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Maternal Nutrition During Late Gestation and Lactation: Association With Immunity and the Inflammatory Response in the Offspring

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The immature immune system at birth and environmental stress increase the risk of infection in nursing pigs. Severe infection subsequently induces intestinal and respiratory diseases and even cause death of pigs. The nutritional and physiological conditions of sows directly affect the growth, development and disease resistance of the fetus and newborn. Many studies have shown that providing sows with nutrients such as functional oligosaccharides, oils, antioxidants, and trace elements could regulate immunity and the inflammatory response of piglets. Here, we reviewed the positive effects of certain nutrients on milk quality, immunoglobulin inflammatory response, oxidative stress, and intestinal microflora of sows, and further discuss the effects of these nutrients on immunity and the inflammatory response in the offspring.
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Maternal Nutrition During Late
Gestation and Lactation: Association
With Immunity and the Inammatory
Response in the Offspring
Qihui Li
1
, Siwang Yang
1
, Xiaoli Zhang
1
, Xinghong Liu
1
, Zhihui Wu
1
, Yingao Qi
1
,
Wutai Guan
1,2,3
, Man Ren
4
*and Shihai Zhang
1,2,3
*
1
Guangdong Provincial Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural
University, Guangzhou, China,
2
College of Animal Science and National Engineering Research Center for Breeding Swine
Industry, South China Agricultural University, Guangzhou, China,
3
Guangdong Laboratory for Lingnan Modern Agriculture,
South China Agricultural University, Guangzhou, China,
4
College of Animal Science, Anhui Science and Technology
University, Anhui Provincial Key Laboratory of Animal Nutritional Regulation and Health, Fengyang, China
The immature immune system at birth and environmental stress increase the risk of
infection in nursing pigs. Severe infection subsequently induces intestinal and respiratory
diseases and even cause death of pigs. The nutritional and physiological conditions of
sows directly affect the growth, development and disease resistance of the fetus and
newborn. Many studies have shown that providing sows with nutrients such as functional
oligosaccharides, oils, antioxidants, and trace elements could regulate immunity and the
inammatory response of piglets. Here, we reviewed the positive effects of certain
nutrients on milk quality, immunoglobulin inammatory response, oxidative stress, and
intestinal microora of sows, and further discuss the effects of these nutrients on immunity
and the inammatory response in the offspring.
Keywords: maternal nutrition, neonate, growth, disease resistance, inammatory, immunoglobulin
INTRODUCTION
During gestation and lactation, maternal nutrition is a predominant factor to regulate the growth
and immunity of piglets (1,2). Since neonates are born without brown fat reserves, timely intake of
colostrum is the guarantee of energy supply for piglets. In addition, colostrum also provides
bioactive molecules such as immunoglobulins and inammatory factors to piglets (3). Even though
maternal immunoglobulins cannot cross the placental barrier (4), these immunoglobulins could
transfer to piglets through colostrum and milk (5). Maternal diets regulate the composition of
colostrum and milk, which further affect the maturation of immune system in neonates (6).
Furthermore, maternal milk-derived cytokines also regulate the immunity of neonates (6). It is
worth noting that maternal intestinal microora play a crucial role in regulation of immune
development and response during the neonatal period (7). Transferring the intestinal ora of sows
during pregnancy into sterile mice improved the intestinal innate immunity and reduced the
inammatory response in their offspring (8). Interestingly, newborn intestinal bacteria is derived
from maternal microbiota during delivery and lactation (9). Thus, the regulation of maternal
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 7585251
Edited by:
Reinaldo B. Oria,
Federal University of Ceara, Brazil
Reviewed by:
Olli Peltoniemi,
University of Helsinki, Finland
Zhiyong Fan,
Hunan Agricultural University, China
*Correspondence:
Man Ren
renman@yeah.net
Shihai Zhang
zhangshihai@scau.edu.cn
Specialty section:
This article was submitted to
Nutritional Immunology,
a section of the journal
Frontiers in Immunology
Received: 14 August 2021
Accepted: 20 December 2021
Published: 21 January 2022
Citation:
Li Q, Yang S, Zhang X, Liu X, Wu Z,
Qi Y, Guan W, Ren M and Zhang S
(2022) Maternal Nutrition During Late
Gestation and Lactation: Association
With Immunity and the Inammatory
Response in the Offspring.
Front. Immunol. 12:758525.
doi: 10.3389/fimmu.2021.758525
REVIEW
published: 21 January 2022
doi: 10.3389/fimmu.2021.758525
intestinal microora by nutrients indirectly affect the offspring
immunity and inammatory response.
Maternal infection or inammatory exposure during pregnancy
impairs the innate response of newborns and increases their
susceptibility to infection (10). During pregnancy, sows undergo
dramatic changes of physiological metabolism and immunity (11),
with markedly increased oxidative stress and inammatory
response (12). Imbalanced inammatory response are closely
related to reproductive disorders, including constipation, abortion
and intrauterine growth retardation (9). In addition, inammatory
factors could transfer frommaternal to fetus andregulate immunity
and inammatory response. Thus, modication of dietary
components of sows during pregnancy might affect neonate
intestinal development, immunity, and inammation. In this
review, we summarized the recently published data regarding
prebiotic and nutrient supplementation to sow diets during late
gestation (mainly during G85-G114) and lactation on maternal
milk quality, inammatory response, oxidative stress and then
discuss their effect on the inammatory response and immunity
in the offspring.
SOLUBLE DIETARY FIBER
As indigestible carbohydrate, dietary ber (DF) is partially or
completely fermented by microorganisms in the large intestine,
which could be categorized into insoluble and soluble ber (13).
Insoluble berspeedsuptheintestinal circulation, reduces
constipation and increases the intestinal volume (14). While
soluble ber is fermented to produce numerous functional
metabolites, such as short-chain fatty acids (SCFAs), which could
be transmitted from maternal to offspring. Among them, acetate
regulates intestinal permeability and anti-inammatory effect (15).
Butyrate improves intestinal morphology, promotes benecial
bacterial growth, and enhances immune defense (16,17). It has
also been shown that maternal DF supplementation could promote
T cell differentiation and reduce the inammatory response in the
offspring by regulating the intestinal microbial composition (18). In
this review, we focused on the effects of several representative DF
supplementation in sow diets (Table 1 and Figure 1).
Isomaltooligosaccharide (IMO) has been reported to activate
the immune system (27) and promotes the proliferative potential
of benecial bacteria (particularly Bidobacterium) of sows (28).
A recent study reported that feeding sow IMO during late
pregnancy (G85-G110) could promote milk GH, IgA and IgG
concentrations, increase litter average daily gain (ADG) of
piglets, and reduce backfat loss in sow during lactation (19).
Similarly, another study showed that IMO given to sows during
late pregnancy increased the concentration of IgA, IgG and IgM
in colostrum and reduced the diarrhea rate of piglets (29).
Chitosan oligosaccharide (COS) has good water solubility
and performs antioxidant (30), anti-inammatory (31), and
immunity-enhancing functions (32). During gestation and
lactation (G85-L21), sows given to COS (100 mg/kg) have higher
milk production as well as IgM and lactose concentration in
colostrum. In addition, COS (100 mg/kg) increased total number
of piglets born and weaning weight per litter (20). Importantly,
feeding sows with 30 mg/kg or 100 mg/kg COS both increase the
serum IgG concentration of piglets, which indicates the
enhancement of immune function in neonates (26,33).
Sugar peat pulp (SBP) contains large amounts of soluble bers
such as pectin and dextran (34). Feeding SBP could increase the
feed intake of sows during lactation by improving insulin
sensitivity, which is benecial to the serum GH and IGF-1
levels and growth of piglets (35). SBP supplementation (20%
during gestation and 10% during lactation) reduced pro-
inammatory cytokines (IL-6 and TNF-a) in serum of sow.
Consistently, pro-inammatory cytokines (IL-6 and TNF-a)in
colostrum, milk and piglet serum are also decreased. Moreover,
SBP supplementation in sow diet increase intestinal SCFA and
colostral IgA levels, which might be benecial for reducing
inammatory response in piglets (21).
Seaweed extracts (SWEs) mainly consists of seaweed
polysaccharide (SDP), laminarin, and fucoidan (36).
Supplementation with SWEs from late gestation to weaning
increased colostrum IgG and IgA concentrations. Correspondingly,
higher serum IgG concentrations were observed in piglets, which
indicates the increased immune function (23). Sudden weaning of
piglets is often accompanied by adverse morphological changes in the
structure of the small intestine, including villous atrophy and crypt
hyperplasia (37). Recent studies have shown the addition of seaweed-
derived polysaccharides (10 g/d) to sow feed signicantly increased
the VH and ratio of villi/crypt (VH:CD) of weaned piglets. In
addition, maternal SWE supplementation increases anti-
inammatory (TGF-b1) and inhibits pro-inammatory factors (IL-
6 and IL-8) in the ileum and colon of piglets. Accordingly, the
diarrhea score of the piglets during lactation was decreased (22).
