Team:Thessaly/Animal Welfare




FlexStart Bootstrap Template - Index

Overview

Animal Welfare, as defined by the American Veterinary Medical Association, is a human responsibility that encompasses all aspects of animal well-being, including proper housing, management, disease prevention and treatment, responsible care, humane handling, and, when necessary, humane euthanasia. Through Gut Microbiome Engineering, AMALTHEA aims to take a step towards maintaining full animal health and well-being.
The European Union has established a detailed legislative framework for animal welfare. According to the Amsterdam Treaty (1997) and the Lisbon Treaty (2009) animals are sentient beings.

"In formulating and implementing the Union's agriculture, fisheries, transport, internal market, research and technological development and space policies, the Union and the Member States shall, since animals are sentient beings, pay full regard to the welfare requirements of animals, while respecting the legislative or administrative provisions and customs of the Member States relating in particular to religious rites, cultural traditions and regional heritage." (Pulina G., 2020).

The Five Freedoms

On the grounds of the European Union’s framework for animal welfare, Europe has established general rules for the protection of animals of all species that are based on the European Convention for the Protection of Animals kept for Farming Purposes and they reflect the so-called 'Five Freedoms' (Figure 1).

Figure 1: The Five Freedoms for promoting animal welfare (McCulloch S., 2012).


Our project, AMALTHEA, aims to contribute to Freedoms 1 and 3 by detecting, evaluating and ameliorating gut dysbiosis, in order to tackle malnutrition but also achieve prevention, rapid diagnosis and treatment of GI disorders.

One health: We are all interconnected

One Health is defined as a collaborative, multisectoral, and transdisciplinary approach—working at the local, regional, national, and global levels—with the goal of achieving optimal health outcomes recognizing the interconnection between people, animals, plants, and their shared environment (Mackenzie et al, 2019).


Figure 2: Animal health affects the World's health.


At the early stages of our project we were invited to two events organized by the Scientific Society of Hellenic Medical Students and Panhellenic Veterinary Students’ Association. During these events, we highlighted the importance of a significant One Health factor, the gut microbiome, as well as the impact of the Synthetic Biology applications on securing a balanced microbiome and gastrointestinal health. Besides that, through our conversations with veterinary students, we were inspired to introduce an animal health approach of AMALTHEA. To achieve that, we first aimed at determining the importance of targeting the animal gut microbiome both in domestic and farm animals.


One Health relationships between microbiomes

Applying the One Health approach to the microbiome allows for consideration of both pathogenic and non-pathogenic microbial transfer between humans, animals, and the environment (Trinh et al, 2018). Different animal species house unique microbiomes, often of equal or greater complexity compared to the human microbiome. As in humans, animal microbiomes influence the health of livestock, pets, disease vectors, and foundational species that uphold ecosystems. Similarly, environments have characteristic microbiomes. We should definitely note that the environmental microbiome as well as the microbiome of animals are in close contact thus affecting both the human microbiome and human health outcomes. A study of children in Kenyan villages with close livestock contact found that while the greatest amount of gut microbiome similarity was between siblings in the same household, in certain households there was evidence of sharing of microbiome components between children and nearby cows (Mosites et al, 2017). Only by diving into and understanding such interactions, will we be able to generate innovative interventions to prevent and manage a variety of human and animal health conditions.


Figure 3: The connection of human, animal and environmental microbiomes through the One Health approach.


Why is microbiome important for animal health ?

Animal gut health affects animal performance, feed efficiency, and overall health (Jha et al, 2019). The gut microbiome refers to the community of microorganisms inhabiting a defined environment along the gastrointestinal tract, and includes bacteria, fungi, protozoa, archaea, and yeasts. Its composition influences host metabolism and body composition. The gut microbiome has the potential to produce or regulate numerous different hormonal products, such as the Short Chain Fatty Acids (SCFAs). These products have the ability to affect the status of the gut and when taken up by the bloodstream and transported throughout the body, can affect the function of remote organs and systems. SCFAs promote the growth of beneficial gut bacteria, support intestinal integrity, and proper immune function. Bacterial SCFA production is considered particularly important, not just as an energy source but also as signaling molecules. The microbiome also communicates with other organs including the brain, lungs, skin and liver, influencing their function in newly discovered ways and highlighting the possible contributions of gastrointestinal dysbiosis to other bodily conditions (O'Callaghan et al, 2016).


