key: cord-0003336-pxvrqxxf
authors: Huang, Qianqian; Liu, Xiuli; Zhao, Guoqi; Hu, Tianming; Wang, Yuxi
title: Potential and challenges of tannins as an alternative to in-feed antibiotics for farm animal production
date: 2017-10-14
journal: Anim Nutr
DOI: 10.1016/j.aninu.2017.09.004
sha: a633596dc4ee28692afaa88122c65b997d1e4d1f
doc_id: 3336
cord_uid: pxvrqxxf

Naturally occurring plant compounds including tannins, saponins and essential oils are extensively assessed as natural alternatives to in-feed antibiotics. Tannins are a group of polyphenolic compounds that are widely present in plant region and possess various biological activities including antimicrobial, anti-parasitic, anti-viral, antioxidant, anti-inflammatory, immunomodulation, etc. Therefore, tannins are the major research subject in developing natural alternative to in-feed antibiotics. Strong protein affinity is the well-recognized property of plant tannins, which has successfully been applied to ruminant nutrition to decrease protein degradation in the rumen, and thereby improve protein utilization and animal production efficiency. Incorporations of tannin-containing forage in ruminant diets to control animal pasture bloat, intestinal parasite and pathogenic bacteria load are another 3 important applications of tannins in ruminant animals. Tannins have traditionally been regarded as “anti-nutritional factor” for monogastric animals and poultry, but recent researches have revealed some of them, when applied in appropriate manner, improved intestinal microbial ecosystem, enhanced gut health and hence increased productive performance. The applicability of plant tannins as an alternative to in-feed antibiotics depends on many factors that contribute to the great variability in their observed efficacies.

Antibiotics for growth promotion in farm animal production have been used for several decades and proved to be effective in increasing animal and poultry production efficiency. However, it is widely believed that use of antibiotics as growth promoters promotes evolution and/or selection of antibiotic-resistant microorganisms in farm animals (Chattopadhyay, 2014) . Extensive researches have been done over the last couple decades to search for natural alternatives to in-feed antibiotics, and plant compounds (or phytogenic compounds) have been identified to have great potentials (Yang et al., 2015) . Among them, plant tannins have received considerable attention and probably are the most studied compounds especially for farm ruminants. Biological activities of tannins and animal responses to dietary tannins have been extensively reviewed mainly focusing on animal nutrition and production (Mueller-Harvey et al., 2006; Waghorn, 2008; Wang and McAllister, 2011; Redondo et al., 2014) . This review, after briefly summarizing some important chemical characteristics and biological properties of plant tannins, mainly focuses on the recent development in applications of anti-microbial, anti-parasitic and immunomodulation properties of tannins in farm animals.

Tannins are naturally an occurring heterogeneous group of phenolic compounds with diverse structures that share their abilities to bind and precipitate proteins. Tannins are primarily classified into 3 major groups: hydrolyzable tannins (HT), condensed tannins (CT) also referred as proanthocyanidins, and phlorotannins (PT). The first 2 groups are found in terrestrial plants whilst PT occur only in marine brown algae (Fig. 1) . Hydrolyzable tannins are made up of a polyol core (commonly D-glucose), which is esterified with phenolic acids (mainly gallic or hexahydroxy diphenic acid). The molecular weights of HT range from 500 to 3,000 Da (Haslam, 1989) . They are susceptible to hydrolysis by acids, bases or esterases, thus can be easily degraded and absorbed in the digestive tract and may cause potential toxic effects in herbivores (Dollahite et al., 1962; Mcleod, 1974) . Condensed tannins are oligomeric or polymeric flavonoids consisting of flavan-3-ol units that include catechin, epicatechin, gallocatechin and epigallocatechin. Compared to HT, CT has more complex structures and higher molecular weights ranging from 1,000 to 20,000 Da. Unlike HT, only strong oxidative and acidic hydrolysis can depolymerize the CT structures that are also not susceptible to anaerobic enzyme degradation (McSweeney et al., 2001) . The PT, which are structurally less complex than terrestrial tannins (HT and CT), is formed as a result of the polymerization of phloroglucinol (1,3,5trihydroxybenzene) (Ragan and Glombitza, 1986) . The molecular weights of PT range from 126 Da to 650 kDa (Targett and Arnold, 1998) and can be classified into 6 classes (Phlorethols, Isofuhalos, Echole, Fucole, Fuhalols, Fucophlorethols) based on their chemical structure. They are mainly synthesized via the acetate-malonate pathway (Herbert, 1989) although the other pathway has been proposed (Chen et al., 1997) .

Tannins are widely distributed in plant kingdom, especially abundant in nutritionally important forages, shrubs, cereals and medicinal herbs (Salunkhe et al., 1982; Wang et al., 1999) . They are also found in many fruit species such as banana, blackberry, apple and grape as well as tea (Nonaka et al., 1984; Bravo et al., 1992; Mertz et al., 2007; Mercurio and Smith, 2008; Kheng, 2010) . Condensed tannins are the most common type of tannin in forage legumes, trees and shrubs while HT is often present in leaves of trees and browse shrubs in tropical areas . Generally, tannins are more abundant in vulnerable parts of the plants, e.g., new leaves and flowers (Terrill et al., 1992; Van Soest, 1982; Frutos et al., 2004) . The PT are concentrated in the physodes located in the cytoplasm of cells within the outer cortical layers of the thalli (Ragan and Glombitza, 1986; Lüder and Clayton, 2004; Shibata et al., 2004) . Chemical structures and concentrations of tannins vary greatly among plant species, growth stages and growing conditions such as temperature, light intensity, nutrient stress and exposure to herbivory (Frutos et al., 2004; Amsler and Fairhead, 2006; Berard et al., 2011; Li et al., 2014; Huang et al., 2017) .

Tannins are plant secondary metabolites that serve as a part of plant chemical defence system against invasion by pathogens and attack by insects. Tannins have shown numerous biological activities and some of them, which are most important to the modern food animal production, are summarized below.