Furthermore, SWEs diet reduced the number of Enterobacteriaceae
in sow feces at delivery and the number of Escherichia coli in piglet
feces at weaning (38). These benets might be attributed to laminarin
could agglutinate certain pathogens and inhibit their adhesion to
mucosal epithelial surfaces (39).
Guar gum is a kind of galactomannan extracted from guar
endosperm. It has high viscosity and water solubility, which is
widely used as a stabilizer and thickener in foods (40). Feeding
2.0% guar gum diet to sow during the gestation and lactation
period (G85-L21) could improve the intestinal barrier function,
accelerate the growth and reduce the diarrhea rate of piglets. In
addition, guar gum increases the abundance of Lactobacilli and
decrease the abundance of Bilophila spp in intestine. Importantly,
IL-10 and TGF-blevels were increased in piglets, which avoids
over-activated immune system in piglets (24).
Mannan oligosaccharide (MOS), derived from the cell wall of
Saccharomyces cerevisiae, has been used as a prebiotic for a long
time (41). Recent supplementation of MOS in sow diets has been
reported to regulate immunity and the inammatory response in
the offspring. Compared with the control treatment, MOS
treatment (400 mg/kg) shortened the weaning estrous of the sows
and increased the weaning weight of the piglets. Besides, sows fed
MOS increased IgA, IgG, IgM in colostrum, and serumIgA and IgG
levels in suckling piglets (25). Additionally, another study shows
that the addition of MOS (400 mg/kg) to sow dietcould signicantly
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 7585252
TABLE 1 | Maternal microbial and soluble dietary ber intake in the regulation of neonatal infection, immunity and production performance.
Breed, feeding time
and products
Reproductive and
lactation performance
Immune and oxidative
stability of sows and piglets
Intestinal health and
inammation
Others References
Breed: Large White ×
Landrace
period: G85-G110
Product:
isomaltooligosaccharide
5.0 g/ kg IMO
0.2 g /kg B. subtilis
0.2 g/ kg B.
licheniformis
Reproductive performance
weaning BW (45.63-55.18 kg)
Average litter gain (28.43-35.87 kg)
Milk
Total milk yield (113.73-143.46 kg)
IgM (1 794.18-1 894.73 g/ mL)
on L0
IgA (607.50-922.07 g /mL)
on L17
N/A N/A Sow plasma (L17)
ALT (37.23-35.49 U/ L)
ALP (40.23-31.82 U /L)
(19)
Breed: Yorkshire
period: G85-L21
Product:chitosan
oligosaccharide
(100 mg/kg COS)
Reproductive performance
daily BW gain: (1.90-2.21 kg)
piglet weaning weight: (53.63-60.04
kg)
Colostrum (L1)
Solids-not-fat: (128.07 -153.33 g/kg)
IgM: (3.27-4.76 g/L)
Milk (L21)
Lactose: (44.12 -56.10 g/kg)
Solids-not-fat: (85.44-101.82 g/kg)
Sow serum (L1)
CAT: (14.25-20.49 U/mL)
T-AOC: (5.93 -8.79 U/mL)
IL-10: (50.57-67.73 pg/mL)
IgA: (71.31-91.48 mg/mL)
IgM: (92.53-117.86 mg/mL)
MDA: (16.97-11.90 nm/mL)
N/A N/A (20)
Breed: Yorkshire ×
Landrace
Period: G85-L21
(weaning)
Product: Sugar beet
pulp (SBP)
20% SBP in gestation
and 10% SBP in
lactation
Piglet at weaning (L21)
Litter weight: (56.94-64.39 kg)
Weaning weight: ((5.74-6.26 kg)
ADG: (196-221 g/d)
Colostrum (L1)
IgA: (7.94-9.17 g/L)
Piglet serum (L21)
DAO: (5.68-3.60 U/L)
Endotoxin: (0.60-0.47 EU/ml)
IL-6: (178.49-154.30 pg/mL)
TNF-a: (102.45-80.28 pg/mL)
IL-10: (4.55-5.13 pg/mL)
Piglet ileum (L21)
TNF-a: (1-0.6)
IL-6: (1-0.6)
IL-10: (1-1.3)
SIgA: (0.8-1.5 mg/mg)
Piglets Ileal Tight
Junction (L21) mRNA
expression
Occluding: (1-1.3)
ZO-1: (1-1.4)
Piglet Jejunum
Villus height: (387-447 mm)
Intestinal microbiota
(Piglet)
the relative abundance of
Christensenellaceae was
increased signicantly
Sow ADFI: (4.80-5.48
kg/d)
Piglet serum (L21)
GH: (3.37-4.23)
IGF-1(156.09-187.86)
(21)
Breed: Yorkshire ×
Landrace
Period: G83-L28
(weaning)
Product: seaweed-
derived
polysaccharides (10·0 g
SDP/d)
gestation period: (113.5-114.5 d) Piglet ileum (weaning)
gene expression
PEPT1: (1.71-0.43)
GLUT1: (0.98-0.65)
GLUT2: (1.76-0.41)
IL-1: (0.99-2.85)
IL-12A (p35): (0.97-1.93)
TNF-a: (0.93-1.66)
IL-10: (0.82-0.29)
IL-6: (1.12-0.64)
IL-8: (1.15-0.77)
Log GCN/g of sow faece
Enterobacteriaceae: (8.55-
7.76) parturition
Piglet weaning
villus height: (347-466 mm)
ileum
villus height: (317-454 mm)
jejunum
crypt depth: (144-108)
ileum
Piglets had a lower
diarrhoea score during
the lactation period
(22)
Breed: Large White x
Landrace
Period: G107-L26
Product: seaweed
extract (10 g/d)
Colostrum
IgA: (8.02-11.61
mg/mL)
Piglet serum (L14)
IgG: (8.59-11.36 mg/ml)
piglet intestinal
microbiology (weaning)
colonie E.col: (6.45-5.11
Log cfu/g)
lactobacilli: E.coli: (1.21-
1.45 Log cfu/g)
log cfu/g of sow feces
(farrowing)
En-terobacteriacea:
(8.60-7.26)
(23)
Breed: Landrace sows
Period: G85-L21
(weaning)
Product: 2.0%
pregelatinized waxy
maize starch plus guar
gum (SF)
Piglet at weaning (L21)
Final BW: (6.49-7.09 kg)
ADG: (233.66-261.20 g/day)
Piglet serum (L14)
IL-6: (310-290 pg/ml)
TGF-b: (650-750 pg/ml)
IL-10: (110-140 pg/ml)
Piglet plasma (L14)
Zonulin: (700-550 ng/ml)
Endotoxin: (0.7-0.5 Eu/ml)
Diamine oxidase: (10-9 U/L)
lipocalin-2 (80-58mg/g
feces)
Intestinal microbiota
(Piglet)
strong increase in relative
abundance of the
Lactobacillus genus
Piglet Diarrhea rate:
(13.69-10.35%)
plasma hormone of
piglets (L14)
GH: (587.65-657.49 pg/
ml)
IGF-1: (309.04-374.63
ng/ml)
(24)
(Continued)
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 7585253
increase the sIgA content in jejunum mucosa and reduce the
intestinal inammatory response of piglets by inhibiting the
TLR2/TLR4/NF-kB p65 pathway. Furthermore, MOS
supplementation in sow diet increased the number of Lactobacilli
and decreased the number of Escherichia coli in the jejunum of
piglets, which is benecial for reducing diarrhea (42).
Besides soluble ber, insoluble dietary ber also plays a crucial
physiology role in sow. Insoluble dietary ber accelerates
gastrointestinal motility, reduces constipation and increases satiety
of sows (43). Wheat bran (WB) is a insoluble ber rich in
arabinoxylan and cellulose, and widely used in the sow diet (44). A
recent study showed that feeding WB to sows during late pregnancy
and lactation (from G110 and L21) reduced inammatory responses
with the downregulation of serum IL-6 concentrations (21). In
addition, the addition of wheat bran (25% during gestation and
14% during lactation) to sow diets increase the duodenal villi and
higher colonic and ileal VH:CD ratios of the weaning piglets (45).
However, excessive level of dietary ber could negatively
affect total tract nutrient digestibility in pigs (46). As soluble
ber might increase digesta viscosity and slow down the diffusion
of digestive enzymes in the small intestine (47). While insoluble
ber could promote the passage rate of chyme and reduce the
mixing time of digestive enzymes and dietary ingredients (47).
Therefore, overmuch high-ber diet may cause reduced nutrient
absorption by sows, which is detrimental to piglets. And the
optimal dosage of ber supplement in the diet of gestational sows
needs further study.
