Diarrhea in piglets

1. Introduction

Diarrhea in piglets continues to be one of the biggest sanitary problems, that veterinarians and producers face in their daily lives. It is relevant either in maternity or in transition.

Diarrhea is an excess of water in the fecal content in relation to the fecal dry matter (Brown CC, 2007). It is a clinical sign, not a disease; but it is considered a syndrome because there are plenty of causes which can provoke it. The loss of water,  also leads to a loss of nutrients, electrolytes and leads into a deleterious condition which can result in  the death of the animal in a matter of hours.

2. Why is still so relevant in the pig production? Economical costs.

Because it reduces the productive performance in both phases, increases the mortality rate, the therapeutic expenses, and especially rise economic costs and decreases income for pig producers.

Neonatal diarrhea in newborn piglets is often endemic, but may also occur as outbreaks with high morbidity and mortality (Miorin et al, 1983; Svensmark B et al, 1988).

In studies conducted in Sweden and Denmark, diarrhea was estimated to account for 5-24% of the overall preweaning mortality (Svendsen et al, 1975) and for a reduction in average daily gain (ADG) by 8-14 g/day in the first week of life (Kongstead et al, 2014). Based on these production losses, the cost of neonatal diarrhea was estimated to be 134€ /sow/year in affected herds (Sjölund M. et al, 2014). In a review done in Spain by Mesonero & Segalés, in 2018 in 109 sows´ farm with 327 litters, 96,3% herds were positive to at least one enteric pathogen (pathogenic E coli-ETEC, C. perfringens A &C, TGEV, PEDV and rotavirus A). The main pathogens involved in persistent neonatal diarrhea in Spain were rotavirus, ETEC and C. perfringens type A.

On the other hand, in postweaning diarrhea (PWD), in piglets challenged withentero toxigenic E. coli (ETEC) F18  increased incidence of diarrhea (28,3%) was observed, along with reductions in ADG (24,1%), average daily feed intake (ADFI)(12,5%), and FCR (14,9%) (Son J, Kim W, 2025).

During acute outbreaks of PWD, mortality due to E. coli infection may reach 20 to 30% over a 1- to 2-month time span  (Johnson TJ, 2009). A survey conducted by National Animal Health Monitoring System reported that mortality rate of nursery pigs ranged from 2.6 to 3.6% in the years 2000, 2006, and 2012, of which deaths caused by diarrhea- accounted for 9.4 to 12.6% of the overall mortality (USDA. Swine 2012; part II:).

About the cost of mortality in PWD, it has been evaluated to be between 37-38 euros, according to published data in Spain in the last BBDD SIP Consultors 2025 and also from SIP consultors  postweaning mortality rate between14,2-13,7 (2025-2024). According to previous research  published by WOAH (Guardabassi et al, 2025), mortality rates in postweaning caused by diarrhea have shown to be between: good sanitary conditions-0,3-0,8%, medium sanitary conditions 0,8-1,5%, harsh sanitary conditions 1,5-3% and ETEC conditions>5%. In a practical case of a farm which weans 1000 piglets/week , and considering diarrhea contributes by 3% to the total mortality and mean price per weaned piglet of37,5€. Every piglet died due to diarrhea is 30 €. In every batch of 1000 piglets, a lost amount of 1125 €. In a year with 52 batches, a total amount of 58,500 €. This is only considering the losses due to mortality, but we could also consider the lost in performance because of diarrhea .

3. Casing agents and types of diarrhea

As a syndrome, it is a multifactorial disease where infectious agents, nutrition, environment, stress, immunity and microbiome have an important role in the presence or absence of disease.

3.1 Infectious agents

the most common agents may be seen below:

Normally, in clinical cases, there is often more than one agent included.

3.2 Types of diarrhea

We can classify the diarrhea by the mechanism of action:

1. Secretory diarrhea: the intestinal cells secret huge amounts of water and electrolytes. Intestine is almost completely normal macroscopically, but the fecal content is very watery. It causes quick dehydration. Examples: ETEC.
2. Malabsorptive diarrhea: less loss of nutrients, significant body weight loss, persistent diarrhea. Example: Rotavirus, PED and Cystoisospora.
3. Osmotic diarrhea: nutrients in the intestinal lumen, high content of gas. Example: low digestibility feed, excess of non-digestible protein, low enzymatic level.
4. Inflammatory diarrhea: there is an important damage and inflammation in the intestinal tissue, it is common to observe fibrine or blood into the lumen, important lesions in the intestine. Example: Salmonella spp. C. perfringens C, Brachyspira spp.

