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Review

Programming Effects of Maternal Nutrition on Intestinal Development and Microorganisms of Offspring: A Review on Pigs

by
Liang Hu
1,2,*,
Fali Wu
1 and
Lianqiang Che
1,*
1
Key Laboratory for Animal Disease-Resistant Nutrition of the Ministry of Education of China, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
2
College of Food Science, Sichuan Agricultural University, Ya’an 625014, China
*
Authors to whom correspondence should be addressed.
Microorganisms 2025, 13(5), 1151; https://doi.org/10.3390/microorganisms13051151
Submission received: 10 March 2025 / Revised: 5 May 2025 / Accepted: 15 May 2025 / Published: 17 May 2025
(This article belongs to the Section Microbiomes)
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Abstract

Intestinal development is a critical determinant of growth and overall health in pigs. Accumulating evidence underscores the significant influence of intestinal microbiota on essential physiological functions and systemic health. Dietary nutrients play a pivotal role in regulating both intestinal development and the composition of intestinal microbiota. Optimal early-life nutrient provision ensures proper intestinal growth and functional maturation, with maternal nutrition emerging as a key factor shaping intestinal development during fetal and neonatal stages. This review synthesizes recent studies on maternal nutrient intake—encompassing protein, energy, carbohydrates, minerals, vitamins, probiotics, and prebiotics—and their effects on intestinal growth and health of offspring. Emerging multi-omics evidence has revealed that gestational and lactational nutrition dynamically coordinates offspring intestinal development through vertical microbial transmission and epigenetic mechanisms, such as DNA methylation and histone acetylation. These processes further regulate intestinal barrier maturation, mucosal immunity, and enteroendocrine signaling. Collectively, this review emphasizes that enhancing maternal nutrition can promote postnatal growth by enhancing intestinal development and early microbial colonization in piglets. Further research is crucial to determining the optimal nutritional strategies during the perinatal period.

1. Introduction

The gastrointestinal tract (GIT) is widely recognized for its central role in digestion and absorption, and it constitutes one of the largest immunological organs in the body [1,2]. Additionally, the GIT functions as a critical barrier between the internal body and the external environment [3]. In pig production, intestinal health in piglets is a significant contributor to economic losses. Weaning is considered a pivotal event in intestinal development, often associated with severe enteric infections and multiple stress factors, including nutritional and environmental stressors [4,5]. Consequently, nutritional strategies for mitigating the adverse effects of weaning stress have become a major focus in the pig industry. In recent decades, extensive research has been conducted on intestinal development and health in weaning pigs, particularly in response to nutritional, psychological, and environmental stressors [4]. However, it is crucial to recognize that intestinal development initiates during the first trimester of gestation, underscoring the importance of fetal intestinal development in utero [6].
Adequate maternal nutrient intake during gestation is essential for fetal development and offspring health [7]. Following porcine embryo implantation, fetal growth and development depend on maternal nutrition and the intrauterine environment, which play critical roles in fetal programming and contribute to the differentiation, growth, and development of organs and tissues [8]. Fetal GIT growth is influenced by maternal diet, placental blood supply, and the extent of amniotic fluid swallowing [9]. Thus, nutrition has the potential to modulate GIT growth at various developmental stages during gestation. A growing body of evidence indicates that maternal diet during gestation exerts long-term effects on offspring intestinal development and microbiota composition [10]. Recent studies have demonstrated that enhancing maternal GIT microbiota composition and function can positively influence the development and maturation of the neonatal GIT [11]. A healthier maternal microbiota is likely to transfer beneficial microbes to the neonatal GIT, either through direct colonization or indirect effects on the succession of indigenous intestinal bacteria [12]. Furthermore, a growing a body of evidence is challenging the traditional assumption of a sterile intrauterine environment, suggesting that maternal–fetal microbial transmission occurs during gestation [13].

2. Intestinal Development (From Fetus to Neonates)

Intestinal development is classically categorized into three distinct phases: the prenatal phase, marked by limited luminal stimulation; the neonatal phase (up to 72 h of after birth), which is a transition from the intrauterine to external environment and dependence on colostrum for passive immunity; the suckling phase, associated with milk suckling; and the weaning phase, characterized by adaptation to solid feed [3]. This progression is critical for ensuring adequate nutrient provision to the fetus and neonate. Given the structural and physiological similarities of GIT between pigs and human beings, pigs have been recognized as a valuable model for the investigation of clinical nutrition [6]. Figure 1 illustrates the intestinal development in relation to gestation, birth, and weaning in pigs.
The intestine of the fetal pig initiates development early in gestation, undergoing extensive morphologic and functional changes throughout this period [14]. The process encompasses mucosal morphogenesis, transitioning from a rudimentary tubular structure to one lined with villi, as well as the differentiation of immature epithelium into four major epithelial cell types [15]. By approximately day 40 of gestation, intestinal morphogenesis has progressed to the point where recognizable villi are present, and mRNA for enzymes and cytoskeletal proteins becomes readily detectable [16]. Between day 45 and 110 of gestation, the mass of GIT escalates over 170-fold in a cubic manner, increasing from 2.4% to 6.3% of total body mass. The most rapid GIT mass accretion occurs during the final gestational week despite minimal somatic growth [17]. Notably, during the last trimester of gestation, the increase in mucosal surface area is particularly dramatic, characterized by significant growth of both villi and microvilli. In the weeks preceding parturition, the pig intestine grows more rapidly than does the body overall, with its relative weight increasing by 70–80% in the last three weeks of gestation [18]. During this rapid growth period, the GIT is sensitive to luminal and systemic nutrients both before and after birth. Intestinal growth, along with increasing activity of brush border membrane enzymes and transporters, determines the intestinal capacity for the final stages of hydrolysis and absorption of dietary ingredients [19]. Furthermore, the development of porcine digestive enzymes closely resembles that of human development during the fetal and neonatal periods [6]. The fetal intestinal mass and the activities of brush-border enzymes increase significantly from days 70 to 110 of gestation [17].
After birth, the shift from parenteral to enteral nutrition induces marked architectural, ultrastructural, and functional intestinal remodeling [20]. Notably, neonatal pigs exhibit a 58% increase in total intestinal weight and an 80% surge in mucosal weight during the first 6 h of suckling, accompanied by a 4.6-fold elevation in mucosal DNA content by 24 h postpartum [21]. During the transition to weaning, pigs undergo nutritional, environmental, and psychological stresses, which are accompanied by significant changes in the structure and function of the small intestine. This change includes a reduction in villus height, an increase in crypt depth, a decrease in disaccharidase activity, and alterations in microbiota composition [5,22].
Microorganisms 13 01151 g001
Figure 1. Onset of key development events in the gastrointestinal tract. AEC, apical endocytic complex [6,15].
Figure 1. Onset of key development events in the gastrointestinal tract. AEC, apical endocytic complex [6,15].
Microorganisms 13 01151 g001

3. Immune System and Microorganism Colonization (From Fetus to Neonates)

Immune system ontogeny initiates during gestation and undergoes progressive maturation postnatally. Peripartum nutritional inputs critically influence neonatal immune system development, as fetal immunological programming exerts lasting effects on innate and adaptive immune competence [23]. Gut microbiota serves as a fundamental regulator of immune system activation and protective immunoglobulin induction [24]. Intestinal immune development commences prenatally, achieving functional maturation through postnatal microbial exposure. The sterile GIT of fetuses is rapidly colonized within 12 h after birth, with bacteria detectable throughout the entire GIT [25].
The microbiota present in early life is a significant determinant of immune and metabolic development, with potential long-lasting consequences. During the neonatal phase, microbial colonization drives mucosal barrier maturation and immune functionality in neonates [26]. Intestinal microbiota exhibits marked interindividual variation, modulated by environmental factors including dietary inputs [27]. Studies with germ-free piglets clearly demonstrates that bacteria are vital for the growth and development of the digestive tract [28]. Bacterial communities regulate transcriptional programs governing epithelial turnover and mucin biosynthesis while concurrently shaping mucosal immune system maturation and anti-inflammatory homeostasis [29]. The maternal gut microbiota during pregnancy and breastfeeding plays a critical role in shaping the gut microbiota of the offspring. Typically, maternal microbiota is considered the primary source for establishing the microbial community in newborns. Emerging evidence suggests microbial modulation represents a potential mechanism of developmental programming, whereby maternal dietary patterns may modulate offspring immune trajectories through microbiota-mediated pathways.

4. The Role of Maternal Nutrition in Intestinal Development and Microorganisms

The GIT development is orchestrated through the transition from placental nutrition prenatally to solely enteral nutrition postnatally, with maternal nutritional status emerging as a principal determinant of fetal intestinal development [30].

