Post weaning diarrhea in piglets: how can we manage the problem with the upcoming ban of ZnO at pharmacological level?

Intestinal health is a concern for everybody working in pig production. Enteric diseases are an often seen problem in raising piglets that can cause severe economic losses and reduced piglet performance. The most pivotal stage of their breeding is weaning, a sudden and extremely stressful moment. Several aspects contribute to the development of this challenging state, both psychosocial and physical: separation from the sow and the littermate, a new social hierarchy with unknown piglets, as well as environmental and dietary changes (Campbell et al., 2013). The switch from a liquid to a solid diet exerts a strong mechanical impact on the intestinal mucosa, which is often not ready to digest all the macromolecules coming from the new complex feed sources. As a result, intestinal villi are damaged and crypt depth increases while attempting to fix the apical loss of cells. Additionally, weaning always means stress and stressors can cause a severe impairment of intestinal integrity by disrupting the “bridges” that link enterocytes together, the tight junctions, thus impairing intestinal absorption and secretion of digestive enzymes. Undigested and unabsorbed proteins can reach the hindgut, where microbial fermentations occur, thus facilitating the growth of undesired pathogens and the production of noxious compounds, such as ammonia. Moreover, because of the sudden lack of passive immunity provided through maternal colostrum and the underdevelopment of piglet immune system at weaning, acute immunological changes occur and an inflammatory status is established (Moeser et al., 2007).

In the immediate post-weaning period, all these interconnected circumstances exert detrimental effects on the overall health status of animals. Gastrointestinal disorders in post-weaning pigs are associated with post-weaning diarrhea (PWD), one of the most difficult challenges in the pig breeding industry all over the world. Enterotoxigenic E. coli, especially the K88 strain, is the main causative agent of this pathology but this bacterium is also commonly harbored in the small intestine of healthy animals. During the post-weaning period, there are always alterations at the intestinal level and inflammation of the intestinal mucosa, affecting the intestinal health and the right nutrient absorption. This leads to a higher risk of toxins and bacterial translocation to the bloodstream. Even if there are no clinical signs, it is demonstrated that there are heavy repercussions on growth performance throughout pig productive life, not only during the post-weaning stage. Studies demonstrated that what happens during the weaning period affects the animal’s live performance for several weeks after weaning. For example, the age of weaning is extremely important: Smith et al. demonstrated that early weaning (15 days) causes huge damages to the intestinal mucosa, compared to the later one (28 days), with reduced piglet growth. At the same time, more than 5 weeks after weaning, the early-weaned piglets had an inflammatory status of the intestinal mucosa worse than the late-weaned (Smith et al., 2010). This means that all stressors in the early life of piglets can affect the intestinal barrier functionality and integrity, with an effect in the second part of the animal life and on their live performance during the growing period.

Prevention is impossible since there is no way to avoid weaning stress, but support is mandatory. In fact, we can help the piglets to face this challenge by maintaining strong intestinal health and supporting a faster recovery.

Antibiotic growth promoters were used worldwide with the aim to modulate intestinal microflora and reduce pathogens load, thus maximizing animals’ growth. Anyway, it is well-known that the uncontrolled use of antibiotics caused a harmful increase of the resistant bacteria, thus nowadays their use is forbidden or reduced as much as possible everywhere (Burch et al., 2008). E. coli K88, for example, is frequently highly resistant to the antibiotics commonly used in pig husbandry (Luppi et al., 2017). The spread of antimicrobial resistance (AMR), along with regulatory restrictions on antibiotics and a renewed attention of consumers towards this issue, are progressively narrowing the utilization of antibiotics only to strictly necessary situations in animal breeding. The increasing AMR of pathogens has led to the need for reducing the use of these drugs worldwide.

Amongst alternatives, zinc has been proposed as an effective feed additive to prevent PWD without the employment of antibiotics. Zinc is one of the most important trace elements in animal nutrition because it ensures the activity of several enzymes involved in cellular signaling, digestion, cellular respiration, and nucleic acid metabolism. Zinc oxide (ZnO) is commonly used at therapeutic dosage to reduce the incidence and the severity of PWD, preventing intestinal damages due to pathogenic bacteria (Hill and Shannon, 2019). Anyway, a recent study of ours indicated that not all the chemical forms of ZnO can reduce E. coli K88 proliferation and that the effective ones have an antimicrobial activity only at the pharmacological level. Moreover, several studies indicated the induction of AMR caused by this trace element and it is well-known the environmental pollution caused by its administration in swine (Slifierz et al., 2014). For these reasons, the use of ZnO at pharmacological dosages will be shortly banned in Europe and, probably, other countries will follow this reduction in use.

So what can we do in view of the upcoming ban of ZnO at therapeutic dosage in 2022?