The antimicrobial activities of tannins have long been recognized and the toxicity of tannins to bacteria, fungi and yeasts has been reviewed (Scalbert, 1991) . The mechanisms proposed so far to explain tannin antimicrobial activity include inhibition of extracellular microbial enzymes, deprivation of the substrates required for microbial growth, direct action on microbial metabolism through inhibition of oxidative phosphorylation, metal ions deprivation or formation of complexes with the cell membrane of bacteria causing morphological changes of the cell wall and increasing membrane permeability (Scalbert, 1991; Liu et al., 2013) . Evidences have shown that the microbial cell membrane is the primary site of inhibitory action by tannins (Mcallister et al., 2005; Liu et al., 2013) through cell aggregation and disruption of cell membranes and functions (Fig. 2) . Although protein precipitation is a universal property for all tannins, anti-microbial activity of tannins is microbial species-specific and is closely related to the chemical composition and structure of tannins. Generally, antimicrobial activity of tannins against Gram-positive bacteria has been reported to be greater than against Gram-negative bacteria (Ikigai et al., 1993; Smith and Mackie, 2004) , because Gramnegative bacteria possess an outer membrane that consists of a lipid bilayer structure which is composed of an outer layer of lipopolysaccharide and proteins and an inner layer composed of phospholipids. However, tannins especially CT isolated from several plants have been shown to possess strong activity against Gram-negative bacteria. It is worth noting that pathogenic bacteria such as Escherichia coli O157:H7, Salmonella, Shigella, Staphylococcus, Pseudomonas and Helicobacter pylori were all sensitive to tannins (Funatogawa et al., 2004; Doss et al., 2009; Banso and Adeyemo, 2010; Liu et al., 2013) . Wang et al. (2013) compared 12 tannins and found only CT isolated from purple prairie clover (Dalea purpurea Vent) and PT from brown alga (Ascophyllum nodosum) possessed strong anti-E. coli and anti-E. coli O157:H7 activity. Phlorotannins also have greater antimicrobial activity than CT and HT (Wang et al., 2009) . It has been shown that number of hydroxyl groups and liberation of hydrogen peroxide upon oxidation of tannins are 2 important factors responsible for the antimicrobial properties of tannins (Akagawa et al., 2003; Smith et al., 2003; Mueller-Harvey, 2006) . It has been proposed that flavonols with a trihydroxy B ring (gallocatechin) have a greater inhibitory effect on Streptococcus, Clostridium, Proteus and Staphylococcus species than catechin with a dihydroxy B ring (Sakanaka et al., 1989) . Similarly, the toxicities of epi-catechin gallate and epigallocatechin gallate towards Clostridium botulinum were greater than those of their ungallated counterparts-epicatechin and epigallocatechin (Okuda et al., 1985) . Because of the vast sources of tannins, which results in great diversity in their antimicrobial activities, screening and identification of tannins that are effective and specific to target microbes would continuously be a research endeavor.

Anti-parasitic properties of tannins have been demonstrated by both in vitro and in vivo studies. Condensed tannins extracted from legume tanniferous forages such as sainfoin (Onobrychis viciifolia), big trefoil (Lotus pedunculatus), birdsfoot trefoil (Lotus corniculatus) and sulla (Hedysarum coronarium) reduced the proportion of Trichostrongylus colubriformis hatched eggs and inhibited egg development of lungworm and gastrointestinal nematodes (mixed species of Ostertagia, Oesophagostomum, Cooperia, Trichostrongylus, and Strongyloides) in a dose-dependent manner (Molan et al., 2000a (Molan et al., , 2000b (Molan et al., , 2002 . Four tropical tanniniferous plant extracts have shown anthelmintic effect on Haemonchus contortus and T. colubriformis, which mainly interfered with the process of larval exsheathment (Alonso-Díaz et al., 2008a , 2008b . Tannins extract from quebracho (Athanasiadou et al., 2001) , chicory (Molan et al., 2003) and green tea (Molan et al., 2004) significantly inhibited the larval migration in a dose dependent manner. These results suggest anti-parasitic effect of tannins occurred throughout different stages of life-cycle of parasite. The anti-parasitic effects of various tannins observed in in vitro studies have also been confirmed in numerous in vivo studies involving in sheep and cattle (Paolini et al., 2003; Heckendorn et al., 2007; Chaweewan et al., 2015; Desrues et al., 2016) .

The anthelmintic mechanisms of plant tannins have been suggested through "direct" action of tannins on parasite cells by 1) reducing establishment of the infective third-stage larvae in the host thereby reducing the host invasion, 2) reducing excretion of nematodes eggs by the adult worms, and 3) reducing development of eggs to third-stage larvae (Athanasiadou et al., 2001 (Athanasiadou et al., , 2005 Brunet et al., 2008; Hoste et al., 2012) and through "indirect" action by improving the host's resistance to nematodes Tzamaloukas et al., 2006; Pathak et al., 2016) . However, similar to their antimicrobial activities, the anthelmintic effects of tannins vary greatly depending on chemical composition and structure of tannins, the parasite species or growth stages and/or the hosts' species (Hoste et al., 2006 (Hoste et al., , 2012 .

Naturally occurring phenolic compounds have long been recognized as effective antioxidants (Rice-Evans et al., 1995 . The antioxidant property of tannins has wide application in food industry and medical field to prevent oxidative stress related diseases such as cardiovascular disease, cancer or osteoporosis (Hollman and Katan, 1999; Scalbert et al., 2005) . It has been shown that CT and HT of relatively high molecular weight exhibited greater antioxidant activities than simple phenolics (Hagerman et al., 1998) . The number of hydroxyl groups and the degree of polymerization of tannins are considered to be correlated with their abilities to scavenge free radicals (Ariga and Hamano, 1990 ). Tannins with the most hydroxyl groups are most easily oxidized (Hodnick et al., 1988) and therefore possess greatest antioxidant activity. Ricci et al. (2016) demonstrated that effectiveness of tannins as natural antioxidants is due to their complex combinations of reducing and redox activities, which also contributes to their abilities to scavenge radicals.

The potential of tannins as biological antioxidants has been indicated in many in vitro studies (Ho et al., 1999; Lin et al., 2001; Beninger and Hosfield, 2003; Barreira et al., 2008) . The in vivo antioxidant activities of tannins were also demonstrated in different animal tissues. Inclusion of forage containing CT improved antioxidant status of both cattle and sheep by increasing serum antioxidant activity (Dutta et al., 2012; Dey and De, 2014; Huang et al., 2015; Peng et al., 2016) . Quebracho tannins in lamb diets improved the antioxidant status of muscle (Luciano et al., 2011) , liver and plasma (L opez-Andr es et al., 2013) and enhanced meat color stability by delaying myoglobin oxidation during refrigerated storage (Luciano et al., 2009) . Given the fact that HT are degraded in the gastrointestinal tract before absorption whilst CT can not be degraded and absorbed from the digestive tract, it is not easily to explain how tannins as intact entities exert anti-oxidant activity within animal body. L opez-Andr es et al. (2013) found that quebracho tannins were not degraded or absorbed in the gastrointestinal tract, but increased the antioxidant capacity of liver and plasma in sheep, which demonstrated that CT may indirectly affect antioxidant status in animal tissues. The tannins-protein complexation has been shown to reduce but not eliminate the antioxidant activities of tannins (Riedl and Hagerman, 2001; Arts et al., 2002) . It has been speculated that dietary tannins may spare other nutritive antioxidants during digestive process or they may protect proteins, carbohydrates, and lipids in the digestive tract from oxidative damage during digestion (Marshall and Roberts, 1990) . However, the antioxidant mechanism of tannins in animal tissues is unknown. Further research in this area is needed, especially because enhancing antioxidant status is suggested to be one of the most benefits of feeding tannins to animal wellbeing and performance.

