Escherichia coli, particularly ETEC, are the primary pathogen associated with PWD. However, other bacterial species, including Salmonella spp. and Clostridium perfringens have also been implicated in the onset and progression of PWD. These pathogens can act individually or synergistically, further exacerbating the severity of the disease. Importantly, numerous in vitro studies have demonstrated that the growth of these bacterial strains is significantly diminished in the presence of tannins. Table 1 summarizes the effects of tannins extracted from various plant sources on bacterial strains commonly associated with PWD in piglets.

The inhibition of E. coli growth was reported in the presence of significant number of hydrolysable tannins (HT), including plant extracts and isolated compounds. For example, extracts of Lythrum salicaria and Phyllanthus muellerianus showed antibacterial activity, as did their isolated compounds, castalagin and geraniin, respectively (Boakye, 2016; Granica et al., 2020). Similarly, 1,2,6-tri-O-galloyl-β-D-glucopyranose, a compound isolated from Terminalia chebula fruits extract, was active against E. coli (Bag et al., 2013). Antimicrobial effects were also demonstrated for extracts of Castanea sativa (Reggi et al., 2020), Miconia latecrenata (Gontijo et al., 2019), Rosa roxburghii root (Ma et al., 2020), and a hydrolysate of Caesalpinia spinosa extract (Aguilar-Galvez et al., 2014). Furthermore, HT-rich commercial products such as corilagin and tannic acid (TA) also showed inhibitory effects (Li et al., 2013; Wang et al., 2013). Comparable antibacterial activity against E. coli was observed with condensed tannins (CT) (Wang et al., 2013; Alejo-Armijo et al., 2017; Klug et al., 2017). For instance, chestnut and quebracho tannins were effective in inhibiting the most relevant E. coli pathotypes associated with PWD—those expressing F4+ and F18+ adhesive fimbriae (Reggi et al., 2020). Moreover, proanthocyanidins from American cranberry demonstrated activity against EPEC and ETEC (Alshaibani et al., 2017). Finally, tannin-rich extract from guava leaves (Psidium guajava L.) displayed antimicrobial properties against E. coli (Mailoa et al., 2014).

The inhibition of Salmonella spp. growth was also observed in the presence of various tannin sources. Punicalagin, HT from pomegranate, demonstrated antibacterial properties against multiple Salmonella isolates from raw chicken as well as S. Typhimurium reference strain SL1344 (Li et al., 2014). This bacterial strain was also inhibited by HT from chestnut wood, tara, and Chinese galls extracts, as well as by CT from quebracho extract, and from isolated fractions of Calliandra calothyrsus (Costabile et al., 2011). Finally, sweet chestnut wood extract Globatan had inhibitory effect on S. Typhimurium isolates from pigs and S. Typhimurium strain 112910a, which is a field isolate commonly used in studies on gastrointestinal infections in swine (Van Parys et al., 2010).

Tannins are associated with a broad spectrum of antimicrobial activity, and numerous studies have demonstrated their simultaneous effectiveness against several PWD-linked pathogens. Plant extracts from Erythrophleum guineensis stem barks, and Muntingia calabura leaves showed inhibitory activity against not only E. coli, but also Salmonella spp. (Mirelle et al., 2016; Gurning et al., 2021). An inhibitory activity against E. coli and S. Typhimurium was observed for proanthocyanidins derived from grape seeds (Ding et al., 2021) and Hepta-O-galloylglucose (HT) from Mango Kernels (Mangifera indica L.) (Engels et al., 2011). An inhibitory activity against E. coli and S. Enteritidis was observed for HT from C. spinosa extract (Aguilar-Galvez et al., 2014). The growth of S. Enteritidis, S. Typhimurium and E. coli was reduced in the presence of TA and mimosa tannins (Widsten et al., 2014). Finally, HT from various plant sources were found to inhibit E. coli and C. perfringens (Puljula et al., 2020).

Tannins exhibit antimicrobial activity through various mechanisms, including the disruption of bacterial membranes (Li et al., 2013; Wang et al., 2013; Alshaibani et al., 2017). Tannins can also chelate essential metal ions such as iron and zinc, which are crucial for bacterial metabolism, and bind to bacterial proteins and enzymes, interfering with their function (Ma et al., 2020). These changes inhibit bacterial growth and viability. Tannins also decreased bacterial swimming and swarming motility via downregulation of the motility-related genes of Salmonella (Li et al., 2014). These findings highlight tannins’ potential as natural antimicrobial agents in addressing the multifactorial causes of PWD. However, many studies do not evaluate the mechanisms of action in detail, warranting further investigation.

Although the exact mechanisms of ETEC pathogenesis are not fully understood, it is known that it binds specifically to receptors on the surface of the intestinal epithelial cells (Brosnahan and Brown, 2012) and releases toxins–either heat-stable or heat-labile–that disrupt gut integrity, trigger inflammation, promote fluid secretion, and ultimately cause diarrhea (Heo et al., 2013; Kim et al., 2022). Multiple studies have reported that tannins not only inhibit the growth of bacteria implicated in PWD, but also interfere with key virulence factors, such as bacterial adhesion, toxin production and binding, and biofilm formation, thereby limiting the pathogenic potential of these microorganisms.

The adhesion of E. coli to receptors on intestinal epithelial cells is a critical step in the infection process (Heo et al., 2013; Kim et al., 2022). Notably, tannins have demonstrated the ability to inhibit bacterial adhesion to the IPEC-J2 cell line, an in vitro model derived from porcine jejunal epithelial cells, commonly used to study the effects of tannins on intestinal health in pigs. Specifically, water extract from L. salicaria L. containing C-glycosylic ellagitannins and isolated castalagin significantly reduced enteropathogenic E. coli (EPEC) adhesion by 20.4% and 37.7%, respectively (Granica et al., 2020). Importantly, similar effects were observed in ex vivo studies. Polyphenol extract from cocoa beans, pentagalloyl glucose crude and purified HT successfully inhibited ETEC adhesion to pig intestinal brush borders (Verhelst et al., 2010). Moreover, cranberry extract prevented the adherence of F4⁺ and F18⁺ E. coli to porcine intestinal villi without reducing bacterial viability (Coddens et al., 2017). These findings suggest that tannins could play an important role in preventing intestinal infections by limiting bacterial adhesion, highlighting their potential as therapeutic agents for improving intestinal health in pigs.

Tannins may also effectively interact with toxins released by ETEC strains after adhesion. Pentagalloyl glucose crude and purified HT inhibited the binding of the heat-labile toxin produced by ETEC (Verhelst et al., 2010). Later pentagalloylglucose significantly inhibited the binding of the heat-labile toxin to the intestinal receptor GM1, potentially due to the formation of large LT–polyphenol aggregates (Verhelst et al., 2013). The findings suggest that tannins’ distinctive composition may play a key role in reducing toxin-mediated damage during PWD in pigs.

Biofilm formation is a crucial virulence factor in bacteria, playing a key role in the development of chronic, drug-resistant infections. The multifactorial nature and complex structure of biofilms make them particularly challenging to treat (Koo et al., 2017). Studies have shown that ellagic acid and TA effectively reduce biofilm formation in E. coli F18 (Hancock et al., 2010). TA has also demonstrated synergy with other antibacterial agents. For instance, nanocomposites of TA and silver have shown potent anti-bacterial and anti-biofilm properties. TA likely exerts its effects by inhibiting quorum sensing—a regulatory process controlling bacterial behaviors such as biofilm formation (Liu L. et al., 2020). Tannins capacity to inhibit biofilm formation renders them a promising class of compounds for the development of alternative treatments against pathogens, including those associated with PWD.

