How to control necrotic enteritis through gut health optimization

Antibiotic growth promoters (AGPs) have routinely been used in intensive poultry production for improving birds’ performance. However, in recent years, reducing the use of antibiotics in animal production has become a top priority, due to concerns about the development of antibiotic-resistant bacteria and mounting consumer pressure. Multiple countries have introduced bans or severe restrictions on the non-therapeutic use of antibiotics, including in the US, where the Food and Drug Administration has implemented measures to curb the use of antibiotics since 2017.

However, the removal of AGPs poses challenges for poultry performance, including reduced feed efficiency, decreased daily weight gain, as well as higher mortality. Moreover, the withdrawal of AGPs in feed is widely recognized as one of the predisposing factors for necrotic enteritis (NE). NE is one of the most common and economically important poultry diseases, with an estimated global impact of US$ 5 to 6 billion per year. As a result of withdrawing AGPs, the usage of therapeutic antibiotics to treat NE has increased. To break out of this vicious cycle and to secure the efficiency of poultry production, alternatives are needed that combat NE where it starts: in the gut.

Necrotic enteritis: a complex disease

NE is caused by pathogenic strains of Clostridium perfringens (CP): ubiquitous, gram-positive, spore-forming anaerobic bacteria. The spores of CP can be found in poultry litter, feces, soil, dust, and contaminated feed. Low levels of different CP strains are naturally present in the intestines of healthy birds, kept in check by a balanced microbiome. However, when gut health is compromised, pathogenic strains can proliferate at the expense of unproblematic strains, resulting in clinical or sub-clinical NE.

Animals suffering from the clinical form show symptoms such as general depression, reluctance to move, and diarrhea, with mortality rates of up to 50%. Infected birds suffer from degenerated mucosa lesions in the small intestines. Even in its “mild”, subclinical form, which often goes unnoticed, the damage to the animals’ intestinal mucosa can result in permanently reduced performance and consequent economic losses for the producer.

Certain predisposing factors have been found to enable the proliferation of pathogenic strains in the gastrointestinal tract. Diet is a key example: the composition of the gut flora is directly linked to feed composition. High inclusion rates of cereals (barley, rye, oats, and wheat) that contain high levels of non-starch polysaccharides (NSPs), high levels of indigestible protein, and inclusion of proteins of animal origin (e.g. fishmeal) have been shown to predispose birds to NE.

A range of diseases (e.g. chicken infectious anemia, Gumboro, and Marek’s disease), but also other factors that have immunosuppressive effects, such as heat or cold stress, mycotoxins, feed changes, or high stocking density, render birds more susceptible to intestinal infections. The single most prominent predisposing factor for the occurrence of NE is the mucosal damage caused by coccidiosis.

Gut health is key to combating necrotic enteritis

To control NE, a holistic approach to optimizing the intestinal health of poultry is needed. It should take into account not only parameters such as diet, hygiene, and stress, but should also make use of innovative tools.

Phytomolecules, also known as secondary plant compounds, are essentially plants’ defense mechanisms against pathogens such as moulds, yeasts, and bacteria. Studies have demonstrated the antimicrobial effects of certain phytomolecules, including against antibiotic-resistant pathogens. Phytomolecules have also been found to boost the production of digestive enzymes, to suppress pro-inflammatory prostaglandins and have antioxidant properties. These features make them a potent tool for optimizing gut health, potentially to the point of replacing AGPs.

Can phytomolecules mitigate the impact of necrotic enteritis?

To study the impact of phytomolecules on the performance of broilers challenged with a NE-causing CP strain, a trial was conducted at a US-based research facility. In this 42-day study, 1050 male day-old Cobb 500 broiler chicks were divided into 3 groups, with 7 replicates of 50 chicks each.

On the first day, all animals were vaccinated against coccidiosis through a live oocyst spray vaccination. The experimental diets met or exceeded the National Research Council requirements, and were fed as crumbles/pellets. On days 19, 20, and 21, all pens, except the negative control group, were challenged with a broth culture of C. perfringens. A field isolate of CP known to cause NE (originating from a commercial broiler operation) was utilized as the challenge organism. On day 21, three birds from each pen were selected, sacrificed, group weighed, and examined for the degree of present NE lesions.

The positive control group received no supplements. The trial group received a synergistic combination of two phytogenic products containing standardized amounts of selected, microencapsulated phytomolecules: an in-feed phytogenic premix (Activo®, EW Nutrition GmbH) and a liquid complementary feed supplied via the drinking water (Activo® Liquid, EW Nutrition GmbH). The products were given at inclusion rates corresponding to the manufacturer’s baseline antibiotic reduction program recommendations (Figure 1):

Figure 1: Trial design

The trial results indicate that the addition of phytomolecules helps to mitigate the impact of NE on broilers’ performance. The group receiving Activo® and Activo® Liquid showed a better feed conversion (Figure 2) compared to the positive control group (NE challenge, no supplement). Also, better lesion scores were noted for animals receiving phytomolecules (0.7 and 1) than for the positive control group (1.6).

