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Specific roles of threonine in intestinal mucosal integrity and barrier function

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Abstract

Threonine is the second or third limiting amino acid in swine or poultry diets. This nutrient plays a critical role in the maintenance of intestinal mucosal integrity and barrier function, which can be indicated by intestinal morphology, mucus production (number of goblet cells), transepithelial permeability, brush border enzyme activity, and growth performance. Dietary threonine restriction may decrease the production of digestive enzymes and increase mucosal paracellular permeability. A large proportion of dietary threonine is utilized for intestinal-mucosal protein synthesis, especially for mucin synthesis, and there is no oxidation of threonine by enterocytes. Because mucin proteins cannot be digested and reused, intestinal mucin secretion is a net loss of threonine from the body. Luminal threonine availability can influence synthesis of intestinal mucins and other proteins. Under pathological conditions, such as ileitis and sepsis, threonine requirement may be increased to maintain intestinal morphology and physiology. Collectively, knowledge about the role of threonine in mucin synthesis is critical for improving gut health under physiological and pathological conditions in animals and humans.
[Frontiers in Bioscience E3, 1192-1200, June 1, 2011]
1192
Specific roles of threonine in intestinal mucosal integrity and barrier function
Xiangbing Mao1, Xiangfang Zeng1, Shiyan Qiao1, Guoyao Wu1,2, Defa Li1
1State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China 100193, 2Department of Animal
Science, Texas A and M University, College station, TX, USA 77843
TABLE OF CONTENTS
1. Abstract
2. Introduction
3. The intestinal mucosal integrity and barrier function
3.1. The intestinal mucosal integrity
3.2. The intestinal mucosal barrier function
4. The maintenance of intestinal mucosal integrity
4.1. Specific immunological responses of intestinal mucosa
4.2. Non-specific barrier mechanisms of intestinal mucosa
5. Metabolic fate of threonine in the intestine
5.1. Intestinal threonine uptake
5.2. Intestinal theronine utilization
6. Threonine and intestinal mucosal integrity and function
6.1. The role of threonine in maintaining the intestinal mucosal integrity
6.2. Threonine and the intestinal mucosal barrier function
7. Conclusion and perspectives
8. Acknowledgements
9. References
1. ABSTRACT
Threonine is the second or third limiting amino
acid in swine or poultry diets. This nutrient plays a critical
role in the maintenance of intestinal mucosal integrity and
barrier function, which can be indicated by intestinal
morphology, mucus production (number of goblet cells),
transepithelial permeability, brush border enzyme activity,
and growth performance. Dietary threonine restriction may
decrease the production of digestive enzymes and increase
mucosal paracellular permeability. A large proportion of
dietary threonine is utilized for intestinal-mucosal protein
synthesis, especially for mucin synthesis, and there is no
oxidation of threonine by enterocytes. Because mucin
proteins cannot be digested and reused, intestinal mucin
secretion is a net loss of threonine from the body. Luminal
threonine availability can influence synthesis of intestinal
mucins and other proteins. Under pathological conditions,
such as ileitis and sepsis, threonine requirement may be
increased to maintain intestinal morphology and
physiology. Collectively, knowledge about the role of
threonine in mucin synthesis is critical for improving gut
health under physiological and pathological conditions in
animals and humans.
2. INTRODUCTION
Threonine (also known as α-amino-β-
hydroxybutyric acid) was first isolated from fibrin by
McCoy, Meyer, and Rose (1). It is well-known as the
second or third limiting amino acid in poultry or swine diet
(2, 3). Since 1970’s, numerous studies have focused on the
requirement, efficacy, and metabolism of threonine (4-7).
Adequate threonine is needed to support optimum growth
and immune function of animals, while threonine excess or
deficiency can reduce feed intake, decrease growth rate,
and impair immune function (8, 9). Recently, many
researchers have investigated the relationship between
intestinal threonine metabolism and intestinal health in
animals and humans (9-11). The intestine, a highly
secretary and proliferative tissue, plays a multitude of
functions, such as nutrient digestion and absorption, and
immune defense from pathogens and toxins (12). To a large
degree, the gut function depends on the intestinal mucosa
integrity. The intestinal mucosa, composed of columnar
epithelial cells, lamina propria and muscular mucosa (12),
can secret considerable amounts of digestive hydrolases
and protect the organisms from harmful substances (13-15).
The purpose of this review is to provide an insight into the
Threonine and intestinal mucosa integrity
1193
critical role of threonine in intestinal mucosal integrity and
barrier function.
3. THE INTESTINAL MUCOSAL INTEGRITY AND
BARRIER FUNCTION
3.1. The intestinal mucosal integrity
Intestinal mucosal integrity can be assessed by
intestinal morphology, mucus production (number of goblet
cells), transepithelial permeability, brush border enzyme
activity, and growth performance (16). Small intestinal
integrity, which is most commonly evaluated by
histological measurements of villus height, villus surface
area, and crypt depth (16). The intestinal mucus covers the
mucosa with a semisolid gel to function as a diffusion
barrier for the solutes with low molecular weight and as a
physical barrier for microorganisms and their toxins (17).
The actual mucus production can hardly be measured
directly. However, it can be estimated indirectly by
numbers of goblet cells (16). Transepithelial permeability
can be determined using passive diffusion of a marker or
Ussing chambers (18, 19). The increase in transepithelial
permeability can decrease the intestinal mucosal integrity.
As a result, pathogens and toxins may cross the mucosal
epithelial barrier. The activities of brush border enzymes
(including sucrase, lactase, maltase, and isomaltase) are
also the indicators of intestinal mucosal integrity and
function. In addition, the mass of intestine and mucosae, as
well as their daily gain, can be indicative of intestinal
mucosal integrity (16). Many factors can affect the
intestinal mucosal integrity, such as the route of nutrient
administration, sources and levels of energy and protein
intake, and specific dietary components (e.g., amino acids,
fatty acids, and probiotics). Among these factors, amino
acids have the most profound effects.
3.2. The intestinal mucosal barrier function
The intestinal mucosal barrier acts as the first
defense line against the luminal hostile environment (20).
Under physiological conditions, this barrier only allows
minute quantities of intact antigens to penetrate into the
mucosa to down-regulate inflammation. Under
pathological conditions, this barrier may be impaired. As a
result, excessive antigens pass through the epithelial layer
and result in chronic gastrointestinal inflammation (21, 22).
Therefore, the intestinal mucosal barrier function is crucial
for animal and human health.
4. THE MAINTENANCE OF INTESTINAL
MUCOSAL INTEGRITY
The maintenance of intestinal mucosal integrity
mainly depends on the mucosal barrier defense which is
composed of specific immunological responses and non-
specific barrier mechanisms (14, 23, 24).
4.1. Specific immunological responses of intestinal
mucosa
The specific immune system in the intestinal
mucosa largely differs from other immune systems of the
body (25). The specific immunological responses of the
intestinal-mucosal immune system include (a) expression
of immunoglobulin A on the apical luminal surfaces; and
(2) the sensitized lymphocytes on Peyer’s patches and
lymphoid follicles, as well as in the lamina propria and the
intramucosal epithelium (23, 26).
4.2. Non-specific barrier mechanisms of intestinal
mucosa
In addition to the specific immunological
responses, the maintenance of intestinal mucosal integrity
depends on the non-specific barrier mechanisms which
consist of the mucosal-epithelial regenerating capacity,
intercellular junctions between the epithelial cells, and the
mucus gel layer (15). The mucosal epithelium has high
regeneration capacity, owing to the potentially powerful
ability of pluripotent stem cells for migration, proliferation
and differentiation (27). During the repair of mucosal
injury, the epithelial cell restitution is normally achieved by
the pluripotent stem cells (28).
The intercellular junctions, including tight
junctions, adherent junctions and desmosomes, are also the
key components of the non-specific mucosal barrier
mechanisms (29, 30). These junctions, formed from
transmembrane proteins and nonmembrane proteins, can
seal the paracellular space and regulate the intestinal
mucosal permeability to macromolecules, such as
endotoxins and other bacterial byproducts (14, 31). The
mucus gel layer may protect the intestinal mucosa against
digestive secretions, pathogens and physico-chemical
damage (32-34). The mucus has the viscoelastic and
polymer-like properties that are derived from the major gel-
forming glycoprotein components, namely mucins. Mucins
are secreted by intestinal goblet cells and can be broadly
classified into neutral and acidic subtypes. Acidic mucins
are further divided into sulfated (sulfomucins) or non-
sulfated (sialamucins) groups (35, 36). Because of the
analogs between the mucins and the glycoprotein of the
enterocyte membrane, they can act as competitors to the
binding of many foreign antigens (37, 38). In 2006, Ven
der Sluis et al. (39) reported that the deficiency of MUC2, a
kind of mucins containing high levels of threonine, could
lead to colon inflammation in MUC2 knockout mice.
