Chris Dean, University of Minnesota
Felipe Pena Mosca, University of Minnesota
Tui Ray, University of Minnesota
Bradley Heins, University of Minnesota
Pablo Pinedo, Colorado State University
Vinicius Machado, Texas Tech University
Luciano Caixeta, University of Minnesota
Noelle Noyes, University of Minnesota
Since the 1960s, the Five-Point Mastitis Control Plan has remained the gold standard for reducing mastitis prevalence and high somatic cell counts on conventional dairy farms, and continues to be revised as new information and tools become available (National Mastitis Council; Barkema et al., 2013). However, organic producers are unable to benefit from the use of some of these tools—antibiotics, for example. If antibiotics are used, the treated animal must be withdrawn from the herd for a period of at least one year (Gradle and Pighetti, 2019). Organic producers must rely on a combination of evidence-based management practices for the prevention of new infections, such as pre- and post-dipping, routine maintenance and cleaning of milking equipment, and methods to promote cow comfort (Gradle and Pighetti, 2019). Alternative therapies such as homeopathic medicines, whey-based products, and vitamin supplements are also used, but these therapies are not soundly supported by the scientific literature (Ruegg, 2009). Despite widespread adoption of these strategies, mastitis remains one of the most costly diseases affecting dairy producers, and ultimately, udder health (Barkema et al., 2009). These observations suggest that organic producers need new tools to further support udder health and productivity on organic dairy farms. In partnership with scientists across the country, our group at the University of Minnesota works on this problem, using a promising tool called the microbiome. You may have heard the term microbiome before, but what does it really mean, and why should you, as a dairy or livestock producer, really care?
History of the Microbiome
Since most of what we know about the microbiome and health stems from research done on humans, our journey into the microbiome will begin from there. The human body is home to trillions of microorganisms, ranging from single-celled organisms like bacteria and protozoa, to more complex organisms like fungi or even viruses. Collectively, these microorganisms make up what is often referred to as the human microbiome, and they are ubiquitous within and on the human body. Why are these microorganisms present and what do they do? Admittedly, what we know and understand about the function of these microorganisms is limited, but what we do know is that they play a critical role in human health, with perturbations to the microbiome contributing to a number of diseases, such as obesity (Davis, 2016), inflammatory bowel disease (Becker et al., 2015), and diabetes (Vallianou et al., 2018).
Applications of the Microbiome
Interestingly, the human microbiome can play a dual role in human health—acting as the root of disease, or acting as a helper to rid the body of disease. We will illustrate this idea with a real-life example. Clostridium difficile infection (CDI) is a major cause of hospital-acquired infections in the United States and is often preceded by the use of antibiotics, which are known to disrupt the human gut microbiome—the microbes inhabiting the human gastrointestinal tract (Hensgens et al., 2012; Lessa et al., 2015). In other words, the good microbes—which normally keep the bad microbes in line—are destroyed, giving the bad microbes the opportunity to take over. Unfortunately, treatments for CDI are limited and relapse rates can be quite high, highlighting the need for new tools—one of which is the microbiome.
The idea is pretty simple and may be something you are already familiar with. Donor feces from a healthy individual is inserted inside the gastrointestinal tract of an individual with CDI, with the goal of restoring a healthy balance between the good and bad microbes. This simple procedure has continued to show positive results, with a majority of individuals undergoing the procedure experiencing eventual resolution of CDI after follow-up (Mattila et al., 2012). If you are a dairy producer or veterinarian, this may sound familiar—indeed, it is similar to a technique that dairy producers and veterinarians have been using for over a century known as rumen transfaunation. This relatively simple procedure involves transferring microorganisms from the rumen of a healthy animal to a diseased animal to treat rumen-related disorders. Similar to the success of microbiome transplants in human CDI patients, the healthy rumen microbiome usually establishes itself quickly within the diseased rumen, thus promoting greatly improved health in the cow itself (Steiner et al., 2020).
Challenges in Microbiome Research
These success stories make it clear that the microbiome can be an extremely powerful tool for the treatment of both human and animal diseases. However, it is important to note that in both cases, the microbiome of the diseased animal or human is dramatically imbalanced. In other words, these microbiomes are nearly completely decimated—much like a forest after a forest fire. Without much competition from other microbes, it is relatively easy for the unhealthy microbes to take root and flourish within these decimated landscapes. But what about situations when that microbiome imbalance is less intense? Unfortunately, it turns out that in these situations, it's not quite as easy to re-establish a healthy microbiome. But we and many others are striving to overcome this challenge, because doing so would open up a vast array of new microbiome-based tools for support of livestock health and performance.
Project Goals and Outcomes
Specifically, our group is trying to understand how the normal skin microbiome of a cow's udder may protect her against mastitis. Previous work in this area has revealed that the udder skin is home to a diverse ecosystem of microorganisms (Braem et al., 2012; Verdier-Metz et al., 2012; Dean et al., 2020), a large majority of which are not easily grown in a lab nor detected using traditional culture techniques. This observation is important because these dark matter bugs could be playing an important role in mastitis resistance, yet we still know very little about them. What we do know is that the numbers and types of bugs found on the udder skin vary greatly between cows with a history of mastitis versus those without (Falentin et al., 2016). Additionally, when cows are followed over time, we know that seasonal factors can influence the composition of the skin microbiome (Andrews et al., 2019). Taken in combination, these initial studies suggest that a healthy skin microbiome may yield protective benefits against invading microorganisms.
So, what does a healthy skin microbiome look like? This is exactly the kind of question we are trying to answer, because the answer could drive the development of innovative, non-antibiotic, and evidence-based microbiome preventives and treatments for mastitis. To accomplish this goal, we are enrolling heifers from multiple organic dairy farms throughout the United States, surveying their skin microbiomes, and culturing their milk for mastitis. In addition, we are using a combination of next-generation molecular tools that will enable us to characterize the vast array of microorganisms residing on the udder skin. Our hypothesis is that certain bacteria within the microbiome will be associated with decreased risk of mastitis, suggesting that these bacteria might be a promising target for development of new microbiome-based interventions. In fact, the power of such interventions are already beginning to emerge in the form of teat-dips containing known mixes of beneficial bugs that act as a kind of microbial barrier to the mammary gland, on guard against the acquisition of new intramammary infections (Yu et al., 2017). While these findings are novel within dairy production, previous work in mice and humans has shown that certain strains of commensal bacteria can protect against colonization by major mastitis-pathogens such as Staphylococcus aureus found on the skin (Nakatsuji et al., 2017). Identifying and characterizing these commensal bacteria and repurposing them into an effective tool that can be used by dairy producers is the chief goal of our work.
To address this important goal, we have partnered with organic dairy farmers across the United States, all of whom are committed to helping discover new ways to curb mastitis in dairy cows. Equally important is our diverse research team, with individuals at the University of Minnesota, Texas Tech University, Colorado State University, and Oregon State University. This team consists of faculty trained in veterinary epidemiology and dairy production; graduate students trained to collect, analyze and interpret large and complex biological datasets from livestock systems; and numerous student and lab workers. One of the major lessons of microbiome research is the need for integrated yet diverse teams, with expertise that spans from on-the-ground livestock production to molecular biology and computer science. We are fortunate to have assembled such a team, all of whom are passionate about dairy cow health and welfare. This team is dedicated to ensuring that the livestock community benefits from microbiome-related advances. We hope to bring these discoveries to the livestock producer community through several channels, including upcoming webinars and YouTube videos. For now, a good place to start is our website: https://eorganic.info/openroamer.
If you are interested in learning more about the microbiome, here are some useful videos and interactive online resources:
References and Citations
- Andrews, T., D. A. Neher, T. R. Weicht, and J. W. Barlow. 2019. Mammary microbiome of lactating organic dairy cows varies by time, tissue site, and infection status. PLOS ONE 14:e0225001. (Available online at: https://doi.org/10.1371/journal.pone.0225001) (verified 15 Mar 2021).
- Barkema, H. W., M. J. Green, A. J. Bradley, and R. N. Zadoks. 2009. The role of contagious disease in udder health. Journal of Dairy Science 92:4717—4729. (Available online at: https://doi.org/10.3168/jds.2009-2347) (verified 15 Mar 2021).
- Barkema, H. W., S. D. Vliegher, S. Piepers, and R. N. Zadoks. 2013. Herd level approach to high bulk milk somatic cell count problems in dairy cattle. Veterinary Quarterly 33:82—93. (Available online at: https://doi.org/10.1080/01652176.2013.799791 (verified 15 Mar 2021).
- Becker, C., M. F. Neurath, and S. Wirtz. 2015. The intestinal microbiota in inflammatory bowel disease. ILAR Journal 56:192—204. (Available online at: https://doi.org/10.1093/ilar/ilv030 (verified 15 Mar 2021).
- Braem, G., S. de Vliegher, B. Verbist, M. Heyndrickx, F. Leroy, and L. de Vuyst. 2012. Culture-independent exploration of the teat apex microbiota of dairy cows reveals a wide bacterial species diversity. Veterinary Microbiology 157:383—390. (Available online at: https://doi.org/10.1016/j.vetmic.2011.12.031) (verified 15 Mar 2021).
- Davis, C. D. 2016. The gut microbiome and its role in obesity. Nutrition Today 51:167—174. (Available online at: https://doi.org/10.1097/NT.0000000000000167) (verified 15 Mar 2021).