OILS
During late pregnancy and lactation period, sows require more
nutrients and energy for fetal growth and milk synthesis. Oil
supplementation in sow diets could prevent excessive
mobilization of body reserves (48), shorten the estrous interval,
improve milk quantity (49), and increase the survival rate and
daily weight gain of weaned piglets (50). In addition, some
specic types of fatty acids also participate in metabolic
regulation and perform antibacterial and anti-inammatory
effects (51). In this section, we discussed the role of three
wildly used oils (soybean oil, sh oil and olive oil) in sow diet.
Soybean oil is rich in linoleic acid. The addition of 2%
soybean oil during pregnancy increased the content of protein
and lipid-free solids in colostrum (Table 2). Furthermore,
supplementation of soybean oil in the lactating diets of sows
also resulted in higher concentrations of protein in maternal milk
(54), which may be due to fatty acids stimulate the development
of mammary duct and alveolar structure (55). In addition,
maternal soybean oil supplementation also improved the
intestinal morphology, digestive enzyme activities, serum
growth factor concentrations and even intestinal immune
function of piglets with the upregulation of immune-related
genes (TLR-4,TLR-9 and MyD88) in the ileum (52,56).
Fish oil (FO) is rich in long-chain n-3 polyunsaturated fatty
acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic
acid (DHA), which have anti-inammatory effects both in vivo
and in vitro (57)(Figure 2). Maternal supplementation of FO
accelerated immune system maturation and enhanced anti-
inammatory response of piglet (58). The addition of 3-5%
sh oil to sow feed during lactation promoted the growth of
piglets during lactation (5961), which might partly due to the
increased secretion of milk fat and immunoglobulins (IgM and
IgG) (62,63). Furthermore, sh oil also reduced the transmission
of pro-inammatory cytokines (IL-1b) from the sow to the
piglets, and up-regulated the expression of IL-10 in the liver
and pro-inammatory cytokines (IL-6, TNF-a) in the skeletal
muscle of piglets to alleviate the inammatory response of the
TABLE 1 | Continued
Breed, feeding time
and products
Reproductive and
lactation performance
Immune and oxidative
stability of sows and piglets
Intestinal health and
inammation
Others References
Breed: Large White ×
Yorkshire
Period: Sow: G86-L20
Piglet: D7-D35
Product Mannan
oligosaccharide
Sow: 400 mg/kg
Piglet: 800 mg/kg
N/A Piglet serum (D35)
IL-2: (146.58-107.83 ng/L)
IL-4: (18.21-12.09 ng/L)
IFN-g: (535.58-448.88 ng/L)
IL-10: (65.82-76.04 ng/L)
Intestinal microbiota
(Piglet on D35)
log10 counts of
Lactobacillus, E. coli
E. coli: (6.83-6.43
Jejunum)
Lactobacillus:(7.63-8.44 in
Jejunum)
(7.82-8.76 in Cecum)
immunoglobulin A in
piglet jejunum
sIgA: (4.48-6.77 mg/g pro)
N/A (25)
Breed:
Landrace×Yorkshire
Period: G86-L21
Product: chitosan
oligosacchari
(30 mg/kg)
Colostrum (L1)
IgM: (0.95-1.3 g/L)
Umbilical cord blood
IgM: (38.36-43.26 g/L)
Piglet serum (D21)
IL-10: (57.04-65.29 ng/L)
IgG: (163.81-192.29 mg/L)
C3: (211.35-254.35 mg/L)
N/A N/A (26)
, increase; , decrease; N/A, No Value; BW, body weight; IgA, Immunoglobulin A; IgG, Immunoglobulin G; IgM, Immunoglobulin M; T- AOC, Total antioxidant capacity; CAT, Catalase;
MDA, Malondialdehyde; IL-10, interleukin 10; IL-6, interleukin 6; IL-8, interleukin 8; IL-4, interleukin 4; IL-2, interleukin 2; TNF-a, tumor necrosis factor-a; GH, growth hormone; IGF-1,
insulin like growth factor 1; ZO-1, zonula occludens-1; ALT, cereal third transaminase; ALP, alkaline phosphatase; ADG, average daily gain; PEPT1, peptide-transporters 1; GLUT1,
glucose transporter-1; GLUT2, glucose transporter-2; TGF-b, transforming growth factor b; IFN-g, interferon-g; C3, complement 3; sIgA, secretedimmunoglobulin A.
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 7585254
piglets (64,65). However, addition of sh oil to sow diets could
increase the sensitivity to oxidative stress in sows and piglets (66,
67). MDA is an indicator of lipid peroxidation, which is higher in
the plasma of pregnant sows after feeding FO (53). This might
due to unsaturated bonds in EPA and DHA were easily attacked
by free radicals (68). Similar to sh oil supplementation, addition
of n-3 PUFA during late pregnancy and lactation (G82-L22)
reduced the weaning-estrous interval of sows, increased the
concentrations of fat, protein and immunoglobulins (IgA, IgG
and IgM) in milk (69). Furthermore, n-3 PUFA supplementation
improved the intestinal barrier, reduced the diarrhea rate, and
minimized the mortalityofsucklingpiglets(69). Besides,
changing the ratio of n-6/n-3 PUFA in the diet of lactating
sows also affect the immune system and antioxidant status of
piglets (70,71).
Olive oil (OO) is rich in monounsaturated fatty acids (72), as
well as antioxidant and anti-inammatory components such as
tocopherols, triterpenoid alcohols, phytosterols and phenolic
compounds (73). Sows fed with olive oil (2% OO) diet during
late pregnancy and lactation resulted in greater milk fat
content, and higher birth weight and survival rate of piglets
(53). This might be due to sows distributed a larger proportion
of nutrients for fetus and neonate growth instead of using them
for fat deposition. In addition, OO signicantly reduced the
contents of IL-1b,IL-6,MDAandTNF-ain milk, and
improved the plasma levels of IL-1band TNF-ain piglets
(53). However, lower feed intake in sows was caused by OO
feeding, which might be due to olive oil derived oleic acid
upregulated plasma oleoyl ceramide (OEA) levels and caused
anorexia in sows (74).
FIGURE 1 | The soluble dietary bers benecial to intestinal health of sow, improves colostrum quality, enhance antioxidant capacity of sows and reduces
inammatory reaction of piglets.
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 7585255
It is worth noting that high fat-induced obese sows have lower
number of live-born piglets (75), piglet birth weight and weaning
weight (76). Moreover, these piglets showed reduced responses to
infection (77). One of the possible reasons is that obesity lead to
lipotoxic placental environment (78,79), which results in placenta
proinammatory response and oxidative stress (80,81). The other
reason is obese sow has higher plasma pro-inammatory cytokines
TNF-a, IL-1b, and IL-6 (75,82). Maternal inammation and
oxidative stress further increase the expression of intestinal pro-
inammatory cytokines (83) and disrupts the homeostasis of
immune cells (such as the number of T cells and macrophages) in
the offspring (84), which makes them more vulnerable to
inammatory bowel disease. These data indicate that the
excessive high-energy feed have catastrophic consequences for
health of sows and piglets. Therefore, oil additive dosage should
be considered in actual production.
ANTIOXIDANTS
During late pregnancy,rapid fetal development increases the
metabolic burden and induces systemic oxidative stress of
pregnant sows (85).Severe oxidative stress leads to postpartum
hemorrhage, decreases neonates birth weight and even causes
fetal death (86). Furthermore, oxidative stress usually causes
inammation and reduces immune system function in sows,
which leads to growth-retarded fetuses (87,88). The detrimental
effect of maternal infection or inammation on fetus
development might be due to maternal inammatory cytokines
that transmitted from maternal to fetus (89,90). Therefore,
nutritional strategies to relieve oxidative stress in sows is
crucial to improve fetus and neonate development (Table 3).
Vitamin E, one of the most effective antioxidants, could
directly react with free radicals and stimulate the expression of
antioxidant enzyme genes, like GSH-Px and CAT (94). In
addition, vitamin E enhances cellular and humoral immune
responses in a variety of animals, including pigs (98,99).
During last week of gestation and lactation, vitamin E (250 IU/
kg) supplementation in sow diet increased the levels of IgG, IgA,
and fat in sow milk and enhanced antioxidant and immune
capacity in piglets with the upregulation of plasma IgG, IgA, T-
AOC and CAT levels (94). Similarly, injection of 1000 IU
vitamin E during gestation also increases serum IgG in
sows (100).
TABLE 2 | Maternal fats intake in the regulation of neonatal infection, immunity and production performance.