The most significant effect was observed concerning mortality: the group receiving Activo® and Activo® Liquid showed a 50% lower mortality rate than the positive control group (Figure 3). These results clearly indicate that phytomolecules can play an important role in mitigating losses due to NE.

Figure 1: Adjusted FCR

Figure 2: Lesion scores and mortality

Tackling necrotic enteritis in a sustainable way

In an age of AGP-free poultry production, a concerted focus on fostering animals’ gut health is key to achieving optimal performance. This study strongly demonstrates that, thanks to their antimicrobial, digestive, anti-inflammatory and antioxidant properties, phytomolecules effectively support birds’ intestinal health when challenged with NE. The inclusion of Activo® and Activo® Liquid, two phytogenic products designed to synergistically support birds during critical periods, resulted in improved feed conversion, better lesion scores, and 50% lower mortality.

In combination with good dietary, hygiene, and management practices, phytomolecules are therefore a potent tool for reducing the use of antibiotics: including Activo® and Activo® Liquid in their animals’ diets allows poultry producers to reduce the incidence of NE, to mitigate its economic impact in case of outbreaks, and therefore to control NE in a sustainable way.

By A. Bhoyar, T. van Gerwe and S. Regragui Mazili

ANTIBIOTIC RESISTANCE IN FISH FARMING ENVIRONMENTS: A GLOBAL CONCERN

ANTIBIOTIC RESISTANCE IN FISH FARMING: A GLOBAL CONCERN

Antibiotic Resistance in Fish Farming

The occurrence and distribution of antibiotic resistance (AR) phenomena in areas designed for fish Farming has exponentially increased in the last decades. AR bacteria have become a global concern due to the massive use or misuse of antibiotics to prevent possible diseases and overcome major production problems, as confirmed by several research reports. As a consequence of the selective pressure exerted by antibiotics, ARB has been developed and multi-drug resistant bacteria (MDR) have become difficult to be controlled and eradicated. Their spread is expected to increase and is recognized to represent one of the most serious threats to public health in this century. Compared to the past, in salmonid farming in Europe and America, an effective range of vaccines has been developed, which have allowed decreasing the use of antimicrobial agents for most of the bacterial diseases . In addition, the husbandry methods and diagnostic techniques have been improved and this has resulted in a more effective control of bacterial pathogens and reduced impacts of fish diseases. However, for some bacterial diseases, no vaccines are available yet and antimicrobials are still used as a prophylactic measure.

This short note aims at drawing a synthesis of the AR occurrence in aquaculture field and of the possible causes for its spread, suggesting the related legislative measures and the possible solutions to this emerging problem, which has been recognized as a research priority issue by the European Community.

Since the first case studies, several reports have documented the occurrence and spread of ARB in both marine and freshwater fish farms . Most frequently, AR has been reported against oxytetracycline , tetracycline , ampicillin  florfenicol. On the contrary, bacteria resistant to gentamicin, kanamycin, flumequine and enrofloxacin have been reported to account for a low percentage of the total of the isolates.

Fish feed have been claimed to be a source of antimicrobialresistant bacteria. Concerning the mechanisms of AR, two main pathways have been suggested : a) inherent or intrinsic resistance, which occurs when a bacterial species is not normally susceptible to an antibacterial agent, due to the inability of this agent to reach its target site inside the cell, or a lack of affinity between the antibacterial and its target site, or b) acquired resistance, when the bacterial species is normally susceptible to a particular drug, but some strains are resistant and proliferate under the selective pressure induced by the use of that agent. AR genes can be transferred between bacteria by transformation; transduction or conjugation processes that involve lateral DNA transfer. Therefore, bacterial AR is a natural defence mechanism realized through genetic modifications triggered to survive to the drug action and in many conditions, mechanisms of horizontal gene transfer have been reported to be responsible for the spread and dissemination of the genetic material bearing AR among different bacterial species. Even in some aquaculture systems of Pakistan and Tanzania where antibiotics were not previously used ; explained the occurrence of AR against various antimicrobials hypothesizing that a pool of resistance genes derived from integrated fish farming practices based on the use of domestic farm and poultry waste along with antibiotic residues from animal husbandry.

The public health hazards related to antimicrobial use in fish farming include, on one hand, the development and spread of AR bacteria and resistance genes, and on the other, the presence of antimicrobial residues both in the environment and in aquaculture products. Since animals and animal waste are a potential reservoir of multi resistance genes that can be transmitted directly or indirectly to humans through contact and food consumption, this can represent a risk to public health. However, the opinions on the possible risks of transfer of such resistances to human consumers are controversial. Antibiotic-resistant bacteria that persist in sediments and farm environments can act as sources of antibiotic-resistance genes for fish pathogens in the vicinity of the farms.

