Toward growth-promoting antibiotic-free poultry production

With the unravelling of antimicrobial-resistant gene spread in both urban and agricultural environments, antimicrobial resistance (AMR) is an undeniable fact which threatens public health worldwide. Earlier in the 2000s, researchers have evaluated the risks of antimicrobial use in animal feeds as growth promotors (Wegener, 2006). At that time, the medical treatment problems that are already attributable to antibiotics in animal feeds remains as today’s problems and gets severer. To respond this global crisis, countries such as China have put the regulation of growth-promoting antibiotics (GPAs) on the priority list, following the action of the European Union. However, if the use of antibiotics in feeds is restricted, it is challenging to run poultry production, the most intensive animal production system among all, in a cost-effective manner. Therefore, nutritional strategies that can maximize efficiency and food safety, and minimize the use of antibiotics during the rearing process are becoming essential. The article discusses the role and implications of medium-chain fatty acids (MCFAs, C6:0 – C12:0) in poultry production under the circumstance of GPA restriction.

What’s in the history

Back in history, with a good intention of combating pathogenic microbes, antimicrobial agents such as antibiotics, have saved countless lives and enabled the development of modern medicine over the past 70 years. Antimicrobial agents include antiseptics, antibiotics, antifungals, anti-helminthics, etc. (Michael et al., 2014), among which antibiotics have been discovered to improve the animal production efficiency (Moore et al., 1946; Stokstad and Jukes, 1950) and applied in feeds for pigs, poultry and cattle since the 1950s. However, administrating antibiotics extensively and often unnecessarily has provoked an evolutionary response among microorganisms (Sykes, 2010), resulting in increased drug-resistant pathogens in both humans and animals (van den Bogaard et al., 2002; Czaplewski et al., 2016).

What are the drivers

AMR has been defined as a threat with three main drivers (Michael et al., 2014). Firstly, the frequency of AMR phenotypes among microbes is increasing significantly (Danko et al., 2021) due to the strong environmental adaptability of microbes (Gogarten et al., 2002; Janetos, 2009). The higher the selective pressure by antibiotic application, the faster the microbial communities adapt and become resistant. Secondly, the human population nowadays is increasing and well-connected globally (United Nations, 2015). This results in rapid spread of pathogens among both humans and domestic animals. Last but not least, overuse of antibiotics in agricultural production is one of the main drivers. As estimated, two-thirds of the world’s increase in antimicrobial consumption is due to the growing number of food-purposed animals from 2010 till 2030 (Baquero et al., 2008; Van Boeckel et al., 2015; Nesme et al., 2014; Wright, 2010; Zhu et al., 2013). Among the prediction models developed to estimate global antibiotic consumption in animal production, a higher dispersion of the posterior distribution suggests that poultry production has a broadened range of antibiotic intensity than swine and cattle production (Van Boeckel et al., 2015; Fig. 1).

Figure 1. Posterior distributions for estimates of antimicrobial consumption in cattle, chickens, and pigs in Economic Cooperation and Development countries (Van Boeckel et al., 2015).

The challenges: both physiological and technological

Alternating GPAs in animal production is challenging due to the increasing demand for animal products and the complexity of the gastrointestinal (GI) ecosystem, let alone a fundamental understanding of how antibiotics improve feed efficiency is lacking. Nine possible mode of actions have been proposed based on the complexity of the GI environment which might inspire the GPA alternative development (Barug et al., 2006). MCFAs (Kim and Rhee, 2013; Wang et al., 2015), botanical extracts (Yang et al., 2015), and organic acids (Diebold and Eidelsburger, 2006; Woźniakowska et al., 2017) have been suggested as possible alternatives to classical GPAs in animal feeds. Although many studies have attempted to find alternatives to GPAs in animal diets, there exists no “holy grail”. Nonetheless, some products may offer a similar growth benefit when applied in combinations to embody multiple mode of actions (Allen et al., 2013; Seal et al., 2013). Besides the physiological complexity, unpleasant odor, low solubility, poor chemical stability, and volatile nature of these alternatives evoke even more challenges to the producers to tackle.

Table 1. Antibacterial fats and their relative antimicrobial activity (Zhou et al., 2019).

Why MCFAs: the antimicrobial fats

The antibacterial effects of certain fats were discovered in the 1950s when researchers observed a range of fatty acids inhibited the growth of gram-positive bacteria such as Lactobacillus helveticus (Desbois and Smith, 2010; Galbraith et al., 1971; Hemsworth and Kochan, 1978; Kodicek and Worden, 1945). MCFAs were ranked the most antimicrobial fat due to the most rapid and the highest unit reduction of both virus titer and bacteria count in an in vitro culture (Zhou et al., 2019; also see table 1 in Thormar and Hilmarsson, 2007). Natural MCFAs usually contain an even number of carbon atoms in a straight chain, including hexanoic acid (C6:0, caproic acid), octanoic acid (C8:0, caprylic acid), decanoic acid (C10:0, capric acid), and dodecanoic acid (C12:0, lauric acid). They are commonly from coconut oil, palm oil, and cuphea oil (Bhatnagar et al., 2009).

The molecular antimicrobial mechanism lies in the amphiphilic chemical structure of MCFAs, which break through the cell membrane, leading to the leakage of intracellular materials and bacterial death (Kim and Rhee, 2013). Figure 2 shows an example of the membrane damage of E. coli O157:H7 caused by a 5-minute incubation with caprylic acid (A vs. B) in vitro. Besides, Hovorková et al. (2018) demonstrated in vitro that MCFAs have no inhibition towards commensal bacteria at the tested concentrations. Other earlier in vitro studies showed the antimicrobial activities of MCFAs on pathogenic microbes like Candida albicans, Pneumococci, Streptococcus, and Micrococci (Bergsson et al., 2001; Kabara et al., 1972).

Figure 2. Transmission electron microscopy images of E. coli O157:H7 treated at 37℃ for 5 min with caprylic acid, citric acid, or a combination
of both. (A) Untreated; (B) 1.0 mmol/l; (C)1.0 mmol/l; (D) 1.0 + 1.0 mmol/l (Kim and Rhee, 2013).

Why MCFAs: essential for immunity defense

MCFAs play an important role in the innate immune defense system discovered naturally present in mammalian breast milk, skin, and mucosa, and also induce host defense peptide expression in humans, pigs, chickens, rabbits, and mice. They provide beneficial supplement to the animals besides antimicrobial property. For example, mammalian breast milk contains a large number of antibacterial MCFAs, which mainly are hexanoic acid (C6:0), octanoic acid (C8:0), decanoic acid (C10:0), and dodecanoic acid (C12:0) (Decuypere and Dierick, 2003; Smith, 1980). Besides, it was recently discovered that MCFAs induce in vitro gene or protein expressions of host defense peptides (HDPs) in chicken, pig, and human cells, shown in Table 2. HDPs are natural antimicrobials produced by plants, insects, animals, and microorganisms (Sierra et al., 2017), which offer advantages to become useful antimicrobials.

Table 2. The in vitro studies showed that MCFAs induced HDPs gene or protein expression.

Why MCFAs: growth-promoting effects

It is always important to translate the health-promoting effects into growth efficiency, as it is directly related to the economical sustainability of the poultry farms. After the success of in vitro antimicrobial testing, researchers dived further into in vivo experiments to verify the effects of MCFA supplementation on growth and production performance of the birds.

One of the laying hen studies demonstrated the positive effects of in-feed MCFAs in a 10-week experimental experiment, showing increased egg production (p<0.001) and egg shell strength (p<0.05) in the treatment of 2 g/kg addition of MCFA and organic acid blend (Lee et al., 2015). For broiler chickens, Baltić et al. (2019) showed that Aromabiotic® significantly increased (p<0.05) weight gain and FCR compared to the control group without any additives. Aromabiotic® is a commercial product of MCFAs containing C6, C8, C10, and C12. The FCR was reduced by 6.4% by adding Aromabiotic®. Besides, MCFAs (Aromabiotic®) supplementation significantly increased the villus length in the duodenal area, which is an indicator of greater enzyme secretion and better nutrient absorption. This might be one of the reasons for the improved growth efficiency observed in this study (Baltić et al., 2019).

Moreover, a dose-response study showed that the inclusion of 2 g/kg Aromabiotic® (highest dosage) in the diet significantly (p<0.001) improved the broiler weight gain at the end of the grower phase compared to the control diet. Besides, a significant increase (p<0.05) in the European performance efficiency index was noted in the group with 2 g/kg dietary MCFAs mainly due to the reduction in mortality (p<0.05) compared to the control birds (Khosravinia, 2015).

Besides MCFAs and nutritional strategies

Although many studies have demonstrated the beneficial effects of all kinds of alternatives such as MCFAs or blends with certain MCFAs, the general voice is that these products lack consistency and the trial results vary remarkably from study to study, farm to farm. It calls for further investigations in their mode of actions. Prototyping and optimizing the combination of various alternatives with technological advances in processing should be on the priority list for alternative development. More importantly, coupling the dietary strategies, precise management, and high-standard hygiene practices should be encouraged to maximize the flock performance (Aarestrup, 2012; Engster et al., 2002).

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