Breed, feeding time
and products
Reproductive and
lactation performance
immune and oxidative
Stability of sows and piglets
Intestinal health others References
Breed: Landrace ×
Yorkshire
Period: G0-L20
Product: 2%
soybean oil
Colostrum
No-fat solids: (15.53-22.90%)
Protein: (5.85-8.79%)
Piglet ileum (After
farrowing) Gene
Expression
TLR-4: (1.00-1.48)
TLR-9: (1.00-1.40)
MyD88: (1.00-1.22)
Piglet Jejunum (After
farrowing)
Villous height: (717-923 mm)
Crypt depth: (76-88 mm)
Piglet Colon (After
farrowing)
Crypt depth: (32-41 mm)
VCR: (6.53-4.40)
(villous height to crypt depth
ratio)
Sow plasma (After
farrowing)
Prolactin: (262.00-432.70
ng/mL)
(52)
Breed: Large White
× Landrace
Period: G109-
weaning (L26)
Product: sh oil and
seaweed extract (100
g of FO/d, 10.0 g of
SWE/d)
Colostrum (SWE)
IgG: (63.27-69.84 mg/ml)
Milk (L12) (SWE)
CP: (5.17-5.39%)
Milk (L12) (FO)
Total n-34: (1.73-4.62%)
Ratio n-6:n-3: (9.75-3.80%)
Piglet serum (L5)
IgG (SWE): (19.31-22.9 mg/
ml)
IgA (SWE): (2.51-3.13 mg/ml)
IgA (FO): (3.12-2.52 mg/ml)
Piglet serum (L12)
IgG (SWE): (9.98-12.04 mg/
ml)
N/A Piglet serum (L26)
Total n-6: (0.99-0.16%)
Total n-3: (1.43-0.030%)
Ratio n-6:n-3: (0.61-
0.232%)
(23)
Breed: large white ×
landrace
Period: G84-L21
Product: Fish Oil
(2%)
Or
Olive Oil (2%)
Litter Performance
Piglet BW: (1.33-1.58 kg) OO
Piglet mortality: (7.2-12.3%) FO
Piglet mortality: (7.2-2.2%) OO
Colostrum
Fat: (4.84-5.69%) OO
MDA: (3.9-5.8 nmol/ml) FO
IL-1b: (14-20 ng/L) FO
Milk (OO)
Fat: (6.77-8.08%) L10
Fat: (5.86-7.99%) L21
IL-1b: (20-10 ng/L) L10
IL-1b: (18-6 ng/L) L21
Milk (FO)
MDA: (3.9-8 nmol/ml) L10
MDA: (3.8-8 nmol/ml) L21
Sow plasma (FO)
MDA: (2-2.25 nmol/ml) L0
MDA: (2-3.5 nmol/ml) L10
MDA: (1.5-2 nmol/ml) L21
Piglet serum (FO)
MDA: (2.75-4 nmol/ml) L0
MDA: (3-4 nmol/ml) L21
GSH-Px: (275-300 U/ml) L0
Piglet serum (OO)
IL-1b: (12-10 ng/L) L21
TNF-a:(90-80 ng/L) L21
N/A N/A (53)
, increase; , decrease. N/A, No Value; TLR-4, toll-like receptor 4; TLR-9, toll-like receptor 9; MgD88, myeloiddifferentiationfactor88 IgG, Immunoglobulin G; IgA, Immunoglobulin A; IL-10,
interleukin 10; TNF-a, tumor necrosis factor-a; MDA, malondialdehyde; IL-1 b, interleukin-1 b; T- AOC, total antioxidant capacity; GSH-Px, glutathione peroxidase IL-6, interleukin 6.
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 7585256
Polyphenol is a bioactive substance with antioxidant,
anticancer, anti-inammatory and antibacterial properties
(101). Supplementation of grape seed polyphenols (GSP)
(300mg/kg) during late pregnancy and lactation reduced the
number of dead fetuses, improved farrowing and pre-weaning
survival (91). This might due to GSP increased antioxidant
ability, progesterone and estradiol levels as well as the content
of colostral IgM and IgG in sow (91). Intriguingly, effects of GSP
on colostral immunoglobin production is better than vitamin E
(91). Supplementation herbal extracts during pregnancy and
lactation also enhance the immune function and antioxidant
capacity of next generation through maternal-offspring
transmission. Forsythia suspensa extract (FSE) is a medicinal
herb extract that mainly consists of forsythiaside A, forythialan
A, phillyrin and phillygenin. FSE has been shown to perform
antioxidant (102), intestinal microora-regulating, and anti-
inammatory effects (103). Dietary supplementation with FSE
(100mg/kg) in sows from the G85 to farrowing could upregulate
the milk fat, milk protein and IgM level in colostrum, and
increase the immune ability of the piglets (104). Mechanistically,
FSE limits the inammatory response with the inhibition of
NF-kB signaling and the activation of Nrf2/HO-1 pathway
(105). In addition, GE has an anti-inammatory effect by
inhibiting the expression of chemokines (106). The sow feed
GE could improve the content of antioxidant and phenolic
compounds in pigletsplasma, and enhance the immune
function by improve the concentration of IgG in colostrum
and the plasma of the piglets (107). Resveratrol is a plant
polyphenol with anti-inammatory and antioxidant properties
(108). Resveratrol (300 mg/kg) supplementation in sow diet
improved the intestinal morphology and reduced intestinal
inammation as well as diarrhea in the offspring (109).
As an essential trace element for sows, selenium (Se) is
incorporated into selenopsroteins and subsequently prevent
intestinal inammation by alleviating oxidative stress (110). In
addition, selenoproteins such as glutathione peroxidase (GPX)
and thioredoxin reductase (TXNRD) play an important role in
the regulation of immune function (111). Organic Se compounds
aremorebioavailablethaninorganicSeforms(112,113).
Supplementing sow gestation diets with HMSeBA (0.3 mg Se/
kg) increases the expression of antioxidant-related selenoprotein
genes in the placenta (GPx2,GPx3) and liver of neonates (GPx1,
GPx2,GPx3 and TXNRD2). Furthermore, administration of
HMSeBA decreased the gene expression of IL-1b,IL-6 and IL-
FIGURE 2 | Benecial effects of adding fat in feed of pregnant sow on piglets.
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 7585257
TABLE 3 | Maternal antioxidant and other substrates intake in the regulation of neonatal Infection, immunity and production performance.
Breed, feeding
time and products
Reproductive and
lactation performance
immune and oxidative
Stability of sows and piglets
Intestinal health others References
Breed: Large
White × Landrace
period: G80-L21
Product: grape
seed polyphenols
(300 mg/kg GSP)
Reproductive performance
dead fetuses: (1.19-0.63)
Farrowing survival: (81.47-89.32%)
Preweaning survivability: (91.85-
95.23%)
Colostrum
IgM: (2.5-6 g/L)
IgG: (38-80 g/L)
Sow plasma (G110)
SOD: (37.51-66.21 IU/mL)
GSH-Px: (417.83-620.33
IU/mL)
N/A Sow plasma (G110)
P4: (35-45 ng/ml)
E2: (40-50 pg/ml)
(91)
Breed: Landrace ×
Yorkshire
period: G85-L21
Product: fully
oxidised b-carotene
(8 mg/kg)
Milk (14)
Lactose: (5.67-6.09%)
IgM: (0.024-0.057 g/L)
Colostrum
IgM: (2.55-4.52 g/L)
IgG: (29.91-33.22 g/L)
IgA: (2.39-5.11 g/L)
TNF-a: (0.34-0.08 ng/mL)
IL-8: (1079.06-605.46 pg/ml)
N/A N/A N/A (92)
Breed: Landrace ×
Yorkshire
period: G90-L21
Product: Rare
Earth Elements
(200 mg REE
mixture/kg)
Reproductive performance
Within-litter birth weight CV: (0.21-
0.18%)
Weight at 21st day: (5.71-6.21 kg)
Daily weight gain: (223.06-241.