- Dean, C. J., I. B. Slizovskiy, K. K. Crone, A. X. Pfennig, B. J. Heins, L. S. Caixeta, and N. R. Noyes. 2020. Investigating the cow skin and teat canal microbiomes of the bovine udder using different sampling and sequencing approaches. Journal of Dairy Science 104:664—661. (Available online at: https://doi.org/10.3168/jds.2020-18277) (verified 15 Mar 2021).
- Falentin, H., L. Rault, A. Nicolas, D. S. Bouchard, J. Lassalas, P. Lamberton, J.-M. Aubry, P.-G. Marnet, Y. Le Loir, and S. Even. 2016. Bovine teat microbiome analysis revealed reduced alpha diversity and significant changes in taxonomic profiles in quarters with a history of mastitis. Frontiers in Microbiology 7:480. (Available online at: https://doi.org/10.3389/fmicb.2016.00480) (verified 15 Mar 2021).
- Gradle, C., and G. Pighetti. 2019. Mastitis control on organic dairies in the United States. NMC Factsheet [Online]. National Mastitis Council, New Prague, MN. Available at: https://www.nmconline.org/fact-sheets/ (verified 15 Mar 2021).
- Hensgens, M.P.M., A. Goorhuis, O. M. Dekkers, and E. J. Kuijper. 2012. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. Journal of Antimicrobial Chemotherapy 67:742—748. (Available online at: https://doi.org/10.1093/jac/dkr508) (verified 15 Mar 2021).
- Lessa, F. C., Y. Mu, W. M. Bamberg, Z. G. Beldavs, G. K. Dumyati, J. R. Dunn, M. M. Farley, S. M. Holzbauer, J. I. Meek, E. C. Phipps, L. E. Wilson, L. G. Winston, J. A. Cohen, B. M. Limbago, S. K. Fridkin, D. N. Gerding, and L. C. McDonald. 2015. Burden of Clostridium difficile infection in the United States. New England Journal of Medicine 372:825—834. (Available online at: https://doi.org/10.1056/NEJMoa1408913) (verified 15 Mar 2021).
- Mattila, E., R. Uusitalo–Seppälä, M. Wuorela, L. Lehtola, H. Nurmi, M. Ristikankare, V. Moilanen, K. Salminen, M. Seppälä, P. S. Mattila, V.-J. Anttila, and P. Arkkila. 2012. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology 142:490—496. (Available online at: https://doi.org/10.1053/j.gastro.2011.11.037) (verified 15 Mar 2021).
- Nakatsuji, T., T. H. Chen, S. Narala, K. A. Chun, A. M. Two, T. Yun, F. Shafiq, P. F. Kotol, A. Bouslimani, A. V. Melnik, H. Latif, J.-N. Kim, A. Lockhart, K. Artis, G. David, P. Taylor, J. Streib, P. C. Dorrestein, A. Grier, S. R. Gill, K. Zengler, T. R. Hata, D.Y.M. Leung, and R. L. Gallo. 2017. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Science Translational Medicine 9:eaah4680. (Available online at: https://doi.org/10.1126/scitranslmed.aah4680) (verified 15 Mar 2021).
- National Mastitis Council. NMC Documents and Reports [Online]. Available at: https://www.nmconline.org/resources/ (verified 15 Mar 2021).
- Ruegg, P. L. 2009. Management of mastitis on organic and conventional dairy farms. Journal of Animal Science 87:43—55. (Available online at: https://doi.org/10.2527/jas.2008-1217) (verified 15 Mar 2021).
- Steiner, S., N. Linhart, A. Neidl, W. Baumgartner, A. Tichy, and T. Wittek. 2020. Evaluation of the therapeutic efficacy of rumen transfaunation. Journal of Animal Physiology and Animal Nutrition 104:56—63. (Available online at: https://doi.org/10.1111/jpn.13232) (verified 15 Mar 2021).
- Vallianou, N. G., T. Stratigou, and S. Tsagarakis. 2018. Microbiome and diabetes: Where are we now? Diabetes Research and Clinical Practice 146:111—118. (Available online at: https://doi.org/10.1016/j.diabres.2018.10.008) (verified 15 Mar 2021).
- Verdier-Metz, I., G. Gagne, S. Bornes, F. Monsallier, P. Veisseire, C. Delbes-Paus, and M. C. Montel. 2012. Cow teat skin, a potential source of diverse microbial populations for cheese production. Applied and Environmental Microbiology 78:326—333. (Available online at: https://doi.org/10.1128/AEM.06229-11) (verified 15 Mar 2021).
- Yu, J., Y. Ren, X. Xi, W. Huang, and H. Zhang. 2017. A novel Lactobacilli-based teat disinfectant for improving bacterial communities in the milks of cow teats with subclinical mastitis. Frontiers in Microbiology 8:1782. (Available online at: https://doi.org/10.3389/fmicb.2017.01782) (verified 15 Mar 2021).