4.1. Protein and Amino Acids

Dietary proteins and amino acids (AAs) exhibit pleiotropic physiological functions extending beyond canonical roles in protein synthesis, particularly in intestinal homeostasis [31]. During gestation, an adequate supply of AAs critically regulates fetal growth trajectories, contingent on placental AA transport efficacy [32,33]. Maternal protein intake modulates intrauterine growth restriction (IUGR) incidence, small intestinal ontogeny, and systemic inflammatory signaling in offspring [34]. Compromised intestinal maturation may mediate postnatal compensatory growth mechanisms. Tuchscherer et al. (2012) demonstrated that maternal dietary protein–carbohydrate ratios during gestation influence neonatal humoral immunity and adaptive stress responses at weaning, as evidenced by altered cytokine profiles following acute immunogenic challenges in pig offspring [35]. The progeny of protein-restricted dams exhibit higher intestinal cell proliferation and upregulated transcriptional expression of sodium-glucose co-transporter 1 (SGLT1) and peptide transporter 1 (PEPT1) in the duodenum, with persistent immunoreactivity of SGLT1, glucose transporter 2 (GLUT2), and PEPT1 in adulthood mediated by transcriptional and proliferative adaptations [36]. Further, maternal protein restriction induces gastrointestinal dysfunction and enteric nervous system remodeling in rodent offspring, characterized by increased proportion of choline acetyltransferase immunoreactive neurons and suppressed autophagy in colonic myenteric neurons [37] (Table 1).
The intestinal microbiota plays a crucial role in the proliferation, apoptosis, immune response, and homeostasis of epithelial cells. The composition and diversity of intestinal microbiota are modulated by dietary protein profiles, although the effects exhibit species-specific patterns. A study in rats revealed that gestational high-protein diets reduce offspring fecal microbial diversity while enhancing milk microbiota diversity and cecal microbial richness, concurrently correlating with elevated abundance of putative probiotic taxa such as Lactobacillus spp. [38]. Contrastingly, maternal low-protein regimens in Huzhu Bamei suckling pigs enhanced microbial alpha diversity and reduced diarrheal incidence [39]. The differences of species and protein levels may explain these divergent outcomes. Furthermore, lactating sows supplemented with 1% spray-dried plasma and their offspring exhibited increased proportions of the phylum Bacteroidota and genus Lactobacillus and Ruminococcus, while displaying reduced levels of phylum Bacillota and genus Bacteroides, Escherichia/Shigella, and Clostridium [40]. Collectively, these findings implicate gestational microbial programming as a determinant of offspring intestinal development.
Essential AAs, acquired exclusively through dietary sources, function as fundamental constituents of polypeptides while orchestrating critical metabolic pathways governing cellular homeostasis, developmental processes, reproductive physiology, and immunoregulatory networks [41]. Sulfur AAs, particularly methionine (Met) and cysteine (Cys), exert indispensable roles in gastrointestinal physiology by facilitating luminal nutrient processing, sustaining mucosal immune functions, enhancing antioxidant ability, and reinforcing epithelial barrier against foreign antigens [42,43]. Perinatal optimization of maternal Met/Cys ratio enhances intestinal development and redox homeostasis in offspring piglets via synergistic mechanisms involving plasma metabolite profile alterations and microbiota compositional shifts. However, supra-nutritional Met exposure elevates susceptibility to metabolic dysregulation, emphasizing the necessity for precision in perinatal essential AA supplementation [44,45].
Maternal non-essential AAs also play an important role in the intestinal development of offspring. Wang et al. (2020) has demonstrated that maternal supplementation with 1% proline (Pro) enhances fetal growth and enterocyte proliferation through polyamine biosynthesis [46]. L-arginine is integral to multiple pathways critical for piglet growth and development, including nitric oxide synthesis, energy metabolism, polyamine synthesis, cellular protein production, muscle accretion, and the synthesis of other functional amino acids [14]. A recent study has demonstrated that maternal L-arginine supplementation could improve the live litter weight at birth and litter weight gain during lactation, but there is no substantial data to support the intestinal development in offspring piglets [47]. Glutamine (Gln) serves not only as an energy substrate and precursor for protein biosynthesis but also as a signaling molecule regulating intestinal gene expression, cell proliferation, immune function, and redox homeostasis [48]. Maternal dietary Gln supplementation has been proposed as a strategy to enhance fetal growth and mitigate IUGR occurrence. Zhu et al. (2018) reported that supplementation in sows with 1% Gln from day 85 of gestation until farrowing alleviated IUGR-induced intestinal impairment by suppressing intestinal miR-29a levels and increasing extracellular matrix and tight junction protein abundance [49]. Overall, beyond essential AAs, particular attention should be given to highlighting the critical role of maternal non-essential AAs in offspring’s intestinal development (Table 1).
Table 1. Effects of maternal protein and amino acid intake on reproductive performance of sows and the intestinal development of the offspring.
Table 1. Effects of maternal protein and amino acid intake on reproductive performance of sows and the intestinal development of the offspring.
SourcesExperimental GroupsStageFindingsStudy
Pro(1) CON
(2) 1% Pro
(3) 1% Pro + 0.0167% adifluoromethylornithine		From day 15 to 70 of gestationFetal weight (+)
Protein and DNA concentrations of the fetal small intestine (+)
mRNA levels for potassium voltage-gated channel, shaker-related subfamily, and member 1 (Kv1.1) in the fetal small and large intestines (+)		[46]
Arg(1) CON
(2) CON+ 0.28% Arg
(3) CON+ 0.79% Arg		Day 70 of gestation to farrowingLive litter weight (+)
Piglet weight gain and litter weight gain (+)		[47]
Met and CysMet/Cys: 46% Met, 51% Met, 56% Met, and 62% MetDay 90 of gestation to lactation46% Met: hippuric acid, retinoic acid, riboflavin, and δ-tocopherol (−)
51% Met: Firmicutes (+) (the optimum Met/Cys ratio)
62% Met: Proteobacteria (+)		[44]
Protein(1) Normal protein: 14% CP
(2) Low protein: 12% CP
(3) Very low protein: 10%		During gestationLow protein: the abundance and diversities of the jejunum microbiome (+); biological functions of the jejunum microbiome (+)[39]
Glutamine(1) CON
(2) CON + 1% Gln		Day 85 of gestation to farrowingAverage birth weight (+)
Gln concentration (+)
Intestinal weight and morphologies (+)
Extracellular matrix, tight junction protein (+)		[49]
Met (1) CON
(2) CON + 0.12% Met
(3) CON+ 0.24% Met		Day 90 of gestation to day 21 of lactationMalondialdehyde (−)
glutathione peroxidase (+)
Phascolarctobacterium and Bacteroidetes (+)		[45]
Met(1) Met
(2) HMTBA		During lactationReduced glutathione (+)
Oxidized glutathione (GSSG)/GSH ratio (−)
Glutathione peroxidase (+)
Villus height and goblet cell numbers (+)		[50]
Protein(1) Adequate protein (AP, 12.1%)
(2) Low protein (LP, 6.5%)
(3) High protein (HP, 30%)		During gestationLP: Mortality (+)
Cortisol (+) IL-6 (+)
HP: CD4+ cell percentage (+)
CD4+/CD8+ ratio (+)
IL-6 (+)		[35]
Protein(1) Adequate protein (AP, 12.1%)
(2) Low protein (LP, 6.5%)
(3) High protein (HP, 30%)		During gestationHP and LP: body weight and catch-up growth (−)
Ki67 and active caspase 3 (−)
IUGR: brush border enzyme activities (−)
Vacuolated enterocytes disappearance (−)		[34]
Protein(1) CON
(2) CON + 1% SDP		Day 30 before farrowing to weaningPhylum Bacteroidota and genus Lactobacillus and Ruminococcus (+)
Phylum Bacillota and genus Bacteroides, Escherichia/Shigella, and Clostridium (−)		[40]
+, increase; −, decrease; CON, control group.

4.2. Fatty Acids

Fatty acids serve as a major energy source, structural components of cell membranes, metabolic substrates in biochemical pathways, signaling molecules, and immunomodulators [51]. Medium-chain triglycerides (MCT), long-chain polyunsaturated fatty acid (LC-PUFA), and SCFA are indispensable for neonatal energy metabolism and GIT development [31]. In our pervious study, maternal over-nutrition (150% of National Research Council [NRC] recommendations) enhanced intestinal function in newborn and weaned piglets by upregulating digestive enzyme activity and transporter gene expression, whereas maternal undernutrition (75% of NRC recommendations) impaired fetal intestinal development due to intrauterine nutrient restriction [52] (Table 2). Maternal energy intake during gestation significantly influences fetal and postnatal outcomes, including birth weight, small intestinal weight, and intestinal morphology, which correlate with changes in intestinal digestion and absorption capacity [53,54]. Reduced maternal energy intake may also elevate intestinal inflammation risk by compromising epithelial barrier integrity [54]. In studies involving primates and humans, maternal high-fat diets during gestation have been shown to reduce offspring intestinal microbiota diversity and persistently alter gut microbial composition [55,56].
n-3 PUFA, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential nutrients that must be obtained exogenously. Inadequate dietary intake of these fatty acids elevates the risk of maternal undernutrition and fetal growth impairment. Innis et al. (2010) demonstrated that maternal dietary supplementation with n-3 LC-PUFA during gestation and lactation augmented colonic permeability and exacerbated inflammatory responses to chemically induced colitis in offspring rats [57]. Parallel findings by Boudry and colleagues revealed that gestational and lactational diets enriched with α-linolenic acid (18:3 n-3) elevated jejunal permeability in piglets [58]; furthermore, such supplementation increased intestinal lipopolysaccharide (LPS) translocation and promoted an anti-inflammatory immune profile in neonatal piglets upon LPS exposure [59]. The intestinal epithelial barrier is critical for maintaining gut homeostasis and shaping neonatal immune system development. Diet-induced neuroplastic modifications in the enteric nervous system (ENS), a primary regulator of gastrointestinal function, may underlie alterations in intestinal permeability. Piglets from sows receiving linseed-oil-supplemented diets during gestation and lactation exhibited transient increases in ileal permeability, likely mediated by ENS architectural and functional neuroplastic adaptations, alongside diminished ileal barrier reactivity to mast cell degranulation [60]. Intestinal health is closely linked to intestinal microbiota composition, with emerging evidence underscoring the substantial influence of dietary fish oil or n-3 PUFA on microbial communities. Maternal fish oil supplementation (60 g/d) during late gestation and lactation enhances growth performance, improves immune function, and reduces post-weaning diarrhea incidence in piglets. These benefits correlate with elevated α-diversity of fecal microbiota and increased abundance of Lactobacillus species [61]. Further, glucose is a major energy source for weaning piglets. Gestational n-3 PUFA-rich diets enhance intestinal glucose absorption and elevate muscle glycogen reserves in newly weaned pigs, which are associated with upregulated intestinal mRNA expression of GLUT2 and SGLT-1 [62]. In summary, maternal dietary fatty acid interventions can modulate gastrointestinal health and function in offspring pigs, enhancing immune homeostasis and disease resistance during the post-weaning period.
Table 2. Effects of maternal energy intake on reproductive performance of sows and offspring’s intestinal development.
Table 2. Effects of maternal energy intake on reproductive performance of sows and offspring’s intestinal development.
SourceExperimental GroupsStageKey FindingsStudy
Fat sources(1) Lard
(2) Linseed oil		During gestation and lactation18:3(n-3) and 20:5(n-3) in maternal RBC and piglet ileum (+)
22:6(n-3) and 20:4(n-6) in maternal RBC and piglet ileum (−)
18:3(n-3) in milk and piglet ileum (+)		[60]
Energy level(1) NRC, 2012 (3.40 MCal DE)
(2) Low-energy diet (3.00 MCal DE)		Day 1 of gestation to farrowingSmall intestinal weight (−)
The ratio of villus height to crypt depth (−)
Lactase and sucrase (−)
IL-6, TNF-a (+)
TLR-4, IL-1b and NF-kB (+)
ZO-1 (−)		[54]
Energy level(1) NRC, 2012
(2) High-energy diet (add 4.6% soybean oil)		Day 1 of gestation to farrowingSmall intestinal weight (+)
Villus height (+)
Lactase, sucrase (+)
Insulin-like growth factor 1 receptor (+)		[53]
Fat sources(1) 18:3n-3
(2) 18:2n-6		Throughout gestation and lactationMesenteric lymph nodes (+)
MHC class II+ antigen-presenting cells (+)		[59]
Nutrition level(1) 75% of NRC
(2) NRC
(3) 150% of NRC 		Day 1 of gestation to farrowingSmall intestine weight (+)
Brush-border lactase (+)
SGLT1, GLUT2, PEPT1, and GLP2R (+)		[52]
Fat sources(1) Lard
(2) Linseed oil		During gestation and lactationPermeability (+)
Paracellular permeability (−)
Choline acetyltransferase (ChAT)-immunoreactive (IR) neurons (+) 		[58]
Fat sources(1) CON
(2) CON + fish oil
(3) CON + gold fat
(4) CON + coconut fat		Entire gestation and lactation periods(2) (3):
Glucose transporter 2 (+)
Sodium glucose transporter 1 protein (+)
AMP-activated protein kinase activity (+)		[62]
Fish oil(1) CON
(2) CON + 30 g/d fish oil
(3) CON + 60 g/d fish oil		Day 90 of gestation
to weaning at day 21 of lactation		Plasma IgG, IgM and IgA (+)
Cortisol (−)
α-diversity of fecal microbiota, Lactobacillus genus (+)		[61]
+, increase; −, decrease; CON, control group.

