Could Udder Microbiome-based Products be Used as an Alternative Strategy for Mastitis Treatment and Prevention?

Introduction

Mastitis, defined as inflammation of the mammary gland, is one of the most expensive diseases for the dairy industry. This disease, that typically follows a bacterial infection, has been associated with decreased milk production, reduced longevity, and impaired reproductive performance (Santos et al., 2004; Aghamohammadi et al., 2018). Additionally, it negatively alters milk composition and quality, leading to a change in flavor and negatively affecting cheese-making qualities (Le Maréchal et al., 2011).

Limitations for Mastitis Control on Organic Dairy Farms

The use of intramammary antibiotics has been shown to be effective in treating and preventing mastitis during the lactating and dry periods, respectively (Halasa et al., 2009b, a; Winder et al., 2019). However, the use of antibiotics is restricted on organic dairy farms in the United States (National Mastitis Council, 2019). Furthermore, conventional dairy farmers are interested in reducing their use of antibiotics, particularly as societal pressure for judicious use of antimicrobials in livestock increases. Preventive measures such as adequate nutrition, keeping the cows in a dry and clean environment, use of screening tools to detect and cull chronically infected cows, adequate upkeep of milking machines, and hygienic milking routines are very important measures for the maintenance of udder health (Ruegg, 2017). Despite the application of these measures, mastitis can still be a problem on organic and conventional dairy farms.

Novel Alternatives for Mastitis Therapy and Prevention

Several recent studies describe the udder microbiome as a diverse range of microorganisms that live in the mammary gland. While the presence of this microscopic ecosystem is intriguing, few studies have evaluated whether it contributes to the development of mastitis. Cows with mastitis seem to have a lower diversity of microorganisms in their udder compared to healthy cows. In other words, there are fewer unique species and more unevenly-distributed microbial populations in the milk of mastitic cows (Oikonomou et al., 2014). This suggests that the udder microbiome may be important for mastitis epidemiology and raises the hypothesis that a microbial imbalance may play a role in mastitis. Furthermore, it has been hypothesized that some bacterial species may be part of the normal microbiome in healthy quarters, suggesting that the microbiome composition may also play a protective and beneficial role in preventing mastitis. However, the results from different studies are inconsistent in regard to which specific taxonomic groups within the udder microbiome are associated with improved udder health (Oikonomou et al., 2012, 2014; Metzger et al., 2018). Thus, evidence-based consensus information on how to effectively use the udder microbiome to control mastitis in dairy cows is non-existent.

Despite this uncertainty, the huge number and types of microorganisms that live on the teat-apex and within the mammary gland means that at least some of these microorganisms could potentially be used to prevent and treat mastitis. For example, probiotics (live microorganisms) are one type of microbiome-based product that could represent an alternative option for organic dairy farms. In fact, previous research has shown that minor mastitis pathogens may themselves have a probiotic effect because they seem to decrease infection with major mastitis pathogens (Reyher et al., 2012). For example, quarters infused with minor pathogens (e.g., non-aureus Staphylococci and Corynebacterium bovis) had a much lower chance of being infected with major pathogens, suggesting that the minor pathogens conferred some resistance to colonization by the major pathogens (Reyher et al., 2012). Additionally, post-dipping with a Lactobacillus-based solution showed equivalent outcomes in udder health compared to a commercial iodine-based post-milking teat disinfectant, suggesting that probiotic dipping solutions may be a viable alternative to commonly used solutions containing iodine (Alawneh et al., 2020). In addition to probiotic-based preventive interventions, probiotics may also be effective in treating mastitis—although previous studies have yielded variable results in this regard. Perhaps most promising was a series of two small studies that used Lactococcus lactis as a probiotic injected into the teats to successfully cure subclinical and clinical mastitis in dairy cows. In these studies, the administration of L. lactis was as effective as antibiotic therapy for treating clinical and subclinical mastitis (Klostermann et al., 2008). In addition to bacteria such as Lactobacilli, yeast-based probiotics have also shown promising results for the prevention and treatment of mastitis (Gao et al., 2020). In spite of the fact that several products have been studied as an alternative way of controlling mastitis, there is still no commercially available probiotic-based product approved for use on organic dairy farms.

Although probiotics are probably more widely known, prebiotics can also be considered a microbiome-based product. Prebiotics are defined as nutritional or other metabolic compounds that selectively promote the growth of certain microorganisms. Prebiotics have been shown to improve dairy cattle health and milk production (Uyeno et al., 2015). However, there are currently no published studies of prebiotics as a method to control or prevent mastitis.

Lastly, postbiotics are substances secreted by microorganisms as part of their normal metabolic functioning that could lead to beneficial effects on host health (Żółkiewicz et al., 2020). Antimicrobial peptides (AMPs) are postbiotics that are naturally produced by certain bacterial strains. This class of compounds is very diverse, and therefore the use of AMPs to control and prevent disease is receiving widespread interest in both human and veterinary medicine. Interestingly, both human and animal studies have shown that some species of non-aureus Staphylococcus are capable of producing AMPs that can function as natural antibiotics that inhibit the growth and decrease the colonization by pathogenic bacteria like Staphylococcus aureus (De Vliegher et al., 2004; Braem et al., 2014; Nakatsuji et al., 2017). Identifying such AMPs can be a laborious task because different strains of bacteria can produce different AMPs. Given promising early results for prevention of Staphylococcus aureus colonization of skin via AMPs, our team is undertaking a research project to try to identify AMP-producing bacteria that are specific to the skin of dairy cow udders. The hope is that these bacteria and their AMPs could be an alternative microbiome-based method for treating and/or preventing mastitis on organic dairy farms.

Conclusions

Despite the lack of commercially-available microbiome-based products, the widespread use of genomic sequencing during the past several years has revealed the intrinsic complexity of the udder microbiome and its potential role in mastitis epidemiology. Based on initial studies and promising results in human trials, these microbiome-based products may lead to numerous alternative strategies to prevent and treat mastitis that would benefit organic and conventional dairies.

IMPORTANT: Before using any pest control product in your organic farming system:

1. Read the label to be sure that the product is labeled for the crop and pest you intend to control, and make sure it is legal to use in the state, county, or other location where it will be applied.
2. Read and understand the safety precautions and application restrictions.
3. Make sure that the brand name product is listed in your Organic System Plan and approved by your USDA-approved certifier. If you are trying to deal with an unanticipated pest problem, get approval from your certifier before using a product that is not listed in your plan—doing otherwise may put your certification at risk.

Note that, although OMRI and WSDA lists are good places to identify potentially useful products, all products that you use must be approved by your certifier. For more information on how to determine whether a pest control product can be used on your farm, see the related article, Can I Use This Input On My Organic Farm?

This article was written by members of the NIFA OREI-funded project Open-Community Resource for Organic Animal Microbiome Education and Research (Open-ROAMER).

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