Tannins possess varying anti-inflammatory activities (Mota et al., 1985; Terra et al., 2007; Sugiura et al., 2013; Park et al., 2014) that are positively associated with their antioxidant activities (Gonçalves et al., 2005; Souza et al., 2007; Park et al., 2014) . In vitro studies have showed that tannins from grape-seed lowered low-grade inflammatory disease such as obesity by modulating cytokine expression (Terra et al., 2007; Chac on et al., 2009 ). Antiinflammatory activity of CT extracted from black raspberry seeds was demonstrated by its ability to inhibit lipopolysaccharideinduced RAW 264.7 cells in producing nitric oxide (NO), a proinflammatory mediator that induces inflammation . Hydrolyzable tannins from Myricaria bracteata showed a significant anti-inflammatory effect on croton oil-induced ear edema in mice and on collagen-induced arthritis in DBA/1 mice (Liu et al., 2015a,b) . The authors speculated that the mechanism of antiinflammatory effects was related to the potent ability for scavenging free radicals rather than inhibitory effects of HT on NO and pro-inflammatory cytokines production. Phlorotannins from A. nodosum and Ecklonia cava also exhibited potent antiinflammatory effects based on their ability to inhibit cytokines release (Dutot et al., 2012) , NO and prostaglandin-E2 productions (Wijesinghe et al., 2013) . It needs to be pointed out that most of the studies in this area were conducted using in vitro models. The efficacy of the anti-inflammatory action of tannins in animal body after digestion needs to be evaluated further in in vivo model.

Tannins have been shown to have significant activity against some virus, e.g., human immunodeficiency virus (HIV), bovine adeno-associated virus and noroviruses (Uchiumi et al., 2003; Di Pasquale et al., 2012; Zhang et al., 2012) . Yang et al. (2013) found that a HT (chebulagic acid) had considerable anti-enterovirus 71 activities in vitro and efficiently reduced mortality and relieved clinical symptoms through the inhibition of viral replication in mice model. It has been demonstrated that tannin exerted inhibitory effect on HIV-1 through inhibiting HIV-1 replication by targeting the virus reverse transcriptase (Tan et al., 1991) , protease (Xu et al., 2000) , and integrase (Au et al., 2001) , or inhibiting HIV-1 entry into target cells by interfering with the gp41 sex-helix bundle formation (Liu et al., 2004) . Epigallocatechin from green-tea was reported to inhibit hepatitis C virus (HCV) entry (Ciesek et al., 2011; Calland et al., 2012) . Liu et al. (2015a,b) revealed that tannic acid (HT) inhibited HCV entry and cell-to-cell transmission but did not interfere with intracellular HCV replication. Three HT (punicalagin, punicalin and geraniin) inhibited hepatitis B virus cccDNA production via a dual mechanism through preventing the formation of cccDNA and promoting cccDNA decay (Liu et al., 2016) . Ueda et al. (2013) found that tannins from persimmon (Diospyros kaki) significantly reduced viral infectivity of 12 tested viruses whereas tannins derived from green tea, acacia and gallnuts were effective only for some of them, and protein aggregation seems to be a fundamental mechanism underlying the anti-viral effect of persimmon tannin. Phlorotannins isolated from E. cava have been demonstrated to possess strong activity against influenza virus neuraminidase (Ryu et al., 2011) , porcine epidemic diarrhea virus (PEDV) by inhibiting viral entry and/or viral replication (Kwon et al., 2013) and HIV-1 (Karadeniz et al., 2014) . Similar antiviral activity was also demonstrated for PT isolated from Eisenia bicyclis against murine norovirus (Eom et al., 2015) and human papilloma virus (Kim and Kwak, 2015) .

All the above information demonstrated that tannins possess varying anti-virus activities depending on chemical compositions and structures. Although the mode of anti-virus action of tannins is not fully understood, information obtained so far suggested that inhibition of virus adsorption to the cells, inhibition of the virus penetration into cell nucleus and inhibition of virus reverse transcriptases might be some of the underlying mechanisms (Buzzini et al., 2008) . In vivo studies are needed to explore the potential of tannins as natural anti-virus agents to be used in animal and poultry industries.

Tannins especially CT are widely distributed in nutritionally important forages, trees, shrubs and legumes, which are commonly consumed by ruminants. Therefore, the effects of CT on ruminant nutrition, health and production have been extensively studies and reviewed (Frutos et al., 2004; Mueller-Harvey, 2006; Waghorn, 2008; Patra and Saxena, 2011; Wang et al., 2015) . Condensed tannins can have beneficial or detrimental effects on ruminants, depending on their amount consumed by animals, their type and chemical structure as well as the composition of the rest of the diet, especially CP concentration of the diet (Mueller-Harvey, 2006) . It is generally believed that CT in temperate forage in low to medium (<50 g/kg DM) concentration benefit ruminants in terms of improving protein utilization without negatively affecting feed intake and nutrient digestion (Barry and Mcnabb, 1999; Waghorn, 2008) , depending on CT source and analytical method/standard used to determine concentration. Protein precipitation capacity, anti-microbial, anti-parasitic and anti-oxidant activities are the most relevant properties of tannins to be considered for their uses in ruminant animals. By summarizing numerous researches, Waghorn (2008) has concluded that when forages are fed as a sole diet, the CT in L. corniculatus (about 30 g CT/kg DM) have been beneficial for ruminant production, but the CT in sainfoin, Hedysarum coronarium and L. pedunculatus (concentration generally greater than 50 g/kg DM) do not appear to benefit productivity other than by mitigating the impact of parasites. In contrast to temperate farming, the CT in browse, typical of warm and hot climates, are nearly always detrimental to ruminants, except for reducing internal parasite numbers (Waghorn, 2008) . Condensed tannins at low to medium concentrations benefit ruminant production efficiency because CT reduce protein degradation in the rumen, increase the amount of dietary protein reaching small intestine for absorption (Wang et al., 1994 (Wang et al., , 1996 . At high concentration, however, CT would impede feed intake due to their astringent nature and reduce protein and other nutrients digestion by "over" protecting protein, decrease rumen microbial activity and inhibit endogenous digestive enzyme activities thereby negatively affect animal performance. The dietary concentrations CT that exert the negative effective on animal performance again depend on CT sources (i.e., chemical compositions and structures). Therefore, the majority of the researches have focused on screening and evaluation of different tannins sources and to define their optimum concentrations in ruminant diets. These include to screen and identify the potential tannin-containing forages (e.g., L. corniculatus, L. pedunculatus, sainfoin) that could be incorporate into animal diets (Barry and Mcnabb, 1999; Berard et al., 2011; Acharya et al., 2013) in temperate farming, to define the optimum supplementation rates of varying external tannins (e.g., quebracho tannin, tannic acid) on animal performance (Dschaak et al., 2011; Anantasook et al., 2015; Rivera-M endez et al., 2017) in intensive feeding operation, and to develop technologies (e.g., alkaline treatment, tannin-binding agent, diet mixing) in utilizing the tannin-rich tree leaves and shrubs in tropical and other areas where feed sources are limited (Murdiati et al., 1990; Smith et al., 2005; Wina et al., 2005; Brown and Ng'ambi, 2017) .