4.3. Carbohydrate

Carbohydrates constitute a critical nutritional component in swine feed formulations, representing 60–70% of total dietary content. These compounds vary structurally from simple sugars (e.g., monosaccharides and disaccharides) to complex polymers, including starch and nonstarch polysaccharides—the latter categorized collectively as dietary fiber [63]. Indigestible carbohydrates serve as the primary energy substrate for gut microbiota, which metabolize them into short-chain fatty acids (SCFAs) through anaerobic fermentation. The fermentability and physicochemical properties of dietary carbohydrates directly modulate microbial community composition and diversity. For instance, Metzler-Zebeli et al. (2010) demonstrated that altering carbohydrate fermentability and viscosity in swine diets reshapes intestinal microbial diversity [64].
Emerging evidence indicates that maternal environmental and phenotypic factors significantly influence offspring phenotypic traits and biological fitness. Strategic modulation of sow microbiota through dietary fiber interventions may directly shape offspring intestinal microbial communities [65]. In our recent study, gestational high-fiber intake elevated proteins associated with oxidative homeostasis, energy metabolism, and immune-inflammatory responses in neonatal piglets while reducing apoptosis-related proteins and those governing cytoskeletal organization and cellular motility in the small intestine. These molecular shifts coincided with structural adaptations in intestinal morphology and microbial community restructuring [66]. Gut microbiota composition demonstrates marked sensitivity to the physicochemical properties of dietary fibers. Gestational fiber supplementation alters sow gut microbiota diversity and composition, systemically influencing nutritional metabolism, physiological adaptation, and immune regulation. For instance, maternal wheat bran and inulin administration during gestation and lactation modifies offspring microbial fermentation patterns [67], with inulin further suppressing Enterobacteriaceae populations [68] (Table 3). Cheng et al. (2018) demonstrated that gestational soluble fiber supplementation (2.0% pregelatinized waxy maize starch and guar gum) enhances offspring growth rates and reduces diarrhea incidence, correlating with improved intestinal barrier integrity (evidenced by plasma zonulin, endotoxin, and diamine oxidase levels) and microbiota-mediated metabolic reprogramming, including increased Bacteroides, Lactobacillus, Roseburia, Fusobacterium, and Acinetobacter abundance [10]. Beyond merely increasing fiber levels, the source of dietary fiber is equally critical. Liu et al. (2021) demonstrated that adding diverse fiber sources (alfalfa meal, beet pulp, and soybean skin) into maternal diets during mid-to-late gestation modulated sow and offspring performance [69]. Notably, alfalfa meal supplementation markedly enhanced maternal and neonatal performance while alleviating gastrointestinal and systemic inflammatory responses. Additionally, this intervention significantly elevated the relative abundance of anti-inflammatory bacterial taxa and reduced proinflammatory microbial populations [69]. Collectively, these findings underscore maternal nutritional programming as a critical determinant of offspring microbial–immune axis development, warranting further investigation into targeted dietary fiber.
Table 3. Effects of maternal carbohydrate intake on reproductive performance of sows and offspring’s intestinal development.
Table 3. Effects of maternal carbohydrate intake on reproductive performance of sows and offspring’s intestinal development.
SourceExperimental GroupsStageKey FindingsStudy
Soluble fiber(1) CON
(2) CON + 2.0% pregelatinized waxy maize starch plus guar gum (SF)		During gestationGrowth rate (+)
The incidence of diarrhea (−)
The fecal and plasma levels of acetate and butyrate (+)
Plasma zonulin and fecal lipocalin-2 (−)
Plasma concentrations of interleukin 10 (IL-10) and Transforming growth factor (TGF-β) (+)
Lactobacillus spp. (+)
Bilophila spp. (−)		[10]
RS(1) Containing 33% of digestible starch (DS diet)
(2) Containing 33% of pea starch (RS) diet		Gestation and lactationFirmicutes/Bacteroidetes ratio (+)
Bifidobacterium (+)
Milk protein concentration (−)
Lactose concentration (+)
Zonula occludens 1 (ZO-1) (+)		[70]
FiberInsoluble/soluble fiber ratio of 3.89 (R1), 5.59 (R2), 9.12 (R3), and 12.81 (R4)During the entire gestationDuodenal weight, jejunal villus height, and villus height/crypt depth (−)
Lactase, sucrase, and maltase (−)
Antioxidant capacity (−)
Inflammatory response (+)		[71,72]
Fiber(1) Control diet (CD, 16.15% dietary fiber)
(2) High-dietary-fiber diet (HFD, 30.14% dietary fiber)		Day 90 of gestation to farrowingα-diversity indices (+)
Acidobacteria and Bacteroidetes at phylum level (+)
Bradyrhizobium and Phyllobacterium at genus level (+)
The abundances of proteins associated with oxidative status, energy metabolism, and immune and inflammatory responses (+)		[66]
Fiber(1) CON
(2) CON + sugar beet pulp (SBP)
(3) CON + wheat bran (WB)		Day 85 of gestation to weaningSBP: sow ADFI, litter. and piglet weaning weight, piglet ADG, immunoglobulin A (IgA), and interleukin-10 (IL-10) levels in the colostrum and IgA levels in the milk (+)
Christensenellaceae and butyrate levels in the colon (+)
WB: IL-10 levels in the milk (+)
Lactobacillaceae in the colon (+)		[73]
RSMaternal diets: digestible starch (DS) or RS diet
Piglet treatment: control diet or high fat diet		Late gestation and lactationRNA sequencing on liver and colon scrapings revealed minor differences[74]
Inulin(1) CON
(2) CON + 3% inulin		Gestation and lactationThe cell numbers of enterococci (+)
Cell numbers of eubacteria (stomach) and C. leptum (caecum) (+)
Cell numbers of enterobacteria and L. amylovorus (stomach) (−)		[68]
Fiber source(1) CON
(2) Alfalfa meal
(3) Beet pulp
(4) Soybean skin		Day 60 of gestation to farrowingAlfalfa meal improved sow and piglet performance and relieved gut and systemic inflammation[69]
+, increase; −, decrease; CON, control group.

4.4. Minerals and Vitamins

Research on the effects of maternal mineral and vitamin on the intestinal health of offspring remains limited. Zinc (Zn) is an essential micronutrient, serving as a cofactor or structural component for numerous enzymatic and metalloenzymatic systems while also regulating acid–base homeostasis and osteochondral development. Payne et al. (2006) observed that offspring from sows receiving ZnSO4 supplementation exhibited greater duodenal and ileal villus width compared to ZnAA groups, implying that maternal Zn form influences offspring intestinal morphogenesis [75] (Table 4). Selenium (Se) attenuates intestinal inflammation by reducing oxidative stress. A comparative analysis of maternal sodium selenite (Na2SeO3) and 2-hydroxy-4-methylselenobutanoic acid (HMSeBA) supplementation demonstrated that gestational HMSeBA administration enhances intestinal antioxidant capacity and suppresses inflammatory signaling (e.g., NF-κB and ERK/Beclin-1 pathways) in offspring pigs [76]. Similarly, compared with Na2SeO3, maternal selenium-enriched yeast (SeY) supplementation during late gestation and lactation improves piglet growth performance, selenium status, antioxidant capacity, and immunoglobulin transfer during the first week of lactation. This supplementation also modulates fecal microbiota in sows by enriching antioxidant-associated and SCFA-producing microbiota. These adaptations enhance small intestinal barrier function and activate the Nrf2/Keap1 pathway in offspring [77].
A mouse study indicated that maternal vitamin D deficiency elevates intestinal permeability in offspring, potentially mediated by the epigenetic suppression of the Wnt/β-catenin signaling pathway via histone modifications [78]. In addition, vitamins and their derivatives are critical regulators of intestinal development. Maternal 25-hydroxycholecalciferol (25-OH-D3) administration enhances dietary calcium bioavailability, modifies lactational milk composition and fatty-acid profiles, and elevates hindgut butyrate concentrations in suckling piglets through the upregulation of calcitropic genes [79,80]. Vitamin A (VA) exerts pleiotropic effects on immune function, playing a critical role in mucosal immunity and intestinal lymphocyte trafficking. Supplementation with 30,000 IU VA during the third trimester in porcine epidemic-diarrhea-virus-(PEDV)-infected gilts demonstrated dual therapeutic benefits for both maternal and neonatal health. VA-supplemented gilts exhibited elevated anti-PEDV IgA levels in systemic circulation, mammary secretions, and ileal tissue, correlating with improved survival rates in PEDV-challenged neonates from VA-treated dams [81].
Table 4. Effects of maternal minerals or vitamins intake on the reproductive performance of sows and offspring’s intestinal development.
Table 4. Effects of maternal minerals or vitamins intake on the reproductive performance of sows and offspring’s intestinal development.
SourceExperimental groupsStageKey FindingsStudy
Mineral(1) CON (contains 100 ppm Zn from ZnSO4)
(2) CON + 100 ppm Zn from ZnSO4
(3) CON + 100 ppm additional Zn from ZnAA		Day 15 of gestation and continuing through lactationZnSO4: duodenal villus width (+)
ZnAA: ileal villus width (−)		[75]
Mineral(1) Na2SeO3
(2) Selenium-enriched yeast		Day 85 of gestation and continuing through lactationSe content in the plasma and milk (+)
T-AOC and GSH-Px in the colostrum (+)
Protein abundances of MUC1, E-cadherin, ZO-1, occludin, and claudin (+)
SCFA-producing microbiota (+)		[77]
Mineral(1) Na2SeO3
(2) HMSeBA		During gestationIleal GPX2 and SePP1 (+)
IL-1β, IL-6 and NF-κB genes (−)
p-NF-κB, Beclin-1 and p-ERK proteins (−)		[82]
Vitamin(1) 2000 IU/kg vitamin D3
(2) 50 μg/kg 25-OH-D3		Day 107 of gestation to day 21 of lactationMilk n-6/n-3 PUFA ratio (+)
Bone-specific alkaline phosphatase (+)
Calcium absorption rate (+)
Milk fat content and immunoglobulin G level (+)
Concentration of butyrate (+)		[79,80]
Vitamin(1) Mock
(2) Mock + Vitamin A (VA)
(3) PEDV
(4) PEDV + VA		Day 76 of gestation throughout lactationMaternal IgA (+)
Lactogenic immune protection in nursing piglets (+)		[81]
+, increase; −, decrease; CON, control group; 25-OH-D3, 25-hydroxycholecalciferol.