Additionally, the mucus gel layer participates in filtering
luminal nutrients and can affect the digestion and
absorption of nutrients. Furthermore, the mucosa can
produce a broad spectrum of antimicrobial agents, such as
antimicrobial peptides, to maintain mucosal integrity (40,
41).
5. METABOLIC FATE OF THREONINE IN THE
INTESTINE
5.1. Intestinal threonine uptake
Studies with both humans and pigs have shown
that 20-70% of the first-pass metabolism of dietary
essential amino acids is consumed by the portal-drained
viscera (PDV), including the intestines, pancreas, spleen,
and stomach (42, 43). Recent studies showed that large
amounts (40-60%) of dietary threonine were extracted by
the PDV (dominated by the intestine) in first pass
metabolism, while the values for other essential amino
acids were 30-60% (42, 44-46). In infant studies involving
Threonine and intestinal mucosa integrity
1194
dual stable-isotope tracer techniques, the intestinal first-
pass threonine metabolism was 82% and 70% for partial
enteral feeding and full enteral feeding, respectively (47).
These values might have been overestimated possibly due
to methodological problems, because the efficiency of
utilization of dietary threonine for protein accretion in
neonates is approximately 60-70%. Dawson et al.
demonstrated that threonine uptake by the colonic mucosa
of humans with carcinoma was higher than that in the
normal mucosa (48). In addition, intestinal inflammation
enhanced gastrointestinal threonine uptake in enterally fed
mini-pigs (49). Likewise, the study conducted by Bertolo et
al. indicated that the whole-body threonine requirement
was decreased by 60% in piglets receiving total parenteral
nutrition (TPN) compared with that in piglets receiving
enteral nutrition (50). Furthermore, dietary threonine
deficiency caused a decrease in intestinal goblet cell
numbers and mucin content, which cannot be reversed by
intravenous administration of threonine (10). These data
indicate that the intestine takes up a large amount of
threonine from the lumen but not from arterial blood.
5.2. Intestinal threonine utilization
The intestine is the major site of amino acid
utilization and plays an active role in amino acid
metabolism (51-53). The amino acids taken up by the
intestine can be utilized for protein synthesis, or oxidation
into CO2 for ATP production, or conversion into other
amino acids and metabolic substrates (54). Threonine has
two metabolic fates in the intestine: (a) incorporation into
mucosal proteins [including mucosal cellular proteins and
secretary proteins (e.g. mucins)); and (b) catabolism (e.g.,
oxidation to CO2) by luminal bacteria (42, 45, 55, 56).
Schaart et al. (2005) observed that intestinal threonine
oxidation in piglets only accounted for 2-9% of the total
threonine utilization, while threonine incorporation into
mucosal proteins accounted for 71% of the total threonine
utilization (46). Thus, threonine extracted by the intestine
is primarily used for the mucosal protein synthesis (55). In
addition, the peptide backbone of mucins contains large
amounts of threonine that represents 28-35% of the total
amino acid residues (57-61). Therefore, a large proportion
of the threonine extracted by the intestine is used for mucin
production. However, mucin proteins cannot be digested
and their amino acids cannot be reutilized by the body (44,
59). Thus, the intestinal mucin secretion represents a net
loss of threonine from the animal.
6. THREONINE AND INTESTINAL MUCOSAL
INTEGRITY AND FUNCTION
It is reported that some specific amino acids,
especially threonine, are of critical importance to intestinal
mucosal integrity (52, 62). A large amount of dietary
threonine taken up and utilized by the intestinal mucosa
may aid in maintaining the integrity and function of the
intestinal mucosa.
6.1. The role of threonine in maintaining the intestinal
mucosal integrity
There is experimental evidence supporting the
notion that the availability of dietary threonine can affect
intestinal morphology. For example, in 0- to 21-day-old
broilers, dietary threonine supplementation significantly
increased the weight of duodenum and jejunum, as well as
the villous height, epithelial thickness, goblet cell numbers
and crypt depth in the duodenum, jejunum, and ileum (63).
In neonatal piglets, feeding a threonine-deficient diet (0.1 g
threonine/kg body weight per day; fed intra-gastrically)
markedly decreased villus heights and villus height-to-crypt
depth ratios, compared with the threonine-adequate diet
(10). In addition, dietary threonine deficiency (6.5 g
threonine/kg diet) in early-weaned piglets induced villus
atrophy and reduced villous height, crypt depth, villous
height to crypt depth ratio, despite no effects on intestinal
weight and length (64). Furthermore, Hamard et al.
reported that dietary threonine deficiency induces villous
hypotrophy in weaned piglets (65). Recently, Wang et al.
found that either deficiency or excess of dietary threonine
dramatically reduced villous area and crypt depth, and
induced villous atrophy (66). Additionally, dietary
threonine imbalance can increase the apoptosis rate of
intestinal epithelial cells (66). These findings indicate that
dietary threonine availability is of crucial importance for
maintaining the intestinal mucosal structure integrity.
Recently, a large number of studies have focused
on the role of dietary threonine availability in the intestinal
mucin synthesis in different animal models (Table 1). For
example, compared with no threonine perfusion, infusion
of threonine (56 mg/g of an amino acid mixture) into
isolated porcine gut loops markedly increased the fractional
synthesis rates of mucins and total mucosal proteins
(66%/day versus 42%/day, and 414%/day versus
323%/day, respectively) (67). This demonstrates that the de
novo synthesis of intestinal mucins and mucosal proteins
critically depends on the availability of threonine in the
intestinal lumen. In addition, piglets fed a deficient or
excess dietary threonine (0.37% and 1.11% true ileal
digestible (TID) threonine, respectively) remarkably
decreased the total amount of mucin in duodenum and
mucin-2 mRNA expression in the duodenum and jejunum,
and greatly changed the mucin subtypes, compared with
piglets fed the optimal level (0.89%) of dietary TID threonine
(66). In rats, feeding a diet containing 30% of the threonine
requirement for growth severely decreased the mucin
fractional synthesis rate in the duodenum, ileum, and colon,
but not mucin mRNA expression or intestinal mucosal protein
synthesis, compared with the control diet. These data suggest
that intestinal mucin synthesis can be substantially impaired by
dietary deficiency or excess of threonine (68). Likewise, in 2-
day-old piglets, the threonine-deficient diet (0.1 g threonine/kg
body weight per day; fed intra-gastrically) severely reduced
the total mucin content in the duodenum and colon, as well
as acidic mucin subtypes in the small intestine, compared
with the threonine adequate diet (0.6 g threonine/kg body
weight per day; fed intra-gastrically). In addition, piglets
fed a threonine-deficient diet plus intravenous infusion of
threonine (0.5 g/kg body weight per day) had smaller goblet
cells (10). These data indicate that dietary threonine
deficiency can decrease intestinal mucin production.
Moreover, threonine supplied by oral route is preferred for
the maintenance of the intestinal integrity and barrier
function (10).
Threonine and intestinal mucosa integrity
1195
Table 1. Effects of dietary threonine imbalance and feed administration route on mucosal integrity in animals
Ref. a Treatments
b Design b Observations
b Remarks
I Dietary Thr levels:
0.23%, 0.46%,
0.77%, and 1.16%
Animals: male Sprague-Dawley
rats, 158 ± 1 g
Duration of experiment: 14 days
n = 8/treatment
Comparing 0.23% vs. 0.77% Thr, the mucin FSR was lower
in the duodenum, ileum and colon; the mucosal protein FSR
and mucin mRNA levels did not differ.
Young rats were used
in the study.
II EN 0.1 g/kg/d Thr,
EN 0.6 g/kg/d Thr,
EN 0.1 g/kg/d Thr +
TPN 0.5 g/kg/d Thr
Animals: neonatal piglets, 1~3 d
(1.8 kg)
Duration of experiment: 8 days
n = 7/treatment
Comparing EN 0.1 g/kg/d Thr vs. EN 0.6 g/kg/d Thr, the
gut mucosal weigh, mucin content and villus height were
reduced; diarrhea occurred in piglets fed the low-Thr diet.
Diarrhea was not due
to any apparent
disease.
III EN 0.1 g/kg/d Thr,
EN 0.6 g/kg/d Thr,
EN 0.1 g/kg/d Thr +
TPN 0.5 g/kg/d Thr
Animals: male Yorkshire piglets,
2 d (1.8 ± 0.3 kg)
Duration of experiment: 8 days
n = 7/treatment
Comparing EN 0.1 g/kg/d Thr vs. EN 0.6 g/kg/d Thr or EN
0.1 g/kg/d Thr + TPN 0.5 g/kg/d Thr, there were higher rates
of nitrogen excretion, higher plasma urea and lower plasma
threonine; mucosal mass and total crude mucin content were
lower in the colons; there were lower numbers of acidic
mucin-producing goblet cells in the duodenum and ileum;
acidic mucin subtypes were lower in the small intestine, but
higher in the colon.
