The impact of gut health and gut integrity on performance of livestock animals

The gastrointestinal tract (GIT) is a highly complex system which acts differently across livestock species. Feed, water, microorganisms and contaminants ingested by the animals exert their impact in the GIT. Therefore, intestinal immunity and intestinal barrier function play a crucial role, covering around 70-80% of the total immune system. Animal performance directly correlates with health status, in particular with the health status of the digestive tract. Compared to standard health animals, the growth rate of animals in a germ-free environment is higher. Consequently, performance of standard health animals is higher compared to animals facing pathogenic challenges (Burch, 2004).

Ways to improve performance

Industrialized production has placed greater demands on animal husbandry and given rise to several challenges related to gut health, including dysbiosis, reduced nutrient digestibility and impaired barrier function. These put pressure on farm profitability and explain, at least in part, the motivations for sub-therapeutic application of antibiotics for disease prevention and growth promotion. As antibiotics enabled animals to grow faster and gain weight more efficiently through reducing inflammation and modulating gut microbiota, their use in growth promotion became common practice. Van Boeckel et al. (2015) estimate that the global average annual consumption of antimicrobials per kilogram of animal produced is 2 and 3 times higher in chicken (148 mg/kg) and pigs (172 mg/kg) respectively compared to cattle (45 mg/kg). Furthermore, global compound feed production and antibiotic consumption data indicate that, on average, each ton of feed contains 66 grams of antibiotics, and this figure is estimated to rise in the future. Teillant and Laxminarayan (2015) have pointed out in their study that recommended dosage of sub-therapeutic antibiotics has increased over last 60 years, from 10-20 g/ton in the early 1950s to 40-50 g/ton in the 1970s, to 30-110 g/ton nowadays.

Considerations regarding safety and efficacy of the sub-therapeutic use of antibiotics in animal nutrition have led to a legal ban of these substances in the European Union, Korea and California and to discussions in several other countries like India and China. Teillant and Laxminarayan (2015) report that antibiotic growth promoters lost productivity in the post-2000 era compared to earlier studies. This might be a result of increasing antibiotic resistance levels among microorganisms, which is not only affected by antibiotic use in livestock, but also in human medicine. In addition to the fact that antibiotic resistance triggers an increase in production costs, antibiotic resistance in animals may affect human disease control. Therefore, besides holistic approach (better management, vaccination programs, biosecurity measurers, and feeding strategy) significant effort has been paid to novel growth promoters (NGPs) in order to reduce usage of AGPs in animal husbandry.

Omics – an emerging technology for future livestock science

Nowadays, emerging genomics, transcriptomics, proteomics and metabolomics technologies allow a deep insight into the cellular metabolism of live organisms. Both the gut microbiota and the host tissue, highly influence the health and performance of animals. While the classical microbiological and histological methods give an insight on “who is there”, these next generation sequencing technologies provide information about the cell “what are you doing”.

Soo-Je et al. (2014) applied high-throughput 16S rRNA gene-based pyrosequencing methods to study the distribution of core bacteria in the swine gut and found that this distribution is associated with meat quality in swine. Sequencing is also an important tool to map the inflammatory processes and mucosal- and epithelial integrity in order to explore the anti-inflammatory, gut protective potential of novel feed additives. As it was stated by Eder et al. (2013) in an in vitro test with Caco-2 cells, that after challenging the cells with TNF-α, phytogenics were able to downregulate the mRNA levels of Nf-kb target genes (IL-1, ICAM-1, MCP-1). This is considered as an anti-inflammatory effect of phytogenic feed additives. This effect was proved also in vivo by Eder and Gessner (2016) when they analyzed different parts of the GIT and observed less inflammation in the tissue when they used phytogenics in feed. It is explained by the downregulation of the Nf-kb target genes and the upregulation of Nrf2 target genes. The transcription factor Nrf2 is responsible for anti-oxidative activity by increasing expression level of its target genes (CYP1A1, HO-1, UGT1A1).

An important part of the GIT barrier function are the epithelial cells which are connected by tight junctions to each other and covered by mucus produced by goblet cells. According to Antonissen et al. (2014), mycotoxins, in particular the Fusarium-produced metabolite deoxynivalenol, are able to increase the permeability of the intestinal epithelial layer. This can be explained by the down-regulation of the genes coding for the transmembrane tight-junction proteins Claudin 1 and Occludin, which reduces the interconnection of intestinal epithelial cells. In consequence, the risk for para-cellular translocation of pathogens increases and can be a precursor for necrotic enteritis and other infectious diseases.