4.5. Probiotics and Prebiotics

Emerging evidence indicates that maternal administration of probiotics and prebiotics modulates GIT microbiota composition and functionality, thereby beneficially influencing offspring GIT development and maturation [83]. Gestational and lactational probiotic supplementation in sows alters intestinal microbiota profiles and mucosal cytokine levels in suckling piglets [84]. Maternal microbiota transmission to offspring occurs via parturition-associated contact or lactation-derived breast milk, shaping neonatal gut microbial colonization patterns [85]. Early microbial colonization critically stimulates mucosal immune system development and functional maturation [86]. Probiotics are defined as live microorganisms administered in sufficient quantities to confer GIT microbial equilibrium [87]. Maternal dietary supplementation with Bacillus subtilis C-3102 during gestation-lactation phases modifies fecal microbiota in sows and post-weaning piglets [88]. Synergistic mixed probiotic formulations enhance pathogen resistance, intestinal health, and nutrient utilization. For instance, maternal supplementation with a multi-strain probiotic (Lactobacillus helveticus BGRA43, Lactobacillus fermentum BGHI14, Streptococcus thermophilus BGVLJ1-44) elevates neonatal piglet microbiota diversity [89]. Wang et al. (2020) demonstrated that gestational–lactational synbiotic supplementation (compound probiotics [L. Plantarum B90 and S. cerevisiae P11] with xylo-oligosaccharide) increases beneficial bacteria (Bifidobacterium and Lactobacillus), suppresses pathogenic Escherichia coli, enhances colonic SCFAs absorption, and improves the immunity and antioxidant capacity in offspring piglets [90]. In addition, probiotic supplementation also shortens farrowing duration and enhances suckling piglet growth performance via persistent gestational–lactational modulation of intestinal microbiota [91,92]. Delivery and weaning are significant stressors for both sows and piglets, negatively impacting reproductive and growth performance. Numerous studies have demonstrated that diets supplemented with probiotics can improve sow reproductive performance and the viability of their progeny [93,94]. Recent studies indicate that probiotics can regulate sow milk metabolism through the gut–mammary axis, influencing the structure of the offspring’s gut microbiota and improving their immune status and antioxidant capabilities [95] (Table 5). However, some reports reported no improvement in the productive performance of sows or piglet growth due to the administration of duration time and dose [96].
Beyond probiotics, prebiotics serve as natural feed additives by functioning as selectively metabolized substrates that promote beneficial microbial activity and host health [97]. Defined as non-digestible carbohydrates and oligosaccharides, prebiotics occur naturally in human and animal diets, with structural diversity influencing their functional specificity [98]. Maternal supplementation with 10.0 g/day seaweed extract (SWE; containing laminarin [1.0 g], fucoidan [0.8 g], and ash [8.2 g]) exhibits significant immunomodulatory effects, evidenced by elevated colostral IgA and IgG concentrations and upregulated ileal TNF-α mRNA expression following ex-vivo LPS challenge, as well as reduces sow fecal Enterobacteriaceae abundance at parturition and suppresses Escherichia coli colonization in piglets at weaning [99,100]. Sow-derived milk oligosaccharides serve as fermentable substrates for neonatal microbiota, suggesting their pivotal role in early microbial colonization patterns [67,101]. Lactational supplementation with short-chain fructooligosaccharides (scFOS) enhances microbial fermentative capacity in suckling piglets, stimulating intestinal immune maturation through elevated ileal cytokine production, expanded goblet cell populations, and enhanced vaccine-specific IgA responses [102]. This enhanced fermentative capacity may stem from scFOS-induced modifications in milk oligosaccharide profiles, consistent with findings indicating that lactating sows supplemented with chitooligosaccharide (COS) have a significantly increased milk oligosaccharide composition [103]. scFOS-supplemented sows exhibit elevated colostral IgA and TGF-β1 concentrations, potentiating neonatal mucosal immunity through enhanced secretory IgA synthesis in Peyer’s patches and T-cell activation [104]. Duan et al. (2019) observed that maternal and/or offspring mannan-oligosaccharide (MOS) supplementation improves intestinal microbial profiles, strengthens mucosal immunity, and attenuates systemic inflammation in piglets [105]. Indigestible oligosaccharides and polysaccharides represent a safer alternative to probiotics for maternal GIT microbiota modulation, thereby benefiting neonatal health [106].
In addition to the prebiotics discussed above, some nutraceuticals and functional nutrients have demonstrated utility in pig industry. Maternal L-carnitine supplementation during gestation and lactation enhances intestinal barrier integrity in both neonatal and 21-day post-weaning piglets [107]. Gestational resveratrol supplementation mitigates weaning-associated diarrhea and intestinal inflammation while improving offspring intestinal morphology, likely through microbiota modulation and transcriptional regulation [108]. Furthermore, dietary mannan-rich fractions during gestation–lactation cycles elevate colostral and milk IgG levels, critical for neonatal intestinal and immune development, while inducing gene expression patterns suggestive of long-term performance enhancements [109]. Recent studies have identified spatially distinct microbial colonization trajectories across intestinal mucosa, driven by vertically transmitted maternal milk and gut microbiota, which prime neonatal immune and barrier function establishment [110]. Overall, the supplementation of diet with probiotics and prebiotics for gestating and lactating sows accelerates offspring small intestinal epithelial maturation and is coupled with enhanced mucosal immunity and colostral antibody transfer during early postnatal stages [111].
Table 5. Effects of maternal probiotic or prebiotic supplementation on the reproductive performance of sows and offspring’s intestinal development.
Table 5. Effects of maternal probiotic or prebiotic supplementation on the reproductive performance of sows and offspring’s intestinal development.
SourceExperimental GroupsStageKey FindingsStudy
Probiotic mixture(1) CON
(2) CON+ probiotic mixture		Day 0 of gestation until 20 days before deliveryLitter size and litter weigh at birth (+)
Diarrhea incidence (−)
Antioxidant capabilities
Systemic immune status 		[95]
Seaweed extracts (SWE)2 × 2 factorial design
(1) CON
(2) CON + SWE 10.0 g/d
LPS challenge		From day 107 of gestation until weaning (d 26)Colostrum IgA, IgG, and serum IgG (+)
Colonic E. coli population (−)
TNF-α mRNA expression (+)		[99]
Seaweed extracts (SWE)2 × 2 factorial design
- SWE vs. +SWE
- ETEC vs. +ETEC		Day 83 of gestation until weaning (day 28)Heat-labile enterotoxin gene (−)
Villus height in the ileum (+)		[100]
Methyl donor (MET)(1) CON
(2) BPA (50 mg/kg)
(3) MET (3 g/kg betaine, 400 mg/kg choline, 150 µg/kg vitamin B12, and 15 mg/kg folic acid)
(4) BPA + MET		Throughout gestationThe ratio of villus height to crypt depth (+)
Lactase activity (+)
Pept1, DNMT1, DNMT3a, and MTHFR (+)
DNA methylation level of jejunum Pept1 (+)		[112]
Prebiotics (scFOS)(1) CON
(2) Mycotoxin deoxynivalenol
(3) scFOS		During the last 4 weeks of gestationT regulatory response (+)[113]
scFOS(1) CON
(2) CON + scFOS		During the last third of gestation and throughout lactationIleal cytokine secretions (IFN)-γ (+)
Cecal goblet cell number (+)
IgA vaccine response (+)
Bacterial fermentative activity (+)
Colonic butyrate (+)		[102]
PrebioticsReceived daily 45 mL lactulose10 days before until 10 days after parturitionDaily weight gains (+)
Total aerobic bacterial counts and C. perfringens counts (+)
IgG antibody levels (+)		[114]
Resveratrol(1) CON
(2) CON + 300 mg/kg resveratrol		20 days after breeding through gestation and lactationButyrate-producing bacteria (+)
Diarrhea and intestinal inflammation (−)
Intestinal morphology (+)
T-cell receptor, MAPK, and Ras signaling (−)		[108]
Mannan oligosaccharide (MOS)2 × 2 factorial design
Sow: (1) CON
(2) CON + 400 mg/kg MOS
Piglets: (1) CON
(2) +800 mg/kg MOS		Day 86 of gestation until weaningLactobacillus (+)
Escherichia coli (−)
sIgA content (+)
Toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), and interleukin 8 (IL-8) (−)
Cytokines IL-2 and IL-4 (−)		[105,115]
L-carnitine2 × 2 factorial design
(soyabean meal vs. DDGS) and two L-carnitine levels		Gestation and lactationTotal superoxide dismutase activity (+)
Malondialdehyde (−)
IL-1β, IL-12, IL-6, and TNF-α (−)
Lactobacillus spp. and bifidobacteria spp. (+)
Tight junction proteins (+)		[107]
Yeast mannan-rich fraction (MRF)(1) CON
(2) CON + MRF (900 mg/kg)		Gestation and lactationProtein and immunoglobulin G (IgG) in milk (+)
Genes related to tissue development, functioning. and immunity, as well as greater cell proliferation and less migration of cells (+)		[109]
Short-chain fructooligosaccharide (scFOS)(1) CON
(2) CON + (10 g scFOS/d)		The last 4 weeks of gestation and the 4 weeks of lactationIgA, scFOS. and TGFb1 concentrations (+)[104]
Oregano essential oils (OEO)(1) CON
(2) CON + 250 mg/kg of OEO		Gestation and lactationFat percentage in milk (−)
T lymphocytes (+)		[116]
Bioactive substances(1) CON
(2) CON + flax seed, rapeseed, linden inflorescence, taurine, L-carnitine and tocopherol acetate		Day 80 of gestation to lactationApoptotic index (−)
p53 expression (−)		[111]
Folic acid (FA)(1) CON (1.8 mg FA per kg)
(2) FA-supplemented diet (30.3 mg FA per kg)		During gestationDNMT-1 and Bcl-2 (+)
p53, Bax, Mpg, and Apex-1 (−)		[112]
+, increase; −, decrease; CON, control group; MTHFR, methylenetetrahydrofolate reductase.

5. The Underlying Mechanism of Maternal Nutrition and Offspring Development

Accumulating evidence suggests that the impact of early nutrition on chronic diseases in offspring may be mediated through epigenetic mechanisms [101]. Epigenetic processes, including DNA methylation, posttranslational histone modifications (e.g., acetylation, methylation, phosphorylation, ubiquitination), and microRNA abundance, are critical for the normal development of tissues across various life stages [117]. Maternal nutritional intake during gestation has been shown to influence the fetal and postnatal epigenome and transcriptome, resulting in measurable changes in intestinal growth [118]. In a recent study, alterations in differentially methylated regions (DMRs) were identified in the intestinal tissues of piglets with IUGR, with these DMR-associated genes interacting with key proteins involved in immunity and metabolism. These findings suggest that IUGR induces DNA methylation changes in intestinal tissues, potentially modulating the expression of genes associated with cell apoptosis, differentiation, and immune function [119]. As a pivotal epigenetic modification, DNA methylation plays a crucial role in transcriptomic regulation [120]. DNA methylation is affected by several external factors such as environmental exposures, nutrient intake, and disease occurrence [121]. Emerging evidence in nutritional epigenetics indicates that maternal supplementation with methyl donors (e.g., betaine, choline, folic acid, vitamin B12) can alter DNA methylation patterns, resulting in lasting phenotypic changes in offspring [122,123]. In our recent study, maternal dietary supplementation with a methyl donor mixture (3 g/kg betaine, 400 mg/kg choline, 150 µg/kg vitamin B12, and 15 mg/kg folic acid) mitigated bisphenol A-induced impairments in intestinal morphology, disaccharidase activity, and nutrient transporter gene expression in offspring piglets by enhancing DNA methylation [112]. Furthermore, maternal methyl donor supplementation exerts persistent effects on the colonic mucosa microbiota of offspring, implicating bacterial involvement in the epigenomic reprogramming of gut function [103]. Beyond DNA methylation, recent studies have demonstrated that maternal supplementation with mineral methionine hydroxy analog chelate can influence histone acetylation and fetal programming, potentially regulating intestinal health and skeletal muscle development in piglets at birth and weaning, thereby promoting enhanced growth [124]. Similarly, in a poultry study, a maternal high-zinc diet attenuated intestinal inflammation in offspring chicks by reducing DNA methylation and increasing H3K9 acetylation in the A20 promoter region [125]. These findings collectively demonstrate that epigenetic gene regulation can be modulated by nutritional interventions, leading to altered gene expression patterns [120]. In summary, maternal supplementation with enzyme cofactors and methyl donors may induce changes in DNA methylation and histone acetylation, thereby influencing global gene expression and biological responses in offspring [118,126].