It is often observed a combination of different types in clinical cases in a farm.

3.3 Stress (weaning) and intestinal health

Piglets may suffer from different stressors such as birth stress (Gill et al, 2012), weaning stress (Cao St,2018), heat stress ( Lin F et al2016), transport stress (Roldan-Santiago P et al,2015). No matter which stress affects the piglets, it usually results in affectingpiglet intestinal health and eventually leading to economic losses.

The integrity of the intestinal structure is the key for nutrient digestion and absorption in piglets. The intestinal morphology, including villus height (VH), crypt depth (CD), and its ratio VCR) reflect the health and absorption status of the intestinal function (Tang X et al, 2022). Reductions in VH and VCR means intestinal mucosal function is impaired, and digestion and absorption capacity is reduced. In contrast, a higher VH and VCR indicated improved intestinal barrier function (Quin L et al, 2019; Tang X et al, 2022).

The intestinal tract is a dynamic self-renewing tissue and its structure and functionality depends on the homeostatic maintenance of the balance between proliferation and apoptosis of intestinal mucosal epithelial cells (Cai X et al,2016, Tang X et al, 2018). The weaning stress disrupts this balance, which increases intestinal permeability and affect intestinal barrier function (Souza et al, 2005). In addition, the alkaline phosphatase (AKP)in the small intestine is a key enzyme associated with digestion and absorption function, which helps to increase the uptake and transport rate of nutrients, and also converts adenosine diphosphate (ADP) into adenosine triphosphate (ATP) and may be used as a marker for this reason (Tang X. et al, 2022).

The intestinal chemical barrier is formed by the mucus layer, composed of mucins (MUCs) secreted by globet cells and antimicrobial proteins secreted by epithelial cells ( Gi P et al, 2020). This layer is the first line of defense to protect intestinal cells from pathogenic microorganisms. This MUCS are glycosylated proteins with a high molecular weight.

The digestive enzymes are key for the efficient digestion of nutrients and modulate the process of nutrient metabolism (Liu X, 2021)(Figure 1).

Figure 1. Adapted by Kemin from Tang et al, weaning stress and intestinal health of piglets: a review.

 

In general, during the first three weeks of life, the digestive system develops quickly due to adequate nutrition intake from sows, and the enzymes like lactase, protease and lipase are increased. However, with the diet change, the activity of these enzymes changes abruptly, the decrease in disaccharidases is considered an important cause of diarrhea in weaned piglets (Marion et al, 2005).

3.4 Nutrition

For weaned piglets, dietary changes are a major challenge to normal intestinal absorption and secretion. There are at least seven major nutritional challenges:

1. Crude protein (CP) levels: the immature digestive system of weaned piglets limits their capacity to secrete sufficient digestive enzymes for efficient protein digestion. Consequently, a proportion of dietary protein escapes digestion in the small intestine and enters the hindgut, where it undergoes microbial fermentation. This process generates a range of metabolites, including short-chain fatty acids (SCFA), sulfur-containing compounds (methyl- and hydrogen sulfides), aromatic compounds (phenols and indoles),polyamines, and ammonia (Wang et al, 2018). Excessive ammonia production increases intestinal pH, creating a favorable conditions for the proliferation of  pathogenic bacteria, which may subsequently contribute to diarrhea (Bhandari et al, 2010).
2. Acid-binding capacity (ABC): in a suckling piglet, gastric pH is naturally low due to the fermentation of lactose from milk into lactic acid. After weaning, the source of lactose is terminated and increases gastric pH (Zhao et al, 2021 ab). In addition, gastrointestinal pH is further reduced to the decrease in gastric acid secretion capacity (Heo et al, 2013). ABC describes the resistance of feed ingredients and diets to acidification within the pig´s stomach. The ABC value of feed has a strong influence on pig gastrointestinal pH, nutrient digestibility and intestinal microbial populations. High-ABC diets tend to increase gastric pH and may impair crude protein digestion, consequently promoting greater protein fermentation in the hindgut.
3. Antigenic proteins: soybean glycinin and ß-conglycinin are the most abundant antigenic proteins in soybeans and are considered the two major antinutritional factors associated to PWD. The ingestion of these proteins can trigger an immune response in the intestinal mucosa causing an allergic reaction and intestinal inflammation (Wang et al, 2023). Moreover, soy proteins activate calcium-sensing receptor (CaSR) and intracellular calcium signaling pathways, potentially disrupting electrolyte homeostasis, thereby contributing to PWD (Wang et al, 2021d).
4. Amino acids: Amino acids play essential roles in the development, maintenance, and function of the gastrointestinal tract (Table 1). Their importance is particularly evident in early-weaned piglets, where intestinal development and functional maturation are often compromised. Intestinal developmental disorders can impair digestive and absorptive capacity, weaken mucosal integrity, and reduce immune competence, elevating the incidence of PWD syndrome and mortality in piglets (Cheng et al.,2018)(Figure 2).