75 g/day)
Sow plasma (farrowing)
GSH-Px: (650-700 U/ml)
CAT: (4.8-6.5 U/mL)
TNF-a: (200-130 pg/ml)
Piglet plasma (weaning)
SOD: (120-130 U/mL)
TNF-a: (120-80 pg/ml)
Fecal Microbiota (lactating
sows)
Firmicutes: (78.2-81.0%)
Bacteroidetes: (13-19.1%)
Piglet Fecal Microbiota
(weaning)
Proteobacteria phylum:
(14.8-6.7%)
Piglet plasma
(weaning)
IGF-1: (180-210 ng/ml)
(93)
Breed: Large
White × Landrace
period: G107-L21
Product: vitamin E
(250 IU/kg)
Reproductive performance
BW of weaned piglets:(4·89-5·67 kg)
Piglet Day 0-21 ADG: (160-194 g/d)
Colostrum
Fat: (44·35-53·80 g/kg)
IgG: (52·78-63·45 g/l)
IgA: (8·02-9·01 g/l)
a-tocopherol: (18·51-26·97 mg/l)
Milk
Fat: (67·01-79·13 g/kg)
IgG: (0·89-0·96 g/l)
IgA: (3·81-4·11 g/l)
a-tocopherol: (4.16-7.97 mg/l)
Piglet plasma (L21)
IgG (0·44-0·49 g/l)
IgA (0·33-0·36 g/l)
T-AOC (6·82-7·65 IU/ml)
CAT (7·38-8·78 U/ml)
N/A N/A (94)
Breed: Yorkshire ×
Landrace
period: G75-L21
Product: Taurine
(1%)
Reproductive performance
Average daily gain: (194.62-230.11 g)
Weaning weight: (5.35-6.29 kg)
Milk
T-AOC: (106.21-165.16 U/ml) on L1
T-AOC: (34.45-105.93 U/ml) on L10
GP-x: (103.75-174.03 U/ml) on L1
CAT: (0.69-0.74 U/ml) on L10
T-SOD: (23.71-29.48 U/ml) on L10
Piglet plasma (L1)
T-SOD: (35.53-104.92 U/ml)
T-AOC: (23.45-41.22 U/ml)
CAT: (0.34-0.38 U/ml)
Piglet Villous height
Duodenum: (249.10-503.08
µm) on L1
Ileum: (318.61-467.21 µm) on
L21
Jejunum : (358.39-524.045
µm) on L7
villus height-to-crypt depth
ratio
Duodenum: (1.47-2.81) on
L1
Jejunum: (1.38-1.99) on L7
N/A (95)
Breed: Yorkshire ×
Landrace
period: G85-L21
Product: lysozyme
(300 g/t)
Stillborn: (0.89-0.15)
Diarrhea rate: (2.24-1.41%)
Colostrum
IgA: (3.21-3.51 mg/mL)
Milk (L7)
IgA: (1.84-2.11 mg/mL)
Sow plasma (L1)
IgM: (0.81-0.98 mg/mL)
Piglet plasma (L21)
IL-10: (209.60-239.21 ng/L)
IgA: (2.16-2.56 mg/mL)
IgG: (2.25-2.65 mg/mL)
IgM: (23.98-28.87 mg/mL)
N/A N/A (96)
Period: G43-
weaning
Product: wheat
bran (25% of WB in
N/A Piglet Ileal mRNA
expression
PPARg: (1-1.37)
IL6: (0.61-1)
Piglet Small Intestine
villi height: (380-450 mm)
duodenum
villi/crypt: (1.4-2) duodenum
N/A (45)
(Continued)
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 7585258
8in placentas and IL-6 serum concentration in neonatal piglets.
Therefore, HMSeBA supplementation in sows during late
pregnancy increased the antioxidant capacity of piglets and
reduced maternal and fetal inammation (114). Similarly,
another study reported that HMSeBA (0.3 mg Se/kg)
supplementation to sows during pregnancy could up-regulate
GPX1, GPX4 and selenoprotein expressions in the thymus and
spleen of the offspring. Besides, the levels of inammation,
autophagy and endoplasmic reticulum stress were reduced,
suggesting favorable outcomes in the immune function of
offspring (115). Moreover, provision of maternal hydroxy-
selenomethionine (OH-SeMet) (0.3 mg Se/kg) during G84 to
L21 showed a signicantly increase of IgG level in piglets at
weaning (2).
Taurine (Tau), a metabolite of methionine and cysteine, have
anti-inammatory and antioxidant properties (116,117). Tau
effectively promotes mammalian growth and intestinal
development (118). Supplementation with Tau (1%) in sow diets
from G75 to weaning could signicantly increase the activity of
antioxidant enzymes (T-SOD, T-AOC, and CAT) in piglet serum
and weaningbody weight of the piglets. Besides, the heightof jejunal
villi, theratio of villi height tocrypt depth (VCR) andthe expression
of tight junction were also increased (95).
Oxidized b-carotene (OxBC) is a complex mixture produced
by complete and spontaneous oxidation of b-carotene. The
addition of OxBC (8 mg/kg) to the perinatal diet (G85-L21)
improved the litter weight and individual body weight of the
weaned piglets. This might be due to OxBC increased the
immune status of sows, which further affect the growth of
piglets. This is evidenced by decreased levels of cytokines
(TNF-aand IL-18) and increased levels of immunoglobulin
(IgM, IgA, and IgG) in colostrum (92).
OTHER NUTRITIONAL STRATEGIES
In this section, we describe some other nutrients which are
advantageous to regulate the immunity and inammation of
piglets when supplemented in sow diets such as rare earth
elements, lysozyme, and yeast nucleotides etc (Table 3).
Rare earth elements (REEs) includes 15 elements such as
lanthanum (La) and cerium (Ce) (119). In addition to promote
growth and feed conversion rate, rare earth elements also have
anti-inammatory and antioxidant properties (120,121). A
recent study showed that maternal supplementation with REEs
(200 mg/kg) during late gestation could improve the antioxidant
capacity and immune system through the up-regulation of serum
CAT and GSH-Px level and downregulation of the serum TNF-a
level of sow. In addition, piglets from REEs fed sow, have higher
uniformity of birth weight and weaning weight, which might be
related to the higher serum IGF-1 level (93). Furthermore,
increased abundance of benecial bacteria (Christensenellaceae
and Ruminocococaceae) and decreased abundance of
opportunistic pathogenic bacteria (Proteus and Campylobacter)
were also found in the intestinal tract of piglets (93).
Lysozyme (LZM) is a natural antibacterial enzyme found in
the tears, saliva and milk of mammals (122). Previous studies
have shown that lysozyme has multiple benecial effects on
piglets, including improving intestinal morphology (123),
regulating the intestinal microora (124), and improving
immunity (125). Sows fed diets containing lysozyme (300 g/t)
from late gestation to weaning exhibited shorter weaning-estrous
intervals and less stillbirths. In addition, serum IgM, IgA, IgG and
IL-1 in sow were increased during lactation. Correspondingly,
serumIgA,IgG,IgM,andIL-10concentrationswerealso
increased in piglet (96). Besides, piglets showed reduced rates of
TABLE 3 | Continued
Breed, feeding
time and products
Reproductive and
lactation performance
immune and oxidative
Stability of sows and piglets
Intestinal health others References
gestation and 14%
of WB in lactation.)
villi/crypt: (1.4-1.6) jejunum
crypts depth: (250-200 mm)
jejunum
Breed: Large
White × Landrace
Period: G85-L20
Product: Yeast-
based nucleotide
(4 g YN/kg diet)
Piglet at Weaning (D20)
litter size: (9-10)
ADG: (190-200 g)
Sow total milk yield: (130-150 kg)
Gene expression of
Intestinal cytokine
(neonatal piglets)
Ileal
(IL)-17: (1-1.8)
IL-8: (1-1.5)
TNF-a: (1-1.8)
Jejunal
(IL)-17: (1-1.8)
IL-6: (1-2.5)
IL-8: (1-1.7)
IFN-g: (1-1.6)
TNF-a: (1-1.8)
Duodenal
IL-6: (1-0.5)
IL-1b: (1-1.6)
Ileum (neonatal piglets)
average villus height: (550-
600 mm)
villus height-to-crypt depth
(V:C): (5-6)
sIgA: (5-6.5 mg/g)
Intestinal tight junction
(neonatal piglets) mRNA
expression
Ileal
ZO-1: (1-0.6)
Jejunal
ZO-1: (1-0.7)
claudin-1: (1-0.5)
Duodenal
claudin-1: (1-0.5)
Diarrhoea rate of
piglets: (4.5-3%)
(97)
, increase; , decrease. N/A, No Value; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; P4, progesterone; E2, estradiol; IgM, Immunoglobulin M; IgG, Immunoglobulin G;
IgA, Immunoglobulin A; TNF-a, tumor necrosis factor-a; IL-8, interleukin 8; IL-6, interleukin 6; IL-10, interleukin 10; IL-17, interleukin 17; IFN-g, interferon-g; CAT, catalase; IGF-1, insulin like
growth factor 1; T- AOC, total an tioxidant capacity; T-SOD, total Superoxide dismutase ; ZO-1, zonula occludens-1; IL-1 b, interleukin-1 b; ADG, av erage daily gain; sIgA,
secretedimmunoglobulin A; PPARg, peroxisome proliferator-activated receptor g.
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 7585259
diarrhea, which may be due to a decreased number of
campylobacter in the feces (126).
Nucleosides could promote the growth and development of
intestinal epithelial cells (127). The addition of nucleotides to infant
formula has a protective effect in preventing diarrhea and
improving immunity (128). As a byproduct of yeast degradation,
yeast-based nucleotides (YN) are rich in nucleotides.
Supplementation of yeast cultures during pregnancy and lactation
decreaseof diarrhea and improvethe growth performance of piglets
(129). In detail,administration of yeast-based nucleotide (4 g YN/
kg) during latepregnancy and lactation (G85-L20) of sowimproved
the development of intestinal morphology, and increased innate
immunity with upregulation of intestinal IL-17, IL -8, IL -1b,IL-10
and TNF-aexpressions in neonatal piglets (97).