6. Conclusions and Future Perspectives

Intestinal development in piglets is a complex, multifactorial process that plays a critical role in ensuring the health and productivity of piglets within production systems (Figure 2). The prenatal and early postnatal periods represent a crucial window for the development of the intestinal tract and immune system. Numerous studies have demonstrated that imbalances in macronutrients, vitamins, minerals, prebiotics, and probiotics—whether provided in excess or deficiency during pregnancy and/or lactation—can exert long-lasting, often detrimental effects on progeny. In this review, we mainly focus on the positive effects of maternal nutrition in the regulation of intestinal development of offspring piglets during gestation and lactation. Based on this review, it can be concluded that appropriately increasing fiber intake during late gestation can improve the phenotype of offspring by regulating intestinal microbiota and alleviating inflammation. Perinatal prebiotic and probiotic administration can modulate offspring health and intestinal development via the gut–mammary axis. Furthermore, given the rapid and profound changes in intestinal development during the perinatal period, further investigation is warranted to optimize dietary composition during this critical phase to support optimal intestinal development in offspring.
The intestinal microbiota plays a pivotal role in immunological development and metabolic health. Emerging evidence suggests that maternal microbiota influences offspring gut colonization through direct exposure during birth (via the vaginal canal) and through breast milk during lactation, thereby contributing to immune system development and long-term health outcomes in offspring (Figure 2). However, in our recent study, we observed distinct colonic microbiota compositions in newborn piglets (prior to suckling) derived from sows fed different fiber diets during gestation [66]. This finding challenges the traditional assumption of a sterile intrauterine environment, suggesting instead that maternal–fetal microbial transmission occurs during gestation. Consequently, further research is necessary to elucidate the mechanisms by which maternal nutrition during gestation influences offspring microbiota.

Author Contributions

L.H. performed the literature search and performed the manuscript writing and proofreading. F.W. helped the literature search. L.C. set up the research project. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the Natural Science Foundation of Sichuan (No. 2024NSFSC1169 and 2023NSFSC1135) and the National Natural Science Foundation of China (No. 32402787).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

No new data were created or analyzed in this study.