Figure 2. Adapted by Kemin from Diagram Animal Nutrition 16 (2024) 267e274X. Zhou, J. Liang, X. Xiong et al.

Table 1. Diagram Animal Nutrition 16 (2024) 267e274X. Zhou, J. Liang, X. Xiong et al.

Tryptophan (Trp) is an essential amino acid that serves as the precursor for synthesizing multiple pivotal bioactive metabolites involved in regulating metabolism, immunity, inflammation, and intestinal homeostasis (Xue et al, 2023b). Trp metabolism disorder is strongly associated with diarrhea in piglets, which alters host and microbial pathways. Diarrhea triggers the synthesis of numerous proinflammatory cytokines in the intestine such as IL-1beta, IL-6, Il-8, which contribute to intestinal inflammation and barrier dysfunction. Trp and its metabolites have demonstrated therapeutic properties with anti-inflammatory effects, and regulating the immune response (Shizume et al, 2013). Therefore, optimizing dietary Trp supply may contribute to improved intestinal resilience and reduced incidence of PWD.

5. Fat absorption.
Fat is the most concentrated dietary source of energy, providing more than twice the energy per gram compared with carbohydrates and proteins. Dietary fat are primarily composed by triglycerides, which consist of glycerol backbone esterified with fatty three acids. The digestion and absorption are mainly occurring in the small intestine (Zhang, 2022). Medium- and short- chain fatty acids possess higher water solubility and lower esterification requirements than long-chain fatty acids. Consequently, they are absorbed directly with minimal lipase activity and micelle formation, and enter into blood circulation through intestinal epithelial cells. In contrast, long-chain fatty acids require emulsification by bile salts, uptake into enterocytes via fatty acid transporters and subsequent re-esterification into triglycerides. These triglycerides are then incorporated into chylomicrons and transported through the lymphatic system before entering the bloodstream (Hussain, 2014).

The digestive system of piglets is still immature during the weaning period, resulting in limited pancreatic lipase secretion and activity. Consequently, fat digestion and absorption are impaired, leading to reduced nutrient utilization, lower energy availability, and an increased risk of diarrhea (Figure 3).

Figure 3. Adapted by Kemin from Animal Nutrition 16 (2024) 299e305 Y. Li, P. Shi, K. Yao et al.

Under weaning stress conditions, pancreatic lipase activity is only 1/300 of that at 8 weeks of age (Corring et al., 1978). Moreover, lipase activity reaches its lowest level approximately five days after weaning and then begins to recover from days 7 to 9, but it still does not reach the pre-weaning levels (Hedemann and Jensen, 2004). The abundance of small intestine fatty acid transport protein also significantly decreases on day 3 and 7 after weaning, which weaken the digestion and absorption of lipids in the intestine (He et al., 2022).

Moreover, piglet diet changes from liquid milk, which is rich in easily digestible and absorbable fat (with an apparent digestibility rate of 96%) to solid feed with less fat content, causing a decrease in feed and energy intake after weaning (Lalles et al., 2007). Among all nutrients, fat undergoes one of the most significant changes during the weaning transition. At the same time, weaning-induced impairment of intestinal function adversely affects the digestion, absorption, and metabolism of major nutrients, including lipids, carbohydrates, and proteins (Shao et al., 2022; Yang et al., 2019). There is a significant difference in the apparent digestibility of fat from sow milk and dry feed for piglets, being the main root cause that breast milk fat is extensively emulsified. However, weaned piglets may not fully emulsify the fat in their feed due to insufficient bile secretion caused by weaning stress (Bach Korsholm Knudsen et al., 2021).