Probably the most successful application of tannins in ruminant production is to reduce frothy bloat. Bloat is a common digestive disorder in ruminants. The condition is characterized by an accumulation of gas in the rumen and reticulum that can impair both digestive and respiratory function (Wang et al., 2012) . Many factors can contribute to the bloat but the rapid lyses of plant cells and release of proteins from plant cells upon their entry into the rumen increasing the viscosity of the rumen fluid is a major contributing factor to pasture bloat. Tannins by precipitating protein during chewing and rumination reduce protein solubility in the rumen thereby decrease bloat occurrence. Therefore, tannins-containing forage are regarded as "bloat free". Li et al. (1996) has estimated that as little as 1.0 mg CT/g DM is needed to prevent pasture bloat. Incorporation of CT-containing forage such as sainfoin into alfalfa has been proved an effective method in controlling alfalfa pasture bloat ( Fig. 3 ; Wang et al., 2006; Sottie et al., 2014) .

Another major application of tannins in ruminants especially in grazing ruminants is to control digestive parasites. Hoste et al. (2006) have summarized in vivo studies that tannins in sainfoin, sulla, L. pedunculatus, Sericea lespedeza, Acacia nilotica and chicory had significant anthelmintic effects in digestive tract of sheep, goat and deer. External tannins such as that from mimosa (HT), chestnut (HT) and quebracho (CT) have been used to control various intestinal parasites in ruminant (Butter et al., 2001; Min and Hart, 2003; Min et al., 2005 Min et al., , 2015 . It seems that dietary concentration below 20 g/kg DM of tannins is ineffective in controlling ruminant intestinal parasites. An interesting phenomenon is that sheep could detect the presence of internal parasites or associated symptoms and increase their preference for the tannin-rich feed (Lisonbee et al., 2009; Juhnke et al., 2012) .

Recently, incorporation of tannins or tannin-containing forage into diets has been investigated as a pre-harvest approach to reduce foodborne pathogens in ruminant digestive tract (Table 1) .

Purple prairie clover has been demonstrated as a potential forage for mitigation of E. coli O157:H7, a deadly food-born pathogenic bacteria that reside in ruminant digestive tract Huang et al., 2015) . Huang et al. (2015) found that lambs challenged with E. coli O157:H7 fed diets containing 36 g of purple prairie clover CT/kg DM shed significant less E. coli O157:H7 than lambs fed diets without CT. The same CT were also demonstrated to decrease E. coli fecal shedding in cattle grazing native pasture containing 16 to 20 g CT/kg DM . In addition, adding chestnut tannin at the concentration of 15 g/kg DM decreased fecal shedding of E. coli for cattle fed hay diets (Min et al., 2007) . However, other tannins such as that from sainfoin and S. lespedeza at lower concentration (<13.5 g CT/kg DM) had no effect on fecal E. coli shedding (Lee et al., 2009a,b; Berard et al., 2009 ). Supplementation of A. nodosum meal at the dietary concentrations of 10 to 20 g/kg DM significantly decreased E. coli O157:H7 fecal shedding in cattle (Table 1) . Tannin concentration was not reported in these studies, but A. nodosum is brown algae contain high levels of PT . These researches demonstrated that feeding plant tannins could be a practical method to effectively decrease the presence of E. coli O157:H7 in ruminant digestive tract thereby reduce the risk of carcass contamination and hence enhance the food safety.

Unlike for ruminants, tannins have traditionally been considered as 'anti-nutritional' factors in monogastric nutrition with negative effects on feed intake, nutrient digestibility and production performance (Butler, 1992; Redondo et al., 2014) . Therefore, it is almost a common practice in feeding industry to minimize the use of tannin-containing feed in swine and poultry diets or to take measures to reduce their dietary concentrations if such feed are used. However, several recent reports showed that low concentrations of several tannin sources improved health status, nutrition and animal performance in monogastric farm animals Zotte and Cossu, 2009; Biagia et al., 2010; Brus et al., 2013; Star cevi c et al., 2015) . The mechanisms of growthpromoting effects of tannins in monogastric animal are much less understood compared with those in ruminants. Although there are some reports indicated that low concentrations of tannins increased feed intake and thus increased performance of monogastric animals, given the astringent nature of tannins, it seems not justified that this is through improving the palatability of feed. Information available to date seems to suggest that the growthpromoting action of tannins in monogastric animal relies on the balance between their negative effects on feed palatability and nutrient digestion through protein and enzyme complexation and positive effects on promoting the health status of intestinal ecosystem through their anti-microbial, anti-oxidant and antiinflammatory activities. The final impact of tannins on animal performance depends on the type of animals and their physiological status, feed, type of tannins and their concentrations in the diets. Compared with other domestic animals, pigs seem to be relatively resistant to tannins in the diets, and they are able to consume relatively high quantities of tannin-rich feedstuffs without presenting any toxic symptoms (Pinna et al., 2007) . This is likely due to parotid gland hypertrophy and secretion in the saliva of proline-rich proteins that bind and neutralize the toxic effects of tannins (Cappai et al., 2010 (Cappai et al., , 2014 . Compared to the vast sources of tannins for ruminants, sources of tannins used for monogastric animals are rather limited and so far only few have been studied and showed potential as feed additive (Table 2) .

Hydrolyzable tannins from chestnut (Castanea sativa Mill.) have recently been assessed as feed additive for monogastric food producing animals. Although in vitro studies showed strong activities against parasites and pathogens residing in animal digestive tract (Chung et al., 1998; Athanasiadou et al., 2000; Butter et al., 2001) , the in vivo assessments have yielded inconsistent results for animal performance. At the concentrations from 0.11% to 0.45% in swine diets, it was found that chestnut HT improved feed efficiency, tended to increase viable counts of Lactobacilli in the jejunum and reduced caecal concentrations of ammonia, iso-butyric, and isovaleric acid, but had no effect on bacterial caecal counts, faecal excretion of Salmonella or colonization of the intestines (Biagia et al., 2010; Parys et al., 2010) . However, increasing concentration from 0.71% to 1.5% reduced feed efficiency although feed intake, growth and carcass weight were not affected (Bee et al., 2016) . Stukelj et al. (2010) reported that chestnut HT at the level of 0.15% in combination with 0.15% of a mixture of acids had no effects on health status or growth performance of pigs whereas Brus et al. (2013) found that 0.19% of it in combination with 0.16% of a mixture of acids increased growth performance, increased lactic acid bacteria and reduced E. coli populations in the intestines. Schiavone et al. (2008) evaluated the effects of adding 0.15%, 0.20% and 0.25% of chestnut tannin product (77.8% HT) on growth performances of broiler chicks. The results showed that inclusion of up to 0.20% of chest nut tannin increased daily feed intake and average daily gain. However, increasing its concentration to 0.25% seemed to lead to negative effects as all the measured parameters were the lowest. Jamroz et al. (2009) assessed the effects of dietary addition of 0.025%, 0.05% and 0.1% of sweet chestnut tannins on the performance, intestinal microbial populations and histological characteristics of intestine wall in chickens. Their results showed that tannin supplementation had no effects on feed conversion and carcass quality, but tannin at 0.1% reduced final body weight and slowed down the proliferation rate in the mother-cell zone. E. coli and coliform bacteria in the small intestines of 28-d-old chickens were also reduced at the tannin levels of 0.05% to 0.1%. In another study, Rezar and Salobir (2014) found that addition of 0.07% and 0.2% of the same tannin product (0.05% and 0.1% HT) did not affect broiler growth performance or the organic matter, crude protein, crude ash, calcium and phosphorus balance and utilization, but increased dry matter content of excreta. In a challenged study, Tosi et al. (2013) reported that chestnut HT at the dietary concentrations of 0.71% and 1.5% reduced Clostridium perfringens (Eimeria tenella, Eimeria acervulina, Eimeria maxima) in the gut of broiler chicken orally challenged with these coccidia.

