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Maternal Nutrition During Late
Gestation and Lactation: Association
With Immunity and the Inflammatory
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
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.
Keywords: maternal nutrition, neonate, growth, disease resistance, inflammatory, 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 inflammatory 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 microflora play a crucial role in regulation of immune
development and response during the neonatal period (7). Transferring the intestinal flora of sows
during pregnancy into sterile mice improved the intestinal innate immunity and reduced the
inflammatory 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 Inflammatory
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 microflora by nutrients indirectly affect the offspring
immunity and inflammatory response.
Maternal infection or inflammatory 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 inflammatory
response (12). Imbalanced inflammatory response are closely
related to reproductive disorders, including constipation, abortion
and intrauterine growth retardation (9). In addition, inflammatory
factors could transfer frommaternal to fetus andregulate immunity
and inflammatory response. Thus, modification of dietary
components of sows during pregnancy might affect neonate
intestinal development, immunity, and inflammation. 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, inflammatory response, oxidative stress and then
discuss their effect on the inflammatory response and immunity
in the offspring.
SOLUBLE DIETARY FIBER
As indigestible carbohydrate, dietary fiber (DF) is partially or
completely fermented by microorganisms in the large intestine,
which could be categorized into insoluble and soluble fiber (13).
Insoluble fiberspeedsuptheintestinal circulation, reduces
constipation and increases the intestinal volume (14). While
soluble fiber 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-inflammatory effect (15).
Butyrate improves intestinal morphology, promotes beneficial
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 inflammatory 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 beneficial bacteria (particularly Bifidobacterium) 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-inflammatory (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 fibers
such as pectin and dextran (34). Feeding SBP could increase the
feed intake of sows during lactation by improving insulin
sensitivity, which is beneficial to the serum GH and IGF-1
levels and growth of piglets (35). SBP supplementation (20%
during gestation and 10% during lactation) reduced pro-
inflammatory cytokines (IL-6 and TNF-a) in serum of sow.
Consistently, pro-inflammatory 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 beneficial for reducing
inflammatory 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 significantly increased
the VH and ratio of villi/crypt (VH:CD) of weaned piglets. In
addition, maternal SWE supplementation increases anti-
inflammatory (TGF-b1) and inhibits pro-inflammatory 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 benefits 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 inflammatory 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 significantly
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 fiber 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
inflammation
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 significantly
↑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 inflammatory 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 beneficial for reducing diarrhea (42).
Besides soluble fiber, insoluble dietary fiber also plays a crucial
physiology role in sow. Insoluble dietary fiber accelerates
gastrointestinal motility, reduces constipation and increases satiety
of sows (43). Wheat bran (WB) is a insoluble fiber 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 inflammatory 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 fiber could negatively
affect total tract nutrient digestibility in pigs (46). As soluble
fiber might increase digesta viscosity and slow down the diffusion
of digestive enzymes in the small intestine (47). While insoluble
fiber could promote the passage rate of chyme and reduce the
mixing time of digestive enzymes and dietary ingredients (47).
Therefore, overmuch high-fiber diet may cause reduced nutrient
absorption by sows, which is detrimental to piglets. And the
optimal dosage of fiber 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
specific types of fatty acids also participate in metabolic
regulation and perform antibacterial and anti-inflammatory
effects (51). In this section, we discussed the role of three
wildly used oils (soybean oil, fish 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-inflammatory effects both in vivo
and in vitro (57)(Figure 2). Maternal supplementation of FO
accelerated immune system maturation and enhanced anti-
inflammatory response of piglet (58). The addition of 3-5%
fish oil to sow feed during lactation promoted the growth of
piglets during lactation (59–61), which might partly due to the
increased secretion of milk fat and immunoglobulins (IgM and
IgG) (62,63). Furthermore, fish oil also reduced the transmission
of pro-inflammatory cytokines (IL-1b) from the sow to the
piglets, and up-regulated the expression of IL-10 in the liver
and pro-inflammatory cytokines (IL-6, TNF-a) in the skeletal
muscle of piglets to alleviate the inflammatory 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
inflammation
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 fish 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 fish 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-inflammatory 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 significantly 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 fibers beneficial to intestinal health of sow, improves colostrum quality, enhance antioxidant capacity of sows and reduces
inflammatory 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
proinflammatory response and oxidative stress (80,81). The other
reason is obese sow has higher plasma pro-inflammatory cytokines
TNF-a, IL-1b, and IL-6 (75,82). Maternal inflammation and
oxidative stress further increase the expression of intestinal pro-
inflammatory 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
inflammatory 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 neonate’s birth weight and even causes
fetal death (86). Furthermore, oxidative stress usually causes
inflammation and reduces immune system function in sows,
which leads to growth-retarded fetuses (87,88). The detrimental
effect of maternal infection or inflammation on fetus
development might be due to maternal inflammatory 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: fish 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-inflammatory 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 microflora-regulating, and anti-
inflammatory 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 inflammatory response with the inhibition of
NF-kB signaling and the activation of Nrf2/HO-1 pathway
(105). In addition, GE has an anti-inflammatory effect by
inhibiting the expression of chemokines (106). The sow feed
GE could improve the content of antioxidant and phenolic
compounds in piglets’plasma, 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-inflammatory and antioxidant properties
(108). Resveratrol (300 mg/kg) supplementation in sow diet
improved the intestinal morphology and reduced intestinal
inflammation 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 inflammation 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 | Beneficial 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 inflammation (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 inflammation,
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 significantly increase of IgG level in piglets at
weaning (2).
Taurine (Tau), a metabolite of methionine and cysteine, have
anti-inflammatory 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 significantly 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 inflammation 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-inflammatory 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 beneficial 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 beneficial effects on
piglets, including improving intestinal morphology (123),
regulating the intestinal microflora (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 fiber regulates inflammatory and immune response in the
offspring by modulating the maternal intestinal microflora 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-inflammatory and anti-oxidant effects. In summary, maternal
nutrition intervention is an effective way to regulate the
inflammatory response and immunity in the offspring.