Figure 4: The impact of gut microbiome on host physiology and well being.


GI disorders in animals

Besides humans, gastrointestinal disorders are also present in animals (Cerquetella et al, 2010). This statement was also confirmed by the Research Institute of Animal Science, for production animals but also by Dr. Xenoulis, Associate Professor of Small Animal Internal Medicine at University of Thessaly, for domestic animals. Chronic enteropathy (CE) is a term used for gastrointestinal diseases present for a duration of three weeks or longer. The most common symptoms are weight loss, persistent or recurrent vomiting and/or diarrhea (Dandrieux et al, 2019). The diagnosis includes collecting blood, urine, and fecal samples, abdominal x-rays or ultrasound, endoscopy, or biopsy.


Furthermore, the gut microbiome of cats and dogs is increasingly recognized as a metabolically active organ inextricably linked to pet health (Wernimont et al, 2020). According to relevant studies, pets in GI diseases have depleted groups of certain bacteria such as Lachnospiraceae, Ruminococcaceae and Faecalibacterium which are important producers of SCFAs (Mosites et al, 2017). Pets with CE have an altered fecal SCFA concentration, as seen in Figure 5 (Minamoto et al, 2019).


Figure 5: Fecal short‐chain fatty acid concentrations in healthy control (HC) dogs and dogs with chronic enteropathy (CE) (Minamoto et al,2019).


It is of utter importance to understand in what range animals affect human health and how important it is to focus on animal health and welfare. There are a lot of aspects that are connected to One Health. One Health issues include zoonotic diseases, antimicrobial resistance, food safety and food security, vector-borne diseases, environmental contamination, and other health threats shared by people, animals, and the environment. Even the fields of chronic disease, mental health, injury, occupational health, and noncommunicable diseases can benefit from a One Health approach involving collaboration across disciplines and sectors.

Figure 6: What is included under the term of One health.


Antimicrobial Resistance

Antimicrobial resistance (AMR) has developed as one of the major urgent threats to public health causing serious issues to successful prevention and treatment of persistent diseases. It occurs when microorganisms including bacteria, viruses, fungi, and parasites become able to adapt and grow in the presence of medications that once impacted them. These medications are antimicrobials – including antibiotics, antivirals, antifungals and antiparasitics. The World Health Organisation (WHO) has declared that Antimicrobial Resistance (AMR) is one of the top 10 global public health threats facing humanity (World Health Organization,2020, Antimicrobial Resistance).


According to the Centers for Disease Control and Prevention (CDC), antibiotic resistance is responsible for 25,000 Trusted Source annual deaths in the European Union and 23,000 annual deaths in the U.S. As many as 2 million U.S. citizens develop a drug-resistant infection each year. By the year 2050, some researchers predict that antibiotic resistance will cause 10 million deaths every year, surpassing cancer as the leading cause of mortality worldwide. (De Kraker et al, 2016).


Figure 7: Percentage of antibiotics in animal production.


A major factor that contributes to drug resistance in sentient beings is the overuse of antibiotics in livestock farming. Using antibiotics in animals may raise the risk of transmitting drug-resistant bacteria to humans, either by direct infection or by transferring “resistance genes from agriculture into human pathogens”. According to the Research Institute of Animal Science, the use of antibiotics as growth factors was very extensive in recent years. Although there were efforts to reduce antibiotics in animal production, a lot of farmers continue to use them.

Figure 8: Antimicrobial Resistance along the food chain.


Although antimicrobial resistance is not mentioned in the SDGs, it is recognized in the Global Action Plan for Healthy Lives and Well-being for All (17) as a barrier to achievement of SDG 3 on human health and directly jeopardizes progress against other SDGs related to food security, clean water and sanitation, and responsible consumption and production. See more in the Sustainability page.