The IPEC-J2 cell line is commonly used as a model to study the effects of tannins on intestinal epithelium. Table 2 summarizes research findings on the influence of tannins on epithelial health and monolayer integrity. Overall, the studies suggest that tannins exert a dose-dependent effect on IPEC-J2 cells viability and proliferation. While higher concentrations may impair cells viability, lower doses have been shown to exert protective or even stimulatory effects (Caprarulo et al., 2020). For instance, TA was found to decrease IPEC-J2 cells viability through several mechanisms, including oxidative stress induction, DNA damage, mitochondrial dysfunction, and the activation of the mitochondrial apoptotic pathway. It also caused S phase arrest, leading to cytotoxicity and reduced cell proliferation (Wang et al., 2019). However, subsequent findings by the same author showed that TA increased cell viability at certain concentrations, suggesting that while high doses or prolonged exposure have adverse effects, appropriate doses may confer benefits (Wang et al., 2022). Similarly, studies with in vitro digested chestnut and quebracho tannins revealed that high concentrations lead to a reduction in cell viability, while lower dosages have a beneficial effect, promoting cell survival (Reggi et al., 2020). Apart from survival ability of cells, there are some investigations focusing on tannins’ effect on growth and division of cells. For example, HT from chestnut and oak were found to accelerate proliferation of IPEC-J2 cell line but the mechanism of this action is unclear (Brus et al., 2013c). Taken together, these findings highlight the complex, dose-dependent effects of tannins on the viability of intestinal epithelial cells.

The measurement of monolayer formation is also an effective parameter for assessing the impact of external agents, such as tannins, on cells. Tight junction proteins, such as claudins (CLDN), occludin (OCLN), zonula occludens proteins (ZO-1, ZO-2, ZO-3), are essential for forming a functional monolayer, providing both the permeability barrier and the cohesive cell-cell adhesion. In most in vitro studies, tannins have been shown to have a positive influence on the expression of tight junction proteins. Purple loosestrife (L. salicaria L.) water extract, along with its isolated ellagitannins—castalagin, vescalagin, salicarinins A and B—stimulated the formation of an IPEC-J2 monolayer. The extract was found to enhance the expression of CLDN-4 and ZO-1 proteins, whereas salicarinins A and B demonstrated the ability to upregulate CLDN-4 (Granica et al., 2020). Similarly, TA has been reported to upregulate the mRNA expression of OCLN and ZO-1 along with increasing protein levels of CLDN-1 and OCLN in cells with oxidative damage induced by tert-butyl hydroperoxide (TBH) (Wang et al., 2022). The other study also confirms that TA increased expression of OCLN, CLDN-1, ZO-1 at both mRNA and protein levels in the intestinal cells injured by E. coli (Liu and Guo, 2024). However, gallic acid has shown mixed results; it reduced monolayer integrity by decreasing CLDN-1 protein expression, although the lower concentrations used in the experiment had no negative effect on tight junction protein abundance (Tretola et al., 2021). These studies show that tannins, at appropriate concentrations, can support the formation of the cell monolayer.

Tannins have been widely studied for their antioxidant properties and potential to mitigate oxidative stress in various IPEC-J2 models. In a model of oxidative stress induced by TBH, TA significantly mitigated the reduction in cell viability and improved cell morphology, highlighting its protective role in maintaining cellular health. The study showed that TA treatment reduces levels of reactive oxygen species and malondialdehyde (MDA), a product of lipid peroxidation, while boosting antioxidant markers like total antioxidant capacity, glutathione, and total glutathione (Wang et al., 2022). Similarly, TA was found to effectively counteract the oxidative stress caused by ETEC infection by increasing cell viability, enhancing the activity of antioxidant enzymes, and reducing MDA levels (Liu and Guo, 2024). The protective mechanism of TA may involve activation of the p62-Keap1-Nrf2 pathway, which plays a crucial role in regulating the cellular antioxidant response. This is supported by the observed increase in Nrf2 and GPX4 protein levels—both associated with enhanced antioxidant defenses—and the decrease in Keap1 protein levels, which normally suppresses Nrf2 activity (Wang et al., 2022; Liu and Guo, 2024). Another tannin source, in vitro digested chestnut and quebracho, were also shown to increase cell viability in a model of oxidative stress induced with hydrogen peroxide and dextran sodium sulfate further (Reggi et al., 2020). These findings underscore the potential of tannins as a protective agent against oxidative damage, especially relevant in conditions like PWD.