In this review, we mainly focus on the positive effects of
nutrients in the regulation of immunity and inflammatory
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 inflammation 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 final editing and proofreading. All authors
contributed to the article and approved the submitted version.
FUNDING
This study was financially 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).
REFERENCES
1. Tuchscherer M, Otten W, Kanitz E, Gräbner M, Tuchscherer A, Bellmann
O, et al. Effects of Inadequate Maternal Dietary Protein: Carbohydrate
Ratios During Pregnancy on Offspring Immunity in Pigs. BMC Vet Res
(2012) 8:1–11. doi: 10.1186/1746-6148-8-232
2. Li N-y, Sun Z-j, Ansari AR, Cui L, Hu Y-f, Li Z-w, et al. Impact of Maternal
Selenium Supplementation From Late Gestation and Lactation on Piglet
Immune Function. Biol Trace Elem Res (2020) 194:159–67. doi: 10.1007/
s12011-019-01754-y
3. Theil PK, Lauridsen C, Quesnel H. Neonatal Piglet Survival: Impact of Sow
Nutrition Around Parturition on Fetal Glycogen Deposition and Production
and Composition of Colostrum and Transient Milk. Animal (2014) 8:1021–
30. doi: 10.1017/S1751731114000950
4. Dividich JL, Herpin P. Nutritional and Immunological Importance of
Colostrum for the New-Born Pig. J Agric Sci (2005) 143:469–85. doi:
10.1017/S0021859605005642
5. Rooke JA, Bland IM. The Acquisition of Passive Immunity in the New-Born
Piglet. Livest Prod Sci (2002) 78:13–23. doi: 10.1016/S0301-6226(02)00182-3
6. Nguyen TV, YuanL, Azevedo MS,Jeong K-I, Gonzalez A-M, Saif LJ. Transfer of
Maternal Cytokines to Suckling Piglets: In Vivo and In Vitro Models With
Implications for Immunomodulation of Neonatal Immunity. Vet Immunol
Immunopathol (2007) 117:236–48. doi: 10.1016/j.vetimm.2007.02.013
7. Matamoros S, Gras-Leguen C, Le Vacon F, Potel G, de la Cochetiere M-F.
Development of Intestinal Microbiota in Infants and its Impact on Health.
Trends Microbiol (2013) 21:167–73. doi: 10.1016/j.tim.2012.12.001
8. Gomez-Gallego C, Garcia-Mantrana I, Salminen S, Collado MC. The
Human Milk Microbiome and Factors Influencing Its Composition and
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 75852510
Activity. Seminars in Fetal and Neonatal Medicine Vol. 21. Elsevier (2016)
p. 400–5.
9. Rainone V, Schneider L, Saulle I, Ricci C, Biasin M, Al-Daghri N, et al.
Upregulation of Inflammasome Activity and Increased Gut Permeability are
Associated With Obesity in Children and Adolescents. Int J Obes (2016)
40:1026–33. doi: 10.1038/ijo.2016.26
10. Beloosesky R, Maravi N, Weiner Z, Khatib N, Awad N, Boles J, et al.
Maternal Lipopolysaccharide-Induced Inflammation During Pregnancy
Programs Impaired Offspring Innate Immune Responses. Am J Obstet
Gynecol (2010) 203:185. doi: 10.1016/j.ajog.2010.04.033
11. Mor G, Aldo P, Alvero AB. The Unique Immunological and Microbial
Aspects of Pregnancy. Nat Rev Immunol (2017) 17:469–82. doi: 10.1038/
nri.2017.64
12. Berchieri-Ronchi CB, Kim SW, Zhao Y, Correa CR, Yeum KJ, Ferreira A.
OxidativeStress Status of Highly Prolific Sows During Gestation and Lactation.
Anim Int J Anim Biosci (2011) 5:1774–9. doi: 10.1017/S1751731111000772
13. Mudgil D, Barak S. Composition, Properties and Health Benefits of
Indigestible Carbohydrate Polymers as Dietary Fiber: A Review. Int J Biol
Macromol (2013) 61:1–6. doi: 10.1016/j.ijbiomac.2013.06.044
14. Shang Q, Liu H, Liu S, He T, Piao X. Effects of Dietary Fiber Sources During
Late Gestation and Lactation on Sow Performance, Milk Quality, and
Intestinal Health in Piglets. J Anim Sci (2019) 97:4922–33. doi: 10.1093/
jas/skz278
15. Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, Yoshimura K, et al.
Bifidobacteria can Protect From Enteropathogenic Infection Through
Production of Acetate. Nature (2011) 469:543–7. doi: 10.1038/nature09646
16. Huang C, Song P, Fan P, Hou C, Thacker P, Ma X. Dietary Sodium Butyrate
Decreases Postweaning Diarrhea by Modulating Intestinal Permeability and
Changing the Bacterial Communities in Weaned Piglets. J Nutr (2015)
12:2774–80. doi: 10.3945/jn.115.217406
17. Fang C, Sun H, Wu J, Niu H, Feng J. Effects of Sodium Butyrate on Growth
Performance, Haematological and Immunological Characteristics of
Weanling Piglets. JAnimPhysiolAnimNutr(2014) 98:680–5. doi:
10.1111/jpn.12122
18. Nakajima A, Kaga N, Nakanishi Y, Ohno H, Miyamoto J, Kimura I, et al.
Maternal High Fiber Diet During Pregnancy and Lactation Influences
Regulatory T Cell Differentiation in Offspring in Mice. J Immunol (2017)
199:3516–24. doi: 10.4049/jimmunol.1700248
19. Gu XL, Song ZH, Li H, Wu S, Fan ZY. Effects of Dietary
Isomaltooligosaccharide and Bacillus Spp. Supplementation During
Perinatal Period on Lactational Performance, Blood Metabolites, and
Milk Composition of Sows. J Sci Food Agric (2019) 99:5646–6653. doi:
10.1002/jsfa.9821
20. Wan J, Xu Q, He J. Maternal Chitosan Oligosaccharide Supplementation
During Late Gestation and Lactation Affects Offspring Growth. Ital J Anim
Sci (2018) 17:994–1000. doi: 10.1080/1828051X.2018.1435313
21. Shang Q, Liu S, Liu H, Mahfuz S, Piao X. Impact of Sugar Beet Pulp and
Wheat Bran on Serum Biochemical Profile, Inflammatory Responses and
Gut Microbiota in Sows During Late Gestation and Lactation. J Anim Sci
Biotechnol (2021) 12:1–14. doi: 10.1186/s40104-021-00573-3
22. Heim, O'Doherty, O'Shea. Maternal Supplementation of Seaweed-Derived
Polysaccharides Improves Intestinal Health and Immune Status of Suckling
Piglets. J Nutr Sci (2015) 4:e27. doi: 10.1017/jns.2015.16
23. Leonard TSSG, Bahar B, Lynch BP, O'Doherty JV. Effect of Maternal Fish Oil
and Seaweed Extract Supplementation on Colostrum and Milk
Composition, Humoral Immune Response, and Performance of Suckled
Piglets1. J Anim Sci (2010) 88:2988–97. doi: 10.2527/jas.2009-2764
24. Chuanshang C, Hongkui W, Chuanhui X, Xiaowei X, Siwen J, Jian P.
Maternal Soluble Fiber Diet During Pregnancy Changes the Intestinal
Microbiota, Improves Growth Performance, and Reduces Intestinal
Permeability in Piglets. Appl Environ Microbiol (2018) 84:e01047–18. doi:
10.1128/AEM.01047-18
25. Duan X, Chen D, Zheng P, Tian G, Wang J, Mao X, et al. Effects of Dietary
Mannan Oligosaccharide Supplementation on Performance and Immune
Response of Sows and Their Offspring. Anim Feed Sci Technol (2016)
218:17–25. doi: 10.1016/j.anifeedsci.2016.05.002
26. Ho T, Jahan M, Haque Z, Kracht S, Wang B. Maternal Chitosan
Oligosaccharide Intervention Optimizes the Production Performance and
Health Status of Gilts and Their Offspring. Anim Nutr (2020) 6:134–42. doi:
10.1016/j.aninu.2020.02.001
27. Wu Y, Pan L, Shang Q, Ma X, Long S, Xu Y, et al. Effects of Isomalto-
Oligosaccharides as Potential Prebiotics on Performance, Immune Function
and Gut Microbiota in Weaned Pigs. Anim Feed Sci Technol (2017) 230:126–
35. doi: 10.1016/j.anifeedsci.2017.05.013
28. Patel S, Goyal A. Functional Oligosaccharides: Production, Properties and
Applications. World J Microbiol Biotechnol (2011) 27:1119–28. doi: 10.1007/
s11274-010-0558-5
29. Zhang L, Wang J, Liao S, Duan Y, Gu X, Li H, et al. Effects of Dietary
Isomaltooligosaccharide Levels on the Gut Microbiota, Immune Function of
Sows and the Diarrhea Rate of Their Offspring. Front Microbiol (2020)
11:3425. doi: 10.3389/fmicb.2020.588986
30. Li J, Tan B, Mai K. Dietary Probiotic Bacillus OJ and Isomaltooligosaccharides
Influence the Intestine Microbial Populations, Immune Responses and Resistance
toWhiteSpotSyndromeVirusinShrimp (Litopenaeus Vannamei). Aquaculture
(2009) 291:35–40. doi: 10.1016/j.aquaculture.2009.03.005
31. Yen MT, Yang JH, Mau JL. Antioxidant Properties of Chitosan From Crab
Shells. Carbohydr Polym (2008) 74:840–4. doi: 10.1016/j.carbpol.2008.05.003
32.MaP,LiuHT,WeiP,XuQS,BaiXF,DuYG,etal.Chitosan
Oligosaccharides Inhibit LPS-Induced Over-Expression of IL-6 and TNF-
ain RAW264. 7 Macrophage Cells Through Blockade of Mitogen-Activated
Protein Kinase (MAPK) and PI3K/Akt Signaling Pathways. Carbohydr
Polym (2011) 84:1391–8. doi: 10.1016/j.carbpol.2011.01.045
33. Duan X, Tian G, Chen D, Yang J, Zhang L, Li B, et al. Effects of Diet Chitosan
Oligosaccharide on Performance and Immune Response of Sows and Their
Offspring. Livest Sci (2020) 239:104114. doi: 10.1016/j.livsci.2020.104114
34. Gomez B, GullonB,Ya
ñez R, Schols H, Alonso JL. Prebiotic Potential of
Pectins and Pectic Oligosaccharides Derived From Lemon Peel Wastes and
Sugar Beet Pulp: A Comparative Evaluation. J Funct Foods (2016) 20:108–21.