Comparing EN 0.1 g/kg/d Thr + TPN 0.5 g/kg/d Thr vs. EN
0.6 g/kg/d Thr, there were smaller colonic goblet cells with
more acidic mucins.
Parenteral threonine
supply could
ameliorate most of
the symptoms of
dietary threonine
deficiency.
IV Dietary Thr levels:
0.37%, 0.74%, and
1.11%
Animals: weaned crossbred
barrows, 21 d
Adaptation period: 4 days
Duration of experiment: 14 days
n = 6/treatment
Comparing 0.37 % or 1.11% Thr vs. 0.74% Thr, the FSR of
protein in jejunal mucosal and mucins was reduced; the ASR
of protein in the jejunal mucosa and mucins was reduced.
The imbalance of
dietary threonine
reduced protein
synthesis of skeletal
muscle.
V Dietary Thr levels:
0.65%, 0.93%
Animals: weaned crossbred
piglets, 7 d
Duration of experiment: 14 days
n = 11/treatment (experiment 1) or
15/treatment (experiment 2)
Comparing 0.65% Thr vs. 0.93% Thr, in the small intestine,
the protein deposition, FSR and amino acid composition of
protein did not differ; ubiquitin mRNA level was decreased
in the jejunum.
The data on FSR and
ubiquitin mRNA
levels were derived
from Experiment 1.
The data on amino
acid composition in
proteins were derived
from Experiment 2.
VI Dietary Thr levels:
0.65% and 0.93%
Animals: weaned crossbred
piglets, 7 d
Duration of experiment: 14 days
n = 7/treatment
Comparing 0.65% Thr vs. 0.93% Thr, the paracellular
permeability was increased in the ileum; the expression of
genes encoding MUC1, SGLT1 and ZO-1 was increased.
Synthesis of mucosal
and mucin proteins
was not measured.
VII Dietary Thr levels:
0.4%, 0.5%, 0.6%,
0.7%, 0.8%, 0.9%,
1.0%, and 1.1%
Animals: male broiler chicken, 1 d
Duration of experiment: 21 days
n = 20/treatment
Thr supplementation affected goblet cell number, epithelial
thickness and morphology in the duodenum, jejunum and
ileum.
Interactions between
crude protein levels
and dietary Thr levels
were studied. The
crude protein levels
were 16% and 19%.
VIII Dietary Thr levels:
0.33%, 0.58%, and
0.82%
Animals: Ross broiler cockerels
and White Pekin drakes, 1 d
Duration of experiment: 28 days
n = 4-8/treatment (experiment 1-
4)
With increasing levels of dietary Thr, intestinal crude mucin
excretion was increased in broilers and ducklings; intestinal
MUC2 mRNA abundance increased as dietary Thr increased
in ducklings, but not in broilers.
The data on crude
mucins were derived
from Experiments 1-
4. The data on mucin
gene expression
were derived from
Experiments 3-4.
IX Intestinal infusion: 0,
21, and 56 mg Thr/g
of total amino acids
Animals: Yorkshire Piglets, ~10
kg
Duration of experiment: 120 min
n = 6/treatment
Increasing the infusion of Thr, the FSR of mucosal and
mucin proteins was increased.
A complete mixture
of amino acids
containing different
levels of Thr was
continuously
infused.
a References: I: Faure et al. 2005 (68); II: Law et al. 2000 (72); III: Law et al. 2007 (10); IV: Wang et al. 2007; V: Hamard et al.
2009; VI: Hamard et al. 2009 (70); VII: Zaefarian et al. 2008 (63); VIII: Horn et al. 2009 (69); IX: Nichols and Bertolo 2008
(67). b Abbreviations: Thr: threonine; EN: enteral nutrition; TPN: total parenteral nutrition; d: day; min: minute; FSR: fractional
protein synthesis rate; ASR: absolute protein synthesis rate; MUC: mucin; SGLT1: sodium/glucose cotransporter; ZO-1: cingulin
and myosin light chain kinase.
There are different reports in the literature
regarding effects of dietary threonine on intestinal-mucosal
protein synthesis, possibly due to different levels of dietary
threonine, animal sepsis, and animal ages. For example, in
broiler chicken and White Pekin ducklings, Horn et al. (69)
observed that dietary threonine restriction impaired
intestinal mucin synthesis. Moreover, Wang et al. (70)
reported that the excess of dietary threonine reduced the
synthesis of mucosal proteins and mucins in piglets.
However, Hamard et al. demonstrated that in early-weaned
piglets, a low threonine diet (6.5 g threonine/kg diet) didn’t
affect the fractional synthesis rate of intestinal mucosal
proteins, in comparison with the control diet (9.3 g
threonine/kg diet) (64). Under pathological conditions, such as
ileitis and sepsis, threonine requirement is enhanced because of
the increase in mucin synthesis to maintain intestinal mucosal
integrity. For instance, mucin fractional synthesis rate was
higher in adult mini-pigs with ileitis induced by direct
administration of trinitrobenzene sulfonic acid into the ileum,
in comparison with the control group (114%/day versus
61%/day) (49). This indicates that intestinal inflammation
would increase mucin synthesis to protect the gut, which may
Threonine and intestinal mucosa integrity
1196
Table 2.. Effects of threonine levels on intestinal mucosal integrity in animals and humans under unhealthy conditions
Ref. a Treatment
b Design Observations Remarks
I Dietary Thr
levels: 0.57%,
1.07%, and
2.07%
Animals: male Sprague-Dawley rats, 10
months of age
Duration of experiment: 20 days
n = 8/treatment
Unhealthy condition: intestinal inflammation
Comparing 1.07 or 2.07% Thr vs. 0.57% Thr, the
number of MUC2-containing goblet cells was
increased in the surfaced epithelium of the ulcerated
area; mucin synthesis and production in the colon
was enhanced; the mucosal mass was increased; the
gut microbiota was reequilibrated.
Intestinal inflammation
was induced by the
treatment of dextran
sulfate sodium
II Dietary Thr
levels 140
mg/kg/d Thr,
i.g. 4 µmol/kg/d
L-[15N]Thr, i.v.
4 µmol/kg/d L-
[U-13C]Thr
Animals: Pitmann-Moore minipigs, 10 mo
Duration of experiment: 7 days
n = 4/treatment
Unhealthy condition: ileitis
Comparing ileitis mini-pigs vs. normal mini-pigs,
intestinal mucin synthesis and PDV utilization of
Thr were increased.
Ileitis was induced by the
direct administration of
Trinitrobenzene sulfonic
acid into ileum
III i.g. 2.1 µmol/g
weight L-[ U-
13C]Thr
Animals: Female MUC2 knockout or normal
mice, 8 weeks of age
Duration of experiment: 120 min
n = 17/treatment
Unhealthy condition: intestinal inflammation
Comparing normal mice vs. MUC2 knockout mice,
there were no differences in the concentration of
free or protein-bound Thr in both serum and colon;
however, there was higher rate of Thr oxidation.
MUC2 knockout could
induced the intestinal
inflammation in mice
IV i.v.
500µmol/100g
weight L-[ U-
13C]Thr
Animals: male Sprague-Dawley rats, 300 g
body weight
Duration of experiment: 2 days
n = 14/treatment
Unhealthy condition: sepsis
Comparing sepsis rats vs. normal rats, Thr
utilization was increased by the mucosa for mucin
synthesis.
The sepsis of rats was
induced by injecting live
E. coli via a tail vein in
day 2 and 6
V i.v. 500
µmol/100 g
weight L-[ U-
13C]Thr
Animals: male Sprague-Dawley rats, 300 g
body weight
Duration of experiment: 6 days
n = 12/treatment (d 2) or 14/treatment (d 6)
Unhealthy condition: sepsis
Comparing sepsis rats vs. normal rats, the mucin
content and mucosal protein synthesis were
increased; plasma protein ASR was increased.
The sepsis of rats was
induced by injecting live
E. coli via a tail vein in
day 2 and 6
VI i.v. 4.6 mg/kg
weight Thr
Men: 30~43 years of age
Duration of experiment: 150 min
n = 7 or 8/treatment
Unhealthy condition: HIV seropositive
Comparing HIV patient vs. normal men, there was a
selective deficiency in threonine.
A complete amino acid
mixture containing
different levels of Thr
was continuously
perfused
VII Thr levels D,L-
[G-3H]Thr 100
µCi/mL
Tissue: intestinal biopsies of patients
Duration of experiment: 0~60 min
n = 6/treatment
Unhealthy condition: carcinoma
Comparing the intestine of carcinoma patients vs.
the intestine of patients with no known intestinal
disease, Thr uptake was increased; most of the Thr
was incorporated into the immature cells at the
bottom of the crypt.