Acknowledgments

We would like to thank the staff at our laboratory for their intellectual contributions.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Lalles, J.P. Long term effects of pre- and early postnatal nutrition and environment on the gut. J. Anim. Sci. 2012, 90, 421–429. [Google Scholar] [CrossRef] [PubMed]
  2. Burkey, T.E.; Skjolaas, K.A.; Minton, J.E. Board-invited review: Porcine mucosal immunity of the gastrointestinal tract. J. Anim. Sci. 2009, 87, 1493–1501. [Google Scholar] [CrossRef]
  3. Zabielski, R.; Godlewski, M.M.; Guilloteau, P. Control of development of gastrointestinal system in neonates. J. Physiol. Pharmacol. 2008, 59 (Suppl. S1), 35–54. [Google Scholar] [PubMed]
  4. Pluske, J.R. Feed- and feed additives-related aspects of gut health and development in weanling pigs. J. Anim. Sci. Biotechnol. 2013, 4, 1. [Google Scholar] [CrossRef] [PubMed]
  5. Montagne, L.; Boudry, G.; Favier, C.; Le Huerou-Luron, I.; Lalles, J.P.; Seve, B. Main intestinal markers associated with the changes in gut architecture and function in piglets after weaning. Br. J. Nutr. 2007, 97, 45–57. [Google Scholar] [CrossRef]
  6. Guilloteau, P.; Zabielski, R.; Hammon, H.M.; Metges, C.C. Nutritional programming of gastrointestinal tract development. Is the pig a good model for man? Nutr. Res. Rev. 2010, 23, 4–22. [Google Scholar] [CrossRef]
  7. Chu, D.M.; Meyer, K.M.; Prince, A.L.; Aagaard, K.M. Impact of maternal nutrition in pregnancy and lactation on offspring gut microbial composition and function. Gut Microbes 2016, 7, 459–470. [Google Scholar] [CrossRef]
  8. Zhang, S.; Heng, J.; Song, H.; Zhang, Y.; Lin, X.; Tian, M.; Chen, F.; Guan, W. Role of Maternal Dietary Protein and Amino Acids on Fetal Programming, Early Neonatal Development, and Lactation in Swine. Animals 2019, 9, 19. [Google Scholar] [CrossRef]
  9. Klurfeld, D.M. Nutritional regulation of gastrointestinal growth. Front. Biosci. A J. Virtual Libr. 1999, 4, D299–D302. [Google Scholar] [CrossRef]
  10. Cheng, C.; Wei, H.; Xu, C.; Xie, X.; Jiang, S.; Peng, J. 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. [Google Scholar] [CrossRef]
  11. Nowland, T.L.; Kirkwood, R.N.; Pluske, J.R. Review: Can early-life establishment of the piglet intestinal microbiota influence production outcomes? Animal 2022, 16, 100368. [Google Scholar] [CrossRef] [PubMed]
  12. Thum, C.; Cookson, A.L.; Otter, D.E.; McNabb, W.C.; Hodgkinson, A.J.; Dyer, J.; Roy, N.C. Can nutritional modulation of maternal intestinal microbiota influence the development of the infant gastrointestinal tract? J. Nutr. 2012, 142, 1921–1928. [Google Scholar] [CrossRef] [PubMed]
  13. Vandenplas, Y.; Carnielli, V.P.; Ksiazyk, J.; Luna, M.S.; Migacheva, N.; Mosselmans, J.M.; Picaud, J.C.; Possner, M.; Singhal, A.; Wabitsch, M. Factors affecting early-life intestinal microbiota development. Nutrition 2020, 78, 110812. [Google Scholar] [CrossRef]
  14. Dekaney, C.M.; Wu, G.; Jaeger, L.A. Gene expression and activity of enzymes in the arginine biosynthetic pathway in porcine fetal small intestine. Pediatr. Res. 2003, 53, 274–280. [Google Scholar] [CrossRef] [PubMed]
  15. Dekaney, C.M.; Bazer, F.W.; Jaeger, L.A. Mucosal morphogenesis and cytodifferentiation in fetal porcine small intestine. Anat. Rec. 1997, 249, 517–523. [Google Scholar] [CrossRef]
  16. Perozzi, G.; Barilà, D.; Murgia, C.; Kelly, D.; Begbie, R.; King, T.P. Expression of differentiated functions in the developing porcine small intestine. J. Nutr. Biochem. 1993, 4, 699–705. [Google Scholar] [CrossRef]
  17. McPherson, R.L.; Ji, F.; Wu, G.; Blanton, J.R., Jr.; Kim, S.W. Growth and compositional changes of fetal tissues in pigs. J. Anim. Sci. 2004, 82, 2534–2540. [Google Scholar] [CrossRef]
  18. Sangild, P.; Fowden, A.; Trahair, J. How does the foetal gastrointestinal tract develop in preparation for enteral nutrition after birth? Livest. Prod. Sci. 2000, 66, 141–150. [Google Scholar] [CrossRef]
  19. Buddington, R.K.; Sangild, P.T.; Hance, B.; Huang, E.Y.; Black, D.D. Prenatal gastrointestinal development in the pig and responses after preterm birth. J. Anim. Sci. 2012, 90 (Suppl. S4), 290–298. [Google Scholar] [CrossRef]
  20. Kelly, D.; Coutts, A. Development of digestive and immunological function in neonates: Role of early nutrition. Livest. Prod. Sci. 2000, 66, 161–167. [Google Scholar] [CrossRef]
  21. Zhang, H.; Malo, C.; Buddington, R.K. Suckling induces rapid intestinal growth and changes in brush border digestive functions of newborn pigs. J. Nutr. 1997, 127, 418–426. [Google Scholar] [CrossRef]
  22. Fan, M.; Stoll, B.; Jiang, R.; Burrin, D. Enterocyte digestive enzyme activity along the crypt-villus and longitudinal axes in the neonatal pig small intestine. J. Anim. Sci. 2001, 79, 371–381. [Google Scholar] [CrossRef]
  23. Goenka, A.; Kollmann, T.R. Development of immunity in early life. J. Infect. 2015, 71 (Suppl. S1), S112–S120. [Google Scholar] [CrossRef] [PubMed]
  24. Nguyen, Q.N.; Himes, J.E.; Martinez, D.R.; Permar, S.R. The Impact of the Gut Microbiota on Humoral Immunity to Pathogens and Vaccination in Early Infancy. PLoS Pathog. 2016, 12, e1005997. [Google Scholar] [CrossRef] [PubMed]
  25. Mackie, R.I.; Sghir, A.; Gaskins, H.R. Developmental microbial ecology of the neonatal gastrointestinal tract. Am. J. Clin. Nutr. 1999, 69, 1035S–1045S. [Google Scholar] [CrossRef] [PubMed]
  26. Nyangahu, D.D.; Lennard, K.S.; Brown, B.P.; Darby, M.G.; Wendoh, J.M.; Havyarimana, E.; Smith, P.; Butcher, J.; Stintzi, A.; Mulder, N.; et al. Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity. Microbiome 2018, 6, 124. [Google Scholar] [CrossRef]
  27. Macpherson, A.J.; de Aguero, M.G.; Ganal-Vonarburg, S.C. How nutrition and the maternal microbiota shape the neonatal immune system. Nat. Reviews. Immunol. 2017, 17, 508–517. [Google Scholar] [CrossRef]
  28. Chowdhury, S.R.; King, D.E.; Willing, B.P.; Band, M.R.; Beever, J.E.; Lane, A.B.; Loor, J.J.; Marini, J.C.; Rund, L.A.; Schook, L.B.; et al. Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets. BMC Genom. 2007, 8, 215. [Google Scholar] [CrossRef]
  29. Hooper, L.V. Bacterial contributions to mammalian gut development. Trends Microbiol. 2004, 12, 129–134. [Google Scholar] [CrossRef]
  30. Sangild, P.T. Prenatal Development of Gastrointestinal Function in the Pig and the Effects of Fetal Esophageal Obstruction. Pediatr. Res. 2002, 52, 416–424. [Google Scholar] [CrossRef]
  31. Jacobi, S.K.; Odle, J. Nutritional factors influencing intestinal health of the neonate. Adv. Nutr. 2012, 3, 687–696. [Google Scholar] [CrossRef] [PubMed]
  32. Terstappen, F.; Tol, A.J.C.; Gremmels, H.; Wever, K.E.; Paauw, N.D.; Joles, J.A.; Beek, E.M.V.; Lely, A.T. Prenatal Amino Acid Supplementation to Improve Fetal Growth: A Systematic Review and Meta-Analysis. Nutrients 2020, 12, 2535. [Google Scholar] [CrossRef] [PubMed]
  33. Hu, L.; Zheng, J.; Wu, F.; Fang, Z.; Che, L.; Wu, D. Effects of energy and amino acid intake during gestation on reproductive performance, milk composition, antioxidant status and placental nutrient transport in high-parity sows. Front. Vet. Sci. 2025, 12, 1585925. [Google Scholar] [CrossRef]
  34. Mickiewicz, M.; Zabielski, R.; Grenier, B.; Le Normand, L.; Savary, G.; Holst, J.J.; Oswald, I.P.; Metges, C.C.; Guilloteau, P. Structural and functional development of small intestine in intrauterine growth retarded porcine offspring born to gilts fed diets with differing protein ratios throughout pregnancy. J. Physiol. Pharmacol. 2012, 63, 225–239. [Google Scholar] [PubMed]
  35. Tuchscherer, M.; Otten, W.; Kanitz, E.; Grabner, M.; Tuchscherer, A.; Bellmann, O.; Rehfeldt, C.; Metges, C.C. Effects of inadequate maternal dietary protein:carbohydrate ratios during pregnancy on offspring immunity in pigs. BMC Vet. Res. 2012, 8, 232. [Google Scholar] [CrossRef]
  36. Pinheiro, D.F.; Pinheiro, P.F.; Buratini, J., Jr.; Castilho, A.C.; Lima, P.F.; Trinca, L.A.; Vicentini-Paulino, M.d.L.M. Maternal protein restriction during pregnancy affects gene expression and immunolocalization of intestinal nutrient transporters in rats. Clin. Sci. 2013, 125, 281–289. [Google Scholar] [CrossRef]
  37. Aubert, P.; Oleynikova, E.; Rizvi, H.; Ndjim, M.; Le Berre-Scoul, C.; Grohard, P.A.; Chevalier, J.; Segain, J.P.; Le Drean, G.; Neunlist, M.; et al. Maternal protein restriction induces gastrointestinal dysfunction and enteric nervous system remodeling in rat offspring. FASEB J. 2019, 33, 770–781. [Google Scholar] [CrossRef]
  38. Warren, M.F.; Hallowell, H.A.; Higgins, K.V.; Liles, M.R.; Hood, W.R. Maternal Dietary Protein Intake Influences Milk and Offspring Gut Microbial Diversity in a Rat (Rattus norvegicus) Model. Nutrients 2019, 11, 2257. [Google Scholar] [CrossRef]
  39. Jin, J.; Zhang, L.; Jia, J.; Chen, Q.; Yuan, Z.; Zhang, X.; Sun, W.; Ma, C.; Xu, F.; Zhan, S.; et al. Effects of Maternal Low-Protein Diet on Microbiota Structure and Function in the Jejunum of Huzhu Bamei Suckling Piglets. Animals 2019, 9, 713. [Google Scholar] [CrossRef]
  40. Lee, J.J.; Kyoung, H.; Cho, J.H.; Park, K.I.; Kim, Y.; Ahn, J.; Choe, J.; Kim, Y.; Kim, H.B.; Song, M. Change in the Gut Microbiota of Lactating Sows and Their Piglets by Inclusion of Dietary Spray-Dried Plasma in Sow Diets. J. Microbiol. Biotechnol. 2023, 34, 516–524. [Google Scholar] [CrossRef]
  41. Wu, G. Amino acids: Metabolism, functions, and nutrition. Amino Acids 2009, 37, 1–17. [Google Scholar] [CrossRef]
  42. Fang, Z.; Yao, K.; Zhang, X.; Zhao, S.; Sun, Z.; Tian, G.; Yu, B.; Lin, Y.; Zhu, B.; Jia, G. Nutrition and health relevant regulation of intestinal sulfur amino acid metabolism. Amino Acids 2010, 39, 633–640. [Google Scholar] [CrossRef] [PubMed]
  43. Zhou, R.; Lai, S.; Yuan, P.; Zhe, L.; Yang, L.; Mercier, Y.; Hu, L.; Zhang, X.; Hua, L.; Zhuo, Y.; et al. Increased maternal consumption of methionine as its hydroxyl analog improves placental angiogenesis and antioxidative capacity in sows. J. Anim. Sci. Biotechnol. 2025, 16, 39. [Google Scholar] [CrossRef] [PubMed]
  44. Azad, M.A.K.; Liu, G.; Bin, P.; Ding, S.; Kong, X.; Guan, G.; Yin, Y. Sulfur-containing amino acid supplementation to gilts from late pregnancy to lactation altered offspring’s intestinal microbiota and plasma metabolites. Appl. Microbiol. Biotechnol. 2020, 104, 1227–1242. [Google Scholar] [CrossRef]
  45. Azad, M.A.K.; Bin, P.; Liu, G.; Fang, J.; Li, T.; Yin, Y. Effects of different methionine levels on offspring piglets during late gestation and lactation. Food Funct. 2018, 9, 5843–5854. [Google Scholar] [CrossRef]
  46. Wang, J.; Tan, B.; Li, J.; Kong, X.; Tan, M.; Wu, G. Regulatory role of l-proline in fetal pig growth and intestinal epithelial cell proliferation. Anim. Nutr. 2020, 6, 438–446. [Google Scholar] [CrossRef]
  47. Hong, J.; Fang, L.H.; Jeong, J.H.; Kim, Y.Y. Effects of L-Arginine Supplementation during Late Gestation on Reproductive Performance, Piglet Uniformity, Blood Profiles, and Milk Composition in High Prolific Sows. Animals 2020, 10, 1313. [Google Scholar] [CrossRef]
  48. Blachier, F.; Boutry, C.; Bos, C.; Tome, D. Metabolism and functions of L-glutamate in the epithelial cells of the small and large intestines. Am. J. Clin. Nutr. 2009, 90, 814S–821S. [Google Scholar] [CrossRef]