doi: 10.1016/j.jff.2015.10.029
35. Tan C, Wei H, Ao J, Long G, Jian P. Inclusion of Konjac Flour in the
Gestation Diet Changes the Gut Microbiota, Alleviates Oxidative Stress, and
Improves Insulin Sensitivity in Sows. Appl Environ Microbiol (2016)
82:5899. doi: 10.1128/AEM.01374-16
36. Gahan DA, Lynch MB, Callan JJ, O’Sullivan J, O’Doherty J. Performance of
Weanling Piglets Offered Low-, Medium- or High-Lactose Diets
Supplemented With a Seaweed Extract From Laminaria Spp. Animal
(2009) 3:24–31. doi: 10.1017/S1751731108003017
37. Pluske JR, Hampson DJ, Williams IH. Factors Influencing the Structure and
Function of the Small Intestine in the Weaned Pig: A Review. Livest Prod Sci
(1997) 51:215–36. doi: 10.1016/S0301-6226(97)00057-2
38. Leonard SG, Sweeney T, Bahar B, O'Doherty JV. Effect of Maternal Seaweed
Extract Supplementation on Suckling Piglet Growth, Humoral Immunity,
Selected Microflora, and Immune Response After an Ex Vivo
Lipopolysaccharide Challenge. J Anim Sci (2012) 90:505–14. doi: 10.2527/
jas.2010-3243
39. Sweeney T, Collins C, Reilly P, Pierce K, Ryan M, O'doherty J. Effect of
Purified b-Glucans Derived From Laminaria Digitata, Laminaria
Hyperborea and Saccharomyces Cerevisiae on Piglet Performance,
Selected Bacterial Populations, Volatile Fatty Acids and Pro-Inflammatory
Cytokines in the Gastrointestinal Tract of Pigs. Br J Nutr (2012) 108:1226–
34. doi: 10.1017/S0007114511006751
40. Fuongfuchat A, Seetapan N, Makmoon T, Pongjaruwat W, Methacanon P,
Gamonpilas C. Linear and Non-Linear Viscoelastic Behaviors of Crosslinked
Tapioca Starch/Polysaccharide Systems. J Food Eng (2012) 109:571–8. doi:
10.1016/j.jfoodeng.2011.10.022
41. Spring P, Wenk C, Connolly A, Kiers A. A Review of 733 Published Trials on
Bio-Mos®, a Mannan Oligosaccharide, and Actigen®, a Second Generation
Mannose Rich Fraction, on Farm and Companion Animals. J Appl Anim
Nutr (2015) 3:e8. doi: 10.1017/jan.2015.6
42. Duan X, Tian G, Chen D, Huang L, Yu B. Mannan Oligosaccharide
Supplementation in Diets of Sow and (or) Their Offspring Improved
Immunity and Regulated Intestinal Bacteria in Piglet. J Anim Sci (2019)
97:4548–56. doi: 10.1093/jas/skz318
43. Jarrett S, Ashworth CJ. The Role of Dietary Fibre in Pig Production, With a
Particular Emphasis on Reproduction. J Anim Sci Biotechnol (2018) 9:1–11.
doi: 10.1186/s40104-018-0270-0
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 75852511
44. Onipe OO, Jideani AI, Beswa D. Composition and Functionality of Wheat
Bran and its Application in Some Cereal Food Products. Int J Food Sci
Technol (2015) 50:2509–18. doi: 10.1111/ijfs.12935
45. Leblois J, Zhang Y, Wavreille J, Uerlings J, Everaert N. Effects of Wheat Bran
Applied to Maternal Diet on the Intestinal Architecture and Immune Gene
Expression in Suckling Piglets. Animals (2020) 10:2051. doi: 10.3390/
ani10112051
46. Agyekum AK, Nyachoti CM. Nutritional and Metabolic Consequences of
Feeding High-Fiber Diets to Swine: A Review. Engineering (2017) 3:716–25.
doi: 10.1016/J.ENG.2017.03.010
47. Wenk C. The Role of Dietary Fibre in the Digestive Physiology of the Pig.
Anim Feed Sci Technol (2001) 90:21–33. doi: 10.1016/S0377-8401(01)00194-8
48. Rosero DS, Boyd RD, Odle J, Heugten EV. Optimizing Dietary Lipid Use to
Improve Essential Fatty Acid Status and Reproductive Performance of the
Modern Lactating Sow: A Review. J Anim Sci Biotechnol (2016) 7:1–18.
49. Tilton LS, Miller SP. Addition of Fat to the Diets of Lactating Sows: I. Effects
on Milk Production and Composition and Carcass Composition of the Litter
at Weaning. J Anim Sci (1999) 77:2491–500. doi: 10.2527/1999.7792491x
50. Jin C, Fang Z, Lin Y, Che L, Wu C, Xu S, et al. Influence of Dietary Fat Source
on Sow and Litter Performance, Colostrum and Milk Fatty Acid Profile in
Late Gestation and Lactation. Anim Sci J (2017) 88:1768–78. doi: 10.1111/
asj.12836
51. Liu Y. Fatty Acids, Inflammation and Intestinal Health in Pigs. J Anim Sci
Biotechnol (2015) 6(1):321–9. doi: 10.1186/s40104-015-0040-1
52. Che L, Liu P, Yang Z, Che L, Hu L, Qin L, et al. Maternal High Fat Intake
Affects the Development and Transcriptional Profile of Fetal Intestine in
Late Gestation Using Pig Model. Lipids Health Dis (2016) 15:90. doi:
10.1186/s12944-016-0261-0
53. Shen Y, Wan H, Zhu J, Fang Z, Che L, Xu S, et al. Fish Oil and Olive Oil
Supplementation in Late Pregnancy and Lactation Differentially Affect
Oxidative Stress and Inflammation in Sows and Piglets. Lipids (2015)
50:647–58. doi: 10.1007/s11745-015-4024-x
54. Jones G, Edwards S, Sinclair A, Gebbie F, Rooke J, Jagger S, et al. The Effect
of Maize Starch or Soya-Bean Oil as Energy Sources in Lactation on Sow and
Piglet Performance in Association With Sow Metabolic State Around Peak
Lactation. Anim Sci (2002) 75:57–66. doi: 10.1017/S1357729800052838
55. Knazek RA, Liu SC, Bodwin JS, Vonderhaar BK. Requirement of Essential
Fatty Acids in the Diet for Development of the Mouse Mammary Gland.
J Natl Cancer Inst (1980) 64:377–82. doi: 10.1093/jnci/64.2.377
56. Peng X, Yan C, Hu L, Liu Y, Xu Q, Wang R, et al. Effects of Fat
Supplementation During Gestation on Reproductive Performance, Milk
Composition of Sows and Intestinal Development of Their Offspring.