Collectively, these factors severely affect the digestion, absorption and utilization of lipids in piglet feed, leading to insufficient energy intake and intestinal barrier dysfunction, exacerbating the weaning stress of piglets (Capurso et al., 2019; Hedemann and Jensen, 2004).

6. Starch

Starch is the primary source of dietary energy in nursery diets, contributing approximately 50% of the metabolizable energy intake of weaned piglets. However, the transition from milk to cereal-based feeds occurs when the digestive system is still immature. Several studies have demonstrated that pancreatic amylase activity decreases immediately after weaning before gradually recovering as the piglet adapts to its new diet (Lindemann et al., 1986; Jensen et al., 1997). This temporary depression in amylase secretion reduces the piglet's capacity to digest dietary starch at precisely the time when dietary starch inclusion increases.

As a consequence, a portion of dietary starch may escape digestion in the small intestine and reach the hindgut, where it is fermented by the resident microbiota rather than being absorbed as glucose. This shift from enzymatic digestion to microbial fermentation reduces energy utilization efficiency and may contribute to gastrointestinal disturbances during the post-weaning period. Therefore, optimizing starch digestion is critical to maximizing energy availability, supporting growth performance, and maintaining intestinal health.

7. Fiber

The role of dietary fiber in piglet nutrition is extensive and complex, encompassing effects on gut development, microbiota composition, immune function, nutrient utilization, and diarrhea control. Today, dietary fiber is recognized as one of the most important nutritional strategies for reducing the incidence of post-weaning diarrhea.

Dietary fiber contributes to the regulation of intestinal morphology, immune responses, and host gene expression, thereby promoting intestinal health and reducing diarrhea in weaned piglets (Molist et al., 2014).

The therapeutic effect depends on the type of dietary fiber, which is divided into soluble fiber and insoluble fiber according to the solubility in water:

• Soluble fiber, including hemicellulose, pectin, gums and soluble oligosaccharides, is commonly found in legumes, fruits, vegetables, oats, wheat, barley and rice (Evans, 2020).
• Insoluble fiber, including lignin, cellulose, resistant starch and part of hemicellulose, is predominantly found in whole grains, wheat bran, oat shell, lignocellulose (Waddel and Orfila, 2022).

The physiological effects of dietary fiber depend largely on its physicochemical properties and fermentability. Canibe et al, 2022 reported improvements in growth performance of piglets and the reductions in both of E.coli abundance and diarrhea incidence when oat hulls, wheat bran, pure cellulose and lignocellulose preparations were added to nursery diets.

Similarly, addition of wheat straw or oat hulls to a diet of weaned piglets has been shown to stimulate amylase activity and promotes the adaptation of the GIT to a solid diet, thereby promoting intestinal health (Gerritsen et al, 2012).

However, not all fiber sources provide similar benefits. Certain soluble fiber fractions may increase digesta viscosity, which can favor the proliferation of pathogenic bacteria and aggravate diarrhea symptoms. For example, barley-based soluble fibers have been associated with increased E. coli growth and poorer gut health outcomes (Hopwood et al., 2014). Therefore, the impact of soluble fiber on diarrhea depends largely on its effect on intestinal viscosity.

On the other hand, insoluble dietary fiber can reduce the time of digesta in the proximal GIT, and increase passage rate, regulate the microbial community, maintain intestinal health and reduce diarrhea in piglets. Moreover, insoluble fiber may inhibit the adhesion of pathogens to the mucosa and reduce their proliferation and colonization in the small intestine.

Short chain fatty acids (SCFA) are the product of the microbial fermentation of dietary fiber in the colon such as acetic, propionic, butyric, valeric, and isovaleric. These metabolites are involved in regulating environmental stability, activating epithelial cells proliferation and differentiation, maintaining mucosal integrity and attenuating inflammation (Martin- Gallusiaux et al, 2021) (Figure 4).

Figure 4. Adapted by Kemin from Han et al, 2024, mechanism of short fatty acids.