  49. Zhu, Y.; Li, T.; Huang, S.; Wang, W.; Dai, Z.; Feng, C.; Wu, G.; Wang, J. Maternal L-glutamine supplementation during late gestation alleviates intrauterine growth restriction-induced intestinal dysfunction in piglets. Amino Acids 2018, 50, 1289–1299. [Google Scholar] [CrossRef]
  50. Kumar, A.; Vlasova, A.N.; Liu, Z.; Chattha, K.S.; Kandasamy, S.; Esseili, M.; Zhang, X.; Rajashekara, G.; Saif, L.J. In vivo gut transcriptome responses to Lactobacillus rhamnosus GG and Lactobacillus acidophilus in neonatal gnotobiotic piglets. Gut Microbes 2014, 5, 152–164. [Google Scholar] [CrossRef] [PubMed]
  51. Fritsche, K. Fatty acids as modulators of the immune response. Annu. Rev. Nutr. 2006, 26, 45–73. [Google Scholar] [CrossRef] [PubMed]
  52. Cao, M.; Che, L.; Wang, J.; Yang, M.; Su, G.; Fang, Z.; Lin, Y.; Xu, S.; Wu, D. Effects of maternal over- and undernutrition on intestinal morphology, enzyme activity, and gene expression of nutrient transporters in newborn and weaned pigs. Nutrition 2014, 30, 1442–1447. [Google Scholar] [CrossRef] [PubMed]
  53. Liu, P.; Che, L.; Yang, Z.; Feng, B.; Che, L.; Xu, S.; Lin, Y.; Fang, Z.; Li, J.; Wu, D. A Maternal High-Energy Diet Promotes Intestinal Development and Intrauterine Growth of Offspring. Nutrients 2016, 8, 258. [Google Scholar] [CrossRef] [PubMed]
  54. Chen, Y.; Mou, D.; Hu, L.; Zhen, J.; Che, L.; Fang, Z.; Xu, S.; Lin, Y.; Feng, B.; Li, J.; et al. Effects of Maternal Low-Energy Diet during Gestation on Intestinal Morphology, Disaccharidase Activity, and Immune Response to Lipopolysaccharide Challenge in Pig Offspring. Nutrients 2017, 9, 1115. [Google Scholar] [CrossRef]
  55. Ma, J.; Prince, A.L.; Bader, D.; Hu, M.; Ganu, R.; Baquero, K.; Blundell, P.; Alan Harris, R.; Frias, A.E.; Grove, K.L.; et al. High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model. Nat. Commun. 2014, 5, 3889. [Google Scholar] [CrossRef]
  56. Chu, D.M.; Antony, K.M.; Ma, J.; Prince, A.L.; Showalter, L.; Moller, M.; Aagaard, K.M. The early infant gut microbiome varies in association with a maternal high-fat diet. Genome Med. 2016, 8, 77. [Google Scholar] [CrossRef]
  57. Innis, S.M.; Dai, C.; Wu, X.; Buchan, A.M.; Jacobson, K. Perinatal lipid nutrition alters early intestinal development and programs the response to experimental colitis in young adult rats. Am. J. Physiology. Gastrointest. Liver Physiol. 2010, 299, G1376–G1385. [Google Scholar] [CrossRef]
  58. De Quelen, F.; Chevalier, J.; Rolli-Derkinderen, M.; Mourot, J.; Neunlist, M.; Boudry, G. n-3 polyunsaturated fatty acids in the maternal diet modify the postnatal development of nervous regulation of intestinal permeability in piglets. J. Physiol. 2011, 589, 4341–4352. [Google Scholar] [CrossRef]
  59. Desaldeleer, C.; Ferret-Bernard, S.; de Quelen, F.; Le Normand, L.; Perrier, C.; Savary, G.; Romé, V.; Michel, C.; Mourot, J.; Le Huërou-Luron, I.; et al. Maternal 18:3n-3 favors piglet intestinal passage of LPS and promotes intestinal anti-inflammatory response to this bacterial ligand. J. Nutr. Biochem. 2014, 25, 1090–1098. [Google Scholar] [CrossRef]
  60. Boudry, G.; Douard, V.; Mourot, J.; Lalles, J.P.; Le Huerou-Luron, I. Linseed oil in the maternal diet during gestation and lactation modifies fatty acid composition, mucosal architecture, and mast cell regulation of the ileal barrier in piglets. J. Nutr. 2009, 139, 1110–1117. [Google Scholar] [CrossRef]
  61. Han, P.; Du, Z.; Liu, X.; You, J.; Shi, X.E.; Sun, S.; Yang, G.; Li, X. Effects of maternal supplementation of fish oil during late gestation and lactation on growth performance, fecal microbiota structure and post-weaning diarrhoea of offspring piglets. Br. J. Nutr. 2022, 130, 966–977. [Google Scholar] [CrossRef]
  62. Gabler, N.K.; Spencer, J.D.; Webel, D.M.; Spurlock, M.E. In utero and postnatal exposure to long chain (n-3) PUFA enhances intestinal glucose absorption and energy stores in weanling pigs. J. Nutr. 2007, 137, 2351–2358. [Google Scholar] [CrossRef] [PubMed]
  63. Aluthge, N.D.; Van Sambeek, D.M.; Carney-Hinkle, E.E.; Li, Y.S.; Fernando, S.C.; Burkey, T.E. BOARD INVITED REVIEW: The pig microbiota and the potential for harnessing the power of the microbiome to improve growth and health. J. Anim. Sci. 2019, 97, 3741–3757. [Google Scholar] [CrossRef]
  64. Metzler-Zebeli, B.U.; Hooda, S.; Pieper, R.; Zijlstra, R.T.; van Kessel, A.G.; Mosenthin, R.; Ganzle, M.G. Nonstarch polysaccharides modulate bacterial microbiota, pathways for butyrate production, and abundance of pathogenic Escherichia coli in the pig gastrointestinal tract. Appl. Env. Microbiol. 2010, 76, 3692–3701. [Google Scholar] [CrossRef] [PubMed]
  65. Chen, X.; Xu, J.; Ren, E.; Su, Y.; Zhu, W. Co-occurrence of early gut colonization in neonatal piglets with microbiota in the maternal and surrounding delivery environments. Anaerobe 2018, 49, 30–40. [Google Scholar] [CrossRef]
  66. He, Y.; Peng, X.; Liu, Y.; Wu, Q.; Zhou, Q.; Hu, L.; Fang, Z.; Lin, Y.; Xu, S.; Feng, B.; et al. Effects of Maternal Fiber Intake on Intestinal Morphology, Bacterial Profile and Proteome of Newborns Using Pig as Model. Nutrients 2020, 13, 42. [Google Scholar] [CrossRef]
  67. Leblois, J.; Massart, S.; Li, B.; Wavreille, J.; Bindelle, J.; Everaert, N. Modulation of piglets’ microbiota: Differential effects by a high wheat bran maternal diet during gestation and lactation. Sci. Rep. 2017, 7, 7426. [Google Scholar] [CrossRef]
  68. Passlack, N.; Vahjen, W.; Zentek, J. Dietary inulin affects the intestinal microbiota in sows and their suckling piglets. BMC Vet. Res. 2015, 11, 51. [Google Scholar] [CrossRef]
  69. Liu, B.S.; Zhu, X.Y.; Cui, Y.L.; Wang, W.J.; Liu, H.; Li, Z.D.; Guo, Z.G.; Ma, S.; Li, D.F.; Wang, C.Z.; et al. Consumption of Dietary Fiber from Different Sources during Pregnancy Alters Sow Gut Microbiota and Improves Performance and Reduces Inflammation in Sows and Piglets. mSystems 2021, 6. [Google Scholar] [CrossRef] [PubMed]
  70. Leblois, J.; Massart, S.; Soyeurt, H.; Grelet, C.; Dehareng, F.; Schroyen, M.; Li, B.; Wavreille, J.; Bindelle, J.; Everaert, N. Feeding sows resistant starch during gestation and lactation impacts their faecal microbiota and milk composition but shows limited effects on their progeny. PLoS ONE 2018, 13, e0199568. [Google Scholar] [CrossRef]
  71. Li, Y.; Liu, H.; Zhang, L.; Yang, Y.; Lin, Y.; Zhuo, Y.; Fang, Z.; Che, L.; Feng, B.; Xu, S.; et al. Maternal Dietary Fiber Composition during Gestation Induces Changes in Offspring Antioxidative Capacity, Inflammatory Response, and Gut Microbiota in a Sow Model. Int. J. Mol. Sci. 2019, 21, 31. [Google Scholar] [CrossRef] [PubMed]
  72. Brink, L.R.; Matazel, K.; Piccolo, B.D.; Bowlin, A.K.; Chintapalli, S.V.; Shankar, K.; Yeruva, L. Neonatal Diet Impacts Bioregional Microbiota Composition in Piglets Fed Human Breast Milk or Infant Formula. J. Nutr. 2019, 149, 2236–2246. [Google Scholar] [CrossRef]
  73. 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, 4922–4933. [Google Scholar] [CrossRef]
  74. Schroyen, M.; Leblois, J.; Uerlings, J.; Li, B.; Sureda, E.A.; Massart, S.; Wavreille, J.; Bindelle, J.; Everaert, N. Maternal dietary resistant starch does not improve piglet’s gut and liver metabolism when challenged with a high fat diet. BMC Genom. 2020, 21, 439. [Google Scholar] [CrossRef]
  75. Payne, R.L.; Bidner, T.D.; Fakler, T.M.; Southern, L.L. Growth and intestinal morphology of pigs from sows fed two zinc sources during gestation and lactation. J. Anim. Sci. 2006, 84, 2141–2149. [Google Scholar] [CrossRef]
  76. Mou, D.; Ding, D.; Yan, H.; Qin, B.; Dong, Y.; Li, Z.; Che, L.; Fang, Z.; Xu, S.; Lin, Y.; 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, 7748–7761. [Google Scholar] [CrossRef]
  77. Xiong, L.; Lin, T.; Yue, X.; Zhang, S.; Liu, X.; Chen, F.; Zhang, S.; Guan, W. Maternal Selenium-Enriched Yeast Supplementation in Sows Enhances Offspring Growth and Antioxidant Status through the Nrf2/Keap1 Pathway. Antioxidants 2023, 12, 2064. [Google Scholar] [CrossRef]
  78. Yang, K.; Zhu, J.; Wu, J.; Zhong, Y.; Shen, X.; Petrov, B.; Cai, W. Maternal Vitamin D Deficiency Increases Intestinal Permeability and Programs Wnt/beta-Catenin Pathway in BALB/C Mice. JPEN J. Parenter. Enter. Nutr. 2020, 45, 102–114. [Google Scholar] [CrossRef]
  79. Zhang, L.; Li, M.; Shang, Q.; Hu, J.; Long, S.; Piao, X. Effects of maternal 25-hydroxycholecalciferol on nutrient digestibility, milk composition and fatty-acid profile of lactating sows and gut bacterial metabolites in the hindgut of suckling piglets. Arch. Anim. Nutr. 2019, 73, 271–286. [Google Scholar] [CrossRef] [PubMed]
  80. Zhang, L.; Hu, J.; Li, M.; Shang, Q.; Liu, S.; Piao, X. Maternal 25-hydroxycholecalciferol during lactation improves intestinal calcium absorption and bone properties in sow-suckling piglet pairs. J. Bone Miner. Metab. 2019, 37, 1083–1094. [Google Scholar] [CrossRef] [PubMed]
  81. Langel, S.N.; Paim, F.C.; Alhamo, M.A.; Lager, K.M.; Vlasova, A.N.; Saif, L.J. Oral vitamin A supplementation of porcine epidemic diarrhea virus infected gilts enhances IgA and lactogenic immune protection of nursing piglets. Vet. Res. 2019, 50, 101. [Google Scholar] [CrossRef]
  82. Mou, D.; Ding, D.; Yang, M.; Jiang, X.; Zhao, L.; Che, L.; Fang, Z.; Xu, S.; Lin, Y.; Zhuo, Y.; et al. Maternal organic selenium supplementation during gestation improves the antioxidant capacity and reduces the inflammation level in the intestine of offspring through the NF-kappaB and ERK/Beclin-1 pathways. Food Funct. 2020, 12, 315–327. [Google Scholar] [CrossRef] [PubMed]
  83. Sanz, Y. Gut microbiota and probiotics in maternal and infant health. Am. J. Clin. Nutr. 2011, 94, 2000S–2005S. [Google Scholar] [CrossRef] [PubMed]
  84. Taras, D.; Vahjen, W.; Macha, M.; Simon, O. Response of performance characteristics and fecal consistency to long-lasting dietary supplementation with the probiotic strain Bacillus cereus var. toyoi to sows and piglets. Arch. Anim. Nutr. 2005, 59, 405–417. [Google Scholar] [CrossRef]
  85. Thompson, C.L.; Wang, B.; Holmes, A.J. The immediate environment during postnatal development has long-term impact on gut community structure in pigs. ISME J. 2008, 2, 739–748. [Google Scholar] [CrossRef]
  86. Liao, S.F.; Nyachoti, M. Using probiotics to improve swine gut health and nutrient utilization. Anim. Nutr. 2017, 3, 331–343. [Google Scholar] [CrossRef] [PubMed]
  87. Markowiak, P.; Slizewska, K. The role of probiotics, prebiotics and synbiotics in animal nutrition. Gut Pathog. 2018, 10, 21. [Google Scholar] [CrossRef]
  88. Menegat, M.B.; DeRouchey, J.M.; Woodworth, J.C.; Dritz, S.S.; Tokach, M.D.; Goodband, R.D. Effects of Bacillus subtilis C-3102 on sow and progeny performance, fecal consistency, and fecal microbes during gestation, lactation, and nursery periods. J. Anim. Sci. 2019, 97, 3920–3937. [Google Scholar] [CrossRef]
  89. Veljovic, K.; Dinic, M.; Lukic, J.; Mihajlovic, S.; Tolinacki, M.; Zivkovic, M.; Begovic, J.; Mrvaljevic, I.; Golic, N.; Terzic-Vidojevic, A. Promotion of Early Gut Colonization by Probiotic Intervention on Microbiota Diversity in Pregnant Sows. Front. Microbiol. 2017, 8, 2028. [Google Scholar] [CrossRef]
  90. Wang, K.; Zhu, Q.; Kong, X.; Song, M.; Azad, M.A.K.; Xiong, L.; Zheng, Y.; He, Q. Dietary Probiotics or Synbiotics Supplementation During Gestation, Lactation, and Nursery Periods Modifies Colonic Microbiota, Antioxidant Capacity, and Immune Function in Weaned Piglets. Front. Vet. Sci. 2020, 7, 597832. [Google Scholar] [CrossRef]