Animals (Basel) (2019) 9:125. doi: 10.3390/ani9040125
57. Calder PC. Polyunsaturated Fatty Acids, Inflammation, and Immunity.
Lipids (2001) 36:1007–24. doi: 10.1007/s11745-001-0812-7
58. Luo J, Huang F, Xiao C, Chen W, Jiang S, Peng J. Effect of Dietary
Supplementation of Fish Oil for Lactating Sows and Weaned Piglets on
Piglet Th Polarization. Livest Sci (2009) 126:286–91. doi: 10.1016/
j.livsci.2009.08.002
59. Schellingerhout A.B. Influence of Dietary (n-3) Polyunsaturated Acids, in
the Form of Either Linseed or Fish Oil, on Growth Performance, Small
Intestinal Morphology and Essential Fatty Acid Status of Weanling Piglets
PhD Dissertation. Netherlands: University of Utretch (2002).
60. Rooke J, Shanks M, Edwards S. Effect of Offering Maize, Linseed or Tuna
Oils Throughout Pregnancy and Lactation on Sow and Piglet Tissue
Composition and Piglet Performance. Anim Sci (2000) 71:289–99. doi:
10.1017/S1357729800055132
61. Gaines A, Carroll J, Yi G, Allee G, Zannelli M. Effect of Menhaden Fish Oil
Supplementation and Lipopolysaccharide Exposure on Nursery Pigs: II.
Effects on the Immune Axis When Fed Simple or Complex Diets Containing
No Spray-Dried Plasma. Domest Anim Endocrinol (2003) 24:353–65. doi:
10.1016/S0739-7240(03)00016-X
62. Jin C, Fang Z, Lin Y, Che L, Wu C, Xu S, et al. Influence of Dietary Fat Source
on Sow and Litter Performance, Colostrum and Milk Fatty Acid Profile in
Late Gestation and Lactation. Anim Sci J (2017) 88:1768–78. doi: 10.1111/
asj.12836
63. Mitre R, Etienne M, Martinais S, Salmon H, Allaume P, Legrand P, et al.
Humoral Defence Improvement and Haematopoiesis Stimulation in Sows
and Offspring by Oral Supply of Shark-Liver Oil to Mothers During
Gestation and Lactation. Br J Nutr (2005) 94:753–62. doi: 10.1079/
BJN20051569
64. Luo W, Luo Z, Xu X, Zhao S, Li S, Sho T, et al. The Effect of Maternal Diet
With Fish Oil on Oxidative Stress and Inflammatory Response in Sow and
New-Born Piglets. Oxid Med Cell Longev (2019) 2019:6765803. doi: 10.1155/
2019/6765803
65. Luo J, Huang F, Xiao C, Fang Z, Peng J, Jiang S. Responses of Growth
Performance and Proinflammatory Cytokines Expression to Fish Oil
Supplementation in Lactation Sows’and/or Weaned Piglets’Diets. BioMed
Res Int (2013) 2013:905918. doi: 10.1155/2013/905918
66. Shen Y, Wan H, Zhu J, Fang Z, Che L, Xu S, et al. Fish Oil and Olive Oil
Supplementation in Late Pregnancy and Lactation Differentially Affect
Oxidative Stress and Inflammation in Sows and Piglets. Lipids (2015)
50:647–58. doi: 10.1007/s11745-015-4024-x
67. Tanghe S, Missotten J, Raes K, De Smet S. The Effect of Different
Concentrations of Linseed Oil or Fish Oil in the Maternal Diet on the
Fatty Acid Composition and Oxidative Status of Sows and Piglets. J Anim
Physiol Anim Nutr (2015) 99:938–49. doi: 10.1111/jpn.12243
68. Cools A, Maes D, Papadopoulos G, Vandermeiren JA, Meyer E, Demeyere
K, et al. Dose-Response Effect of Fish Oil Substitution in Parturition Feed on
Erythrocyte Membrane Characteristics and Sow Performance. JAnim
Physiol Anim Nutr (2011) 95:125–36. doi: 10.1111/j.1439-0396.2010.01119.x
69. Chen J, Xu Q, Li Y, Tang Z, Sun W, Zhang X, et al. Comparative Effects of
Dietary Supplementations With Sodium Butyrate, Medium-Chain Fatty
Acids, and N-3 Polyunsaturated Fatty Acids in Late Pregnancy and
Lactation on the Reproductive Performance of Sows and Growth
Performance of Suckling Piglets. JAnimSci(2019) 97:4256–67. doi:
10.1093/jas/skz284
70. Lauridsen C, Stagsted J, Jensen SK. N–6 and N–3 Fatty Acids Ratio and
Vitamin E in Porcine Maternal Diet Influence the Antioxidant Status and
Immune Cell Eicosanoid Response in the Progeny. Prostaglandins Other
Lipid Mediat (2007) 84:66–78. doi: 10.1016/j.prostaglandins.2007.04.003
71. Yao W, Li J, jun Wang J, Zhou W, Wang Q, Zhu R, et al. Effects of Dietary
Ratio of N-6 to N-3 Polyunsaturated Fatty Acids on Immunoglobulins,
Cytokines, Fatty Acid Composition, and Performance of Lactating Sows and
Suckling Piglets. J Anim Sci Biotechnol (2012) 3:1–8. doi: 10.1186/2049-
1891-3-43
72. Mataix J, Battino M, Ramirez-Tortosa MC, Bertoli E, Quiles JL. Virgin Olive
Oil: A Key Healthy Component of the Mediterranean Diet. Mediterr J Nutr
Metab (2008) 1:69. doi: 10.3233/s12349-008-0012-5
73. Cheng Z. Antimicrobial, Antioxidant and Anti-Inflammatory Phenolic
Activities in Extra Virgin Olive Oil. Food Sci Technol (2012) 23:129–35.