SCFA exert antimicrobial effects through several complementary mechanisms:

1. Intracellular acidification: SCFA entering into the bacterial cytoplasm will dissociate to release a H+ and reduce the intracellular pH (Jackman et al, 2020). To maintain the pH homeostasis, the bacteria must spend huge amount of energy to pump out the excess of H+. This will disrupt cellular metabolism ultimately leading to the death of the bacteria.
2. Modulation of microbial ecology: SCFA lower intestinal pH, creating conditions that favor beneficial bacteria such as Lactobacillus and Bifidobacterium while suppressing pathogens such as E. coli and Salmonella. Increased microbiota diversity following butyrate supplementation has been reported in piglets.
3. Disruption of bacterial membranes: Undissociated SCFA can interact with phospholipids and lipoproteins in the cell membrane to destroy the stability of the bacterial membrane (Alakomi et al, 2000)
4. Inhibition of cellular metabolism: SCFA inhibit the growth and metabolism of bacteria by changing the intracellular protein and DNA synthesis.

3.5 Environmental conditions

Environmental conditions are critical because they can increase the stress in piglets. A study run by Yu et al, 2021 to assess the effect of exposure to cold on performance and skeletal muscle fiber in weaned piglets showed that low temperatures increased the incidence of diarrhea of weaned piglets during the first week, but not during the second and third week. This indicates that weaned piglets may gradually adapt to cold exposure.

But it is not only low temperatures, ventilation, concentrations of gases like CO2, NH3, etc. can also help or prevent diarrhea incidence in the postweaning phase.

3.6 Immunity

The intestinal immunity barrier is well developed and really complex. It is composed by immune organs, immune cells (intraepithelial lymphocytes, lamina propria lymphocytes, neutrophiles and macrophages), and immune molecules (antibacterial peptides, immunoglobulins and cytokines) (Gough et al, 2022).

Conventionally, the intestinal immune system of pigs does not reach the level of adult pigs until 7 weeks of age (Zheng I, et al, 2021). Weaned piglets are around 3-4 weeks of life when weaned, the intestinal immune barrier is not mature yet which results into disease susceptibility (Xiong X, et al, 2021).

Weaning results into dysfunction of intestinal immune cells.

Studies have shown that late weaned piglets (28 days of age) versus early weaned pigs (19 days of age) have higher numbers of intestinal mast cells at 24h after weaning (Catalioto RM et al, 2011) and sustained hyperplasia of intestinal mast cells at 7 weeks after weaning.(Pohl CL. Et al, 2017).

Weaning stress activates the intestinal immune system and produces a large number of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α), interferon ɣ (IFN-ɣ), interleukin (IL)-1β, IL-6,IL-8 (Deng Q et al, 2020). The overproduction of cytokines can lead to intestinal damage and dysfunction.

Weaning leads to the destruction of intestinal integrity, microbial invasion stimulates the expression of immunoglobulin A (IgA) and defensin in the jejunum of the piglets( de Groot et al,2021).

3.8 Microbiome

The gut microbiota plays a key role in regulating nutrient metabolism in the gut, as well as contributing significantly to the establishment of an intact intestinal barrier and the development of a robust immune system within the gut (Hermann-Bank ML,2015). Weaning-induced impairment of the gut mucosal barrier allows pathogenic microorganisms to invade the gut, further destabilizing the microbiota.

Yang et al, 2019 showed that the diarrheic piglets had lower relative abundance of Bacteroides, Ruminococcus, Bulleidia and Treponema. They play key roles in nutrient metabolism that are abundant in healthy piglets after weaning. Similarly, Sun et al, 2019 showed that diarrheic pigs had lower relative abundances of Bacteroidales than non diarrheic pigs during weaning. Arguello et al, 2014 showed that there was an increase in pathogenic bacteria (Citrobacter) and a decrease  in the population of beneficial bacteria such as Bifidobacterium and Lactobacillus at the ileum mucosa of weaned piglets infected with S. typhimurium. Tao Huang et al 2025, made a study comparing the microbiome between piglets with diarrhea and with no diarrhea in day 35 of age. It showed that there were significant differences in Shannon index between the healthy and non healthy ones.

Conclusions

There are many factors, as we have seen, which may affect the incidence of diarrhea in piglets; so, trying to have all of them under control require utilizing tools and interventions such as microbiome modulators, like probiotics, organic acids, enzymes, etc. to help the piglets go through this stressful period. This will mean better performance, and healthy piglets which are the objective for producers and vets in pig production.