Spray-dried plasma (SDP) is a protein-rich feed additive that
contains immunoglobulins, peptides, glycoproteins and other
active ingredients (130). Previous studies have shown that
supplementation of SDP improved the immune response of
pigs (131). From late pregnancy to weaning (G85-L27),
maternal supplemented with 1% SDP reduced the serum
concentrations of TNF-a, TGF-b1 and cortisol in sows and
serum concentrations of TNF-a,TGF-b1 and cortisol in
piglets. Additionally, the average daily gain of piglets at
weaning was greater, and serum concentrations of cortisol,
TGF-b1, TNF-aand C- reactive protein were lower (132).
CONCLUSION AND OUTLOOK
Dietary ber regulates inammatory and immune response in the
offspring by modulating the maternal intestinal microora and milk
immunoglobulin content. The antioxidant substances could
directly react with the free radicals and enhance the maternal
antioxidant capacity, thereby indirectly reducing infection in the
offspring. The oiland fat products not only provide adequate energy
to sows, but also supply functional fatty acids to alleviate infection
and enhance the immune function in the offspring by exerting the
anti-inammatory and anti-oxidant effects. In summary, maternal
nutrition intervention is an effective way to regulate the
inammatory response and immunity in the offspring.
In this review, we mainly focus on the positive effects of
nutrients in the regulation of immunity and inammatory
response of sows and piglets during pregnancy and lactation. It
worth noting that these effects would be affected by timing and/
or dosage of nutrient supplementation. Moreover, it is well
known that excessive addition of fat usually has a negative
effect on pigs. The toxic effects of excessive addition of other
products, such as vitamin E and selenium (133) are also worthy
of attention. Therefore, we have given the current dosage of these
products. However, the adverse effects of excessive maternal
supplementation of such products on the immune system of
piglets still need further research. In addition, applying nutrients
to piglets and sows at the same time during lactation could
produce better results (93). Even though nutrient mixture might
produce synergistic and addictive effects, but economic cost
should be considered in pig production. Future study needs to
identify the best time and dosage for nutrient supplementation in
sow diet. In addition, current studies only observe the change of
phenotypic indicators, in vitro cell experiments are required to
clarify the potential mechanism. Lastly, whether the metabolites
of these nutrients were involved in the regulation of immunity
and inammation in the offspring is still unclear and require
more research.
AUTHOR CONTRIBUTIONS
QL, SZ, and MR initiated the idea, the scope, and the outline of
this review paper. QL, SY, XZ, XL, ZW, YQ, WG, MR, and SZ
studied and analyzed all of the publications cited in this paper
and were involved in the manuscript preparation. SZ and MR
conducted the nal editing and proofreading. All authors
contributed to the article and approved the submitted version.
FUNDING
This study was nancially supported by the National
Natural Science Foundation of the P.R. of China (No.
31872364 and No. 31802067), Guangdong Basic and Applied
Basic Research Foundation (No. 2021A1515010440), Science
and Technology Program of Guangzhou (No. 202102020056),
Anhui Provincial Science and Technology Major Special
Project (201903a06020002).
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Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 75852514
... Early weaned piglets are prone to oxidative stress due to incomplete development of the liver-gut system and low immunity, which is mainly manifested by impaired growth performance and diarrhea [1]. The disruption of the intestinal integrity is one of the important factors leading to diarrhea and growth impairment of piglets after weaning [2,3]. In production, rapid changes in diet and invasion of pathogenic microorganisms are the main factors that disrupt the intestinal function of weaned piglets, as which can easily induce acute inflammation of the piglet intestine [4][5][6]. ...
... Gastrointestinal tract of early weaned piglets is highly susceptible to functional damage caused by external stimuli due to incomplete development, which ultimately damages their growth potential [2,3]. This study found that dietary bile acid supplementation improved the growth performance, and reduced F/G and diarrhea rates of piglets, but there was no significant difference in feed intake. ...
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Background Maintaining the integrity of the structure and function of piglet intestines is crucial for their growth and health. This study aims to evaluate the effects of an antibiotic free diet supplemented with bile acid on gut health and growth performance of weaned piglets, and to explore their regulatory mechanisms. Methods Thirty-two weaned piglets were randomly divided into two groups and fed either a basal diet or a basal diet supplemented with 350 mg/kg bile acid. Results Dietary supplementation with bile acid increased the average daily gain (ADG) and final weight of piglets, and reduced the diarrhea incidence ( P < 0.05), which was verified to be related to the improvement of lipid absorption, amino acid transport, and intestinal barrier function. Bile acid increased the concentration of lipase and decreased the concentration of total cholesterol, total glyceride, low-density lipoprotein, and urea nitrogen in serum ( P < 0.05). Meanwhile, bile acid improved the mRNA expression of amino acid transporters in the intestine. On the other hand, bile acid decreased the pH values of the stomach, jejunum, and colon, and improved intestinal morphology ( P < 0.05). The real-time quantitative PCR results showed that bile acid increased the mRNA expression of Occludin and ZO-1 in the duodenum and ileum ( P < 0.05). Moreover, dietary bile acid supplementation altered the composition of the ileal microbiota in piglets and increased the relative abundance of Ligilactobacillus . In vitro, bile acid improved the repair of IPEC-J2 cells after injury and was shown to be associated with the activation of farnesoid X receptors (FXR) and increased expression of tight junction proteins and aquaporins (AQPs) proteins. Conclusion This study found that dietary bile acid supplementation promotes the intestinal health and nutrient absorption partially through the FXR/AQPs pathway, ultimately improving growth performance of piglets.
... The immature immune system and different common stressors at birth and weaning transition, including physiological, nutritional, and environmental factors, increase the risk of infection of piglets, which can seriously lead to intestinal and respiratory diseases, and even death (1). The nutritional and physiological status of sows during pregnancy and lactation is directly associated with the development and disease resistance of fetuses and neonates (2). During pregnancy and lactation, maternal nutrient intake shapes the development of the fetal immune system (3). ...
... After birth, the foremost function of suckling is to support the essential nutrients of newborns. Piglets are born without accumulated brown fat, while breast milk can provide energy promptly (2). At the same time, colostrum also provides bioactive molecules such as immunoglobulins for piglets (5). ...
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Maternal nutrition is one of the main factors regulating the growth and immunity of piglets. This study aimed to investigate the effects of maternal or maternal-offspring supplementation of antibiotics, probiotics, and synbiotics on the immunity of offspring (21, 65, and 125 day-old) in Bama mini-pigs. The results showed that adding antibiotics to maternal diets increased the plasma IFN-γ level of offspring piglets at 21 day-old. Compared with maternal supplementation, maternal-offspring supplementation of antibiotics decreased the IL-10 level in the spleen, probiotics decreased IL-2, IL-10, and TNF-α levels in the ileum, and synbiotics decreased IL-10 and IFN-γ levels in the ileum of offspring piglets. Moreover, maternal-offspring antibiotics supplementation increased the IL-1β level in the ileum, while probiotics supplementation increased the IL-1β level in the spleen of offspring piglets. Maternal antibiotics supplementation increased the TNF-α level in the ileum at 95 day-old compared with maternal probiotics and synbiotics supplementation. Maternal-offspring antibiotics supplementation increased the IL-1β level in the ileum compared with the probiotics supplementation, while synbiotics supplementation increased the IL-6 level in the ileum than the probiotics and antibiotics supplementation at 95 day-old. Moreover, maternal-offspring probiotics supplementation increased the IL-1β level in the spleen of offspring pigs, which was higher than the maternal probiotics supplementation. These findings suggest that the immune function of the offspring piglets varied depending on the specific approach used for probiotics and synbiotics supplementation.
... After weaning, factors such as dietary changes and immature development of digestive tract and endocrine systems result in severe oxidative stress in the intestin piglets [4,6,21]. Oxidative stress results in diarrhea, reduced feed intake, and growth tardation in weaned piglets [22,23]. CGA is a polyphenolic compound with potent ant idant activity [11]. ...
... After weaning, factors such as dietary changes and immature development of the digestive tract and endocrine systems result in severe oxidative stress in the intestine of piglets [4,6,21]. Oxidative stress results in diarrhea, reduced feed intake, and growth retardation in weaned piglets [22,23]. CGA is a polyphenolic compound with potent antioxidant activity [11]. ...