doi: 10.1016/j.copbio.2011.09.006
74. Diep TA, Madsen AN, Holst B, Kristiansen MM, Wellner N, Hansen SH,
et al. Dietary Fat Decreases Intestinal Levels of the Anorectic Lipids Through
a Fat Sensor. FASEB J (2011) 25:765–74. doi: 10.1096/fj.10-166595
75. Cheng C, Wu X, Zhang X, Zhang X, Peng J. Obesity of Sows at Late
Pregnancy Aggravates Metabolic Disorder of Perinatal Sows and Affects
Performance and Intestinal Health of Piglets. Animals (2020) 10:49. doi:
10.3390/ani10010049
76. Zhou Y, Xu T, Cai A, Wu Y, Wei H, Jiang S, et al. Excessive Backfat of Sows
at 109 D of Gestation Induces Lipotoxic Placental Environment and is
Associated With Declining Reproductive Performance. J Anim Sci (2018)
96:250–7. doi: 10.1093/jas/skx041
77. Wilson RM, Messaoudi I. The Impact of Maternal Obesity During
Pregnancy on Offspring Immunity. Mol Cell Endocrinol (2015) 418:134–
42. doi: 10.1016/j.mce.2015.07.028
78. Jarvie E, Hauguel-de-Mouzon S, Nelson SM, Sattar N, Catalano PM,
Freeman DJ. Lipotoxicity in Obese Pregnancy and its Potential Role in
Adverse Pregnancy Outcome and Obesity in the Offspring. Clin Sci (2010)
119:123–9. doi: 10.1042/CS20090640
79. Saben J, Lindsey F, Zhong Y, Thakali K, Badger TM, Andres A, et al.
Maternal Obesity is Associated With a Lipotoxic Placental Environment.
Placenta (2014) 35:171–7. doi: 10.1016/j.placenta.2014.01.003
80. Challier J, Basu S, Bintein T, Minium J, Hotmire K, Catalano P, et al. Obesity
in Pregnancy Stimulates Macrophage Accumulation and Inflammation in
the Placenta. Placenta (2008) 29:274–81. doi: 10.1016/j.placenta.2007.12.010
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 75852512
81. Oliva K, Barker G, Riley C, Bailey MJ, Permezel M, Rice GE, et al. The Effect
of Pre-Existing Maternal Obesity on the Placental Proteome: Two-
Dimensional Difference Gel Electrophoresis Coupled With Mass
Spectrometry. J Mol Endocrinol (2012) 48:139–49. doi: 10.1530/JME-11-
0123
82. Zhou Y, Xu T, Wu Y, Wei H, Peng J. Oxidative Stress and Inflammation in
Sows With Excess Backfat: Up-Regulated Cytokine Expression and Elevated
Oxidative Stress Biomarkers in Placenta. Animals (2019) 9:796. doi: 10.3390/
ani9100796
83. Xue Y, Wang H, Du M, Zhu M-J. Maternal Obesity Induces Gut
Inflammation and Impairs Gut Epithelial Barrier Function in Nonobese
Diabetic Mice. J Nutr Biochem (2014) 25:758–64. doi: 10.1016/j.jnutbio.
2014.03.009
84. Innis SM, Dai C, Wu X, Buchan AM, Jacobson K. Perinatal Lipid Nutrition
Alters Early Intestinal Development and Programs the Response to
Experimental Colitis in Young Adult Rats. Am J Physiol Gastrointest Liver
Physiol (2010) 299:G1376–85. doi: 10.1152/ajpgi.00258.2010
85. Tan C, Wei H, Ao J, Long G, Peng J. Inclusion of Konjac Flour in the
Gestation Diet Changes the Gut Microbiota, Alleviates Oxidative Stress, and
Improves Insulin Sensitivity in Sows. Appl Environ Microbiol (2016)
82:5899–909. doi: 10.1128/AEM.01374-16
86. Pereira AC, Martel F. Oxidative Stress in Pregnancy and Fertility
Pathologies. Cell Biol Toxicol (2014) 30:301–12. doi: 10.1007/s10565-014-
9285-2
87. Casanueva E, Viteri FE. Iron and Oxidative Stress in Pregnancy. J Nutr
(2003) 133:1700S–8S. doi: 10.1093/jn/133.5.1700S
88. Chaudhari N, Talwar P, Parimisetty A, Lefebvre d’Hellencourt C, Ravanan
P. A Molecular Web: Endoplasmic Reticulum Stress, Inflammation, and
Oxidative Stress. Front Cell Neurosci (2014) 8:213. doi: 10.3389/
fncel.2014.00213
89. Bunders MJ, van Hamme JL, Jansen MH, Boer K, Kootstra NA, Kuijpers
TW. Fetal Exposure to HIV-1 Alters Chemokine Receptor Expression by
CD4+ T Cells and Increases Susceptibility to HIV-1. Sci Rep (2014) 4:1–8.
doi: 10.1038/srep06690
90. Hong M, Sandalova E, Low D, Gehring AJ, Fieni S, Amadei B, et al. Trained
Immunity in Newborn Infants of HBV-Infected Mothers. Nat Commun
(2015) 6:1–12. doi: 10.1038/ncomms7588
91. Wang X, Jiang G, Kebreab E, Yu Q, Li J, Zhang X, et al. Effects of Dietary
Grape Seed Polyphenols Supplementation During Late Gestation and
Lactation on Antioxidant Status in Serum and Immunoglobulin Content
in Colostrum of Multiparous Sows. J Anim Sci (2019) 97:2515–23. doi:
10.1093/jas/skz128
92. Chen J, Chen J, Zhang Y, Lv Y, Qiao H, Tian M, et al. Effects of Maternal
Supplementation With Fully Oxidised Beta-Carotene on the Reproductive
Performance and Immune Response of Sows, as Well as the Growth
Performance of Nursing Piglets. Br J Nutr (2021) 125:62–70. doi: 10.1017/
S0007114520002652
93. Xiong Y, Jiaman P, Liangkang L, Yujun W, Shimeng H, Zhi F, et al. Effects of
Maternal Supplementation With Rare Earth Elements During Late Gestation
and Lactation on Performances, Health, and Fecal Microbiota of the Sows
and Their Offspring. Animals (2019) 9:738. doi: 10.3390/ani9100738
94. Lin W, Xiaodong X, Ge S, Baoming S, Anshan S. High Concentration of
Vitamin E Supplementation in Sow Diet During the Last Week of Gestation
and Lactation Affects the Immunological Variables and Antioxidative
Parameters in Piglets. JDairyRes(2017) 84:8–13. doi: 10.1017/
S0022029916000650
95. Xu M, Che L, Gao K, Wang L, Yang X, Wen X, et al. Effects of Dietary
Taurine Supplementation to Gilts During Late Gestation and Lactation on
Offspring Growth and Oxidative Stress. Animals (Basel) (2019) 9:220. doi:
10.3390/ani9050220
96. Xu SY, Shi JK, Shi XL, Dong YP, Shen YP. Effects of Dietary
Supplementation With Lysozyme During Late Gestation and Lactation
Stage on the Performance of Sows and Their Offspring. J Anim Sci (2018)
96:4768–79. doi: 10.1093/jas/sky338
97. Gao L, Xie C, Liang X, Li Z, Yin Y. Yeast-Based Nucleotide Supplementation
in Mother Sows Modifies the Intestinal Barrier Function and Immune
Response of Neonatal Pigs. Anim Nutr (2021) 7:84–93. doi: 10.1016/
j.aninu.2020.06.009
98. Brennan LA, Morris GM, Wasson GR, Hannigan BM, Barnett YA. The
Effect of Vitamin C or Vitamin E Supplementation on Basal and H2O2-
Induced DNA Damage in Human Lymphocytes. Br J Nutr (2000) 84:195–
202. doi: 10.1017/S0007114500001422
99. Hidiroglou M, Batra T, Farnworth E, Markham F. Effect of Vitamin E
Supplementation on Immune Status and a-Tocopherol in Plasma of Piglets.