Oxidative and inflammatory processes are closely interrelated, and TA’s dual capacity to mitigate both stresses in IPEC-J2 model is well documented. TA treatment was shown to reduce the levels of pro-inflammatory markers, such as TNF-α, IL-1β and IL-6, as well as the protein abundance of TLR4, MyD88, phosphorylated NF-κB, and NLRP3, in cells exposed to TBH- or ETEC-induced inflammation (Wang et al., 2022; Liu and Guo, 2024). These results indicate that TA may reduce inflammatory responses by modulation of components of the TLR4-MyD88-NF-κB-NLRP3 pathway, which are known to mediate inflammatory responses (Liu and Guo, 2024). TA was also shown to modify the protein levels of LC3 and SQSTM1/p62 in TBH-treated cells, indicating that it may regulate autophagy, a cellular process responsible for removing damaged organelles, proteins, and pathogens, to maintain cellular health and prevent further inflammation (Wang et al., 2022).

Most of the studies on the anthelmintic properties of tannins have been performed in vivo, but some important in vitro studies have also been reported. Diverse tannin-rich plant extracts and isolated CT have shown strong in vitro anthelmintic activity against Ascaris suum, affecting larval migration, survival, and tissue integrity (Williams et al., 2014a) as well as against Oesophagostomum dentatum, affecting especially larval development and motility of adult worms (Williams et al., 2014b). These findings highlight the potential of tannins as effective anthelmintic agents in pigs, offering a promising strategy to reduce reliance on conventional synthetic drugs.

The gastrointestinal microbiota plays a critical role in pig health, particularly during stressful periods such as weaning. Beyond their antimicrobial effects, tannins have been shown to act as eubiotics influencing the structure and composition of the gut microbiota, potentially promoting a more balanced microbial ecosystem (Huang et al., 2018; Caprarulo et al., 2021). In the following, only recent studies that are not listed in the previous reviews are highlighted (Table 3).

Supplementation of 1.5 g/kg TA from gallnut to a diet for weaned piglets led to a higher abundance of Proteobacteria and a decrease of Firmicutes in the caecum digesta compared to piglets of the control group. This effect was not observed in a group with 3 g/kg supplementation. In contrast to that, the group with 3 g/kg TA supplementation had a lower abundance of Eubacterium oxidoreducens and Escherichia-Shigella compared to control animals. Candidatus brocadia was reduced in the 1.5 and 3 g/kg TA supplementation. The authors hypothesized that the altered composition of bacteria in the 3 g/kg group might be related to the higher level of antioxidants in the gut due to the TA supplementation (Deng et al., 2024). Supplementation of 0.05, 0.1, 0.2% and 0.4% TA from gallnut resulted in linear increase of Bacillus spp. in the caecum content. Escherichia coli numbers in colon content were lower in 0.1% TA group than in 0% and 0.4% TA. Moreover, 0.05% and 0.2% TA addition resulted in higher counts of total bacteria in caecum content than in 0.4% group (Song et al., 2021). An addition of 2,000 mg/kg tannins of black wattle tannins led to a higher abundance of Brevibacillus spp. in rectum content than in control piglets (Souza et al., 2025). A diet with 1.25 chestnut/quebracho extract decreased the abundance of Bacteroidetes and Actinobacteria while Spirochaetae and Cyanobacteria increased. Moreover, Clostridiaceae, Peptococcaceae, Spirochaetaceae and Peptostreptococcaceae had a higher abundance and Prevotellacea, Eubacteriaceae, Coriobacteriaceae, Desulfovibrionaceae, Veillonellaceae, Rikenellaceae, and Deferribacteraceae a lower abundance in the tannin group. On the genus level, the rel. abundance of Shuttleworthia, Pseudobutyrivibro, Anaerostipes, Solobacterium and Peptococcus was higher and Synotrophococcus, Mitsuokella, Sharpea, Atopbium and Prevotella were lower in the feces of tannin supplemented piglets (Miragoli et al., 2021). When coated chestnut tannins were supplemented to the diet of weaned pigs, Ruminococcaceae dominated followed by Lachnospiraceae where it was the other way around for the control. The addition of coated tannins resulted in higher abundance of the genera Faecalibacterium, Faecalitalea, Acidaminococcus, Methanobrevibacter smithii, and Turicibacter than in the control group in the digesta of the same segment as before (Xu et al., 2022).

Mentioned studies also examined the impact of tannin supplementation on microbial diversity and richness, revealing inconsistent changes in Shannon, Simpson, and Chao1 indices. Shannon index in caecum digesta did not differ due to TA supplementation (Deng et al., 2024) nor were Shannon and Simpson indices different in colon digesta after addition of coated tannins (Xu et al., 2022). In addition, Chao 1, Shannon and Simpson in colon digesta were unaffected by supplementation of condensed tannins in a trial with a challenged environment (Yi et al., 2023). Also, an addition of black wattle tannins had no impact on the Shannon index in rectum digesta (Souza et al., 2025). Moreover, the Chao 1 was unaffected in the later study (Souza et al., 2025) and in faeces samples from a trial with 1.25 chestnut/quebracho extract (Miragoli et al., 2021) as well as in the colon digesta of piglets that received an addition of coated tannins in the diet (Xu et al., 2022). In contrast to that 3 g/kg TA led to a reduction in OTUs in caecum content related to the control (Deng et al., 2024), while an addition of coated tannins to a diet had no impact on observed species in colon digesta (Xu et al., 2022). Contrary, in a trial with 1.25% chestnut/quebracho extract the observed species, Shannon and Simpson indices were increased (Miragoli et al., 2021).

The studies show that tannin supplementation can have an impact on the bacterial composition and may lead to a shift on phyla and some families or genera, while the observations are very diverse. This might be also related to the different dosages and tannin sources. The stability of diversity indices, despite compositional shifts, suggests that tannins reorganize the gut microbiota without reducing richness. This reorganization may favour beneficial taxa, such as short-chain fatty acids (SCFA) producers, which support gut health through improved barrier function and anti-inflammatory effects.

Variability across studies is likely driven by tannin type, source, concentration, and form of administration, all of which influence bioactivity. To better understand functional outcomes, future research should combine microbiota profiling with metabolomic or metagenomic analyses. This integrated approach will clarify how tannins modulate microbiota function and contribute to gut health in piglets.

The metabolic pathways by which tannins are degraded by the microbiome, along with information on their stability and the absorption of tannin compounds, were described in a previous review (Girard and Bee, 2020). Tannins can also affect microbial metabolites in the gastrointestinal tract. However, only a few in vivo studies have addressed the change of metabolite composition within the digesta (Table 3).

Dietary inclusion of TA from gallnut (0.05%–0.4%) altered the SCFA profile in the cecal and colonic digesta. Specifically, 0.2% TA resulted in the highest concentrations of acetic and propionic acids in the caecum, while all tannin-supplemented groups had elevated levels of butyric acid. A dose-dependent increase in propionic, butyric, and valeric acids was observed in the caecum, while acetic acid was elevated in the colon at the highest inclusion level. Conversely, isobutyric acid decreased linearly with increasing tannin dosage (Song et al., 2021). Faecal butyrate concentration increased when 1.25% chestnut/quebracho extract was included in the diet, while valerate concentration decreased compared to the control group (Miragoli et al., 2021). Moreover, the animals fed diets with tannins showed an increased concentration of phenolic compounds and nitrogen, whereas ammonia and urea concentrations were not altered (Caprarulo et al., 2020).

A supplementation of a weaner diet with 150 mg/kg of grape extract resulted in a tendency towards a higher lactic acid content in colon digesta although the effect diminished at later stages of the experiment. The supplementation had no effect on the short chain fatty acids and lactate concentrations in the ileum digesta. Ammonia and composition and biogenic amines in colon content were unaffected by the addition of tannins to the diet. In contrast to that a decrease in ammonia concentration in ileum digesta was observed after 27/28 days of supplementation in comparison to piglets fed the control diet (Rajković et al., 2021). In addition, lower iso-butyric and iso valeric acid concentrations and tended lower ammonia concentrations in caecum digesta were observed in a trial, where 1.13 g/kg, 2.25 g/kg, and 4.5 g/kg were added to the basal diet (Biagi et al., 2010). In summary, diverse effects on postbiotic concentrations could result from different tannin sources and tannin dosages.

The main site of digestion and absorption of macro- and micronutrients is the small intestine, which consists of duodenum, jejunum and ileum. The small intestine has villi and microvilli, which increase the surface area for absorption. Longer, more developed villi contribute to a larger villous surface area. This in turn enhances nutrient absorption, promotes growth, feed conversion efficiency, and overall health and nutrition in pigs (Itza-Ortiz et al., 2019). At the base of the villi are crypts, where new epithelial cells form and migrate upward to replace old cells. Smaller crypts and faster epithelial cell turnover are associated with better gut health and nutrient absorption efficiency, while deeper crypts may indicate intestinal damage or inflammation, which can reduce the pig’s ability to properly digest and absorb nutrients (Spreeuwenberg et al., 2001).

Weaning triggers distinct morphological and histological changes in the piglet’s small intestine, including a reduction in villous height (VH) and villous surface area, as well as an increase in crypt depth (CD) (Spreeuwenberg et al., 2001). Recent studies have highlighted the beneficial effects of tannin supplementation on gut morphology (Table 4).

It was shown that tannins consumption enhances VH in intestines. In the duodenum, higher VH was observed after supplementation with HT from chestnut (Bilić-Šobot et al., 2016) and gallnut (Song et al., 2021; Deng et al., 2024). In the jejunum, supplementation with tannins from chestnut, quebracho, and grape has been shown to enhance VH (Han et al., 2016; Liu H. et al., 2020; Ma et al., 2021). Similar positive effects have been reported for gallnut and grape tannins by other authors (Song et al., 2021; Rajković et al., 2022; Deng et al., 2024). Furthermore, HT from chestnut and CT from grapes positively affected ileal VH (Han et al., 2016; Liu H. et al., 2020; Rajković et al., 2022). However, TA at a concentration of 1% was reported to negatively affect VH in the ileum suggesting that the positive effect of tannins may be dose-dependent (Yu et al., 2020).

By enhancing VH, tannin supplementation was shown to positively affect villous surface area. An increase in surface area in duodenum was observed in piglets supplemented with 3% chestnut wood extract (Bilić-Šobot et al., 2016). In the jejunum and ileum, greater villus surface area was observed following the supplementation with dried grape extract (Rajković et al., 2022). Moreover, tannin supplementation in the diet of piglets challenged with ETEC significantly increased VH and, consequently, the surface area in both the duodenum and ileum (Zhang et al., 2023).

Supplementation with tannins was also shown to decrease CD, minimizing the stress-induced changes. TA reduced CD in the duodenum (Wang et al., 2020; Yu et al., 2020). Similarly, reductions in CD within the jejunum and ileum were observed following the application of TA (Deng et al., 2024) and CT from grapes (Han et al., 2016). A tendency for reduction of ileal CD was also observed after supplementation with HT from chestnut (Biagi et al., 2010) and TA from gallnut (Yu et al., 2020). In another study, a decrease in ileal CD was noted with quebracho tannin supplementation (Ma et al., 2021). Hydrolytic Chinese gallnut TA also reduced CD of the ileum compared to ZnO diet, as a control (Sun et al., 2021). A lower CD was observed in all intestinal sections of piglets challenged with ETEC in the tannin-supplemented diet group (Zhang et al., 2023).

As a result of changes in VH and CD, weaning impacts the villus height to crypt depth (VH/CD) ratio which is a key parameter for assessing nutrition quality. A high VH/CD ratio indicates healthy gut morphology and good absorption capacity, whereas a low ratio suggests impaired absorption function (Montagne et al., 2003). Supplementation with chestnut tannins positively affected the VH/CD ratio in the duodenum and increased mucosal thickness, reflecting the combined measurement of VH and CD (Bilić-Šobot et al., 2016). Gallnut tannins also increased VH/CD ratio in the duodenum (Yu et al., 2020; Deng et al., 2024; Wang et al., 2020). In the jejunum, this ratio increased following supplementation with TA (Deng et al., 2024) and grape seed proanthocyanidins (Han et al., 2016). Similarly, the VH/CD ratio in the ileum improved with HT from chestnut wood (Liu H. et al., 2020), grape seed extract (Han et al., 2016) and dried grape extract (Rajković et al., 2022). Natural tannin increased VH/CD ratios in duodenum, jejunum and ileum of piglets challenged with ETEC (Zhang et al., 2023). Moreover, diets supplemented with commercial tannin products resulted in a narrower crypt/villi ratio (CD/VH) in the small intestine, meaning that the villi were relatively larger compared to the crypt depth in the intestinal mucosa (Brus et al., 2013a).