Article
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Chlorogenic acid (CGA) is a natural polyphenol with potent antioxidant and anti-inflammatory activities. However, the exact role of it in regulating intestinal health under oxidative stress is not fully understood. This study aims to investigate the effects of dietary CGA supplementation on the intestinal health of weaned piglets under oxidative stress, and to explore its regulatory mechanism. Twenty-four piglets were randomly divided into two groups and fed either a basal diet (CON) or a basal diet supplemented with 200 mg/kg CGA (CGA). CGA reduced the diarrhea rate, increased the villus height in the jejunum, and decreased the crypt depth in the duodenum, jejunum, and ileum of the weaned piglets (p < 0.05). Moreover, CGA increased the protein abundance of Claudin-1, Occludin, and zonula occludens (ZO)-1 in the jejunum and ileum (p < 0.05). In addition, CGA increased the mRNA expression of pBD2 in the jejunum, and pBD1 and pBD2 in the ileum (p < 0.05). The results of 16S rRNA sequencing showed that CGA altered the ileal microbiota composition and increased the relative abundance of Lactobacillus reuteri and Lactobacillus pontis (p < 0.05). Consistently, the findings suggested that the enhancement of the intestinal barrier in piglets was associated with increased concentrations of T-AOC, IL-22, and sIgA in the serum and T-AOC, T-SOD, and sIgA in the jejunum, as well as T-AOC and CAT in the ileum caused by CGA (p < 0.05). Meanwhile, CGA decreased the concentrations of MDA, IL-1β, IL-6, and TNF-α in the serum and jejunum and IL-1β and IL-6 in the ileum (p < 0.05). Importantly, this study found that CGA alleviated intestinal inflammation and oxidative stress in the piglets by inhibiting the TLR4/NF-κB signaling pathway and activating the Nrf2 signaling pathway. These findings showed that CGA enhances the intestinal health of weaned piglets by inhibiting the TLR4/NF-κB pathway and activating the Nrf2 pathway.
... Piglets have limited postnatal immunity and require the consumption of sow colostrum, which is rich in immunoglobulins and plays a critical role in promoting the maturation of the piglet immune system (Xiong et al., 2019). Nutritional interventions during the late stages of gestation and lactation in sows facilitate the establishment of the piglet immune system by increasing the levels of immunoglobulins present in colostrum (Li et al., 2021). Furthermore, exosomes are also abundant in mammalian milk, and milk-derived microRNAs (miRNAs) may influence the development of the immune system and gut health in offspring (Melnik et al., 2021;Miura et al., 2022;Sundaram et al., 2022). ...
... Due to the colostrum and milk are the guarantee for suckling piglets intestinal development and growth during lactation (Declerck et al., 2017;Devillers et al., 2011;Mach et al., 2015), heat stress would result in nutritional imbalance in sows and also have detrimental effects on the intestinal health and growth of suckling piglets (Guo et al., 2020). Therefore, nutritional strategies are used to alleviate heat stress in sows and improve the development and growth of piglets during high summer temperatures (Cottrell et al., 2015;Li et al., 2021Li et al., , 2022. In the present study, we found that maternal resveratrol supplementation improved the intestinal health and further increased the total daily gain of piglets during high summer temperatures. ...
Article
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Previous studies have shown that maternal resveratrol improved growth performance and altered the microbial composition of suckling piglets under hot summer conditions. However, it remains unclear how maternal resveratrol improves growth performance of suckling piglets during high summer temperatures. A total of 20 sows (Landrace × Large White; three parity) were randomly assigned to 2 groups (with or without 300 mg/kg resveratrol) from d 75 of gestation to d 21 of lactation during high ambient temperatures (from 27 to 30 °C). The results showed that maternal resveratrol supplementation increased total daily weight gain of piglets under hot summer conditions, which is consistent with previous studies. Furthermore, we found that maternal resveratrol improved the intestinal morphology and intestinal epithelial proliferation in suckling piglets. Dietary resveratrol supplementation affected the characteristics of exosome-derived microRNAs (miRNAs) in sow colostrum, as well as the genes targeted by differentially produced miRNAs. MiRNAs are concentrated in the tight junction pathway. As a result, the expression of intestinal tight junction proteins was increased in suckling piglets (P < 0.05). Notably, maternal resveratrol increased the intestinal secretory immunoglobulin A (sIgA) levels of suckling piglets via colostrum immunoglobin (P < 0.05), which could increase the abundance of beneficial microbiota to further increase the concentration of short chain fatty acids (SCFA) in suckling piglets' intestine (P < 0.05). Finally, our correlation analysis further demonstrated the positive associations between significantly differential intestinal microbiota, intestinal sIgA production and SCFA concentrations, as well as the positive relation between total daily weight gain and intestinal health of suckling piglets. Taken together, our findings suggested that maternal resveratrol could promote intestinal health to improve piglet growth during high summer temperatures, which might be associated with the immunoglobin and exosome-derived miRNAs in sows' colostrum.
... It is well documented that many nutrients are involved in regulating immune responses against many diseases. 134 In contrast, many studies showed that increased body mass index (calculated as weight in kilograms divided by the square of height in meters) has a negative association with long-term vaccine immune responses 135,136 such as in hepatitis A and hepatitis B vaccinations. 137,138 However, many studies recognized that a nutritional deficiency before or during pregnancy may adversely affect the health of the mother, 139 alter fetal growth, and alter the immune response of the mother and neonate against tetanus, 140 145,146 Similarly, the low maternal intake of omega-3 fatty acids during pregnancy has been associated with alteration in blood cytokines and increased prenatal or postnatal depression risk. ...
... 147,148 Likewise, different animal studies suggested the positive role of maternal supplementation of micronutrients and antioxidants in optimizing the immune response during pregnancy for both mother and infant. 136,149,150 It was observed that supplementation of different vitamins and minerals such as vitamin A, vitamin E, zinc sulfate, and plant extracts have pronounced effects on parturient cows in the form of reduction of parturition stress, improvement in the immune system, and rise in the quality of colostrum. 151 The provision of dietary β-carotene, the primary precursor of vitamin A, causes critical immune regulatory functions. ...
... The composition of colostrum and milk is regulated by the mother's diet, which directly influences the maturation of the newborns' immune systems, providing protection against infections and supporting the development of a healthy gut microbiome. Overall intestinal health is, in turn, extremely important in combating piglet weaning stress, which is often combined with diarrhoea (11). However, the shaping of the offspring's health starts earlier, in prenatal life. ...
Article
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Introduction The global swine industry faces significant challenges related to improving the survival and health of newborn piglets. Attention has come to β-hydroxy-β-methylbutyrate (HMB), a metabolite of leucine, for its potential in prenatal nutritional programming in sows, which can improve piglet body weight and support the development of the skeletal and digestive systems. The effects of prenatal HMB supplementation were investigated on the chemical coding of the enteric nervous system (ENS) in the small intestine of neonatal piglets. Material and Methods The experiment was conducted on piglets from 12 sows divided into a control and an experimental group. Sows in the experimental group received HMB at a dose of 0.2 g/kg body weight per day from day 70 to 90 of gestation. After parturition, one piglet from each litter was euthanised and parts of the duodenum, jejunum and ileum were exsected. Tissue sections were fixed in paraffin, reacted with anti–vasoactive intestinal peptide (VIP), anti–cocaine- and-amphetamine-regulated transcript (CART), anti–neuronal nitric oxide synthase (nNOS) and anti-substance P (SP) antibodies, and the immunoexpression of VIP, CART, nNOS and SP was determined histomorphometrically by calculating the area of fibres which were immunoreactive with each. Results Supplementation with HMB in sows caused significant changes in the ENS of newborn piglets, including an increase in the area of fibres reactive to CART and nNOS in certain layers and sections of the small intestine, and a decrease in the area of fibres reactive to SP and VIP. Conclusion The results indicate that prenatal supplementation with HMB in sows may significantly influence the functioning of the gastrointestinal tract in newborn piglets.
... Oxidative stress during gestation and lactation in sows can have severe detrimental effects on the growth and development of offspring, particularly impacting their antioxidant capacity [51]. Firstly, during early embryogenesis, oxidative stress can disrupt normal cell division and development by damaging the DNA, proteins, and lipids of embryonic cells. ...
Article
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Sows and piglets face heightened oxidative stress during gestation and lactation, yet strategies to simultaneously mitigate these challenges remain underexplored. This study investigated the effects of β-carotene and superoxide dismutase (SOD) supplementation on 140 Landrace × Yorkshire sows (parity 3–5) randomly assigned to (1) a control; (2) long-term low-dose treatment (25 mg/kg β-carotene, 4 mg/kg SOD, or both) throughout gestation–lactation; or (3) short-term high-dose treatment (100 mg/kg β-carotene, 14 mg/kg SOD, or both) administered 7 days pre/post-weaning and farrowing. Our data indicate that the antioxidants enhanced the productive performance of both sows and piglets, with the most pronounced effect observed in the long-term, low-dose combined administration of β-carotene and SOD. The composite antioxidants significantly improved the systemic antioxidant capacity in sows, while concurrently reducing the cortisol and lipopolysaccharide concentrations in the serum. This enhancement contributed to elevations in serum progesterone and prolactin levels at day 40 of gestation and farrowing, respectively, ultimately increasing the number of weaned piglets and decreasing the backfat loss. In addition, the compound antioxidants improved the serum antioxidant indices of piglets, increased the growth hormone concentrations, and improved the litter weight gain. Mechanistically, the placental upregulation of CAT, GPX1, and GLUT3, alongside Claudin1, Occludin, and ZO-1 expression, underpinned improved nutrient transport and barrier function. These findings demonstrate that β-carotene and SOD synergistically transfer antioxidant capacity via placental and colostrum pathways, offering a viable strategy for integrated sow–piglet management.
