Oregano Essential Oil: MOA for Coccidiosis Management

INTRODUCTION
The goal of any coccidiosis management programme is to control the severity of coccidiosis and to attempt to regulate when the primary damage will occur. Over recent years, concern has been expressed regarding the long-term effectiveness of conventional methods of coccidiosis control, meaning natural alternatives have gained interest. Natural oregano essential oil (OEO) comprises of over 100 active compounds, most of which are phenolic compounds with varying antioxidant, antimicrobial and antifungal activity. The effect of all constituents of natural OEO work together to help support coccidiosis management. Orego-Stim® (OS) is a high quality eubiotic composed of 100% natural OEO. It has been extensively researched to demonstrate it can help support animal performance during a coccidiosis challenge. The following information discusses the mode of action of oregano essential oil and Orego-Stim in coccidiosis management.  

DIRECT ANTICOCCIDIAL EFFECTS OEO has been shown in trials to exhibit potent anticoccidial properties. An in vitro study showed OEO to significantly inhibit Eimeria sporozoite invasion, as much as robenidine; a well-known anticoccidial. The specific mechanism of action is due to the hydrophobic characteristics and low molecular weight of the main phenolic compounds within OEO, which allow them to disrupt outer cell membranes. This causes an increase in cytoplasmic membrane permeability and leads to cell death caused by leakage of ions, energy loss and diffusion of cell contents. In addition, the high lipid solubility of OEO permits rapid diffusion through parasite and host cell membranes. Another proposed mechanism includes interference with calcium-mediated signaling which is a necessary mechanism for invasion by Eimeria sporozoites (Sidiropoulou et al., 2020). These mechanisms lead to inhibition of invasion as well as impairment of Eimeria spp. development within the host (Nazzaro et al., 2013). Several in vitro studies with E. tenella have shown OEO to inhibit intracellular invasion and the formation of schizonts (associated with decreased pathogenicity), as well as inducing morphological abnormalities in sporozites and modulating the primary immune response. When compared with individual active component treatment groups, the whole OEO groups elicited better results, highlighting the importance of multiple active components in natural OEO (Felici et al., 2023).

GUT HEALING AND REPAIR In a normal healthy gut, the epithelial lining is shed regularly, and replacement occurs by cell division from within the crypts. Phenols in OEO act on the epithelial lining by increasing the rate of enterocyte turnover by around two times the normal rate. The phenolic compounds in OS therefore disrupt the life cycle of coccidia parasites by speeding up the rate of shedding of the gut lining. Through this mode of action, intracellular sporozoites are shed before they have the opportunity to penetrate deeper into the gut wall or form new oocysts. The risk of clinical coccidiosis is therefore reduced by creating an environment that is hostile to the parasite. OEO has also been shown to significantly increase cell proliferation in the duodenum and jejunum of broilers, whilst resulting in deeper crypt depths (Tzora et al., 2016). 

ANTIBACTERIAL EFFECTS Coccidiosis infection is known to influence enteric microbiota, contributing towards disease pathology. Infections have been found to increase the abundance of Escherichia, Shigella and Klebsiella, members of the Enterobacteriaceae family, that are opportunistic pathogens. In contrast, it has been reported that parasitic infections can reduce the population of Lactobacillus spp., which are regarded as beneficial for gut health (MacDonald et al., 2017). Based upon results of antimicrobial sensitivity tests, OS has a higher antibacterial affinity towards first the Clostridium and Salmonella groups, followed by E. coli, then the Streptococcus, Staphylococcus and Enterococcus groups, and lastly other bacteria, including beneficial microbes such as Bifidobacterium and Lactobacillus. If OS inhibits pathogenic bacteria in comparison to beneficial bacteria, it can represent a large percentage of pathogen reduction, and this improves the gut microbial population by managing pathogens and helping the reestablishment of beneficial bacteria via competitive exclusion. Continuous use of OS will help to maintain and preserve healthy levels of beneficial bacteria populations in the intestine which in turn work to control potentially pathogenic bacteria.

IMMUNE SUPPORT AND ANTI-INFLAMMATORY RESPONSES Various markers of inflammation are upregulated during and following coccidiosis infection.  Inflammation also results from damage to the intestinal tract, which can compromise gut integrity. Inflammation and damage to the gut also leads to repartitioning of nutrients which suppresses inflammatory state and gut repair, eventually leading to reduced animal performance (Lu et al., 2014).  IL-10 is an anti-inflammatory cytokine that controls the nature of inflammatory responses during infection. Broilers supplemented with OS have been shown to have a significant increase in IL-10 gene expression during Eimeria infection, demonstrating better control of inflammation. This helps support growth and performance by reducing energy partitioning towards inflammatory responses. In this same study, OS significantly increased IFN-y levels in infected broilers. IFN-y is a major factor in the development of resistance to Eimeria. Increased IFN-y levels support better clearance of infection, the development of immunity against reinfection and assists in the development of resistance to Eimeria (Eraky et al., 2018).  

ANTIOXIDANT EFFECTS Eimeria infection has been associated with lipid peroxidation in the intestinal mucosa (Naidoo et al., 2008). Antioxidants inhibit oxidation and reduce oxidative stress caused by increased levels of reactive oxygen species (ROS) and free radicals that can start chain reactions in the cell, resulting in cell death or damage. Free radicals and ROS production increase during the host’s cellular immune response to coccidiosis. When these levels exceed the capacity of the body’s natural antioxidant defence system, high concentrations may cause tissue damage and cytotoxicity, contributing to disease pathology. The phenolic compounds within OEO, and OS, are excellent sources of natural antioxidants.  

LIVER AND KIDNEY FUNCTION Concerning kidney function, Eimeria infection causes an elevation in creatinine and uric acid levels, indicative of kidney dysfunction, metabolic acidosis and intravascular hemolysis. OS has been shown to significantly decrease serum uric acid and creatinine levels due to its anti-inflammatory and antioxidant properties. This can help reduce wet droppings. Regarding liver function, cellular damage of hepatocytes caused by Eimeria infection causes an increase in AST and ALT enzyme activities. OS has been shown to significantly decrease serum AST and ALT in Eimeria challenged broilers indicating reduced damage to hepatocytes important for metabolic and immune function (Eraky et al., 2018). In conclusion, OEO and OS have a complex mode of action, however extensive research shows a number of underlying mechanisms which help support broiler health and performance during challenge periods.