intestinal in the small intestine vary along the intestinal tract
absorption capacity remained unchanged during the and are affected by the age of weaning. The changes
first day of life, although the specific absorption in the pig weaned at 14 days of age are more
capacity per unit mucosal tissue mass decreased conspicuous than those weaned at 21 days of age,
during this period Zhang et al., 1997. The decline and the reduction of villus height is more prominent
of specific absorption capacity was unlikely due to at the proximal region while the increase in crypt
losses of brush membrane transporters, but rather to depth is more prominent at the distal region of the
a dilution effect resulting from transient retention of intestine Pluske et al., 1997.
colostral protein in the epithelial cells Xu et al., Concomitant with the structural changes, there are
1992b. marked alterations in intestinal functions following
A distinct feature of the newborn small intestine is weaning. Hampson and Kidder 1986 reported rapid
its ability to absorb macromolecules and, during the reductions in the specific activities of lactase and
first day of life, a large quantity of colostral protein, sucrase during the first 4–5 days after weaning.
particularly immunoglobulins, are absorbed across Miller et al. 1986 reported that the specific ac-
the brush border membrane and a considerable tivities of sucrase, lactase and isomaltase fell by at
proportion of the protein is transiently retained in the least 50 during the first 5 days of after weaning in
epithelial cells Burrin et al., 1992; Xu et al., 1992b. pigs weaned at 28 or 42 days of age. On the other
The ability of macromolecule absorption diminishes hand, the activities of maltase and glucoamylase
within 2 days of postnatal life and the phenomena is increased in response to weaning Kelly et al., 1991.
called gut closure Westrom et al., 1984. Increases in these polysaccharidases are likely the
result of substrate induction. Several studies have shown that the decrease in villus height and the loss
3. Adaptive changes in the GI tract after of brush-border digestive enzyme activity after