Intestinal biopsies of
patients were cultured as
the model of in vitro
experiment.
VIII Dietary Thr
levels: 0.51%,
0.58%, 0.65%,
0.72%, 0.79%,
and 0.86%
Animals: male Ross × Ross chickens, 21 days
of age
Duration of experiment: 21 days
n = 8/treatment
Unhealthy condition: unclean environment
Comparing the unclean environment vs. clean
environment, the basal need for Thr by broilers was
increased; the relative thymus weight was higher;
monocyte NO production was decreased; the higher
needs for Thr of broilers could reflect the resulting
changes in mucin production.
A good gradient of Thr in
the diets; Thr may
influence immunity in
chickens.
IX Dietary Thr
level: 0.63%
Animals: male piglets, 10 kg body-weight
Duration of experiment: 16 days
n = 6/treatment
Unhealthy condition: anti-nutritive factors in
diets
Comparing diets containing anti-nutritive factors vs.
the control diet, Thr digestibility was lower; the
reduction in apparent Thr digestibility was
correlated to an increase in intestinal mucin
production.
A short-term study;
luminal Thr is crucial for
mucin production by the
gut.
a References: I: Faure et al. 2006 (11); II: Rémond et al. 2009 (49); III: Van Der Sluis et al. 2009 (73); IV: Faure et al. 2004 (74); V: Faure et al. 2007 (75); VI:
Laurichesse et al. 1998 (76); VII: Dawson and Filipe 1982 (48); VIII: Corzo et al. 2007 (77); IX: Myrie et al. 2003 (78). b Abbreviations: Thr: threonine; i.v.:
intravenous administration; i.g.: intragastric administration; d: day; min: minute; wk: week; mo: month; ASR: absolute protein synthesis rate; MUC: mucin; PDV:
portal-drained viscera; NO: nitric oxide; HIV: human immunodeficiency viurs.
necessitate a greater amount of dietary threonine. Besides,
Faure et al. demonstrated that sepsis increased mucin fractional
synthesis rate and absolute synthesis rate in rats. Collectively,
dietary threonine availability is a major determinant of
intestinal mucin production.
As mentioned above, intestinal paracellular
permeability can be used to assess the intestinal mucosal
integrity. With the increase in paracellular permeability, the
intestinal integrity and epithelial barrier may decrease. A
moderate threonine deficiency (6.5 g threonine/kg diet)
increased the intestinal mucosal paracellular permeability in
the ileum of piglets, and changed the expression of genes
related with the regulation of intestinal mucosal paracellular
permeability, such as tight junction protein ZO-1, cingulin, and
myosin light chain kinase (65). Furthermore, the digestive
enzymes contain abundance of threonine which accounts for 5-
11% of the total amino acid residues. Research findings have
shown that dietary threonine restriction decreased the
production of digestive enzymes (71). Thus, we can speculate
that dietary threonine availability may the digestion and
absorption of dietary nutrients. Collectively, both intestinal
paracellular permeability and brush border enzyme activities
are important indicators of the intestinal mucosal integrity.
6.2. Threonine and the intestinal mucosal barrier
function
Dietary threonine imbalance influences the
intestinal-mucosal integrity and barrier function. In 2000,
Law et al. (72) reported that dietary threonine deficiency
(0.1 g threonine/kg body weight per day; fed intra-
gastrically) resulted in diarrhea in piglets. Recently, studies
with animals and humans with intestinal inflammation (11,
49, 73), sepsis (74, 75), colonic carcinoma (48), HIV
Threonine and intestinal mucosa integrity
1197
infection (76) or other types of immunological challenge
(77, 78) revealed an increase in threonine requirement by
the intestinal mucosa due to enhanced synthesis of
intestinal proteins (Table 2). Under these pathological
conditions, supply of threonine in regular diets designed for
healthy animals may be inadequate for the maintenance of
intestinal mucosal integrity, leading to the impairment of
intestinal barrier function. Interestingly, some of these
studies also showed increasing dietary threonine provision
with or without other amino acids enhanced mucin
synthesis and re-equilibrated the gut microbiota to benefit
gut function (11, 49, 75).
Threonine is a major component of plasma
immunoglobulins in animals and humans (79-81). Some
studies (8, 12, 82-84) with different animal species
demonstrated that dietary threonine levels influenced
plasma antibody concentrations and whole-body immune
function. Furthermore, results of our research indicated that
dietary threonine supplementation improved the intestinal
morphology and specific immunological responses in the
piglets challenged with E. coli K88+ (data no published).
These findings suggest that dietary threonine availability is
of great importance for supporting both intestinal-mucosal
and whole-body immunity.
7. CONCLUSION AND PERSPECTIVES
Intestinal mucosal integrity, which is essential
for nutrient digestion and absorption, as well as mucosal
barrier function (e.g., protecting the host from gut-related
diseases), critically depends on adequate provision of
dietary threonine. Deficiency or excess of dietary
threonine is deleterious to the intestinal mucosal integrity
and barrier function. While considerable advances have
been made in threonine nutrition research, much remains to
be learned about the signaling pathways through which
dietary threonine regulates villous height, crypt depth,
goblet cell numbers, and mucin synthesis. Moreover,
because many factors can affect the intestinal mucosal
integrity, including the route of nutrient administration, the
source and level of energy and protein intake, and specific
dietary component, attention should be paid to interactions
between threonine and these factors. Solving such problems
requires combined applications of modern high-throughput
and high-efficient technologies, such as genomics,
proteomics, and metabolomics (85-88). This is expected to
be a challenging but fruitful area of investigation in protein
nutrition.
8. ACKNOWLEDGEMENTS
This work was financially supported by the
National Natural Science Foundation of China (30525029),
the Thousand-People-Talent program at China Agricultural
University, and Texas AgriLife Research (H-8200).
9. REFERENCES
1. R.H. McCoy, C.E. Meyer and W.C. Rose: J Biol Chem
112, 283 (1935)
2. C.I. Saldana, D.A. Knabe, K.Q. Owen, K.G. Burgoon
and E.J. Gregg: Digestible threonine requirements of starter
and finisher pigs. J Anim Sci 72, 144-150 (1994)
3. A. Corzo, M.T. Kidd, W.A. Dozier III, G.T. Pharr and
E.A. Koutsos: Dietary threonine needs for growth and
immunity of broilers raised under different litter conditions.
J Appl Poult Res 16, 574-582 (2007)
4. W.C. Rose, R.E. Koeppe and H.J. Sallach: The threonine
requirement for growth. J Biol Chem 317-320 (1952)
5. Samadi and F. Liebert: Threonine Requirement of slow-
growing male chickens depends on age and dietary
efficiency of threonine utilization. Poult Sci 86, 1140-1148
(2007)
6. A.T. Davis and R.E. Austic: Threonine metabolism of
chicks fed threonine-imbalanced diets. J Nutr 112, 2177-
2186 (1982)
7. Y.A. Kang-Lee and A.E. Harper: Threonine metabolism
in vivo: effect of threonine intake and prior induction of
threonine dehydratase in rats. J Nutr 108, 163-175 (1978)
8. D.F. Li, C.T. Xiao, S.Y. Qiao, J.H. Zhang, E.W. Johnson
and P.A. Thacker: Effects of dietary threonine on
performance, plasma parameters and immune function of
growing pigs. Anim Feed Sci Technol 78, 179-188 (1999)
9. X. Wang, S.Y. Qiao, M. Liu and Y.X. Ma: Effects of
graded levels of true ileal digestible threonine on
performance, serum parameters and immune function of
10–25 kg pig. Anim Feed Sci Technol 129, 264-278 (2006)
10. G.K. Law, R.F. Bertolo, A. Adjiri-Awere, P.B.
Pencharz and R.O. Ball: Adequate oral threonine is critical
for mucin production and gut function in neonatal piglets.
Am J Physiol 292, G1293-G1301 (2007)
11. M. Faure, C. Mettraux, D. Moennoz, J.P. Godin, J.
Vuichoud, F. Rochat, D. Breuillé, C. Obled and I.