Reprod Nutr Dev (1995) 35:443–50. doi: 10.1051/rnd:19950409
100. Hayek MG, Mitchell GE, Harmon RJ, Stahly TS, Cromwell GL, Tucker RE,
et al. Porcine Immunoglobulin Transfer After Prepartum Treatment With
Selenium or Vitamin E. J Anim Sci (1989) 67:1299–306. doi: 10.2527/
jas1989.6751299x
101. Zhang H, Tsao R. Dietary Polyphenols, Oxidative Stress and Antioxidant and
Anti-Inflammatory Effects. Curr Opin Food Sci (2016) 8:33–42. doi: 10.1016/
j.cofs.2016.02.002
102. Han X, Piao X, Zhang H, Li P, Yi J, Zhang Q, et al. Forsythia Suspensa Extract
has the Potential to Substitute Antibiotic in Broiler Chicken. Asian-Australas
J Anim Sci (2012) 25:569. doi: 10.5713/ajas.2011.11425
103. Zhao P, Piao X, Zeng Z, Li P, Xu X, Wang H. Effect of Forsythia Suspensa
Extract and Chito-Oligosaccharide Alone or in Combination on
Performance, Intestinal Barrier Function, Antioxidant Capacity and
Immune Characteristics of Weaned Piglets. Anim Sci J (2017) 88:854–62.
doi: 10.1111/asj.12656
104. Long S, Wu D, He T, Piao X. Dietary Supplementation With Forsythia
Suspensa Extract During Late Gestation Improves Reproductive
Performance, Colostrum Composition, Antioxidant Status,
Immunoglobulin, and Inflammatory Cytokines in Sows and Newborn
Piglets. Anim Feed Sci Technol (2021) 271:114700. doi: 10.1016/
j.anifeedsci.2020.114700
105. Wang Y, Zhao H, Lin C, Ren J, Zhang S. Forsythiaside A Exhibits Anti-
Inflammatory Effects in LPS-Stimulated BV2 Microglia Cells Through
Activation of Nrf2/HO-1 Signaling Pathway. Neurochem Res (2016)
41:659–65. doi: 10.1007/s11064-015-1731-x
106. Phan PV, Sohrabi A, Polotsky A, Hungerford DS, Lindmark L, Frondoza CG.
Ginger Extract Components Suppress Induction of Chemokine Expression
in Human Synoviocytes. J Altern Complement Med (2005) 11:149–54. doi:
10.1089/acm.2005.11.149
107. Lee SD, Kim JH, Jung HJ, Kim YH, Kim IC, Kim SB, et al. The Effect of
Ginger Extracts on the Antioxidant Capacity and IgG Concentrations in the
Colostrum and Plasma of Neo-Born Piglets and Sows. Livest Sci (2013)
154:117–22. doi: 10.1016/j.livsci.2013.02.001
108. Meng Q, Guo T, Li G, Sun S, He S, Cheng B, et al. Dietary Resveratrol
Improves Antioxidant Status of Sows and Piglets and Regulates Antioxidant
Gene Expression in Placenta by Keap1-Nrf2 Pathway and Sirt1. J Anim Sci
Biotechnol (2018) 9:1–13. doi: 10.1186/s40104-018-0248-y
109. Meng Q, Sun S, He S, Shi B, Shan A, Cheng B. Maternal Dietary Resveratrol
Alleviates Weaning-Associated Intestinal Inflammation and Diarrhea in
Porcine Offspring by Altering Intestinal Gene Expression and Microbiota.
Food Funct (2019) 10:5626–43. doi: 10.1039/C9FO00637K
110. Short SP, Pilat JM, Williams CS. Roles for Selenium and Selenoprotein P in
the Development, Progression, and Prevention of Intestinal Disease. Free
Radical Biol Med (2018) 127:26–35. doi: 10.1016/j.freeradbiomed.2018.
