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Minimising antibiotic usage with integrated gut health management

Feed products designed for intestinal health have emerged to contribute to health management practices, generally focusing on promoting the growth of beneficial microbiota and reducing pathogens. However, recent insights demonstrate that the efficacy of a gut health concept can be markedly improved by optimising both microbiota and gut barrier function. This integrated approach includes stabilisation of the microbiota and enforcing the mucosal barrier properties.

By Coen Smits , Nutreco Research and Development and Jaco Eissen, Selko Feed Additives, the Netherlands
Since the ban on antimicrobial growth promoters (AMGP) in the European Union, poultry farming is dealing with a greater challenge to maintain a high health status. Antimicrobial growth promoters contributed to prevention of gastrointestinal bacterial infections caused by various stress factors. In the modern day high throughput farming, stress on the production animals is inevitable.
Every animal goes through it to some extent. Stress can be multi-factorial including disease pressure, transportation, vaccination, feed transitions and environmental factors. In recent scientific literature, it has become more evident that stress plays a major role in disturbing the gut environment. There are essentially two ways, by which stress contributes to gut health problems;
1. by causing disturbances in gastrointestinal motility and feed intake patterns leading to microbial imbalance and increased risk of infections and,
2. by causing systemic changes in the animal such as oxidative stress and inflammation leading to loss of gut barrier integrity.
Microbial dysbiosis along with gut barrier dysfunction causes poor digestion and inflammation. These, in turn, can lead to poor feed efficiency and daily gain as well as wet litter and infections. For the farmer, this means more use of drugs, increased veterinary costs, high mortality rates and – ultimately – financial loss.
The ban on AMGP led in some countries initially to a serious increase in the use of therapeutic antibiotics in Europe. Nowadays there is public and industry concern about the prudence and sustainability of antibiotic use and its potential long-term impact on public health. For a responsible use of antibiotics, the need for a highly effective prophylactic approach to animal health is clear. Recent advances indicate that a combined dietary strategy of microbiota stabilisation and gut barrier enforcement is highly promising.
Microbiota management
New scientific opinions on gut microbiota management demand a more in depth look in population changes than just measuring single species to understand and solve the problems of the gut microbial ecosystem. To modulate the microbiota dynamics in the gut, Nutreco R&D developed a database with information about the microbial growth modulating properties of a wide range of natural compounds using high-throughput methods.
Target microbial species were amongst others Lactobacillus spp, and pathogenic strains of Clostridium spp., E. coli spp. and Salmonella spp. From the database, compounds were selected for further in vivo studies in the complex microbial ecosystem of the poultry gastrointestinal tract. Based on the results of compound screening studies, various test blends were formulated for poultry for further research. Final blends were integrated in the new gut health product ‘Presan’.
Furthermore, quantitative real time PCR and one of the latest technologies in the “omics” area, called “bar-coded pyrosequencing”, were applied. The latter technology also requires advanced bioinformatics tools to analyse and interpret the data. The pyrosequencing technique enables the user to make a complete overview of the intestinal microbiota population in one analytical run and can be used to study changes in microbiota associated with poor animal health. Scientific studies done in poultry by triggering microbial growth in the small intestine, clearly show the negative effects of excessive microbial activity on gut health, affecting nutrient digestibility and absorption (Figure 1). Furthermore, exposure of the more sensitive upper small intestinal tract to high numbers of microbes can cause inflammation, which will lower feed intake and reduce daily gain.
The dietary inclusion of our blend of selected natural ingredients reduced the microbial numbers in the small intestine effectively. Lower numbers of total bacterial count were determined in the upper and lower small intestine.
Furthermore, pyrosequencing data clearly showed that the addition of Presan in the diet, increased small intestinal microbial diversity at D21 of age (Figure 2). The number of observed species were higher at age of 21 days, in jejunum of birds fed Presan, compared to control group. This was also visible in the community profiles.
Gut barrier management
Focusing alone on microbiota management, limits the success of a gut health concept, as the important part of the gut barrier defence is ignored. Gut barrier dysfunction may lead to a higher exposure to antigens, toxins and pathogens and is therefore critical for maintaining good health. Key components of the gut barrier are nowadays well described in literature and include the mucus layer, the permeability of the epithelial cell layer covering the intestinal mucosa and the response of the gut associated immune system. The very first thing that needed to be solved was to find a reliable and reproducible in vivomodel to study barrier function in nutritional intervention studies. This led to the development of a novel gut barrier stress model in collaboration with leading universities in this field of research.
The model induces a gut barrier dysfunction and various parameters that are critical in relation to gut barrier function can be studied. Attention for example is paid to gut barrier characteristics, such as gut permeability, in relation to inflammation and/or oxidative stress parameters. Inflammation and/or oxidative stress may be the result of a ‘leaky’ gut, but also vice versa, inflammation and/or oxidative stress may be the causative factor for a leaky gut by damaging the mucosa.
Specific natural ingredients in Presan have shown in research to exert anti-inflammatory and anti-oxidant effects along with antimicrobial potency. In the “In-vivo gut barrier stress model”, when tested against the control diet group, Presan significantly reduced expression of inflammatory cytokines. Control group showed clear decrease in TEAC (trilox equivalent antioxidant capacity) and compensatory increase of anti-oxidant enzyme (GSHPx) activity (see Figure 3 and Figure 4). Control of inflammation is an important prerequisite for control of gut barrier function.
Combined approach works
Promising results have been obtained testing the combination of these microbiota and gut barrier management strategies on performance and health of birds. In various experimental studies done under challenge and non-challenge conditions, the new concept showed significant improvements in performance, feed efficiency, improved litter quality and reduced incidence of footpad lesions. The results to date suggest that the microbiota and barrier management concept may contribute to establish a prudent use of antibiotics. This would have important positive implications for animals, farmers and society.
Authors would like to acknowledge our scientific partners from NIZO Food Research, Utrecht University for their valuable scientific support. For further information contact Jaco.Eissen@nutreco.com.

Coen Smits and Jaco Eissen

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