As previously mentioned , it is necessary to reduce the use of antibiotics both in animal production but also in pets. Through our discussions with veterinarians, it was clear that antibiotics are administered to treat virtually any symptom related to enteropathies, even though they take into consideration that this treatment lasts for a short amount of time. In order to reduce the use of antibiotics we aim to provide a tool which will be able to give more information about GI disorders and the gut microbiome, paving the path towards a more accurate diagnosis. In addition, we intend to propose an alternative to in-feed antibiotics in order to restrict antibiotic use in animal production. This alternative could be SCFA, including butyrate, which possess antimicrobial activity, and have been widely used as feed additives in an effort to control pathogenic bacteria (Bedford, A. & Gong, J.,2018).


Food Security

Figure 9: It is of great importance to optimize animal production.


Feeding the growing global population is one of the key challenges the world is facing today, creating a need for sustainable agriculture practices (Karl-Heinz Erb et al, 2012). Food security exists when “all people, at all times have physical and economic access to sufficient, safe and nutritious food that meets their dietary needs and food preferences for an active and healthy life” (Food and Agriculture Organization,1996, November 17, World Food Summit, FAO). Food security is related to all of the United Nations Sustainable Development Goals (SDGs) (Pérez-Escamilla R., 2017). Indicatively, SDG 2 focuses explicitly on food by seeking to “end hunger, achieve food security and improved nutrition and promote sustainable agriculture”, but there are multiple other goals which relate to challenges in the food system (Brooks, Jonathan 2016). According to Animal microbiome congress “The global market is forecasted to grow to 9,775 million by 2028”. Thus, sustainable agriculture plays a central role in achieving multiple other SDGs such as 6, 12, 13, 15. Learn more on the Sustainability page.


Figure 10: Framing the food security challenge.


AMALTHEA aims to ensure food security by improving animal production. Gut microbiome plays an important role in the host physiology and well being. Our ultimate objective is the engineering of the gut microbiome of animals so as to aid in this challenge. Especially, SCFAs demonstrate positive effects on animal production, including enhancement of gut development, control of enteric pathogens, reduction of inflammation, improvement of growth performance and modulation of gut microbiome (Bedford, A. & Gong, J.,2018) (Figure 13). So, by improving the gut microbiome we aim to help maximize production, leading to sustainable agriculture.


Figure 11: The positive effects of SCFAs in animal production





THERE IS NO FOOD SECURITY WITHOUT FOOD SAFETY, WHICH IS THE BASE FOR HEALTHY DIETS AND LIVES- José Graziano da Silva FAO Director-General



Food safety

Food is essential to life; hence food safety is a basic human right. Billions of people in the world are at risk of unsafe food. The food chain starts from farm to fork while challenges include microbial, chemical, personal and environmental hygiene (Fung et al, 2018).


Microbiome and the stress response: relevance to animal and food safety.

Stress in farm animals has an impact on food safety risk (Mosites et al, 2017). Many factors in any animal production system can cause stress in animals, including handling practices, housing systems, overcrowding, transport, excess heat or cold, and food or water deprivation. Stress can result in reduced feed intake, decreased activity, as well as physiological, hormonal, and immunologic deficiencies, which in turn result in reduced animal performance standards and can also have negative effects on the quality of animal derived food products (O'Callaghan et al, 2016). The relationship between gut microbiome and stress response is bidirectional, with various stressors applied inducing an alteration in the composition of the gut microbiome with implications for host physiology.


AMALTHEA as a toolkit for safeguarding One Health

Capsule

AMALTHEA proposes a bioelectronic capsule as a detection tool for GI disorders in animals. Through our system, real time assessment of the gut microbiome’s state via monitoring the levels of SCFAs can be achieved.

Diagnosis of GI disorders in animals, especially pets, is a difficult and complex procedure. During our conversation with Dr Xenoulis, Associate Professor of Small Animal Internal Medicine at University of Thessaly, we were informed that dysbiosis shows low levels of SCFAs and several enteropathies are correlated with their absence. To evaluate the gut conditions, Real-TimePCR and other molecular methods are used to identify the specific strains occurring on those disorders but means for the metabolic evaluation of the gut flora are still scarce.

Our bio-electronic capsule is an extra tool for understanding the connection between gut microbiome and gut related diseases, but it can also serve as a means for restricting the administration of antibiotics. Through our discussions with veterinarians, it was clear that antibiotics are administered to treat virtually any symptom related to enteropathies, even though they take into consideration that this treatment lasts for a short amount of time. In animal production, the data collected with the capsule can help in both detecting the stress level of animals, and finding the cause of low growth performance and weak immune system. During our visit to the Research Institute of Animal Science, it is important to move away from the constant usage of antibiotics and move to a more preventative approach, by monitoring in real-time the microbial conditions in the gut of production animals and through probiotic administration strengthen their immunity and performance.


