An insights into the Udder Homeostasis to Safeguard the Health of Dairy Animals

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An insights into the Udder Homeostasis to Safeguard the Health of Dairy Animals

Lija*

 *PhD Research Scholar, Division of Animal Physiology, ICAR-NDRI, Karnal, Haryana -132001, India

lijas2k9@gmail.com

Abstract

Mastitis is a polyethiological and multifactorial disease therefore it is necessary to find the areas of risk in udder health programs and monitoring systems. Despite the increasing level of technological support and veterinary measures, still bovine mastitis is one of the main health problems and reasons for huge economic losses faced by dairy farmers. Mammary gland microbiota diversity plays a major role in defense mechanisms, any dysbiosis occurred leads altered composition and diversity of commensal microbiome, triggers the immune mechanisms through increased somatic cell count subsequent cytokine mediated immune response occur for restoring the udder health. Considering this fact, preserving the good health of dairy cows through host, microbes, environment interaction is a daily challenge for all involved in primary milk production. The proper strategies should be aimed at minimizing external and internal factors that increase the risk of intramammary infection. Great effort in longitudinal studies exploring the dynamics of the bovine udder microbiota, mechanistic investigations of links in  BoLA gene polymorphisms, practical utility in somatic cell score selection criteria as well as methods to enhance the cytokine pharmacodynamics response for the effective vaccine recombinant preparations is still needed. Cost effective new technological interventions suitable for a herd are the need of the hour for optimum udder homeostasis.

Key words: Intramammary infections, udder microbiota, SCC, Cyokine, udder homeostasis

Introduction

Mastitis is a most serious and demanding disease of dairy cows which cause economic burden for dairy farmers. National Mastitis council (NMC) (www.nmconline.org), SCC of normal milk is nearly always less than 200000 cells/ml. According to Krishnamoorthy et al., 2021, in India prevalence for SCM and CM is 45 and 18 per cent respectively.  More than 137 different organisms as causative agent of bovine mastitis which includes bacteria, viruses, mycoplasma, yeast and algae. Bacteria is the major causative agent for ~ 95% of all Intra-mammary Infections (IMI). A quarter that becomes infected during dry period or from the previous lactation will produce 30–40% less milk. Current understanding of the microbial ecosystem of the udder suggests that optimal diversity of intramammary microbiota, composed of a healthy balance between commensal and opportunistic bacterial groups, is essential for maintaining an equilibrium between pro- and anti-inflammatory responses, and thus maintaining mammary homeostasis.

Potential sources and composition of udder microbiota

Potential environmental sources of mammary microbiota are from bedding materials, milking equipments, milker’s hand, flies and cross suckling. Staphylococcus chromogenes, followed by Staphylococcus simulans, Staphylococcus xylosus, Staphylococcus haemolyticus, and Staphylococcus epidermidis, are the NAS species most frequently isolated from cow milk. According to Bouchard et al., 2015 lactic acid bacteria isolated from the milk or TC, for example, can adhere to and internalize bovine mammary epithelial cells and modulate production of pro-inflammatory cytokines. Phylum Firmicutes have dominated the healthy milk and the usual most abundant phyla were Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. A higher representation of Phylum Proteobacteria was observed in mastitis milk (Derakhshani et al., 2020). Bacteriocins from non-aureus Staphylococci and Corynebacterium species colonizing the teat apices and teat canals inhibit growth of major mastitis pathogens. Various factors such as host, genetic, nutritional and environmental influencing udder microbiota are discussed below for maintaining udder homeostasis.

Host factors

Teat spincture muscle, inherent diameter of the TC or the shape of the teat end influence on the composition of udder microbiota by blocking the leakage of milk and by preventing IMI caused by environmental pathogens. Keratin seal also has antimicrobial activity due to some bacteriostatic fatty acids (lauric, myristic, palmitoleic, and linoleic). However, in dairy cow teat canal remain open for 30minutes to 2 – 6 hrs after milking. After dry off teat spincture remains open in 50–60 day in 45% animals and in 5% animal’s teat sphincture was not closed even in 90 days (Cobirka et al., 2020). Prepartum teat edema usually accompanied by leakage of milk, is also considered as a contributing factors to shaping udder microbiota during late stages of pregnancy. Hyperkeratosis of the teat end over time occurs in multiparous animals, incorrect intramammary therapy infusion or by faulty machine milking has been also reported to increase susceptibility of the teat canal to bacterial invasion and colonization.

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The mammary epithelium is a sentinel line of defense. The innate cells in mammary gland can sense bacteria and trigger inflammation. Dentritic Cells and (CD)8+ T lymphocytes are closely associated with the Mammary Epithelial Cells (MECs). Neutrophil extracellular trap (NET) formation is an additional antimicrobial defense mechanism in the innate immune system. NK cells isolated from bovine mammary tissue exhibit bactericidal activity against S aureus and, therefore, these lymphoid populations could be an important aspect of innate defense in preventing mastitis. Cytokines regulate the intensity and duration of the host response to infection by regulating (enhancing or inhibiting) the involved in the immune response. Vlasova and Saif, 2020 reported that IFN-γ and IL-2 can enhance T-cell responses to specific antigen and hence it can be used as effective mastitis vaccine adjuvants.