The observed differences in the effects of tannins on intestinal morphology reflect the previously discussed structural and functional diversity among tannin types. HT, such as those from chestnut or gallnut, are rapidly hydrolyzed in the upper gastrointestinal tract which may explain their pronounced effects on duodenal VH, CD, and VH/CD ratio (Bilić-Šobot et al., 2016; Song et al., 2021; Deng et al., 2024). In contrast, CT, derived from sources like grape seed or quebracho, are much more resistant to degradation and thus no significant effects on the duodenum have been observed. However, they were shown to influence their morphological effects further along the intestine, particularly in the jejunum and ileum (Han et al., 2016; Ma et al., 2021; Rajković et al., 2022). TA, although classified as a HT, has a relatively simple and uniform molecular structure compared to other HT. This structural simplicity contributes to its strong protein-binding capacity and rapid hydrolysis in the upper gastrointestinal tract. As a result, TA exerts its effects already in duodenum (Wang et al., 2020; Yu et al., 2020), but its effects are highly dose-dependent—low to moderate levels may support epithelial integrity, whereas excessive doses can disrupt villus morphology, particularly in the ileum (Yu et al., 2020).

In the large intestine, which comprises the caecum, colon, and rectum, the primary roles include water and electrolyte absorption, fermentation of undigested material, and feces formation and storage (Szabó et al., 2023). The balance between mitotic and apoptotic cell counts in the large intestine influences epithelial turnover and mucosal health. Chestnut tannin supplementation in fattening boars led to significant, dose-dependent reductions in both apoptotic and mitotic cell counts, particularly in the caecum and descending colon. A notable decrease in apoptotic cell counts was observed in all treatment groups, especially in the ascending colon, where reductions ranged from 16% to 32% depending on the dosage. This decline in apoptotic cells, particularly in the ascending colon, suggests potential improvements in epithelial health following a commercial tannin product supplementation (Bilić-Šobot et al., 2016). In addition, supplementation with quebracho tannins has been shown to reduce colonic mucosa thickness, allowing better water absorption from the stool and lowering the incidence of diarrhea in piglets (Ma et al., 2021).

In summary, supplementation with tannins, particularly from chestnut, gallnut, and grape seed extracts, positively affected gut morphology in pigs by enhancing VH and villus surface area, reducing CD and improving the VH/CD ratio in the small intestine. These effects contribute to better nutrient absorption and overall gut health. Additionally, tannin supplementation in the large intestine led to dose-dependent reductions in mitotic and apoptotic cell counts, indicating improved epithelial integrity, especially in the caecum and colon.

Maintaining the integrity of the intestinal barrier is crucial for preventing the entry of harmful substances and pathogens to the bloodstream. Tight junction proteins, such as previously mentioned claudins, occludin, and zonula occludens proteins help “seal” the spaces between epithelial cells in the gut, ensuring a selective barrier and controlling the permeability of the intestinal barrier (Hu et al., 2013). Weaning stress associated with inflammation can disrupt tight junction function, leading to a condition known as “leaky gut,” where the intestinal barrier becomes weakened and more susceptible to infections (Wei et al., 2021). Nutritional strategies, such as supplementation with tannins, may mitigate the negative effects of weaning stress and maintain a healthy gut barrier. As shown in Table 5, several studies have demonstrated the impact of different tannin sources on tight junction protein expression in the porcine intestinal epithelium.