Through AMALTHEA, we provide a useful toolkit for animal health monitoring and prevention of enteropathies aiming to maximise animal production.

Overall, our bio-electronic capsule system serves as a(n):

  •  Extra tool to establish the connection between gut microbiome and GI disorders
  •  Extra tool for diagnosis of GI Disorders in pets which will also help decrease antibiotic use
  •  Research tool for extra information of time frame of disease onset and gut dysbiosis


Synbiotic Supplement in animal production

AMALTHEA proposes a living bio-therapeutic synbiotic supplement that can contribute to animal nutrition and overall health. It includes a prebiotic, alginate, that serves as food for the gut microflora and a probiotic which is able to produce SCFAs in certain amounts and utilize gut cellulose as a carbon source. Alginate, as the Research Institute of Animal Science, confirmed, has also a protective role for the probiotic in ruminants, by forming beads that encapsulate the engineered bacteria, and keep them intact at the conditions of the forestomach. SCFAs supplementation through our probiotic is an alternative strategy in order not only to tackle the imbalances in the gut microbiome but also to decrease the use of in-feed antibiotics. Limiting the possibilities of gut dysbiosis, we try to decrease the stress level of animals and aim for long-term animal welfare, while SCFAs’ supplementation, and especially butyrate, can have a positive effect on animal production. Therefore, our live biotherapeutic constitutes an indirect solution to secure food security and food safety.


Considering all the above, our synbiotic supplement is a(n):

  •  SCFAs supplement which will enhance food security by improving animal production
  •  SCFAs supplement, especially, butyrate an alternative strategy for antibiotic use
  •  SCFAs supplement, reduce the stress of farm animals through gut microbiome, contributing to food safety


Future Vision



Our modular system can shed light to a crude research field, highlighting the importance of the microbial communities in animals and how, through the prism of One Health, they affect us. We aspire to provide researchers a tool to accelerate their work and implement our system to lesser known microbial communities, to explore, apart from the bacterial strain abundance, their metabolic capabilities and macroscopic interactions with plants, livestock, domesticated animals and of course us humans.

References

  1. Bedford, A., & Gong, J. (2018). Implications of butyrate and its derivatives for gut health and animal production. Animal Nutrition, 4(2), 151-159. https://doi.org/https://doi.org/10.1016/j.aninu.2017.08.010

  2. Brooks, Jonathan (2016), “Food security and the Sustainable Development Goals”, in Patrick Love (ed.), Debate the Issues: New Approaches to Economic Challenges, OECD Publishing, Paris. https://doi.org/10.1787/9789264264687-27-en

  3. Cerquetella, M., Spaterna, A., Laus, F., Tesei, B., Rossi, G., Antonelli, E., Villanacci, V., & Bassotti, G. (2010). Inflammatory bowel disease in the dog: differences and similarities with humans. World journal of gastroenterology, 16(9), 1050–1056.https://doi.org/10.3748/wjg.v16.i9.1050

  4. Dandrieux, J., & Mansfield, C. S. (2019). Chronic Enteropathy In Canines: Prevalence, Impact And Management Strategies. Veterinary medicine (Auckland, N.Z.), 10, 203–214.https://doi.org/10.2147/VMRR.S162774

  5. De Kraker, M. E., Stewardson, A. J., & Harbarth, S. (2016). Will 10 Million People Die a Year due to Antimicrobial Resistance by 2050?. PLoS medicine, 13(11), e1002184. https://doi.org/10.1371/journal.pmed.1002184

  6. Dhama, Kuldeep & M, Mahendran & Tomar, Simmi & Chauhan, Ramswaroop. (2008). Beneficial effects of probiotics and prebiotics in livestock and poultry: the current perspectives. Polivet. 9. 1-13.

  7. ECDC/EFSA/EMA second joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food‐producing animals. (2017), 15(7).https://doi.org/10.2903/j.efsa.2017.4872

  8. Evans JM, Morris LS, Marchesi JR. The gut microbiome: the role of a virtual organ in the endocrinology of the host. J Endocrinol. 2013 Aug 28;218(3):R37-47.