Supplementations of chestnut HT at levels of 0.45% and 0.5% also have been shown to increase live weight gain and feed intake of rabbits (Maertens and Struklec, 2006; Zoccarato et al., 2008) . However, Liu et al. (2009) found that inclusion of chestnut HT at the concentrations of 0.5% and 1.0% had no effect on growth performance of rabbits. All above information suggest that depending on the type of animals and the type of diets, dietary addition of chestnut HT at the levels lower than 0.5% for swine and rabbit and lower than 0.2% for chicken may have positive effects on their growth performance and improve intestinal health. Higher chestnut HT concentration in the diets than the above mentioned will mostly lead to decreased animal growth performance by decreasing nutrient digestion and absorption (Iji et al., 2004; Ebadi et al., 2005; Mansoori, 2009; Mansoori et al., 2015) .

Extracts of grape (Vitis vinifera) seed and grape pomace contain significant amount of polyphenolic compounds including CT (Prieur et al., 1994; Choy et al., 2014) , which have been assessed for their uses as natural feed additives to monogastric food producing animals. Choy et al. (2014) reported that adding 1% of grape seed extract to pig diets increased abundances of Lachnospiraceae, Clostridales, Lactobacillus and Ruminococcaceae in fecal microbiome. They found that oligomers (dimerepentamer) of grape tannin were only partially metabolized by the gut microbiota, producing phenolic metabolites that are known to be more readily absorbed. These phenolic compounds may have contributed to the altered bacterial populations thereby exerted the beneficial effects on the colon. Wang et al. (2008) found that CT in grape seed extract at the dietary concentrations from 5 to 80 mg/kg significantly decreased fecal shedding of E. tenella, improved antioxidant status, reduced mortality and increased growth performance of E. tenella infected broiler chicken and the most favorable results were observed with diets containing 10 to 20 mg CT/kg DM. Farahat et al. (2017) showed that grape seed extract possessed significant antioxidant and immunostimulant effects when fed to broiler chickens at the dietary concentrations of 0.125% to 2% with 0.125% to 0.25% being the optimum dosages. Further increasing the concentration negatively affected birds' growth performance, protein and amino acid digestion (Chamorro et al., 2013) .

Grape pomace, which includes skins, pulp and contain significant amount of CT and other simple phenolic compounds, is the byproduct of grape processing. Several studies evaluating the effects of grape pomace on swine and poultry performance indicated that addition of such tannin-rich product up to 10% of the diet had no effect on growth performance of broiler chicken, but enhanced anti-oxidant status and increased intestinal populations of beneficial bacteria (Brenes et al., 2008; Viveros et al., 2011; Chamorro et al., 2015) . Yan and Kim (2011) showed that supplementation of a Saccharomyces boulardii fermented grape pomace to pig diets at the level of 0.3% improved growth performance, nutrients digestibility and altered the fatty acid pattern in the subcutaneous fat as well as some attributes of pork meat. The grape pomace was also found to improve antioxidant activity of pork and reduced the gastrointestinal absorption of mycotoxins in swine. These effects of grape pomace, however, may not be exclusively attributed to the CT because other phenolic compounds also are present in the product.

Tannic acid is a HT from varying plants including tara pods (Caesalpinia spinosa), gallnuts from Rhus semialata, Quercus infectoria or Sicilian Sumac leaves (Rhus coriaria). Lee et al. (2010) reported that addition of tannic acid at the dietary levels of 0.0125% to 0.1% negatively impacted growth performance, hematological indices and plasma iron status of pigs, and linearly reduced faecal coliform bacteria count. However, the same authors found that feeding 0.0125% of tannic acid had no effect on growth performance, but negatively affected blood hematology and plasma Fe status when pigs were fed Fe deficient diets. It was also observed Lee et al. (2009a,b) (continued on next page) that total anaerobic bacteria, Clostridium spp. and coliforms were decreased but Bifidobacterium spp. and Lactobacillus spp. were increased by 0.0125% tannin acid (Lee et al., 2009a,b) . Tannic acid at the concentration of 0.5% increased growth performance and fat content in breast and thigh meat, but reduced blood glucose concentration and cholesterol content in the liver of broiler chicken (Star cevi c et al., 2015) . It is also reported that tannic acid at the dietary concentrations of 0.75% and 1.5% did not alter Salmonella cecal culture-positive chicks or the numbers of Salmonella typhimurium in the cecal contents of broiler chickens (Kubena et al., 2001) . Increasing concentrations to 2.5% and 3.0% reduced weight gain and protein efficiency and impaired the immune function of growing chickens by decreasing weight of bursa of fabricius, thymus and spleen, reducing total immunoglobulin (Ig) M and IgG immunoglobulin levels and total white blood cells and absolute lymphocytes in a dose-dependent manner (Marzo et al., 1990) . Ebrahim et al. (2015) found that 1% of tannic acid decreased body weight gain and feed intake but improved the fatty acid profile of breast muscle of broilers under heat stress by decreasing monounsaturated fatty acids. From above results, it seems that application rates of tannic acid in both swine and poultry are higher than those of other sources of tannins, but No effects on feed intake, improved feed efficiency; no effect on gastric mucosa Cappai et al. (2013) rarely result in positive effect on animal performance although increased antioxidant status were reported in several studies. High concentrations (e.g., 1%) appear to be toxic to animals in terms of decreasing production efficiency.

There are a few studies that assessed several other sources of tannins for monogastric animals. Iji et al. (2004) reported that addition of mimosa (Mimosa pudica) tannin extract (CT) to broiler diets at the levels of 0.5%, 1.5%, 2.0%, 2.5% reduced feed intake and body weight gain but improved feed efficiency at the levels less than 1.5%. Birds fed tannin supplemented diets also reduced ileal digestibilities of energy, protein and amino acids. However, no negative effect was observed on pancreatic and jejunal enzymes activities. Cappai et al. (2014) found that supplementing acorn (Quercus pubescens Willd.) HT at the dietary level of 0.516 tannic acid equivalent/kg diets did not affect feed intake or gastric mucosa but improved feed efficiency. Red quebracho (Schinopsis lorentzii) CT was assessed for its effects on decreasing coccidiosis in E. tenella challenged broilers (Cejas et al., 2011) . The study revealed that addition of 10% quebracho CT extract increased body weight gain of challenged birds, increased crypt:villi ratio of the intestine and decreased oocyst excretion. This study suggest that quebracho CT could be a potential prophylactic anti-coccidials agent. Zotte and Cossu, 2009 also found that 1% and 3% of red quebracho tannins improved significantly weight gain and feed conversion of rabbits in a 6-week feeding trial.