Grenier et al. (2011) experienced an effect on immune cells, as well on the expression of cytokines and the junction proteins E-cadherin and Occludin at feeding co-contaminated diets with deoxynivalenol and fumonisin to piglets. In an experiment with broiler chickens, the mycotoxins deoxynivalenol and fumonisin B1 and B2 downregulated the expression of the duodenal genes coding for MUC2. Also the composition of the duodenal mucin was influenced by the presence of mycotoxins (Antonissen, 2015). Mountzouris (2016) reports an increased expression of intestinal MUC-2 in presence of phytogenics, which indicates that in certain extent mucus layer, barrier function of GIT can be also positively influenced by PFAs. If barrier function has been damaged (thinner mucus layer, shorter villus, destroyed tight junctions) then pathogen bacteria may cross to blood circulation, besides diminishing metabolism and growth of animal.

Omics-technologies are also used to study antibiotic resistances by sequencing the gut microbiome. A relevant question is whether multi-resistant bacteria, which cannot be controlled by the antibiotic growth promoters, can be influenced by novel growth promoters. Roth (2014) observed that an acid-based product significantly reduced ampicillin resistant and multi-resistant E.coli to (Tetracycline + Streptomycine + Sulfamethoxazol) in piglet’s fecal samples.

Economic impact of gut health

Concentration and consolidation has been accelerated in agriculture especially in livestock production where the number of large animal feeding operations has been sharply increased in last decades. Intensive, automatized production systems together with high genetic potential, high quality feeding, biosecurity and management programs have to be established in order to maintain profitability in a highly volatile market where margins are often tight. Competitiveness of the companies is also closely related to gut health and animal performance.

The underlying idea of the “-Omics” approaches is that a complex system can be understood more thoroughly. Precisely at this point, the industry practitioner may question the relevance of such technologies. From an animal nutritionist’s, veterinarian’s or livestock producer’s perspective, such new technologies might appear overly theoretical. In the end, the kilogram and quality of meat, milk and egg generate revenue - and this must be weighed against the cost, complexity and informative value of an overwhelming amount of data generated by whole genome sequencing technologies. One of the major challenges in today’s livestock science is to understand the interrelationship of parameters, provided by such novel technologies on cellular and molecular level, with animal health and performance.

When gut health is harmed by malnutrition, bacteria or toxic compounds, the host will try to restore optimal condition through an immune response. Such defense mechanisms do require energy and nutrients, which compete with the animal´s nutrient demand for maintenance and growth. Klasing (2007) has observed a productivity loss - up to 10% of the nutrient use - during an acute phase response which otherwise would have gone towards growth. Other researchers have estimated this nutrient cost to be 1.3 times that of maintenance (Webel et al., 1998) or a daily cost of 0.27 g ideal protein per kg body weight (Sandberg et al., 2007). Applegate (2009) compared growth performance of LPS-challenged broilers with an untreated control group, with a non-challenged pair fed group and with a LPS-challenged probiotic group. The LPS-challenged group achieved a 22% lower weight gain from day 14 to day 21, while the non-challenged pair fed group performed only 13% below control group. According to Applegate, 40% of the LPS effect is not accountable to feed intake, but can be considered as the net effect of acute phase response. The probiotic group could recover 17% of growth compared to LPS group. Liu et al. (2003) measured the impact of a lipopolysaccharides (LPS) challenged on performance in weaning piglets. Due to the challenge, inflammation markers like cortisol, PGE2 and IL-1β were 3 to 4 times higher in LPS challenged groups while IGF-1 was reduced by around 45%. This resulted in a 13% drop in average daily gain (ADG) in the LPS-challenged group. These studies show, that the focus on a few target genes or proteins, belonging to a specific biological pathway (e.g. inflammation or oxidative pathway) allows the correlation with animal performance parameters.

Reducing complexity increases the relevance of such novel technologies for practitioners, providing a tool to better understand the mode of action of feed additives on gut health and animal performance.

Good gut health is the best growth promoter.