First, an approach could be aimed to microencapsulate ZnO to allow a higher dose to reach the small intestine, without being transformed in the stomach because of its solubility at acidic pH, thus allowing a significant reduction of ZnO concentration in animal feed. Cho et al. (2018) demonstrated that microencapsulated ZnO can be a good alternative to the free form at pharmacological dosages (Cho et al., 2018). They compared a standard diet for weaned piglets with free ZnO at 3 kg/MT or microencapsulated ZnO (Zincoret®S, Vetagro) at 0.3 kg/MT (equal to 150 g/MT of free ZnO). The trial lasted 34 days, starting from piglets weaned at 21 days of life. After this period, there were no statistically significant differences among groups for what concerns average daily feed intake (ADFI), while the final body weight (BW), average daily gain (ADG), and gain/feed ratio were significantly higher for animals fed Zincoret®S compared to those fed the free ZnO (Fig. 1). These results corroborate our previous study: we demonstrated that 0.3-0.8 kg/MT of Zincoret®S improved live performance (ADG, BW, FCR) and intestinal health (inflammatory cytokines, mucosal morphology, and barrier function) compared to the control group and allowed to reach the same results of piglets fed ZnO at 3 kg/MT (Grilli et al., 2015).

Figure 1: Effect of microencapsulation of ZnO on body weight (BW), daily weight gain (BWG), daily feed intake (ADFI), feed conversion rate (kg gain : kg feed) and fecal Zn.

Another way to face the increase in diarrhea incidence is to help piglets to restore their intestinal health in the post-weaning period. As known, organic acids (OA), for example, are strong antimicrobials and they modulate the microflora in favor of the beneficial populations (Tugnoli et al., 2020). Other very well-known antimicrobials are nature-identical compounds (NIC), which exert their antimicrobial power not only by forming pores in the bacterial membrane (pore-forming agents) but also interfering negatively with the bacterial quorum sensing and biofilm formation. Moreover, NIC are able to exert antioxidant and/or anti-inflammatory activity, by directly scavenging free radicals and indirectly upregulating antioxidant gene expression or inhibiting pro-inflammatory factors, thus allowing a general improvement of intestinal health and functionality (Rossi et al., 2020). In an experiment conducted by Vetagro’s team, Caco-2 cells grown with OA and NIC recovered from an LPS-caused drop in barrier function in a faster and better way compared to the control cells, that did not have any OA or NIC added to their medium. These results indicated that OA and NIC help to restore the epithelial initial status and integrity after an inflammatory insult, demonstrating a powerful and synergistic anti-inflammatory activity of these molecules on the intestinal mucosa, and this can be useful in field conditions during and after stressful periods such as weaning (Rossi et al., 2017). This combination of OA and NIC in a microencapsulated form can be a good solution to improve piglet growth and to preserve and restore their intestinal health. Vetagro started investigating a long time ago the antimicrobial effect of OA and NIC and their patented synergy, both against pathogens and as anti-inflammatory agents on the intestinal mucosa. AviPlus® line is the cutting-edge result of our in vitro and in vivo research activity: the microencapsulated blend of citric and sorbic acid, thymol and vanillin, is recognized by the EU as a zootechnical feed additive for animal growth promotion. Microencapsulation protects these molecules at the gastric level allowing their release along the whole intestinal tract and their full availability for absorption. In our latest studies, we evaluated the effect of AviPlus®S fed to growing pigs through a feeding and a metabolic trial. Results indicated that the product improved animal live performance and fecal digestibility for dry matter and protein, compared to the control. At the same time, the animals fed AviPlus®S had lower malodor gas emission compared to the control (Tugnoli et al., 2020). Thus, this microencapsulated blend of OA and NIC can be a valid tool to support animal growth during the stressful period of weaning. In fact, as recently confirmed by Oh et al. (2018), 1-2 kg/MT of AviPlus®S can improve BW, ADG, ADFI, and FCR in weaned piglets (Fig 2). In the same study, after 42 days of trial, lactobacilli count in fecal samples was higher in the group fed 1 or 2 kg/MT AviPlus®S compared to the control, numerically and statistically respectively. For the rest of the trial (154 days total), the number of these bacteria was not affected by the product (Fig 2) (Oh et al., 2018). At the same time, the synergistic antimicrobial activity of AviPlus®S ingredients was demonstrated against different pathogens, and their slow release due to the microencapsulation technology allows their activity along the whole intestinal tract. For what concerns intestinal health, our previous studies demonstrated a reduction in pro-inflammatory cytokine expression, as well as the reduction of paracellular flux to large molecules through the intestinal epithelium, so an improvement of the general health and function of the intestinal mucosa (Grilli et al., 2015).

Figure 2: Effect of AviPlus®S on growth performance and the fecal colony-forming units of Lactobacillus ssp. from weaning to the end of fattening.

In conclusion, to face the ban of zinc oxide at therapeutic dosages, in a context of a general reduction of the use of antibiotics, PWD is a very urgent problem and the improvement of piglet intestinal health is the target. Vetagro has an ongoing commitment to find out innovative and science-based solutions. Zincoret®S, our microencapsulated ZnO solution, allows reducing the level of this trace element in piglets diet, maintaining good life performance. On the other hand, AviPlus®S, due to its anti-inflammatory and antimicrobial properties, can help animals preserving and restoring intestinal health.For more information: