Impact of Antibiotic Use in Poultry on Human Health

Antibiotic use in farm animals has increased the prevalence of antimicrobial resistant strains of pathogenic bacteria. Given that the human population is increasing, the demand for animal protein is continually increasing. Specifically, poultry is the most valuable source of animal protein around the world (Abd El-Ghany, 2003). To increase product output and decrease costs of production, chickens are often raised in small confined spaces. This high-density containment facilitates the spread of disease. To combat this issue, antibiotics are used prophylactically to prevent diseases and increase the growth of poultry (Abd El-Ghany, 2003). The growing use of antibiotics in this way has contributed to the rise in antibiotic resistant strains following the advent of antibiotics. The worldwide consumption of antibiotics is large and increasing; between 100,000 to 200,000 tons are used annually, with more than half being used in animals (Muhammad, et. al 2020).

The use of antibiotics continues to be a controversial issue due to new data that alters the balance of risks and benefits (Hao, et. al 2014). Antimicrobial resistance is not a new phenomenon and does occur naturally, but humans are accelerating the spread of antibiotic resistant bacteria through the increased use of antibiotics (Wang, et. al 2019; WHO 2020, July). The issue of antibiotic resistance is not one that should be taken lightly. The World Health Organization states that uncontrolled antibiotic use is the biggest threat to global health, food security, and development (WHO 2020, July). As an increasing number of infections are becoming more difficult to treat, there have been longer hospital stays, higher medical costs, and increased mortality associated with antibiotic resistant infections (WHO 2020, July). Research demonstrates the rapid increase in multidrug resistant pathogens, which are dangerous because there are no other treatment options (Shea, 2003). Thus, antibiotic resistance is estimated to cause 23,000 deaths in the U.S. each year and ten million deaths annually worldwide by 2050 (Chang, et. al 2015). In addition to the cost of thousands of lives, antibiotic resistance expenses account for a significant portion of healthcare expenses. It is estimated that two to three percent of the U.S. GDP by 2050 will go towards issues surrounding antibiotic resistant infections (Wang, et. al 2019). The problems associated with antibiotic use and misuse, including the negative impacts on human health, are worsening and antibiotic use in animals is one of the main contributors.

Antibiotics have been used in animals to prevent, control, and treat infectious diseases since the 1940s (Hao, et. al 2014). Intensive animal husbandry practices increase infections between conspecifics and treatment requires the increased use of antimicrobials (Hao, et. al 2014). Over 100 antimicrobials have been used in food-producing animals around the world and 52.1% of all antimicrobials in the U.S. are used for treatment in animals as the primary strategy for preventing and treating infections (Hao, et. al 2014). Besides treatment and prevention, antimicrobials have also been used as growth promoters since 1950 to increase the weight of animals through a subtherapeutic application (Castro-Vargas, et. al 2003; Chang, et. al 2015). Low doses have been shown to play an important role in the improvement of feeding efficiency, allowing animals to grow faster on less food in a shorter time which ultimately increases profits (Hao, et. al 2014; Shea 2003). Studies show that subtherapeutic antimicrobials work by attenuating the intestinal wall to promote nutrient absorption and inhibiting the growth of pathogenic bacteria to improve the profile of intestinal flora (Hao, et. al 2014). Although the use of antimicrobial agents as growth promoters has benefited the production of food animals, it is important to note that these antibiotics are the same as the ones used to treat human infections (Shea 2003).

It is important to consider how natural selection tends to favor the development of resistant bacterial strains. The three mechanisms that allow bacteria to survive and grow in the presence of antibiotics are tolerance, persistence, and resistance (Rodriguez-Verdugo, et. al 2019). Antibiotic tolerance develops when antibiotics target microorganism growth and causes physiological changes that slow down growth. In persistence, only a subpopulation of cells is able to transiently survive antibiotics. As for resistance, cells evolve genetic mutations that allow them to survive at higher concentrations of antibiotics (Rodriguez-Verdugo, et. al 2019). Resistance is the most dangerous mechanism because it leads to the development of enduring resistant strains. Antibiotics act as a selective pressure and resistance is an evolutionary response to this selective force (Shea 2003). Resistance genes are estimated to arise once in every one million to one billion cells and selected for in environments where bacteria and antibiotics coexist (Shea 2003). The short generation time in bacteria allows rapid multiplication which facilitates the proliferation of antibiotic resistant cells and destruction of those that lack resistance.

Low doses of antibiotics, like those used prophylactically in animals, are most dangerous. These levels select for existing multidrug resistance, but also allow susceptible microbes to survive longer which increases the likelihood that they will adapt (Ter Kuile, et. al 2016). In the presence of low doses, bacteria induce protection mechanisms that increase the mutation rate by favoring cells that have a gene that makes them resistant (Ter Kuile, et. al 2016). Antibiotic resistance genes (ARGs) are ubiquitously present in the environment as plasmids and tend to spread through transformation, conjugation, and conformation (Ter Kuile, et. al 2016). Over time, bacteria can build up resistance and survive higher doses of various types of antibiotics. Methods of resistance include increasing the efflux of antibiotics from the cell using pumps, decreasing the influx of antibiotics into the cell, and the presence of enzymatic destruction of antibiotics (Shea 2003).

Antimicrobial resistance is an issue that needs to be addressed because resistance is increasing and making bacterial infections more difficult to treat (Hao, et. al 2014). The development of resistance in farm animals increases during long-term, low-level exposure to antibiotics when they are used as growth promoters (Hao, et. al 2014). Additionally, there are significant correlations between strains from animals and humans for resistance to multiple drugs (Hao, et. al 2014). Studies have established that poultry harbors the highest abundance and diversity of ARGs (Wang, et. al 2019). One study found multidrug resistant Salmonella strains in 91% of poultry farms and 98% of raw chicken meat processing plants worldwide (Castro-Vargas, et. al 2003). In another study, chickens were split into control and antibiotic fed groups in order to determine a causal relationship between antibiotic use and the development of resistance. The group fed with antibiotics did in fact harbor a higher number of resistant strains of bacteria compared to the control (Shea 2003). Many other studies indicate antibiotic use increases resistance in farm animals.

Antibiotic resistant bacteria can be transferred in a number of ways from animals to humans, making resistance in animals an issue for human health. Live poultry markets represent a high-risk environment for the dissemination of animal origin ARGs through means of direct contact (Wang, et. al 2019). Resistant strains can also be acquired by directly consuming animals that had antibiotics used in their feed or insufficiently cooking raw meat to kill pathogens (Chang, et. al 2015; Ter Kuile, et. al 2016). There can also be indirect contact with antibiotics through contaminated environmental water that has active antibiotics from wastewater treatment plants, animal waste lagoons, surface waters, and river sediments (Shea 2003). Additionally, antibiotics may be released into the soil from animal manure because the majority of consumed antibiotics are excreted (Muhammad, et. al 2020). Plants, including fruits and vegetables, accumulate antibiotics by absorbing them from the soil. The antibiotics make their way into the food web as the plants harboring them are then consumed by other animals and humans (Hao, et. al 2014). There is also evidence of transmission of resistant strains between humans as well as horizontal gene transfer of resistance genes into human pathogens (Chang, et. al 2015).

Antibiotic resistant strains impact human health negatively in multiple ways. Trace amounts of antibiotics can affect endocrine activity, metabolism, and developments in humans. For instance, antibiotics can cause an inflammatory reaction in the liver and disrupt embryonic growth and development (Muhammad, et. al 2020). Antibiotics in the environment can also pose a risk of toxicity to plants and animals, which can disrupt the food supply (Muhammad, et. al 2020). The most significant result of the increasing prevalence of antibiotic resistant pathogens is their potential to cause hard to treat illness in humans and lead to mortality (Shea 2003). Those who are immunocompromised, children, or elderly are more susceptible and suffer more serious complications from harboring a resistant strain, including sepsis (Castro-Vargas, et. al 2003). Salmonella is one of the most serious foodborne pathogens that leads to 93 million annual cases and results in 155,000 annual deaths globally, and the rise in drug-resistant strains is making this pathogen even more problematic (Castro-Vargas, et. al 2003). Antibiotic resistant bacteria is a global health risk that needs to be addressed.

Increasing global temperature affects bacterial growth and the development of resistant strains. Increased temperatures are an environmental stressor, and exposure to one stressor can change a cell’s response to a subsequent stressor (Rodriguez-Verdugo, et. al 2019). Additionally, temperature stress causes similar physiological changes as antibiotics, such as the inhibition of protein synthesis (Rodriguez-Verdugo, et. al 2019). Antibiotics that increase protein misfolding induce heat shock machinery and overexpression of some heat shock chaperones can confer protection against lower concentrations of antibiotics (Rodriguez-Verdugo, et. al 2019). Alarmingly, pre-exposing cells to high temperature or other stressors has been shown to provide protection against subsequent exposure to antibiotics (Rodriguez-Verdugo, et. al 2019). One study demonstrated that cells pretreated with heat have a 50% greater chance of survival when exposed to streptomycin. Therefore, temperature stress selects for the evolution of antibiotic resistance. Temperature can increase the likelihood of phenotypic and genotypic variation, increases the likelihood of resistance mutations developing, and increases spontaneous mutation rate. For every 10 degree Celsius increase in minimum temperature, there is a significant increase in the percentage of resistant bacteria strains (Rodriguez-Verdugo, et. al 2019).

The main efforts to control resistance involve restricting the use of antibiotics. Governments around the world have urged limited and cautious antibiotic use in veterinary and human medicine alike (Castro-Vargas, et. al 2003). For instance, in 1969, Britain first took action to restrict antibiotic use in animals; in 1986, Sweden banned all growth use antibiotics in animals; in 2006, the EU and FDA banned all low dose antibiotics in food animals (Hao, et. al 2014; NIH 2020). However, It is not clear if removal or reduction of antibiotic use will lead to a reduction in resistant organisms (Chang, et. al 2015). Banning antimicrobials can lead to decreased drug resistance in specific species; withdrawing enrofloxacin in poultry reduced Salmonella resistance (Hao, et. al 2014). On the flip side, another study found that banning fluoroquinolones in chicken did not decrease ciprofloxacin resistance. Withdrawal of low-dose antimicrobials as feed additives can increase levels of pathogens in animals’ gut, increases contamination of food, increases the potential for humans to be infected (Hao, et. al 2014). The restriction of antibiotic use may also have negative economic consequences. Without antibiotics, the livestock industry will require more space to raise animals to maintain current production levels (Hao, et. al 2014). It has been estimated that the cost of banning antimicrobial use in animals will be a ten-dollar increase per person in food consumption, but it is important to note that antibiotic resistance costs the healthcare system up to sixty billion dollars annually (Hao, et. al 2014). There is also less awareness about the impacts of antibiotics leading to resistance in developing countries.

The need for new antibiotics is not being met as the pace of production cannot keep up with the demand for the production of new antibiotics. (Shea, 2003). There is insufficient private investment in the development of new antibiotics leading to a slowing rate of developing new antimicrobial agents (WHO 2020, January). The FDA approval of new antibacterial agents has decreased by 56% over the last 20 years (WHO 2020, January). The constant development of new antibiotics is also a costly endeavor. As it is clear that antibiotics may not be the solution to resistant strains, many have turned to alternatives including prebiotics, symbiotics, paraprobiotics, and probiotics (Abd El-Ghany 2003). Probiotics are live bacterial or fungal cultures that have beneficial health functions to the host by enhancing the growth of beneficial microbial populations and inhibiting pathogenic ones (Abd El-Ghany 2003). They work by altering the gut microflora, colonizing intestinal niches, and modulating the cell-mediated and humoral immune response. Prebiotics are soluble non-viable metabolites produced by a bacterial or probiotic metabolic process (Abd El-Ghany 2003). Prebiotics are produced by intestinal microbiota to reduce gut pH and prohibit opportunistic pathogen proliferation and this has a positive influence on the host’s health (Abd El-Ghany 2003). Symbiotics are a combination of probiotics and prebiotics. Paraprobiotics are non-viable microbial cells or crude cell extracts that provide benefit to consumers (Abd El-Ghany 2003). The most common species are lactobacillus and bifidobacterium, which have been found to enhance epithelial barrier and inhibit pathogen adhesion to the gut mucosa (Abd El-Ghany 2003). These alternative options still need to be further researched before they can be safely implemented.

We propose that reducing antibiotic resistance will have to come from coordinated efforts with multiple strategies. There needs to be long term policies for international regulation of antibiotic use. This will require monitoring use in all sectors, especially use in food-producing animals. Antibiotics should not be eliminated completely from animal use as this could have detrimental economic consequences. However, antibiotics should be used cautiously in animals and alternative growth promoters should be considered. The agriculture sector can prevent and control resistance by only giving antibiotics to livestock under veterinary supervision and not use antibiotics for growth promotion. Farmers can also choose to vaccinate to decrease the need for antibiotics for treatment (WHO 2020, July). In humans, doctors should use the highest concentrations safe for patients that leads to the fastest time to achieve the elimination of the pathogen to prevent the development of resistance (Ter Kuile, et. al 2016). Once the infection is controlled, antibiotic treatment needs to be discontinued to avoid the selection of for resistant strains. However, stopping antibiotics too early can cause the infection to reoccur and AMR variants to dominate. There is a need for balance in the timing of antibiotic use to prevent resistance from developing. Consumers can also play a role in controlling resistance by choosing foods that have been grown without antibiotics.

It is clear that actions need to be taken to combat antibiotic resistance from multiple sources, and animal antibiotic use is a significant part. Antibiotic resistance is one of the biggest threats to global health, food security, and development and humans are accelerating the natural process of resistance from the misuse of antibiotics. Increasing numbers of infections are becoming harder to treat leading to longer hospital stays, higher medical costs, and increased mortality. Common infections due to minor injuries may soon become fatal once again as the arsenal of antibiotics is being depleted. There is a growing desire for meat raised without antibiotics, but the consequences for health would be too dire to just remove antibiotics. It is important to preserve effective antibiotics as long as possible but also use them when we need to.

Works Cited

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