6. Challenges of using tannins as alternative to in-feed antibiotics for farm animals Information presented above clearly demonstrate that although plant tannins possess strong anti-bacterial and anti-parasitic action in vitro, the observed in vivo effects varied greatly. Many factors, including variations of the chemical compositions of the products due to the differences in plant sources, growing conditions, processing methods as well as different application methods and feeding conditions, contribute to this vast variability. Because of the complexity of these issues, it is difficult to conduct systematic and comprehensive evaluations toward the efficacy and safety of these compounds, which undoubtedly hinders the adaptation of tannins and tannin products as a viable alternative to antimicrobial growth promoters in animal and poultry industries. Therefore, controlling this variability is the key in developing tannin products to be used as natural antimicrobial feed additives. This probably would include all procedures from production to application.

One of the reasons that medicinal plants and herbs have been used for a long history without concern of antimicrobial resistance is probably that multiple compounds presented in the formula or complex prescription act synergistically. Such synergisms among individual compounds in complex and dynamic mixtures make microorganism difficult to adapt to the multiple compounds. However, this may not be the case in prolonged use of the isolated single plant-based antimicrobial compound, which may result in the development of resistance in some microorganisms. A good example is antimalarial compound, artemisinin, in traditional Chinese medicinal plant Qinghao (Artemisia annua L, Asteraceae). Qinghao as a medicinal herb has been used to effectively treat malaria for a long history in Chinese medicine (Miller and Su, 2011) . However, the reduction of the effectiveness of the purified form of artemisinin against malaria after using for several decades indicates that the microorganism have developed some sort of resistance to this compound. This trend is similar to the development of antibiotics resistance of bacteria. This suggests that prolonged use of plant compounds in their purified forms as antimicrobial growth promoter in animal feed has the risk to develop antimicrobial resistance. The majority of the tannins used presently in animal industry are either crude extract of mixtures of different molecular sizes or whole plant with a whole array of secondary compounds. This, coupled with the variations in chemical compositions and structures of the compounds from different sources and growing conditions, would reduce the likelihood of forming resistance by microorganisms to the complex tannins. However, little research has been done in this area and regulatory agent, scientific community and production industry need to make joint efforts to prevent microorganisms from forming resistance to tannins and other plant secondary compounds that are important to human health as this will have huge implication to humankind.

The authors declare no conflict of interest.

New sainfoin populations for bloat-free alfalfa pasture mixtures in western Canada

Production of hydrogen peroxide by polyphenols and polyphenol-rich beverages under quasi-physiological conditions

In vitro larval migration and kinetics of exsheathment of Haemonchus contortus exposed to four tropical tanniniferous plant extracts

The effects of four tropical tanniniferous plants on the in vitro larval migration and kinetics of exsheathment of Trichostrongylus colubriformis stages

Defensive and sensory chemical ecology of brown algae

Effect of tannins and saponins in Samanea saman on rumen environment, milk yield and milk composition in lactating dairy cows

Effect of a tannin from chestnut wood (Castanea sativa Miller) on cholesterol and fatty acids of eggs

Radical scavenging action and its mode in procyanidins B-1 and B-3 from azuki beans to peroxyl radicals

Interactions between flavonoids and proteins: effect on the total antioxidant capacity

Consequences of long-term feeding with condensed tannins on sheep parasitised with Trichostrongylus colubriformis

Direct anthelmintic effects of condensed tannins towards different gastrointestinal nematodes of sheep: in vitro and in vivo studies

Testing for direct anthelmintic effects of bioactive forages against Trichostrongylus colubriformis in grazing sheep

A comparison of hiv-1 integrase inhibition by aqueous and methanol extracts of Chinese medicinal herbs

Effect of seaweed (Ascophyllum nodosum) on fecal shedding of Escherichia coli O157:H7 by feedlot cattle and on growth performance of lambs

Evaluation of antibacterial properties of tannins isolated from Dichrostachys cinerea

Effects of Tascor14 on prevalence levels of enterohemorragic Escherichia coli and Salmonella spp. in feedlot steers

Antioxidant activities of the extracts from chestnut flower, leaf, skins and fruit

The implications of condensed tannins on the nutritive value of temperate forages fed to ruminants

Hydrolysable tannin-based diet rich in gallotannins has a minimal impact on pig performance but significantly reduces salivary and bulbourethral gland size

Tasco supplementation in feedlot cattle: effects on pathogen loads

Antioxidant activity of extracts, condensed tannin fractions, and pure flavonoids from Phaseolus vulgaris L. seed coat color genotypes

Potential to reduce Escherichia coli shedding in cattle feces by using sainfoin (Onobrychis viciifolia) forage, tested in vitro and in vivo

Condensed tannin concentrations found in vegetative and mature forage legumes grown in western Canada

Inclusion of grape pomace in the diet of pigs on pork quality and oxidative stability of omega-3 enriched fat

Effect of hydrolysable tannins on intestinal morphology, proliferation and apoptosis in entire male pigs

Ascophyllum nodosum supplementation: a preharvest intervention for reducing Escherichia coli O157:H7 and salmonella spp. in feedlot steers

Effects of dietary fibre and tannins from apple pulp on the composition of faeces in rats

Effect of grape pomace concentrate and vitamin E on digestibility of polyphenols and antioxidant activity in chickens

Effect of polyethylene glycol 4000 supplementation on the performance of yearling male Pedi goats fed dietary mixture levels of Acacia karroo leaf meal and Setaria verticillata grass hay

Effect of the consumption of Lysiloma, latisilliquumon the larval establishment of parasitic nematodes in goats

Effect of chestnut (Castanea sativa Mill.) wood tannins and organic acids on growth performance and faecal microbiota of pigs from 23 to 127 days of age

Antinutritional effects of condensed and hydrolyzable tannins

Effect of dietary condensed tannins on gastrointestinal nematodes

Antimicrobial and antiviral activity of hydrolysable tannins

Epigallocatechin-3-gallate is a new inhibitor of hepatitis C virus entry

Pigs use endogenous proline to cope with acorn (quercus pubescens willd.) combined diets high in hydrolysable tannins

The bilateral parotidomegaly (hypertrophy) induced by acorn consumption in pigs is dependent on individual's age but not on intake duration

Effect of whole acorns (Quercus pubescens) shred based diet on parotid gland in growing pigs in relation to tannins

Evaluation of quebracho red wood (Schinopsis lorentzii) polyphenolic vegetable extract for the reduction of coccidiosis in broiler chicks

Effects of dietary grape seed extract on growth performance, amino acid digestibility and plasma lipids and mineral content in broiler chicks

Influence of dietary enzyme addition on polyphenol utilization and meat lipid oxidation of chicks fed grape pomace

Grape-seed procyanidins modulate inflammation on human differentiated adipocytes in vitro

Use of antibiotics as feed additives: a burning question

A hypothesis on phaeophyceae polyphenols, their structural unit and mechanism of the formation

Phenolic metabolites and substantial microbiome changes in pig feces by ingesting grape seed proanthocyanidins