  9. Fung, F., Wang, H. S., & Menon, S. (2018). Food safety in the 21st century. Biomedical journal, 41(2), 88–95.https://doi.org/10.1016/j.bj.2018.03.003

  10. Jha, R., Fouhse, J. M., Tiwari, U. P., Li, L., & Willing, B. P. (2019). Dietary Fiber and Intestinal Health of Monogastric Animals. Frontiers in veterinary science, 6, 48.

  11. Karl-Heinz Erb, Andreas Mayer, Thomas Kastner, Kristine-Elena Sallet, Helmut Haberl, 2012: The Impact of Industrial Grain Fed Livestock Production on Food Security: an extended literature review. Commissioned by Compassion in World Farming, The Tubney Charitable Trust and World Society for the Protection of Animals, UK. Vienna, Austria

  12. Mackenzie, J. S., & Jeggo, M. (2019). The One Health Approach-Why Is It So Important?. Tropical medicine and infectious disease, 4(2), 88.https://doi.org/10.3390/tropicalmed4020088

  13. McCulloch, S. (2012). A Critique of FAWC’s Five Freedoms as a Framework for the Analysis of Animal Welfare. Journal Of Agricultural And Environmental Ethics, 26(5), 959-975. https://doi.org/10.1007/s10806-012-9434-7

  14. Minamoto, Y., Minamoto, T., Isaiah, A., Sattasathuchana, P., Buono, A., & Rangachari, V. et al. (2019). Fecal short‐chain fatty acid concentrations and dysbiosis in dogs with chronic enteropathy. Journal Of Veterinary Internal Medicine, 33(4), 1608-1618. doi: 10.1111/jvim.15520

  15. Mosites, E., Sammons, M., Otiang, E., Eng, A., Noecker, C., & Manor, O. et al. (2017). Microbiome sharing between children, livestock and household surfaces in western Kenya. PLOS ONE, 12(2), e0171017. doi: 10.1371/journal.pone.0171017

  16. O'Callaghan TF, Ross RP, Stanton C, Clarke G. The gut microbiome as a virtual endocrine organ with implications for farm and domestic animal endocrinology. Domest Anim Endocrinol. 2016 Jul;56 Suppl:S44-55.

  17. Pérez-Escamilla R. (2017). Food Security and the 2015-2030 Sustainable Development Goals: From Human to Planetary Health: Perspectives and Opinions. Current developments in nutrition, 1(7), e000513.https://doi.org/10.3945/cdn.117.000513

  18. Pulina G. (2020). Ethical meat: respect for farm animals. Animal frontiers : the review magazine of animal agriculture, 10(1), 34–38. https://doi.org/10.1093/af/vfz052

  19. Racioppi, F., Martuzzi, M., Matić, S., Braubach, M., Morris, G., Krzyżanowski, M., Jarosińska, D., Schmoll, O., & Adamonytė, D. (2020). Reaching the sustainable development goals through healthy environments: are we on track?. European journal of public health, 30(Suppl_1), i14–i18.https://doi.org/10.1093/eurpub/ckaa028

  20. Trinh, P., Zaneveld, J. R., Safranek, S., & Rabinowitz, P. M. (2018). One Health Relationships Between Human, Animal, and Environmental Microbiomes: A Mini-Review. Frontiers in public health, 6, 235. https://doi.org/10.3389/fpubh.2018.00235

  21. Wernimont, S. M., Radosevich, J., Jackson, M. I., Ephraim, E., Badri, D. V., MacLeay, J. M., Jewell, D. E., & Suchodolski, J. S. (2020). The Effects of Nutrition on the Gastrointestinal Microbiome of Cats and Dogs: Impact on Health and Disease. Frontiers in microbiology, 11, 1266.https://doi.org/10.3389/fmicb.2020.01266

  22. World Health Organization. (2020) Antimicrobial Resistance. WHO Official Website.https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance?fbclid=IwAR1w0j3nw1BZmFUxdSTgzsfgSKBCcj-uguIuNiGmU55_F06C0QwCqM_G1C

igem.thessaly@gmail.com