... The maternal environment is crucial for embryonic development and significantly influences the growth and development of infants [1]. Folic acid has been demonstrated to be an indispensable nutrient for the proper development of embryos and newborns [2]. ...
Article
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Simple Summary Maternal folic acid intake is crucial for offspring growth and development. This study investigated the impact of maternal folic acid supplementation on the small intestine development in piglets. We found that folic acid supplementation during gestation and lactation significantly increased the body weight, villus length, and expression of nutrient transporters in the duodenum and jejunum of offspring piglets. Additionally, maternal folic acid supplementation also enhanced the proliferation and differentiation of intestinal stem cells of piglets. These results highlight the beneficial effects of maternal folic acid supplementation on growth performance and gut health of offspring by enhancing the balance of epithelial cell renewal. Abstract Maternal folic acid intake has important effects on offspring growth and development. The mechanism involved in the renewal of intestinal epithelial cells remains unclear. Thus, this study aimed to investigate the potential effect of maternal folic acid supplementation during gestation and lactation on the structural and functional development of the small intestine in piglet offspring. Twenty-four Duroc sows were assigned to a control group (CON) and a folic-acid-supplemented group (CON + FA, supplemented with 15 mg/kg of folic acid). The results showed that maternal folic acid supplementation throughout gestation and lactation significantly increased the body weight, serum folate level, and intestinal folate metabolism in piglets. It also improved the villus length, villus height-to-crypt depth ratio, and transcript levels of nutrient transporters (GLUT4, SNAT2, FABP2, and SLC7A5) in piglets’ duodenum and jejunum. In addition, maternal folic acid supplementation increased Ki67-positive cells and the expression of proliferation-related marker genes (C-Myc, CyclinD1, and PCNA) in piglets’ intestinal stem cells. It also boosted the expression of genes associated with mature secreted cells (ChrA, Muc2, Lyz, Vil1), indicating enhanced proliferation and differentiation of intestinal stem cells. These findings demonstrate that maternal folic acid supplementation enhances growth performance and gut health in piglet offspring by promoting epithelial cell renewal equilibrium.
... Maternal oxidative stress can change the milk nutrition composition [33], which might cause offspring oxidative stress and impair organ health before weaning [34][35][36]. In this study, we found that a maternal oxidized oil diet increased serum MDA content, while decreasing hepatic T-AOC, SOD and GSH-px activities in offspring. ...
Article
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Dietary oxidized fat contains harmful materials such as hydrogen peroxide and malondialdehyde (MDA). Excessive oxidized fat intake during pregnancy and lactation not only leads to maternal body injury but also damages offspring health. Our previous study demonstrated that vitamin D (VD) had antioxidative capability in sows. This study was conducted to investigate the effect of maternal VD and inulin supplementation in oxidized oil diet on the growth performance and oxidative stress of their offspring. Sixty 5-month-old C57BL/6N female mice were randomly divided into five groups: Control group (basal diet, n = 12), OF group (oxidized-soybean-oil-replaced diet, n = 12), OFV group (oxidized-soybean-oil-replaced diet + 7000 IU/kg VD, n = 12), OFI group (oxidized-soybean-oil-replaced diet + 5% inulin, n = 12) and OFVI group (oxidized-soybean-oil-replaced diet + 7000 IU/kg VD + 5% inulin, n = 12). Mice were fed with the respective diet during pregnancy and lactation. The offspring were then slaughtered on day 21 of age at weaning. Results showed that a maternal oxidized oil diet impaired body weight and liver weight gain of offspring during lactation compared to the control group, while maternal VD, inulin or VD and inulin mixture supplementation reversed this effect. In addition, the activity of T-AOC in the liver of offspring was lower in the OF group than that in the control group, but could be restored by maternal VD and inulin mixture supplementation. Furthermore, the gene expression of both proinflammatory and anti-inflammatory cytokines, such as Il-6, Tnfα and Il-10, in offspring liver were downregulated by a maternal oxidized oil diet compared with the control group, but they were restored by maternal VD or VD and inulin mixture supplementation. The expressions of Vdr and Cyp27a1 were decreased by a maternal oxidized oil diet compared with the control group, while they could be increased by VD or VD and inulin mixture supplementation. Conclusion: maternal oxidized oil diet intake could impair the growth performance by inducing oxidative stress, but this can be relieved by maternal VD and inulin supplementation.
Article
Relevance . Immunometabolic status plays an important role in the formation of post-vaccination immunity against porcine circovirus type 2 in sows. Methods . The object of the study was sows that were vaccinated with the “Ingelvac CircoFLEX” vaccine (Germany) on the 21st day of lactation after weaning their piglets (control group). In the experimental group, vaccination was combined with the administration of “Transfer Factor” obtained from leukocytes of hyperimmunized animals. The effectiveness of vaccination was assessed by parameters of immunometabolic status and production indicators. Results . The introduction of “Transfer Factor” into the vaccination scheme of sows against pig circovirus of the second type makes it possible to form an immunometabolism profile in the animals› body, promoting the production of virus-neutralizing antibodies in the required quantity, which is reflected in the value of production and economically important indicators as markers of the effectiveness of postvaccination immunity. This is achieved due to the fact that post-vaccination immunological reactions occur predominantly through the mechanism of a secondary immune response, as evidenced by an increase in the concentration of IgG by 1.46–1.55 times and a decrease in IgM by 1.63–2.11 times, compared with the control. The hepatoprotective properties of “Transfer Factor” modulate the functional ability of liver cells and stabilize the state of their membrane structures, which determines the orientation of protein and lipid metabolism in the body of sows in an anabolic direction, promoting the retention of protein nitrogen and the accumulation of reserve fats in the body of animals, the use of carbon residues of amino acids in the Krebs cycle through the regulation of the activity of transamination enzymes (AlAT, AST), control of the choleretic ability of hepatocytes, rational cholesterol metabolism. Correction of the immunometabolism status of sows in the post-vaccination period allows, in comparison with the control, to reduce the retirement of sows from the pig farm population by 21.05%, the stillbirth of piglets by 38.15%, increasing the number of adopted ones by 10.55%, and increasing the yield of piglets by 1 farrowing. 12.5 heads to 13 and their safety at farrowing is 0.80%.
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The study was conducted to evaluate the effects of spray-dried plasma (SDP) supplementation during late gestation and lactation on productive performance and immune responses of sows and their litters. Twelve sows (227.78 ± 2.16 kg average body weight; 2.0 average parity) were randomly allotted to two dietary treatments: a basal diet (CON) and the basal diet supplemented with 1% SDP. Sows were fed experimental diets from d 30 before farrowing to weaning of their piglets. Blood samples were collected from sows on d 1, 3, and 7 of lactation and from two randomly selected nursing pigs per litter on d 3 and 7 after birth, and d 1, 3, and 7 after weaning. Productive performance and immune responses of sows and their piglets were measured. There was a trend of less body weight loss in sows supplemented with SDP (p < 0.10) during the lactation period and a trend of greater (p < 0.10) average daily gain in SDP piglets compared to those in the CON group. Sows in the SDP group tended to have lower (p < 0.10) serum concentrations of tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and cortisol on d 3 and lower serum concentration of TNF-α on d 7 compared with sows in CON group. In comparison with CON piglets, piglets from SDP sows tended to have lower (p < 0.10) serum concentrations of TNF-α, TGF-β1, and cortisol on d 7 after birth, lower (p < 0.10) serum TNF-α and C-reactive protein on d 3 and 7 after weaning, and greater (p < 0.10) average daily gain after weaning. Moreover, weaned pigs from sows fed SDP had significantly lower (p < 0.05) serum concentrations of cortisol and TGF-β1 on d 3 and 7 postweaning, respectively, than CON piglets. In conclusion, SDP supplementation in sow diets from late gestation to weaning improved the productive performance of sows and their offspring; the beneficial effects of SDP may be mediated in part through modulation of immune responses of both sows and piglets.
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Abstract Background Sows are frequently subjected to various stresses during late gestation and lactation, which trigger inflammatory response and metabolic disorders. Dietary fiber can influence animal health by modulating gut microbiota and their by-products, with the effects depending upon the source of the dietary fiber. This study aimed to evaluate the impacts of different fiber sources on body condition, serum biochemical parameters, inflammatory responses and fecal microbiota in sows from late gestation to lactation. Methods Forty-five multiparous sows (Yorkshire × Landrace; 3–6 parity) were assigned to 1 of 3 dietary treatments from d 85 of gestation to the end of lactation (d 21 post-farrowing): a control diet (CON, a corn-soybean meal diet), a sugar beet pulp diet (SBP, 20% SBP during gestation and 10% SBP during lactation), and a wheat bran diet (WB, 30% WB during gestation and 15% WB during lactation). Results Compared with CON, supplementation of SBP decreased (P
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