Mechanism of inhibition of tannic acid and related compounds on the growth of intestinal bacteria

The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry

Influence of host nutrition on the development and consequences of nematode parasitism in ruminants

Influence of condensed tannins from Ficus bengalensis leaves on feed utilization. milk production and antioxidant status of crossbred cows

Bovine AAV transcytosis inhibition by tannic acid results in functional expression of CFTR in vitro and altered biodistribution in vivo

The toxicity of gallic acid, pyrogallol, tannic acid, and Quercus havardi in the rabbit

Antibacterial activity of tannins from the leaves of Solanum trilobatum Linn

Effects of supplementing condensed tannin extract on intake, digestion, ruminal fermentation, and milk production of lactating dairy cows

Antioxidant, anti-inflammatory, and antisenescence activities of a phlorotannin-rich natural extract from brown seaweed Ascophyllum nodosum

Effect of supplementing tanniferous tree leaves mixture on immune response and GI nematodes in kids

Amino acid content and availability in low, medium and high tannin sorghum grain for poultry

Effects of tannic acid on performance and fatty acid composition of breast muscle in broiler chickens under heat stress

In vitro antiviral activity of dieckol and phlorofucofuroeckol-a isolated from edible brown alga Eisenia bicyclis against murine norovirus

Effect of dietary supplementation of grape seed extract on the growth performance, lipid profile, antioxidant status and immune response of broiler chickens

Gir aldez FJ, Mantec on AR. Review. Tannins and ruminant nutrition

Antibacterial activity of hydrolyzable tannins derived from medicinal plants against Helicobacter pylori

Grape pomace, an agricultural byproduct reducing mycotoxin absorption: in vivo assessment in pig using urinary biomarkers

Antioxidant properties of proanthocyanidins of Uncaria tomentosa bark decoction: a mechanism for anti-inflammatory activity

High molecular weight plant polyphenolics (tannins) as biological antioxidants

Plant polyphenols. Vegetable tannins revisited

Individual administration of three tanniferous forage plants to lambs artificially infected with Haemonchus contortus and Cooperia curticei

The biosynthesis of secondary metabolites. London: Chapman and Hall

Antioxidant activity of tannin component from Vaccinium vitis-idaea L

Electrochemistry of flavonoids

The effects of tanninrich plants on parasitic nematodes in ruminants

Direct and indirect effects of bioactive tanninrich tropical and temperate legumes against nematode infections

Dietary flavonoids: intake, health effects and bioavailability

Effects of purple prairie clover (Dalea purpurea Vent) on feed intake, nutrient digestibility and faecal shedding of Escherichia coli O157: H7 in lambs

Structural composition and protein precipitation capacity of condensed tannins from purple prairie clover (Dalea purpurea Vent

Bactericidal catechins damage the lipid bilayer

Intestinal function and body growth of broiler chickens on maize-based diets supplemented with mimosa tannins and a microbial enzyme

Effect of sweet chestnut tannin (SCT) on the performance, microbial status of intestine and histological characteristics of intestine wall in chickens

Purple prairie clover (Dalea purpurea Vent) reduces fecal shedding of Escherichia coli in pastured cattle

Preference for condensed tannins by sheep in response to challenge infection with Haemonchus contortus

Anti-hiv-1 activity of phlorotannin derivative 8,4 000 -dieckol from Korean brown alga ecklonia cava

Changes in tannin concentration of rastali banana (Musa AAB rastali) during growth and development

Antiviral phlorotannin from Eisenia bicyclis against human papilloma virus in vitro

Effects of tannic acid on cecal volatile fatty acids and susceptibility to Salmonella typhimurium colonization in broiler chicks

In vitro antiviral activity of phlorotannins isolated from ecklonia cava, against porcine epidemic diarrhea coronavirus infection and hemagglutination

Influence of dietary condensed tannins from Sericea lespedeza on bacterial loads in gastrointestinal tracts of meat goats

Effects of tannic acid supplementation on growth performance, blood hematology, iron status and faecal microflora in weanling pigs

Effects of tannic acid added to diets containing low level of iron on performance, blood hematology, iron status and fecal microflora in weanling pigs

Condensed tannins concentration of selected prairie legume forages as affected by phenological stages during two consecutive growth seasons in western Canada

The DMACAeHCl protocol and the threshold proanthocyanidin content for bloat safety in forage legumes

Antioxidant and free radical scavenging effects of the tannins of Terminalia catappa L

Tannins and self-medication: implications for sustainable parasite control in herbivores

Identification of hydrolyzable tannins (punicalagin, punicalin and geraniin) as novel inhibitors of hepatitis b virus covalently closed circular DNA

Effects of chestnut tannins on carcass characteristics, meat quality, lipid oxidation and fatty acid composition of rabbits

Anti-inflammatory hydrolyzable tannins from myricaria bracteata

Tannic acid inhibits hepatitis c virus entry into huh7.5 cells

Anti-Escherichia coli O157: H7 properties of purple prairie clover and sainfoin condensed tannins

Dietary quebracho tannins are not absorbed, but increase the antioxidant capacity of liver and plasma in sheep

Antioxidant status, colour stability and myoglobin resistance to oxidation of longissimus dorsi muscle from lambs fed a tannin-containing diet

Dietary tannins improve lamb meat color stability

Induction of phlorotannins in the brown macroalga Ecklonia radiata (Laminariales, Phaeophyta) in response to simulated herbivory, the first microscopic study

Technical note: preliminary results with a tannin extract on the performance and mortality of growing rabbits in an enteropathy infected environment

Absorption capacity of chicken intestine for D-xylose in response to graded concentrations of tannic acid

The effect of canola meal tannins on the intestinal absorption capacity of broilers using a d-xylose test

In vitro and in vivo assessment of lipid peroxidation of infant nutrient preparations: effect of nutrition on oxygen toxicity

Effect of tannic acid on the immune response of growing chickens

Characterization of condensed tannins purified from legume forages: chromophore production, protein precipitation, and inhibitory effects on cellulose digestion

Plant tannins-Their role in forage quality

Microbial interactions with tannins: nutritional consequences for ruminants

Tannin quantification in red grapes and wine: comparison of polysaccharide-and protein-based tannin precipitation techniques and their ability to model wine astringency

Analysis of phenolic compounds in two blackberry species (rubus glaucus and rubus adenotrichus) by high-performance liquid chromatography with diode array detection and electrospray ion trap mass spectrometry

Tannins for suppression of internal parasites

The effect of condensed tannins on the nutrition and health of ruminants fed fresh temperate forages: a review

The effect of grazing forage containing condensed tannins on gastro-intestinal parasite infection and milk composition in angora does

Effects of plant tannin extracts supplementation on animal performance and gastrointestinal parasites infestation in steers grazing winter wheat

Effect of tannins on the in vitro growth of Escherichia coli O157: H7 and in vivo growth of generic Escherichia coli excreted from steers

Artemisinin: discovery from the Chinese herbal garden

Effects of condensed tannins and crude sesquiterpene lactones extracted from chicory on the motility of larvae of deer lungworm and gastrointestinal nematodes