  91. Cao, M.; Li, Y.; Wu, Q.J.J.; Zhang, P.; Li, W.T.T.; Mao, Z.Y.Y.; Wu, D.M.M.; Jiang, X.M.M.; Zhuo, Y.; Fang, Z.F.F.; et al. Effects of dietary Clostridium butyricum addition to sows in late gestation and lactation on reproductive performance and intestinal microbiota. J. Anim. Sci. 2019, 97, 3426–3439. [Google Scholar] [CrossRef]
  92. Zhang, Q.; Li, J.; Cao, M.; Li, Y.; Zhuo, Y.; Fang, Z.; Che, L.; Xu, S.; Feng, B.; Lin, Y.; et al. Dietary supplementation of Bacillus subtilis PB6 improves sow reproductive performance and reduces piglet birth intervals. Anim. Nutr. 2020, 6, 278–287. [Google Scholar] [CrossRef] [PubMed]
  93. Baker, A.A.; Davis, E.; Spencer, J.D.; Moser, R.; Rehberger, T. The effect of a Bacillus-based direct-fed microbial supplemented to sows on the gastrointestinal microbiota of their neonatal piglets. J. Anim. Sci. 2013, 91, 3390–3399. [Google Scholar] [CrossRef]
  94. Hayakawa, T.; Masuda, T.; Kurosawa, D.; Tsukahara, T. Dietary administration of probiotics to sows and/or their neonates improves the reproductive performance, incidence of post-weaning diarrhea and histopathological parameters in the intestine of weaned piglets. Anim. Sci. J. Nihon Chikusan Gakkaiho 2016, 87, 1501–1510. [Google Scholar] [CrossRef]
  95. Hu, T.; Song, Z.; Yang, L.; Chen, K.; Wu, Y.; Xie, F.; Wang, J.; Yang, G.; Zhu, Y. Maternal probiotic mixture supplementation optimizes the gut microbiota structure of offspring piglets through the gut–breast axis. Anim. Nutr. 2024, 19, 386–400. [Google Scholar] [CrossRef]
  96. Additives, E.P.o.; Products or Substances used in Animal, F.; Rychen, G.; Aquilina, G.; Azimonti, G.; Bampidis, V.; Bastos, M.L.; Bories, G.; Chesson, A.; Cocconcelli, P.S.; et al. Safety and efficacy of Bacillus subtilis PB6 (Bacillus subtilis ATCC PTA-6737) as a feed additive for sows. EFSA J. Eur. Food Saf. Auth. 2017, 15, e04855. [Google Scholar] [CrossRef]
  97. Swanson, K.S.; Gibson, G.R.; Hutkins, R.; Reimer, R.A.; Reid, G.; Verbeke, K.; Scott, K.P.; Holscher, H.D.; Azad, M.B.; Delzenne, N.M. The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 687–701. [Google Scholar] [CrossRef] [PubMed]
  98. Gaggia, F.; Mattarelli, P.; Biavati, B. Probiotics and prebiotics in animal feeding for safe food production. Int. J. Food Microbiol. 2010, 141 (Suppl. S1), S15–S28. [Google Scholar] [CrossRef]
  99. Leonard, S.G.; Sweeney, T.; Bahar, B.; O’Doherty, J.V. 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, 505–514. [Google Scholar] [CrossRef]
  100. Heim, G.; Sweeney, T.; O’Shea, C.J.; Doyle, D.N.; O’Doherty, J.V. Effect of maternal supplementation with seaweed extracts on growth performance and aspects of gastrointestinal health of newly weaned piglets after challenge with enterotoxigenic Escherichia coli K88. Br. J. Nutr. 2014, 112, 1955–1965. [Google Scholar] [CrossRef]
  101. McKay, J.A.; Mathers, J.C. Diet induced epigenetic changes and their implications for health. Acta Physiol. 2011, 202, 103–118. [Google Scholar] [CrossRef] [PubMed]
  102. Le Bourgot, C.; Le Normand, L.; Formal, M.; Respondek, F.; Blat, S.; Apper, E.; Ferret-Bernard, S.; Le Huerou-Luron, I. Maternal short-chain fructo-oligosaccharide supplementation increases intestinal cytokine secretion, goblet cell number, butyrate concentration and Lawsonia intracellularis humoral vaccine response in weaned pigs. Br. J. Nutr. 2017, 117, 83–92. [Google Scholar] [CrossRef] [PubMed]
  103. Schaible, T.D.; Harris, R.A.; Dowd, S.E.; Smith, C.W.; Kellermayer, R. Maternal methyl-donor supplementation induces prolonged murine offspring colitis susceptibility in association with mucosal epigenetic and microbiomic changes. Hum. Mol. Genet. 2011, 20, 1687–1696. [Google Scholar] [CrossRef]
  104. Le Bourgot, C.; Ferret-Bernard, S.; Le Normand, L.; Savary, G.; Menendez-Aparicio, E.; Blat, S.; Appert-Bossard, E.; Respondek, F.; Le Huerou-Luron, I. Maternal short-chain fructooligosaccharide supplementation influences intestinal immune system maturation in piglets. PLoS ONE 2014, 9, e107508. [Google Scholar] [CrossRef]
  105. Duan, X.; Tian, G.; Chen, D.; Huang, L.; Zhang, D.; Zheng, P.; Mao, X.; Yu, J.; He, J.; Huang, Z.; et al. Mannan oligosaccharide supplementation in diets of sow and (or) their offspring improved immunity and regulated intestinal bacteria in piglet. J. Anim. Sci. 2019, 97, 4548–4556. [Google Scholar] [CrossRef]
  106. Shadid, R.; Haarman, M.; Knol, J.; Theis, W.; Beermann, C.; Rjosk-Dendorfer, D.; Schendel, D.J.; Koletzko, B.V.; Krauss-Etschmann, S. Effects of galactooligosaccharide and long-chain fructooligosaccharide supplementation during pregnancy on maternal and neonatal microbiota and immunity—A randomized, double-blind, placebo-controlled study. Am. J. Clin. Nutr. 2007, 86, 1426–1437. [Google Scholar] [CrossRef]
  107. Wei, B.; Nie, S.; Meng, Q.; Qu, Z.; Shan, A.; Chen, Z. Effects of l-carnitine and/or maize distillers dried grains with solubles in diets of gestating and lactating sows on the intestinal barrier functions of their offspring. Br. J. Nutr. 2016, 116, 459–469. [Google Scholar] [CrossRef] [PubMed]
  108. Meng, Q.; Sun, S.; Luo, Z.; Shi, B.; Shan, A.; Cheng, B. Maternal dietary resveratrol alleviates weaning-associated diarrhea and intestinal inflammation in pig offspring by changing intestinal gene expression and microbiota. Food Funct. 2019, 10, 5626–5643. [Google Scholar] [CrossRef]
  109. Graugnard, D.E.; Samuel, R.S.; Xiao, R.; Spangler, L.F.; Brennan, K.M. Intestinal gene expression profiles of piglets benefit from maternal supplementation with a yeast mannan-rich fraction during gestation and lactation. Animal 2015, 9, 622–628. [Google Scholar] [CrossRef]
  110. Liu, H.; Zeng, X.; Zhang, G.; Hou, C.; Li, N.; Yu, H.; Shang, L.; Zhang, X.; Trevisi, P.; Yang, F.; et al. Maternal milk and fecal microbes guide the spatiotemporal development of mucosa-associated microbiota and barrier function in the porcine neonatal gut. BMC Biol. 2019, 17, 106. [Google Scholar] [CrossRef]
  111. Strzałkowski, A.; Godlewski, M.M.; Hallay, N.; Kulasek, G.; Gajewski, Z.; Zabielski, R. The effect of supplementing sow with bioactive substances on neonatal small intestinal epithelium. J. Physiol. Pharmacol. 2007, 58, 115–122. [Google Scholar] [PubMed]
  112. Liu, H.; Wang, J.; Mou, D.; Che, L.; Fang, Z.; Feng, B.; Lin, Y.; Xu, S.; Li, J.; Wu, D. Maternal Methyl Donor Supplementation during Gestation Counteracts the Bisphenol A-Induced Impairment of Intestinal Morphology, Disaccharidase Activity, and Nutrient Transporters Gene Expression in Newborn and Weaning Pigs. Nutrients 2017, 9, 423. [Google Scholar] [CrossRef] [PubMed]
  113. Ferret-Bernard, S.; Le Normand, L.; Rome, V.; Le Bourgot, C.; Seeboth, J.; Savary, G.; Laurent, F.; Le Huerou-Luron, I.; Guzylack-Piriou, L. Maternal Supplementation of Food Ingredient (Prebiotic) or Food Contaminant (Mycotoxin) Influences Mucosal Immune System in Piglets. Nutrients 2020, 12, 2115. [Google Scholar] [CrossRef]
  114. Krueger, M.; Schroedl, W.; Isik, W.; Lange, W.; Hagemann, L. Effects of lactulose on the intestinal microflora of periparturient sows and their piglets. Eur. J. Nutr. 2002, 41 (Suppl. S1), I26–I31. [Google Scholar] [CrossRef] [PubMed]
  115. Duan, X.D.; Chen, D.W.; Zheng, P.; Tian, G.; Wang, J.P.; Mao, X.B.; Yu, J.; He, J.; Li, B.; Huang, Z.Q.; 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. [Google Scholar] [CrossRef]
  116. Ariza-Nieto, C.; Bandrick, M.; Baidoo, S.K.; Anil, L.; Molitor, T.W.; Hathaway, M.R. Effect of dietary supplementation of oregano essential oils to sows on colostrum and milk composition, growth pattern and immune status of suckling pigs. J. Anim. Sci. 2011, 89, 1079–1089. [Google Scholar] [CrossRef]
  117. Elolimy, A.; Vailati-Riboni, M.; Liang, Y.; Loor, J.J. Cellular Mechanisms and Epigenetic Changes: Role of Nutrition in Livestock. Vet. Clin. N. Am. Food Anim. Pract. 2019, 35, 249–263. [Google Scholar] [CrossRef]
  118. Wu, G.; Bazer, F.W.; Cudd, T.A.; Meininger, C.J.; Spencer, T.E. Maternal nutrition and fetal development. J. Nutr. 2004, 134, 2169–2172. [Google Scholar] [CrossRef]
  119. Hu, Y.; Hu, L.; Gong, D.; Lu, H.; Xuan, Y.; Wang, R.; Wu, D.; Chen, D.; Zhang, K.; Gao, F.; et al. Genome-wide DNA methylation analysis in jejunum of Sus scrofa with intrauterine growth restriction. Mol. Genet. Genom. MGG 2018, 293, 807–818. [Google Scholar] [CrossRef]
  120. Anderson, O.S.; Sant, K.E.; Dolinoy, D.C. Nutrition and epigenetics: An interplay of dietary methyl donors, one-carbon metabolism and DNA methylation. J. Nutr. Biochem. 2012, 23, 853–859. [Google Scholar] [CrossRef]
  121. Bai, G.; Yuan, H.; Cao, M.; Jiang, X.; Shi, B.; Bin, P. Glyphosate-Based Herbicide Stress During Pregnancy Impairs Intestinal Development in Newborn Piglets by Modifying DNA Methylation. J. Agric. Food Chem. 2025, 73, 2483–2498. [Google Scholar] [CrossRef]
  122. Murdoch, B.M.; Murdoch, G.K.; Greenwood, S.; McKay, S. Nutritional influence on epigenetic marks and effect on livestock production. Front. Genet. 2016, 7, 182. [Google Scholar] [CrossRef] [PubMed]
  123. Waterland, R.A.; Jirtle, R.L. Transposable elements: Targets for early nutritional effects on epigenetic gene regulation. Mol. Cell. Biol. 2003, 23, 5293–5300. [Google Scholar] [CrossRef] [PubMed]
  124. Jang, K.B.; Kim, J.H.; Purvis, J.M.; Chen, J.; Ren, P.; Vazquez-Anon, M.; Kim, S.W. Effects of mineral methionine hydroxy analog chelate in sow diets on epigenetic modification and growth of progeny. J. Anim. Sci. 2020, 98, skaa271. [Google Scholar] [CrossRef] [PubMed]
  125. Li, C.; Guo, S.; Gao, J.; Guo, Y.; Du, E.; Lv, Z.; Zhang, B. Maternal high-zinc diet attenuates intestinal inflammation by reducing DNA methylation and elevating H3K9 acetylation in the A20 promoter of offspring chicks. J. Nutr. Biochem. 2015, 26, 173–183. [Google Scholar] [CrossRef]
  126. Delage, B.; Dashwood, R.H. Dietary manipulation of histone structure and function. Annu. Rev. Nutr. 2008, 28, 347–366. [Google Scholar] [CrossRef]
Microorganisms 13 01151 g002
Figure 2. Summary of contributions of maternal nutrition to the intestinal development and composition of microbiota in offspring pigs.
Figure 2. Summary of contributions of maternal nutrition to the intestinal development and composition of microbiota in offspring pigs.
Microorganisms 13 01151 g002
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Hu, L.; Wu, F.; Che, L. Programming Effects of Maternal Nutrition on Intestinal Development and Microorganisms of Offspring: A Review on Pigs. Microorganisms 2025, 13, 1151. https://doi.org/10.3390/microorganisms13051151

AMA Style

Hu L, Wu F, Che L. Programming Effects of Maternal Nutrition on Intestinal Development and Microorganisms of Offspring: A Review on Pigs. Microorganisms. 2025; 13(5):1151. https://doi.org/10.3390/microorganisms13051151

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Hu, Liang, Fali Wu, and Lianqiang Che. 2025. "Programming Effects of Maternal Nutrition on Intestinal Development and Microorganisms of Offspring: A Review on Pigs" Microorganisms 13, no. 5: 1151. https://doi.org/10.3390/microorganisms13051151

APA Style

Hu, L., Wu, F., & Che, L. (2025). Programming Effects of Maternal Nutrition on Intestinal Development and Microorganisms of Offspring: A Review on Pigs. Microorganisms, 13(5), 1151. https://doi.org/10.3390/microorganisms13051151

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