Differences in tight junction proteins were observed at both the protein and mRNA levels. At the protein level, the supplementation of TA in pig diets has been shown to increase the ZO-1 expression in the jejunum (Wang et al., 2022) and OCLN expression in the duodenum, jejunum, and ileum (Yu et al., 2020). Additionally, coated tannins from chestnut increased ZO-1, OCLN, CLDN-1 protein level in the colon at a dietary inclusion level of 0.15% (Xu et al., 2022). Finally, grape seed proanthocyanidins significantly elevated OCLN expression in the ileal and colonic mucosa of piglets (Han et al., 2016). At the mRNA level, tannin commercial product, which contains TA, was found to increase the expression of tight junction-related genes in the jejunum: ZO-1 in the 0.4% TA group, ZO-2 in all TA groups and CLDN-2 in 0.2% TA group (Song et al., 2021). Both the 0.2% and 1.0% TA diets promoted higher levels of OCLN mRNA in the duodenum. Notably, a 0.2% concentration of tannin was associated with increased ZO-2 mRNA expression levels in the duodenum and a tendency to upregulate ZO-1 mRNA levels in the ileum, while 1.0% tannin content tended to upregulate OCLN mRNA expression levels in the jejunum (Yu et al., 2020). Furthermore, CT enhanced the mRNA expression of ZO-1 in the jejunum and OCLN in the ileum of weaned piglets in an ETEC strain K88-challenged environment (Yi et al., 2023).

Based on these studies, it can be seen that both HT and CT positively affect the levels of tight junction proteins. By doing so, these phytochemicals reduce inflammation, strengthen the integrity of the intestinal barrier, and enhance its protective functions.

Due to their unique structure, tannins exhibit other biological effects that are beneficial for pigs during critical weaning and post-weaning periods. Their antioxidant properties are strongly linked to gut health, where they protect the gastrointestinal tract from oxidative damage. This protection may enhance the integrity of intestinal tissues and support the animal’s immune response by reducing inflammation caused by oxidative stress. These effects were summarized in a systematic review that synthesized data from multiple trials and highlighted how tannins from different sources influence the antioxidant status of piglets (Nuamah et al., 2024). Although these antioxidant effects are largely attributed to the tannins chemical structure, particularly those with higher molecular weights showing stronger antioxidant activity, the precise pathways remain unclear and warrant further investigation (Tong et al., 2022).

Tannins are also known for their anti-inflammatory properties. Few studies have examined the impact of tannins on cytokines, which are signaling molecules responsible for regulating inflammation and immune responses. Cytokines such as IL-1β and TNF-α are key mediators of the inflammatory response, and their dysregulation can lead to chronic inflammation and tissue damage. Importantly, TA from gallnut was found to downregulate the pro-inflammatory cytokines IL-1β and TNF-α in the jejunum of weaning pigs (Deng et al., 2024). This suggests that tannins may help modulate the inflammatory processes in the gut, thereby alleviating the inflammatory challenges commonly faced by piglets during the weaning period.

As previously mentioned, the antioxidant and anti-inflammatory activity of tannins are thought to contribute to their immunomodulatory properties; however, the exact mechanisms are not fully understood. Some studies suggest that by reducing oxidative stress and inflammation, tannins help create a more favorable environment for immune cells. This, in turn, promotes the production of immunoglobulins such as IgM and IgG, which are essential for neutralizing pathogens and maintaining immune homeostasis (Liu H. et al., 2020).

Tannins also show promise in the treatment and prevention of parasites in farming. CT, in particular, have been shown to reduce gastrointestinal parasites and improve livestock health. For instance, the consumption of acorn (Quercus robur), which is rich in CT, reduced fecal parasite egg counts in Black Slavonian pigs infected with A. suum by 96.56%. Similar effects were observed for other gastrointestinal nematodes (Oesophagostomum spp., Strongyloides, and Hyostrongylus spp.), with reductions of up to 93.55% (Rodríguez-Hernández et al., 2023). Tannins effect on worm burdens is likely to protein precipitation on the parasite’s cuticle or digestive tract (Kresˇimir et al., 2004). However, tannins may also act indirectly by stimulating the host’s immune response to the parasite infection as it was shown for grape pomace (Williams et al., 2017).

In summary, tannins exhibit a range of beneficial effects, including antioxidant, anti-inflammatory, anti-parasitic and immune modulating, which can be beneficial in pig farming.