Effect of condensed tannins extracted from four forages on the viability of the larvae of deer lungworms and gastrointestinal nematodes

The effect of condensed tannins from seven herbages on Trichostrongylus colubriformis larval migration in vitro

Green tea flavan-3-ols and oligomeric proanthocyanidins inhibit the motility of infective larvae of Teladorsagia circumcincta and Trichostrongylus colubriformis in vitro

Effect of condensed tannins on egg hatching and larval development of Trichostrongylus colubriformis in vitro

Anti-inflammatory actions of tannins isolated from the bark of Anacardium occidentale L

Unravelling the conundrum of tannins in animal nutrition and health

Prevention of hydrolysable tannin toxicity in goats fed Clidemia hirta by calcium hydroxide supplementation

Hydrolysable tannins and proanthocyanidins from green tea

Relationship of the structures of tannins to the binding activities with hemoglobin and methylene blue

Effects of condensed tannins on established populations and on incoming larvae of Trichostrongylus colubriformis and Teladorsagia circumcincta in goats

Antioxidant and anti-inflammatory activities of tannin fraction of the extract from black raspberry seeds compared to grape seeds

The use of tannins to control Salmonella typhimurium infections in pigs

Effect of condensed tannins supplementation through leaf meal mixture on voluntary feed intake, immune response and worm burden in Haemonchus contortus infected sheep

Exploitation of dietary tannins to improve rumen metabolism and ruminant nutrition

Effect of purple prairie clover (Dalea purpurea, vent.) hay and its condensed tannins on growth performance, wool growth, nutrient digestibility, blood metabolites and ruminal fermentation in lambs fed total mixed rations

Vegetable and animal food sorts found inthe gastric content of Sardinian Wild Boar (Sus scrofa meridionalis)

Oligomeric and polymeric procyanidins from grape seeds

Phlorotannins, brown algal polyphenols

Fernandez Miyakawa ME. Perspectives in the use of tannins as alternative to antimicrobial growth promoter factors in poultry

Effects of tannin-rich sweet chestnut (Castanea sativa mill.) wood extract supplementation on nutrient utilisation and excreta dry matter content in broiler chickens

Antioxidant activity of commercial food grade tannins exemplified in a wine model

The relative antioxidant activities of plant-derived polyphenolic flavonoids

Structure-antioxidant activity relationships of flavonoids and phenolic acids

Tannineprotein complexes as radical scavengers and radical skins

Effect of level and source of supplemental tannin on growth performance of steers during the late finishing phase

Influenza virus neuraminidase inhibitory activity of phlorotannins from the edible brown alga ecklonia cava

Antibacterial substances in Japanese green tea extract against Streptococcus mutans, a cariogenic bacterium

Chemical, biochemical, and biological significance of polyphenols in cereals and legumes

Antimicrobial properties of tannins

Dietary polyphenols and the prevention of diseases

Effects of a natural extract of chestnut wood on digestibility, performance traits, and nitrogen balance of broiler chicks

Local and chemical distribution of phlorotannins in brown algae

Effect of condensed tannins on bacterial diversity and metabolic activity in the rat gastrointestinal tract

Dichrostachys cinerea and Acacia nilotica fruits as dry season feed supplements for goats in a semi-arid environmentdsummary results from a DFID funded project in Zimbabwe

Alfalfa pasture bloat can be eliminated by intermixing with newly-developed sainfoin population

Production performance, meat composition and oxidative susceptibility in broiler chicken fed with different phenolic compounds

The effect of the combination of acids and tannin in diet on the performance and selected biochemical, haematological and antioxidant enzyme parameters in grower pigs

Antiinflammatory and antiulcer properties of tannins from Myracrodruon urundeuva allemão (anacardiaceae) in rodents

The anti-inflammatory effects of phlorotannins from eisenia arborea, on mouse ear edema by inflammatory inducers

Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (hiv-1) reverse transcriptase

Predicting the effects of brown algal phlorotannins on marine herbivores in tropical and temperate oceans

Grape-seed procyanidins act as antiinflammatory agents in endotoxin-stimulated RAW 264.7 macrophages by inhibiting NFkB signaling pathway

Determination of extractable and bound condensed tannin concentrations in forage plants, protein concentrate meals and cereal grains

Efficacy test of a hydrolysable tannin extract against necrotic enteritis in challenged broiler chickens

The effect of chicory (Cichorium intybus) and sulla (Hedysarum coronarium) on larval development and mucosal cell responses of growing lambs challenged with Teladorsagia circumcincta

Transcriptional suppression of the HIV promoter by natural compounds

Inactivation of pathogenic viruses by plant-derived tannins: strong effects of extracts from persimmon (Diospyros kaki) on a broad range of viruses

Effects of dietary polyphenol-rich grape products on intestinal microflora and gut morphology in broiler chicks

Beneficial and detrimental effects of dietary condensed tannins for sustainable sheep and goat productiondprogress and challenges

Influence of grape seed proanthocyanidin extract in broiler chickens: effect on chicken coccidiosis and antioxidant status

Feed intake, ruminal fermentation, and development of bloat in steers grazing pastures of alfalfa or mixed alfalfa-sainfoin

Screening of condensed tannins from canadian prairie forages for anti-Escherichia coli O157:H7 with an emphasis on purple prairie clover (Dalea purpurea vent)

Frothy bloat in ruminants: cause, occurrence, and mitigation strategies

Brown algae as feed additive: nutritional and health impacts on ruminant animals e a review

Condensed tannins in sainfoin: composition, concentration, and effects on nutritive and feeding value of sainfoin forage

The effects of proanthocyanidins, dehusking and depericarping on the digestion of barley grain by ruminants

The effect of condensed tannins in Lotus corniculatus on plasma metabolism of methionine, cystine and inorganic sulphate by sheep

Effects of condensed tannins in Lotus corniculatus upon the digestion of methionine and cysteine in the small intestine of sheep

Sensitivity of Escherichia coli O157:H7 to seaweed (Ascophyllum nodosum) phlorotannins and terrestrial tannins

Anti-inflammatory activity of phlorotannin-rich fermented ecklonia cava processing byproduct extract in lipopolysaccharide-stimulated raw 264.7 macrophages

Effects of chopping, and soaking in water, hydrochloric acidic and calcium hydroxide solutions on the nutritional value of Acacia villosa for goats

Inhibitory activity of flavonoids and tannins against hiv-1 protease

Effect of dietary grape pomace fermented by saccharomyces boulardii on the growth performance, nutrient digestibility and meat quality in finishing pigs

Phytogenic compounds as alternatives to infeed antibiotics: potentials and challenges in application

Chebulagic acid, a hydrolyzable tannin, exhibited antiviral activity in vitro and in vivo against human enterovirus 71

Tannic acid inhibited norovirus binding to HBGA receptors, a study of 50 Chinese medicinal herbs

Effect of extract of chestnut wood inclusion (ENC) in normal and low protein aminoacid supplemented diets on heavy broiler rabbits

Dietary inclusion of tannin extract from red quebracho trees (Schinopsis spp.) in the rabbit meat production

This project was partially funded by Alberta Agriculture and