With respect to the legislative issues of the AR in fish farming, this issue has been recognized as a global concern by the Council and the European Parliament, as well as by the EU Commission. The Regulation (EC) No 470/2009 established the antibiotic maximum residue limits (MRL) in foodstuff of animal origin, taking into account the toxicological risks and the pharmacological effects of residues. The recently launched research programme Horizon 2020, in the framework of the Societal Challenge 3.2 (Food Security, Sustainable Agriculture and Forestry, Marine, Maritime and Inland Water Research and the Bioeconomy), promotes the reduction of antibiotics in animal farming and the setup of measures to prevent their spread, to increase agriculture environmental sustainability. This underlines the relevance of AR in fish farming as a problem with significant scientific, social and economic impacts.

In 2011, a 5-year Action Plan was launched to address the growing risks posed by AR based on a holistic approach; a prudent use of antimicrobial in veterinary medicine was recommended. To comply with this Action, in 2015 specific guidelines have been issued (2015/C 299/04, Commission Notice-Guidelines for the prudent use of antimicrobials in veterinary medicine), with the aim of limiting AR bacteria originated from livestock animals. Among the actions recommended to prevent and reduce the use of antimicrobials in aquaculture, it has been underlined to encourage the use of vaccines, when possible; to implement specific biosecurity measures and to develop specific disease surveillance programmes to prevent or reduce possible disease outbreaks; to develop production systems optimal with respect to water quality, oxygen levels and able to warrant the welfare of the reared animals.

Compared to the studies available until now on the antibiotic use in aquaculture or other farm environments and the presence of AR, relatively few studies focused on the possible solutions to this problem. To implement the appropriate control strategies, a clear evidence of the link between abuse of antibiotics in aquaculture, antibiotic resistance in bacterial pathogens and antibiotic residues is needed. In order to contain and manage the emergence of AR, several solutions can be suggested, that aim at the development of sustainable aquaculture practices, such as those including the use of probiotics, essential oils to increase fish immune status of fish, as well as the adoption of measures able to warrant the fast abatement of antimicrobial residues in animal wastes (The Review on Antimicrobial resistance 2015). Particularly, the use of probiotics to promote health maintenance and disease prevention has recently gained an increasing interest as an alternative to antibiotics. Supplementation with pro- and prebiotics in fish nutrition is increasing in parallel with increasing demand by consumers and with the need for environmentally friendly aquaculture practices. The beneficial effects of probiotics in fish and shellfish culture – improved growth performance, activity of gastrointestinal microbiota and feed utilization, enhanced immunity and disease resistance – have recently been reviewed. Most probiotics proposed as biological control agents in aquaculture belong to the lactic-acid bacteria (LAB), the genus Bacillus, or the genera Pseudomonas and Burkholderia.

Another possible solution to chemotherapies in aquaculture is related to the use of vegetable extracts. Herbal extracts from plants or algae are known to contain natural compounds, such as phenolic compounds, polysaccharides, proteoglycans and flavonoids which are able to stimulate the fish immune system and therefore may play a major role in the prevention or control of infectious microbes.These are recognized as eco-friendly alternatives for therapeutic and prophylactic purposes in health management of aquatic animals, which combine sustainable production systems with high quality of seafood products; nevertheless, further studies are needed to assess any potential impact of these substances on the host microbiota and on the environment.

About the treatment of aquaculture effluents, antibiotic residues should be removed before being released to the environment. Physical, chemical, and biological methods including adsorption, biodegradation, disinfection, membrane separation, hydrolysis, photolysis, and volatilization have been applied in aquaculture systems to remove antibiotics. Tetracyclines are removed mainly by adsorption onto the biomass flocs; beta-lactams by hydrolysis reactions driven by bacteria or physical chemical processes, while removal of erythromycin and ciprofloxacin by biodegradation is difficult. Advanced oxidation processes have been found to be cost-effective mechanisms for the abatement and removal of flumequine from aqueous systems, as conventional processes in wastewater treatment plants fail to remove this antibiotic.

In synthesis, on the basis of the experimental evidences proving the spread of AR, the best way to solve this problem is to avoid abuse antibiotic use in aquaculture. A holistic approach to the use of antibiotics in fish farming is suggested, which relies on reducing the need for antibiotics through prevention (i.e. vaccines), nutrition, and better management of rearing sites.

Source: http://www.fisheriessciences.com/fisheries-aqua/antibiotic-resistance-in-fish-farming-environments-a-globalconcern.php?aid=11240