Corthésy-Theulaz: Specific amino acids increase mucin
synthesis and microbiota in dextran sulfate sodium-treated
rats. J Nutr 136, 1558-1564 (2006)
12. J.R. Turner: Intestinal mucosal barrier function in
health and disease. Nat Rev Immunol 9, 799-809 (2009)
13. A.S. Ismail and L.V. Hooper: Epithelial cells and their
neighbors. IV. Bacterial contributions to intestinal
epithelial barrier integrity. Am J Physiol 289, G779-G784
(2005)
14. A. Farhadi, A Banan, J. Fields and A. Keshavarzian:
Intestinal barrier: an interface between health and disease. J
Gastroen Hepatol 18, 479-497 (2003)
15. J.A. Jankowski, R.A. Goodlad and N.A. Wright:
Maintenance of normal intestinal mucosa: function,
structure, and adaptation. Gut 35 (Suppl 1), S1-S4 (1994)
Threonine and intestinal mucosa integrity
1198
16. M.A.M. Vente-spreeuwenberg and A.C. Beynen: Diet-
mediated modulation of small intestinal integrity in weaned
piglets. In: J.R. Pluske, J. Le Dividich, and M.W.A.
Verstegen, editors. Weaning the pig: concepts and
consequence. Netherlands:Wageningen Academic
Publishers; 2003.
17. J.T. Lamont: Mucus: the front line of intestinal mucosal
defense. Annals of the New York Academic of Science
664, 190-201 (1992)
18. J.J. Uil, R.M. van Elburg, F.M. van Overbeek, C.J.
Mulder, G.P. VanBerge-Henegouwen and H.S. Heymans:
Clinical implications of the sugar absorption test: intestinal
permeability test to assess mucosal barrier function. Scand
J Gastroenterol Suppl 223, 70-78 (1997)
19. M. Wirén,J.D. Söderholm,J. Lindgren,G. Olaison,J.
Permert,H. Yang and J. Larsson: Effects of starvation and
bowel resection on paracellular permeabiliy in rat small-
bowel mucosa in vitro. Scand J Gastroenterol 34, 156-
162 (1999)
20. A.T. Blikslager, A.J. Moeser, J.L. Gookin, S.L.
Jones and J. Odle: Restoration of barrier function in
injured intestinal mucosa. Physiol Rev 87, 545-564
(2007)
21. J.R. Turner: Intestinal mucosal barrier function in
health and disease. Nat Rev Immunol 9, 799-809 (2009)
22. J.D. SÖderholm and M.H. Perdue: Stress and the
gastrointestinal tract II. stress and intestinal barrier
function. Am J Physiol Gastrointest Liver Physiol 280,
G7-G13 ( 2001)
23. J.G. Magalhaes, I. Tattoli and S.E. Girardin: The
intestinal epithelial barrier: how to distinguish between
the microbial flora and pathogens. Semin Immunol 19,
106-115 (2007)
24. B. Langkamp-Henken, J.A. Glezer and K.A. Kudsk:
Immunologic structure and function of the
gastrointestinal tract. Nutr Clin Pract 7, 100-108 (1992)
25. B.M. Wittig and M. Zeitz: The gut as an organ of
immunology. Int J Colorectal Dis 18, 181-187 (2003)
26. V. Snoeck, B. Goddeeris and E. Cox: The role of
enterocytes in the intestinal barrier function and antigen
uptake. Microbes Infect 7, 997-1004 (2005)
27. J.Y. Wang: Polyamines regulate expression of E-
cadherin and play an important role in control of intestinal
epithelial barrier function. Inflammopharmacol 13, 91-101
(2005)
28. A.U. Dignass: Mechanisms and modulation of intestinal
epithelial repair. Inflamm Bowel Dis 7, 68-77 (2001)
29. M.G. Laukoetter, M. Bruewer and A. Nusrat:
Regulation of the intestinal epithelial barrier by the apical
junctional complex. Curr Opin Gastroenterol 22, 85-89
(2006)
30. C.S. Potten, M. Kellet, S.A. Roberts, D.A. Rew and
G.D. Wilson: Measurement of in vivo proliferation in
human colorectal mucosa using bromodeoxyuridine. Gut
33, 71-78 (1992)
31. J. Kong, Z. Zhang, M.W. Musch, G. Ning, J. Sun, J.
Hart, M. Bissonnette and Y.C. Li: Novel role of the vitamin
D receptor in maintaining the integrity of the intestinal
mucosal barrier. Am J Physiol 294, G208-G216 (2008)
32. M. Mantle and A. Allen: Gastrointestinal mucus. In:
Gastrointestinal secretion. Ed: Davison, JS, Butterworth
Co. Ltd., Londen, UK, pp. 202-229 (1989)
33. C. Stokes and J.F. Bourne: Mucosal immunity. In:
Veterinary clinical immunology. Ed: Halliwell, REW, W.B.
Saunders Co., PA, pp. 164-191 (1989)
34. J.F. Forstner and G.G. Forstner: Gastrointestinal mucus.
In: Physiology of the gastrointestinal tract. 3rd edition. Ed:
Johnson, LR, Raven Press, NY, pp. 1255-1283 (1994)
35. B. Deplancke and H.R. Gaskins: Microbial modulation
of innate defense: goblet cells and the intestinal mucus
layer. Am J Clin Nutr 73 (Suppl 1), 1131S-1141S (2001)
36. L. Montagne, C. Piel and J.P. Lalles: Effect of diet on
mucin kinetics and composition: nutrition and health
implications. Nutr Rev 62, 105-114 (2004)
37. R.A. Gibbons: Mucus of the mammalian genital tract.
Br Med Bull 34, 34-38 (1981)
38. L.Z. Jin and X. Zhao: Intestinal receptors for adhesive
fimbriae of enterotoxigenic Escherichia Coli (ETEC) K88
in swine. Appl Microbiol Biotechnol 54, 311-318 (2000)
39. M. Van Der Sluis, B.A. De Koning, A.C. De Bruijn, A.
Velcich, J.P. Meijerink, J.B. Van Goudoever, H.A. Büller,
J. Dekker, I. Van Seuningen, I.B. Renes and A.W.
Einerhand: Muc2-deficient mice spontaneously develop
colitis, indicating that MUC2 is critical for colonic
protection. Gastroenterol 131, 117-129 (2006)
40. R.I. Lehrer, T. Ganz: Defensins of vertebrate animals.
Curr Opin Immunol 14, 96-102 (2002)
41. R.I. Lehrer, T. Ganz: Cathelicidins: a family of
endogenous antimicrobial peptides. Curr Opin Hematol 9:
18-22 (2002)
42. B. Stoll, J. Henry, P.J. Reeds, H.Yu, F. Jahoor and D.G.
Burrin: Catabolism dominates the first-pass intestinal
metabolism of dietary essential amino acids in milk
protein-fed piglets. J Nutr 138, 606-614 (1998)
43. B. Stoll, D.G. Burrin, J. Henry, H.Yu, F. Jahoor and
P.J. Reeds: Substrate oxidation by the portal drained
viscera of fed piglets. Am J Physiol 277, E168-E175 (1999)
Threonine and intestinal mucosa integrity
1199
44. S.R. Van Der Schoor, P.J. Reeds, B. Stoll, J.F. Henry,
J.R. Rosenberger, D.G. Burrin and J.B. Van Goudoever:
The high metabolic cost of a functional gut. Gastroenterol
123, 1931-1940 (2002)
45. J.B. Van Goudoever, B. Stoll, J.F. Henry, D.G. Burrin
and P.J. Reeds: Adaptive regulation of intestinal lysine
metabolism. Proc Natl Acad Sci USA 97, 11620-11625
(2000)
46. M.W. Schaart, H. Schierbeek, S.R. Van Der Schoor, B.
Stoll, D.G. Burrin, P.J. Reeds and J.B. Van Goudoever:
Threonine utilization is high in the intestine of piglets. J
Nutr 135, 765-770 (2005)
47. S.R. Van Der Schoor, D.L. Wattimena, J. Huijmans, A.
Vermes and J.B. Van Goudoever: The gut takes nearly all:
threonine kinetics in infants. Am J Clin Nutr 86, 1132-1138
(2007)
48. P.A. Dawson and M.I. Filipe: Uptake of [3H]threonine
in human colonic mucosa associated with carcinoma: an
autoradiographic analysis at the ultrastructural level.
Histocheml J 14, 385-401 (1982)
49. D. Rémond, C. Buffière, J.P. Godin, P.P. Mirand, C.
Obled, I. Papet, D. Dardevet, G. Williamson, D. Breuillé
and M. Faure: Intestinal inflammation increases
gastrointestinal threonine uptake and mucin synthesis in
enterally fed minipigs. J Nutr 139, 1-7 (2009)
50. R.F. Bertolo, C.Z. Chen, P.B. Pencharz and R.O. Ball:
Threonine requirement of neonatalpiglets receiving
totalparenteral nutrition is considerably lower than that of
piglets receiving an identical diet intragastrically. Nutr 128,
1752–1759 (1998)
51. G. Wu: Intestinal mucosal amino acid catabolism. J
Nutr 128, 1249-1252 (1998)
52. J.M. Rhoads and G. Wu: Glutamine, arginine, and
leucine signaling in the intestine. Amino Acids 37, 111-122
(2009)
53. J. Lallès, G. Boudry, C. Favier, N. Le Floc’h, I. Luron,
L. Montagne, I.P. Oswald, S. Pié, C. Piel and B. Sève: Gut
function and dysfunction in young pigs: physiology. Anim
Res 53, 301-316 (2004)
54. Barbara Stoll. Intestinal Uptake and Metabolism of
Threonine: Nutritional Impact. Advances in Pork
Production. 17, 257-263 (2006)
55. S.R. Van Der Schoor, J.B. Van Goudoever, B. Stoll,
J.F. Henry, J.R. Rosenberger, D.G. Burrin and P.J. Reeds:
The pattern of intestinal substrate oxidation is altered by
protein restriction in pigs. Gastroenterol 121, 1167-1175
(2001)
56. A.M. Roberton, B. Rabel, C.A. Harding, C. Tasman-
Jones, P.J. Harris and S.P. Lee: Use of the ileal conduit as a
model for studying human small intestinal mucus
glycoprotein secretion. AM J Physiol 261, G728-G734
(1991)
57. J. Dekker, J.W. Rossen, H.A. Buller and A.W.
Einerhand: The MUC family: An obituary. Trends Biochem
Sci 27, 126-131 (2002)
58. S. Bengmark and B. Jeppsson: Gastrointestinal surface
protection and mucosa reconditioning. JPEN J Parenter
Enteral Nutr 19, 410-415 (1995)
59. M. Mantle and A. Allen: Isolation and characterization
of the native glycoprotein from pig small-intestinal mucus.
Biochem J 195, 267-275 (1981)
60. K.A. Lien, W.C. Sauer and M. Fenton: Mucin output in
ileal digesta of pigs fed a protein-free diet. Z Ernaehrwiss
36, 182-190 (1997)
61. B.J. Van Klinken, J. Dekker, H.A. Buller and A.W.
Einerhand: Mucin gene structure and expression: protection
vs. adhesion. Am J Physiol 269, G613-G627 (1995)
62. W.W. Wang, S.Y. Qiao and D.F. Li: Amino acids and
gut function. Amino Acids 37, 105-110 (2009)
63. F. Zaefarian, M. Zaghari and M. Shivazad: The
threonine requirements and its effects on growth
performance and gut morphology of broiler chicken fed
different levels of protein. Int J Poult Sci 7, 1207-1215
(2008)
64. A. Hamard, B. Sèvea and N. Le Floc’h: A moderate
threonine deficiency differently affects protein metabolism
in tissues of early-weaned of piglets. Comp Biochem Phys
A 152, 491-497 (2009)
65. A. Hamard, D. Mazurais, G. Boudrya, I. Le Huërou-
Lurona, B. Sèvea and N. Le Floc’h: A moderate threonine
deficiency affects gene expression profile, paracellular
permeability and glucose absorption capacity in the ileum
of piglets. J Nutr Biochem (2009)
doi:10.1016/j.jnutbio.2009.07.004
66. W.W. Wang, X.F. Zeng, X.B. Mao, G.Y. Wu and S.Y.
Qiao: Optimal dietary true ileal digestible threonine for
supporting mucosal barrier in the small intestine of
weanling pigs. J Nutr 140, 981-986 (2010)
67. N.L. Nichols and R.F. Bertolo: Luminal threonine
concentration acutely affects intestinal mucosal protein and
mucin synthesis in piglets. J Nutr 138, 1298-1303 (2008)
68. M. Faure, D. Moënnoz, F. Montigon, C. Mettraux, D.
Breuillé and O. Ballèvre: Dietary threonine restriction
specifically reduces intestinal mucin synthesis in rats. J
Nutr 135, 486-491 (2005)
69. N.L. Horn, S.S. Donkin, T.J. Applegate and O. Adeola:
Intestinal mucin dynamics: response of broiler chicks and
White Pekin ducklings to dietary threonine. Poult Sci 88,
1906-1914 (2009)
Threonine and intestinal mucosa integrity
1200
70. X. Wang, S.Y. Qiao, Y.L. Yin, L.Y. Yue, Z.Y. Wang
and G. Wu: A deficiency or excess of dietary threonine
reduces protein synthesis in jejunum and skeletal muscle of
young pigs. J Nutr 137, 1442-1446 (2007)
71. W.A. Dozier III, E.T. Moran Jr. and M.T. Kidd: Male
and female broiler responses to low and adequate dietary
threonine on nitrogen and energy balance. Poult Sci 80,
926-930 (2001)
72. G.K. Law, A. Adjiri-Awere, P.B. Pencharz and R.O.
Ball: Gut mucins in piglets are dependent upon dietary
threonine. Advances in Pork Production. Proceeding of the
2000 Banff Pork Seminar 11, 10 (Abstr.) (2000)
73. M. Van Der Sluis, M.W. Schaart, B.A. De Koning, H.
Schierbeek, A. Velcich, I.B. Renes and J.B. Van
Goudoever: threonine metabolism in the intestine of mice:
loss of mucin 2 induces the threonine catabolic pathway. J
Pediatr Gastroenterol Nutr 49, 99-107 (2009)
74. M. Faure, F. Choné, F. Béchereau, J.P. Godin, I. Papet,
D. Breuillé and C. Obled: Threonine utilization in the gut
during sepsis. Clin Nutr 23, 807 (2004)
75. M. Faure, F. Choné, C. Mettraux, J.P. Godin, F.
Béchereau, J. Vuichoud, I. Papet, D. Breuillé and C. Obled:
Threonine utilization for synthesis of acute phase proteins,
intestinal proteins, and mucins is increased during sepsis in
rats. J Nutr 137, 1802-1807 (2007)
76. H. Laurichesse, I. Tauveron, F. Gourdon, L. Cormerais,
C. Champredon, S. Charrier, C. Rochon, S. Lamain, G.
Bayle, H. Laveran, P. Thieblot, J. Beytout and J. Grizard:
Threonine and methionine are limiting amino acids for
protein synthesis in patients with AIDS. J Nutr 128, 1342-
1348 (1998)
77. A. Corzo, M.T. Kidd, W.A. Dozier III, G.T. Pharr and
E.A. Koutsos: Dietary threonine needs for growth and
immunity of broilers raised under different litter conditions.
J Appl Poult Res 16, 574-582 (2007)
78. S.B. Myrie, R.F. Bertolo, W.C. Sauer and R.O. Ball:
Diets that increase mucin production in pigs reduce
threonine and amino acid retention. Advances in Pork
Production. Proceeding of the 2003 Banff Pork Seminar
14, 9 (Abstr.) (2003)
79. H.S. Tenenhouse and H.F. Deutsch: Some physical-
chemical properties of chicken γ-globulins and their pepsin
and papain digestion product. Immunochem 3, 11-20 (1966)
80. E.L. Smith and R.D. Greene: Further studies on the
amino acid composition of immune protein. J Biol Chem
171, 355-362 (1977)
81. M.J. Crumpton and J.M. Wilkinson: Amino acid
compositions of human and rabbit G-globulins and of the
fragments produced by reduction. Biochem J 88, 228-234
(1963)
82. K.K. Bhargava, R.P. Hanson and M.L. Sunde: Effects
of threonine on growth and antibody production in chicks
infected with Newcastle disease virus. Poult Sci 50, 710-
713 (1971)
83. J.A. Cuaron, R.P. Chapple and R.A. Easter: Effect of
lysine and threonine supplementation of sorghum gestation
diets on nitrogen balance and plasma constituents in first-
litter gilts. J Anim Sci 58, 631-637 (1984)
84. C.B. Hsu, S.P. Cheng, J.C. Hsu and H.T. Yen: Effect of
threonine addition to a low protein diet on IgG levels in
body fluid of first-litter sows and their piglets. Asina-Aust J
Anim Sci 14, 1157-1163 (2001)
85. G. Wu, F.W. Bazer, T.A. Cudd, C.J. Meininger and
T.E. Spencer: Maternal nutrition and fetal development. J
Nutr 134, 2169-2172 (2004)
86. J.J. Wang, D.F. Li, L.J. Dangott and G. Wu: Proteomics
and its role in nutrition research. J Nutr 136, 1759-1762
(2006)
87. J.C. Mathers: Nutritional modulation of ageing:
genomic and epigenetic approaches. Mech Ageing Dev 127,
584-589 (2006)
88. P. Li, Y.L. Yin, D.F. Li., S.W. Kim and G. Wu: Amino
acids and immune function. Br J Nutr 98, 237-252 (2007)
Abbreviations: Thr: threonine; i.v.: intravenous
administration; i.g.: intra-gastric administration; d: day;
min: minute; wk: week; mo: month; ASR: absolute protein
synthesis rate; MUC: mucin; PDV: portal-drained viscera;
NO: nitric oxide; HIV: human immunodeficiency viurs
Key Words: Threonine; Intestinl mucosal; Metabolism;
Integrity; Function, Review
Send correspondence to: Defa Li, State Key Laboratory
of Animal Nutrition, China Agricultural University,
Beijing, China 100193, Tel: 86-10-6273-1456, Fax: 86-10-
6273-3688, E-mail: defali@public2.bta.net.cn
http://www.bioscience.org/current/volE3.htm
... It has been suggested that the extreme physiological and psychological stress of re-entry to the Earth's environment may dysregulate immune functions [114]. The downregulation of threonine, unique to the comparisons pre-launch/recovery and return to Earth/recovery time-points in females, suggests reduced maintenance of intestinal mucosal integrity which may weaken immune function [115]. Alternatively, downregulation of threonine may also occur as a consequence of an increased utilization of dietary threonine for intestinal mucosal protein synthesis [115]. ...