05.066
111. Avery JC, Hoffmann PR. Selenium, Selenoproteins, and Immunity. Nutrients
(2018) 10:1203. doi: 10.3390/nu10091203
112. Briens M, Mercier Y, Rouffineau F, Mercerand F, Geraert P-A. 2-Hydroxy-4-
Methylselenobutanoic Acid Induces Additional Tissue Selenium Enrichment
in Broiler Chickens Compared With Other Selenium Sources. Poult Sci
(2014) 93:85–93. doi: 10.3382/ps.2013-03182
113. Couloigner F, Jlali M, Briens M, Rouffineau F, Geraert P-A, Mercier Y.
Selenium Deposition Kinetics of Different Selenium Sources in Muscle and
Feathers of Broilers. Poult Sci (2015) 94:2708–14. doi: 10.3382/ps/pev282
114. Mou D, Ding D, Yan H, Qin B, Dong Y, Li Z, et al. Maternal
Supplementation of Organic Selenium During Gestation Improves Sows
and Offspring Antioxidant Capacity and Inflammatory Status and Promotes
Embryo Survival. Food Funct (2020) 11:7748–61. doi: 10.1039/D0FO00832J
115. Ding D, Mou D, Zhao L, Jiang X, Che L, Fang Z, et al. Maternal Organic
Selenium Supplementation Alleviates LPS Induced Inflammation,
Autophagy and ER Stress in the Thymus and Spleen of Offspring Piglets
Li et al. Maternal Nutrition Regulates Neonatal Infection
Frontiers in Immunology | www.frontiersin.org January 2022 | Volume 12 | Article 75852513
by Improving the Expression of Selenoproteins. Food Funct (2021)
12:11214–28. doi: 10.1039/D1FO01653A
116. Lourenco R, Camilo ME. Taurine: A Conditionally Essential Amino Acid in
Humans? An Overview in Health and Disease. Nutr Hosp (2002) 17:262.
117. Winiarska K, Szymanski K, Gorniak P, Dudziak M, Bryla J. Hypoglycaemic,
Antioxidative and Nephroprotective Effects of Taurine in Alloxan Diabetic
Rabbits. Biochimie (2009) 91:261–70. doi: 10.1016/j.biochi.2008.09.006
118. SukhotnikI, Aranovich I, ShaharYB, Bitterman N, PollakY. Effectof Taurine on
Intestinal Recovery Following Intestinal Ischemia-Reperfusion Injury in a Rat.
Pediatr Surg Int (2016) 32:161–8. doi: 10.1007/s00383-015-3828-3
119. Bruce DW, Hietbrink BE, Dubois KP. The Acute Mammalian Toxicity of
Rare Earth Nitrates and Oxides. Toxicol Appl Pharmacol (1963) 5:750–9. doi:
10.1016/0041-008X(63)90067-X
120. Kraatz M, Taras D, Männer K, Simon O. Weaning Pig Performance and
Faecal Microbiota With and Without in-Feed Addition of Rare Earth
Elements. J Anim Physiol Anim Nutr (2010) 90:361–8. doi: 10.1111/j.1439-
0396.2005.00594.x
121. Fei G, Guo X, Xie A, Yuan LL, WangY. The SuppressiveEffectsof Lanthanum on
the Production of Inflammatory Mediators in Mice Challenged by LPS. Biol
Trace Elem Res (2011) 142:693–703. doi: 10.100 7/s12011-010-8792-0
122. Masschalck B, Michiels CW. Antimicrobial Properties of Lysozyme in
Relation to Foodborne Vegetative Bacteria. Crit Rev Microbiol (2003)
29:191–214. doi: 10.1080/713610448
123. Oliver WT, Wells JE. Lysozyme as an Alternative to Antibiotics Improves
Growth Performance and Small Intestinal Morphology in Nursery Pigs.
J Anim Sci (2013) 91:191–214. doi: 10.2527/jas.2012-5782
124. Cooper CA, Garas K, Maga EA, Murray JD, Riccardo M. Consuming
Transgenic Goats’Milk Containing the Antimicrobial Protein Lysozyme
Helps Resolve Diarrhea in Young Pigs. PloS One (2013) 8:e58409. doi:
10.1371/journal.pone.0058409
125. Nyachoti CM, Kiarie E, Bhandari SK, Zhang G, Krause DO. Weaned Pig
Responses to Escherichia Coli K88 Oral Challenge When Receiving a
Lysozyme Supplement. J Anim Sci (2012) 90:252. doi: 10.2527/jas.2010-3596
126. Wells JE, Berry ED, Kalchayanand N, Rempel LA, Kim M, Oliver WT. Effect
of Lysozyme or Antibiotics on Faecal Zoonotic Pathogens in Nursery Pigs.
J Appl Microbiol (2015) 118:1489–97. doi: 10.1111/jam.12803
127. Uauy R, StringelG, Thomas R, Quan R. Effect of Dietary Nucleosides on Growth
and Maturation of the Developing Gut in the Rat. J Pediatr Gastroenterol Nutr
(1990) 10:497–503. doi: 10.1097/00005176-199005000-00014
128. Hess JR, Greenberg NA. The Role of Nucleotides in the Immune and
Gastrointestinal Systems: Potential Clinical Applications. Nutr Clin Pract
(2012) 27:281. doi: 10.1177/0884533611434933
129. Hung I. The Effect of Dietary Nucleotides in Sow and Nursery Piglet Diets on
Reproduction, Growth, and Immune Response (2015). Dissertations &
Theses - Gradworks University of Kentucky.
130. Pettigrew J. Reduced Use of Antibiotic Growth Promoters in Diets Fed to
Weanling Pigs: Dietary Tools, Part 1. Anim Biotechnol (2006) 17:207–15. doi:
10.1080/10495390600956946
131. Bosi P, Casini L, Finamore A, Cremokolini C, Merialdi G, Trevisi P, et al.
Spray-Dried Plasma Improves Growth Performance and Reduces
Inflammatory Status of Weaned Pigs Challenged With Enterotoxigenic
Escherichia Coli K88. J Anim Sci (2004) 82:1764–72. doi: 10.2527/2004.
8261764x
132. Kim K, Kim B, Kyoung H, Liu Y, Campbell JM, Song M, et al. Dietary Spray-
Dried Plasma Supplementation in Late-Gestation and Lactation Enhanced
Productive Performance and Immune Responses of Lactating Sows and
Their Litters. J Anim Sci Technol (2021) 63:1076. doi: 10.5187/jast.2021.e83
133. Poulsen HD, Danielsen V, Nielsen TK, Wolstrup C. Excessive Dietary
Selenium to Primiparous Sows and Their Offspring. Acta Vet Scand (1989)
30:371–8. doi: 10.1186/BF03548012
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