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The development of antibiotics has been lauded as a public health achievement of the 20th century, allowing the effective treatment of infectious diseases. Resistance to antibiotics reduces the efficacy of this core tool of modern medicine. A globally coordinated approach is needed to preserve the effectiveness of antibiotics and prevent a health care catastrophe where drug-resistant infections claim millions of lives each year. The use of antibiotic growth promotors (AGPs) in animal production has been noted as an important contributor to antibiotic resistance worldwide.
The genomics technologies at BaseClear contribute to research into reducing antibiotic resistance in many ways. BaseClear’s Patrick Koning, Head of Marketing, spoke with Dr. Diko Becker from PHYTOBIOTEC about their recent work on the microbiota of different animals and how this approach has the potential to reduce antibiotic use in the livestock industry.
PHYTOBIOTEC is a company based in Brazil and Germany that has developed several feed additives based on plant extracts that work synergistically with the animal’s microbiome. PHYTOBIOTEC was founded in 2020 based on six years of research exploring how the bioactive components of plants – phytobiotics – can increase the health and resilience of various production species, thus improving performance and reducing the need for AGPs. The products, intended for swine, poultry (both laying hens and broilers), dairy and beef cattle, use microencapsulated essential oils, plant extracts and organic acids, combined with pre- and probiotics targeted at improving the gut microbiome of animals.
As Patrick Koning explains: “Farmers have relied on antibiotics for an animal health and performance boost for many decades. Unfortunately, excessive use of anti-microbials has hastened resistance, which threatens our ability to treat infectious diseases in humans. Farmers need sustainable solutions to maintain the health of their production animals without the use of antibiotics. Microbiome research represents a new frontier, which illustrates why we’ve seen an uptick in demand for microbiome analysis for animal health and performance at BaseClear.”
AGPs have been used successfully for many years to increase animal performance. When given in sub-therapeutic doses, AGPs selectively modify the animals’ microbiomes, resulting in improved production efficiency and a reduction in low-level infections. However, the use of AGPs also create selection pressure: bacteria that contain antibiotic resistance genes survive, thus requiring a higher dose or a change to a different type of antibiotic to remain effective. The key to slowing antibiotic resistance is to only use antibiotics when necessary. The use of antibiotics for non-therapeutic, and recently, for therapeutic reasons in animals has been banned or restricted in several regions around the world to help reduce antibiotic resistance. In terms of sustainability in the industry, there is considerable interest in developing new, effective feed additives that will not contribute to antibiotic resistance.
Plants contain many bioactive molecules with a broad array of effects. One particular plant extract will contain many different components that are naturally present in the plant. Each component can then have specific or broad effects on physiology, which could potentially affect animal health or metabolism. As they contain many different compounds, they can act on several physiological targets at once. There are many plant extracts that could be useful as feed additives.
Due to the importance of gut health in animal performance, a current field of interest in non-AGP feed additives involves the microbiome-modulatory effects of plant extracts. For example, oregano extract contains aromatic volatile compounds such as thymol, carvacrol and others that have anti-bacterial, anti-inflammatory and immune-regulating effects. In a study conducted recently in mature laying hens, an oregano extract had various effects on immune function, the microbiome, digestive enzymes and the intestinal barrier function that together improved feed conversion ratio. The general improvements in gut health were thought to contribute to the production increases seen (Feng, 2021).
Solid evidence is needed to show that novel feed additives are effective. Researchers into new products for livestock producers also want to confirm the mode of action. Genomics technologies and expertise, such as offered by BaseClear, can help identify and measure the impact of ingredients on the microbiota and its function. “As we are able to control the living conditions and diet of production animals to a high degree, the effect of complex interventions such as plant extracts on outcomes are relatively easy to determine. Tools such as species-level shotgun sequencing and dedicated databases allow functional and taxonomic microbiome changes from feed additives to be linked to the overall health and performance of animals,” says Patrick Koning.
PHYTOBIOTEC recently conducted several field trials and they have been very interested to see the results in terms of the effect of their products on the microbiome of broilers. They compared a standard antibiotic growth promotor with three of their products:
In the first of several studies, encouraging results have been found from the microbiome analysis. They found that the microbial richness and diversity was preserved over the first 42 days of a chick’s life when using the ENTEROSAN and ENTEROBIOSAN products. In particular, the product that included a pre- and probiotic helped to rapidly diversify the microbiome of broiler chicks, which was maintained throughout growth. A Principle Component Analysis showed a divergence in metabolic activity between the antibiotic and phytobiotic treatments. Becker hopes to identify how plant extracts work synergistically with the microbiome to achieve increases in livestock performance, while reducing the use of AGPs and working towards improving sustainable farming practices.
A single substance cannot address all production challenges, therefore it’s important to look carefully at the production system as a whole and work out what is going wrong. Targeted interventions address the most critical issues within livestock production and are inherently more sustainable. Improvements and innovations in on-farm measurement will allow farmers to make more informed decisions about managing their livestock in a precise way. “Feed additive producers need to provide a solution that is simple, helps the farmer work out what to do, and can be used on a day-to-day basis,” says Becker.
There is a lot of variation between livestock producers, and even day-to-day changes in weather can affect productivity or risk of disease. Products that increase overall resilience of livestock to stressors are beneficial. “The microbiota is very important factor relating to livestock production that we are just beginning to uncover” says Becker, speaking about the two-pronged approach to microbiome research. “On the one hand, we need to understand the impact of our phytobiotic formulations on the microbiota. On the other, microbiome analysis is essential to precision livestock nutrition in future. We need both.”
Patrick Koning elaborates: “The microbiome has become a useful target for products that seek to improve the sustainability of animal production, hoping to drive production and sustainability in tandem. There has been a lot of progress made in the area of microbiome research. However, the relationships studied are incredibly complex.” Advancing the science requires cooperation between the feed industry, microbiome experts such as BaseClear, and academia to understand how to effectively influence the microbiome. “Even though different feed producers are competitors, collaboration and data sharing will improve the industry as a whole,” concludes Becker.
Feng J, Lu M, Wang J, et al. Dietary oregano essential oil supplementation improves intestinal functions and alters gut microbiota in late-phase laying hens. J Anim Sci Biotechnol. 2021;12(1):72. Published 2021 Jul 6. https://dx.doi.org/10.1186%2Fs40104-021-00600-3
Interagency Coordination Group (IACG) on Antimicrobial Resistance (2019), ‘No Time to Wait: Securing the future from drug-resistant infections’, https://www.who.int/docs/default-source/documents/no-time-to-wait-securing-the-future-from-drug-resistant-infections-en.pdf
Van Boeckel TP, Brower C, Gilbert M, Grenfell BT, Levin SA, Robinson TP, Teillant A, Laxminarayan R. Global trends in antimicrobial use in food animals. Proc Natl Acad Sci U S A. 2015 May 5;112(18):5649-54. https://doi.org/10.1073/pnas.1503141112