... The downregulation of threonine, unique to the comparisons pre-launch/recovery and return to Earth/recovery time-points in females, suggests reduced maintenance of intestinal mucosal integrity which may weaken immune function [115]. Alternatively, downregulation of threonine may also occur as a consequence of an increased utilization of dietary threonine for intestinal mucosal protein synthesis [115]. Immune dysregulation following return to Earth was also observed in previous cosmonaut missions [114][115][116][117][118] and suggested to be facilitated by altered pathogenicity of bacteria and biofluid redistribution [48]. ...
... Alternatively, downregulation of threonine may also occur as a consequence of an increased utilization of dietary threonine for intestinal mucosal protein synthesis [115]. Immune dysregulation following return to Earth was also observed in previous cosmonaut missions [114][115][116][117][118] and suggested to be facilitated by altered pathogenicity of bacteria and biofluid redistribution [48]. ...
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... There are many studies concerned with using a low-protein diet to reduce the cost of feed and this leads to a decrease in essential amino acids (Kerr and Kidd 1999). The safety acidosis plays an ssential role in the maintenance of mucosa and cells (Mao et al 2011). Over the past few years the importance of aspartic acid in the endocrine glands and its important role in reproductive activity is documented (Auiello 2007, Ota 2012. ...
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This experiment was conducted at Al-Qasim Green University, to study the effect of aspartic acid on the product characteristics and the percentages of cuts of broilers. In the experiment 135 birds were used, of 308 Rose, one day old, unsexed, with an average weight of 42 g/ bird , and randomly distributed to three treatments. Aspartic acid was added to drinking water for the treatments as 0 (T1), 500 (T2) and 700 mg-1 /liter of water (T3). There was significant effect of adding aspartic acid as compared to control in live body weight for the third, fourth and fifth-1 weeks, respectively, as well the weight gain in second, third, fourth and fifth weeks, respectively and in the feed consumption. The efficiency of the food conversion was also significantly higher for aspartic acid at 500 and 700 mg /liter of water compared to the control treatment for the-1 first, third, and fourth weeks. Moreover, for the carcass cuts, the significantly higher for the T2 treatment only for the chest and neckpieces compared to the rest of the other treatments. The aspartic acid improves the product characteristics as well as the proportions of the meat chicken pieces.
... Ketiga rumput laut ini juga mengandung lisina yang memiliki fungsi penting dalam pertumbuhan sel normal dan metabolisme (Yang et al. 2016) dan treonina yang penting dalam pemeliharaan mukosa usus (Mao et al. 2011). Selain itu, ditemukan juga tirosina yang berperan sebagai antioksidan yang tinggi terhadap radikal peroksi (Matsui et al. 2018). ...
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Makroalga telah digunakan industri pangan sejak lama karena komponen yang dikandungnya misalnya alginat, karagenan, dan agar. Selain itu alga mengandung nutrisi dan komponen bioaktif lainnya sebagai pangan fungsional. Kandungan protein dan keragaman jenis asam amino dapat menjadi informasi penting untuk memaksimalkan potensi yang dimiliki alga. Penelitian ini bertujuan mengetahui kandungan protein dan profil asam amino pada S.aquifolium, U. lactuca, dan G. longissima. Ekstraksi protein menggunakan pelarut 0,4 M NaOH dan ultrasonikasi 5 menit dengan amplitudo 70%. Analisis kandungan protein menggunakan metode Bradford. Komposisi asam amino dianalisis menggunakan ultra performance liquid chromatography. Protein tertinggi di antara ketiga makroalga tersebut adalah S. aquifolium yakni mengandung protein 4,17% dan teridentifikasi 16 jenis asam amino dengan 10 jenis asam amino esensial (AAE) dan 6 asam amino non esensial (AANE). U lactuca teridentifikasi 9 AAE dan 6 AANE. Untuk G. longissima teridentifikasi 8 jenis AAE dan 6 jenis AANE. Asam glutamat merupakan asam amino tertinggi pada S. aquifolium sebesar 400,27±62,27 mg/kg, sedangkan pada U. lactuca dan G. longissima asam aspartat merupakan AANE yang tertinggi kandungannya yakni 274,60±50,14 mg/kg dan 435,57±25,81mg/kg. Edible makroalga tersebut mengandung protein dan asam amino yang penting dan beberapa memiliki konsentrasi lebih tinggi dibandingkan sumber protein makroalga sejenis dari perairan lain. Asam amino yang dimiliki ketiga makroalga ini memiliki potensi untuk dikembangkan lebih lanjut menjadi produk pangan berbasis tanaman dengan karakter flavor dan rasa umami.
... Hence, an intact intestinal mucosal barrier is crucial to guarantee the provision of adequate dietary nutrition to the whole body. The mechanical barrier, such as claudin-1, occludin, ZO-1, which regarded as principal constitution of tight junction and essential regulators in paracellular permeability [56], and chemical barriers, such as mucin-1, mucin-2, which were secreted by goblet cell and played crucial roles in modulating intestinal inflammation [57], were usually applied to assess the integrity of the intestinal barrier [58]. In the current study, dietary supplemented MOA showed a positive effect on the relative gene expression of claudin-1 and mucin-2 in ileum of piglets. ...
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Background: The objective of this experiment was to evaluate the effect of a combination of microencapsulated essential oils and organic acids (MOA) on growth performance, immuno-antioxidant status, intestinal barrier function and microbial structure of the hindgut in piglets. A total of 120 piglets (Duroc × [Landrace × Yorkshire]; weighted 7.66 ± 1.79 kg, weaned at d 28) were randomly selected and allocated to 3 treatments with 4 replicates per group and 10 piglets per replicate according to the initial body weight and gender. The dietary treatments were as follows: 1) basal diet (Ctrl); 2) Ctrl + chlortetracycline (75 mg/kg) (AGP); 3) Ctrl+ MOA (1500 mg/kg). The experiment period was lasted for 21 d. Results: Compared to the Ctrl group, dietary supplemented MOA alleviated (P < 0.05) the diarrhea rate from d 12 to 21, enhanced (P < 0.05) the concentration of serum interlukin-10 and glutathione peroxidase in piglets on d 11 after weaning and serum superoxide dismutase in 21-day piglets. The MOA group also improved (P < 0.05) the apparent digestibility of dry matter (DM), organic matter (OM) and gross energy (GE), up-regulated (P < 0.05) the mRNA expression level of occludin, claudin-1 and mucin-2 in ileum and increased (P < 0.05) the contents of propionic and butyric acids in the cecum of piglets. The MOA group modulated the cecal and colonic microbial community structure and increased (P < 0.05) the abundance of Faecalibacterium and Muribaculaceae in cecum and Streptococcus and Weissella in colon. Additionally, AGP group decreased (P < 0.05) apparent digestibility of DM, OM and GE as well as down-regulated (P < 0.05) relative gene expression level of claudin-1 in duodenum and jejunum, ZO-1 and mucin-1 in jejunum of piglets. Conclusion: In summary, dietary supplemented MOA alleviated diarrhea and improved nutrient apparent digestibility in piglets via enhancing immuno-antioxidant properties, increasing digestive enzyme activity, up-regulating the expression of intestinal barrier-related genes, and modifying the microbial community structure of the cecum and colon. Therefore, dietary supplementation with MOA as an alternative to antibiotics was feasible to improve intestinal health of piglets in practical production.
... Other amino acids are absorbed by the small intestines and arrive in the liver via the portal vein (Hou et al., 2020). Synthesis of tyrosine, precursor for the synthesis of catecholamine neurotransmitters Fernstrom and Fernstrom, 2007;Matthews, 2007 Tryptophan Serotonin and melatonin synthesis, kynurenine pathway Stavrum et al., 2013 Tyrosine Precursor for the synthesis of catecholamine neurotransmitters and thyroid hormones Levine and Conn, 1967 Branched-chain amino acids Isoleucine Improvement of insulin resistance and immune function Doi et al., 2007;Gu et al., 2019 Leucine Regulation of protein turn-over, inhibition of proteolysis Wu, 2009;Duan et al., 2016 Valine Improvement of immune function, contribution of de novo lipogenesis of odd-chained fatty acids Regulation of immune function, ammonia detoxification Li et al., 2007;Wu et al., 2009 Aspartate Substrate in urea cycle and nucleotide synthesis, activation of NMDA receptors, Wu, 2009;Zhu et al., 2017 Cysteine Synthesis of anti-oxidants, crucial role in protein structure and protein-folding pathways Brosnan and Brosnan, 2006b;Colovic et al., 2018 Glutamate Excitatory neurotransmitter, ammonia assimilation He et al., 2010;Zhou and Danbolt, 2014 Glutamine Substrate in urea cycle, for gluconeogenesis and nucleotide synthesis, energy substrate for cells of the immune system; regulating the proliferation and activation of hepatic stellate cells Newsholme et al., 2003;Li et al., 2017;Zhu et al., 2017 Glycine Inhibitory neurotransmitter, anti-oxidant, regulates production of cytokines and immune function Brosnan, 2001;Fang et al., 2002;Zhong et al., 2003 Histidine Hemoglobin structure and function, modulation angiogenesis, cell adhesion and migration, complement activation, immune complex clearance and phagocytosis of apoptotic cells Proline Protein metabolism, collagen structure and function, wound healing, anti-oxidant reactions, immune function Wu, 2009;Wu et al., 2011 Serine Protein phosphorylation, nucleotide synthesis, one-carbon unit metabolism Wu, 2009 Threonine Immune function, synthesis of mucin protein required for intestinal integrity Wu, 2009;Mao et al., 2011 ...
... Threonine participates in the protein synthesis and maintenance of body protein turnover (Figueiredo et al. 2012), as well as acts to generate essential metabolic products as glycine, acetyl-CoA, pyruvate (Kidd and Kerr 1996), and uric acid (Martinez-Amezcua et al. 1999). Additionally, Thr is essential for mucin production, which plays a significant role in intestinal health and nutrient absorption (Mao et al. 2011), as well as for the production of antibodies (Kidd 2004) and feather development (Fouad et al. 2016). In laying hens, dietary supplementation with L-threonine enhances the egg production, egg weight, feed conversion ratio (FCR), and antibody production during different phases of production (Martinez-Amezcua et al. 1999;Faria et al. 2002;Azzam et al. 2011;Abdel-Wareth and Esmail 2014;Azzam et al. 2014;Cardoso et al. 2014). ...
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The current experiment was conducted to evaluate the effects of digestible threonine (dThr) on performance, egg quality, blood metabolites, and immune responses in laying hens fed a wheat-based diet during the second cycle. Also, dThr requirements were determined based on nutrient dose-response data. A total of 384, 105-week-old post-molt Hy-line-W36 laying hens were allocated to six groups, 0.02% increments, ranging from 0.44 to 0.54% dThr, with eight replicates/treatment and eight birds each, from 105 to 116 wk. By increasing, dThr levels improved egg weight with a linear trend (p <.01), and egg production (EP), egg mass (EM), and feed conversion ratio (FCR) with quadratic trends (p <.05). Hens fed diet contained 0.48% dThr, dThr/digestible Lys (dLys) of 66% showed the best egg production traits. However, feed intake, egg quality traits, blood metabolites, and immune responses were unaffected by dThr levels. Based on the quadratic broken‐line regression models, the dThr requirements of laying hens during the second production cycle for optimised the EP, EM, and FCR were estimated at 507, 514, and 520 mg/hen per day, respectively. These values correspond to 9.84–10.1 mg/g of EM. It is concluded, in the laying hens fed a wheat-based diet during the second cycle, the dietary dThr level of 0.48%, dThr/dLys of 66%, and a daily intake of 520 mg dThr/bird are adequate for optimised performance. The amino acids requirements of laying hens vary depending on trait is considered for optimisation. The dThr requirement estimated for FCR was higher than those for EP and EM. • HIGHLIGHTS • In the laying hens that feed a wheat-based diet during the second cycle. • A dietary digestible threonine concentration of 0.48% and a daily intake of digestible threonine 520 mg/bird are adequate for optimised performance.
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The beneficial effect of elevated concentrations of copper (Cu) on growth performance of pigs has been already demonstrated; however, their mechanism of action is not fully discovered. The objective of the present experiment was to investigate the effects of including Cu from copper sulfate (CuSO4) or monovalent copper oxide (Cu2O) in the diet of growing pigs on oxidative stress, inflammation, gene abundance, and microbial modulation. We used 120 pigs with initial body weight (BW) of 11.5 ± 0.98 kg in 2 blocks of 60 pigs, 3 dietary treatments, 5 pigs per pen, and 4 replicate pens per treatment within each block for a total of 8 pens per treatment. Dietary treatments included the negative control (NC) diet containing 20 mg Cu/kg and 2 diets in which 250 mg Cu/kg from CuSO4 or Cu2O was added to the NC. On day 28, serum samples were collected from one pig per pen and this pig was then euthanized to obtain liver samples for the analysis of oxidative stress markers (Cu/Zn superoxide dismutase, glutathione peroxidase, and malondialdehyde, MDA). Serum samples were analyzed for cytokines. Jejunum tissue and colon content were collected and used for transcriptomic analyses and microbial characterization, respectively. Results indicated that there were greater (P < 0.05) MDA levels in the liver of pigs fed the diet with 250 mg/kg CuSO4 than in pigs fed the other diets. The serum concentration of tumor necrosis factor-alpha was greater (P < 0.05) in pigs fed diets containing CuSO4 compared with pigs fed the NC diet or the diet with 250 mg Cu/kg from Cu2O. Pigs fed diets containing CuSO4 or Cu2O had a greater (P < 0.05) abundance of genes related to the intestinal barrier function and nutrient transport, but a lower (P < 0.05) abundance of pro-inflammatory genes compared with pigs fed the NC diet. Supplementing diets with CuSO4 or Cu2O also increased (P < 0.05) the abundance of Lachnospiraceae and Peptostreptococcaceae families and reduced (P < 0.05) the abundance of the Rikenellaceae family, Campylobacter, and Streptococcus genera in the colon of pigs. In conclusion, adding 250 mg/kg of Cu from CuSO4 or Cu2O regulates genes abundance in charge of the immune system and growth, and promotes changes in the intestinal microbiota; however, Cu2O induces less systemic oxidation and inflammation compared with CuSO4.
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First-litter gilts were used to determine how different dietary treatments during gestation affect the reproductive performance of gilts and immunity development of their piglets. Twenty-two crossbred Landrace×Yorkshire gilts were randomly assigned to three dietary treatments. Following conception, the gilts were fed experimental diets until farrowing occurred. The diet for treatment 1 was low protein diet (8% CP), treatment 2 had an additional supplement of 0.14% threonine that was added to the low protein diet, and treatment 3 was a control diet containing 12% CP. During gestation, net body weight gain of sows in treatment group 2 was higher than in treatment group 1 (p=0.075). However, during lactation there was no difference between all treatments groups on body weight loss and their live piglets at birth. Although milk IgG between treatments did not differ, treatment groups 2 and 3 were slightly higher than treatment group 1 was. Plasma IgG concentrations in piglets were however equal within all treatment groups at birth and at 7 days of age, at 21 days of age, it was higher in treatment group 1 than it was in the other two groups (p<0.01). Threonine supplementation to a low protein diet during gestation slightly increases milk IgG of sows. It is beneficial for piglets to acquire more passive immunity, but a suppressive effect was also noted on the endogenous IgG synthesis in piglets. A gestation diet of 8% CP for gilts can stimulate immuno-system of her piglets.
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Sixty-four growing pigs (Beijing Black×Landrace×Duroc), weighing an average of 17.5±0.5kg, were divided into four groups with four pens per treatment (two gilts and two castrates per pen) and fed diets containing various levels of threonine to determine its effects on performance, plasma levels of free amino acids, plasma urea nitrogen and immune function during a 4 week trial. The basal diet was based on maize and soybean meal, supplemented with rapeseed meal and cottonseed meal, and contained 9.2gkg−1 lysine and 5.9gkg−1 threonine. l-threonine was added to the basal diet to provide 6.8, 7.7 and 8.9gkg−1 threonine in the remaining three diets. On day 7, all pigs were injected with either Bovine Serum Albumin (BSA) or Swine Fever Attenuated Vaccine (SFAV) to determine humoral antibody response. The addition of threonine improved weight gain with the quadratic and cubic polynomial contrasts being significant (p