Genetic factors

Candidate genes encoding the major histocompatibility complex (MHC) molecules/ bovine leukocyte antigens (BoLA) have role in modulation of innate and acquired immune responses. BoLA-DRB3 gene has a critical role in various aspects of immune responsiveness of the udder, recognition of exogenous antigens and leukocyte recruitment, elimination of infectious agents by milk SCC and modulation of udder microbiota (NAS enrichment). According to Derakhshani et al., 2018, more than 130 BoLA-DRB3 alleles have been identified so far in various breeds of cattle

Somatic Cell Count is an important effector and marker and can be used as a criteria for genetic selection (Rainard et al., 2018). There is high genetic correlation between SCC and Clinical Mastitis (>70%) and higher heritability coefficient of SCC (0.05–0.25). Thus, genetic selection for mastitis resistance should be considered to maintain healthy and productive cows. However, the SC Score-based selection does not reduce the reactivity of the healthy glands to infection.

Nutritional factors

Negative energy Balance (NEB) leads to mobilization of fatty acids from adipose tissue which in turn increases the blood concentrations of Non Esterified Fatty Acids (NEFA) and glycerol. Excessive oxidation of NEFA during the periparturient period results in accumulation of acetyl-CoA and upregulation of an alternative pathway that results in biosynthesis of ketone bodies such as acetoacetate, BHB, and acetone (Suriyasathaporn et al., 2000).  Increased NEFA and ketone bodies cause impairment in recruitment, translocation, cytokine production, phagocytic activity and reactive oxygen species production of macrophages and neutrophils.

In dry period , initial phase of lactation, peripartum period Sahiwal and Karen Fries fed daily vitamin E supplementation of 1,000–2,000 IU/head with 0.3–0.4mg Se/kg DM found to reduce the risk of mastitis. Cu, Vit A, β-carotene supplementation increased bactericidal function of phagocytes. Cows were supplemented individually with VE (1000 IU/cow/day), Cu (20 ppm/cow/day) and Zn (80 ppm/cow/day) increased the phagocytic activity (PA) and lymphocyte proliferation response (LPR) during the pre-partum period ((Dang et al., 2013). Humic acids are natural organic substances that are formed by the chemical and biological decomposition of organic matter of plant origin and synthetic activity of microorganisms. It alongside fulvic acids and humin are among humic substances that are part of humus. They are based on lignin collectively with other components of plant biomass (sugars, fats, proteins, waxes and resins). Oral administration of humic acids @ 100 g per dairy cow for 60 to 70 days decreases milk Somatic Cell Count, subclinical mastitis and   increase of milk protein levels and fat up to 0.5% (Zigo et al., 2021).

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Environmental factors

Currently, changing climatic conditions are important factors that influence the productive performance and disease incidence of animals. Sinha et al. (2021) reported a significant increase in clinical mastitis cases in high producing Karan Fries and indigenous Sahiwal cows during the rainy season and this could be due to high levels of droplet infection, dampness, and muddy floors. Bedding using Recycled Manure Solids (RMS) a substitute bedding material with hygienic quality combined with straw and components like limestone or zeolite was found to reduce the chance of IMI.  A proper milking hygiene program that meets all biological and hygienic requirements of the dairy cow significantly influences the maintenance of good udder health. The standard measure of the milk hygiene is the total bacteria count (TBC) is measured routinely by the dairies collecting milk off farm. A marker of good practice would be TBC that were consistently <15 000/mL (Webster, 2020).

Potential role of microbiota dysbiosis and susceptibility to mastitis

Association of mastitis with dysbiotic microbiota, based on differences in microbial composition (β-diversity) and/or richness and evenness (α-diversity) when comparing milk from mastitic quarters to healthy. In mastitic quarter lower species richness, reduced diversity and decreased resilience. Following IMI partial recovery of commensal bacteria and subsequent antimicrobial therapy may facilitate both recurrence of persistent infections and development of new IMI. Mastitic quarter have higher proportions of genera Burkholderia, Sphingomonas, and Stenotrophomonas and in healthy quarters Pseudomonas, Psychrobacter, and Ralstonia were overrepresented in the microbiota. Quarters infected with Staphylococcus aureus showed greater infiltration of lymphocytes and neutrophils as well as a greater percentage of interalveolar stroma compared with uninfected tissues (Zigo et al., 2021)

The antibiotic concentrations more than 3 weeks during drying period leads to microbiota dysbiosis, which may increase the susceptibility to infections during colostrogenesis. Teat dip using a novel probiotic lactobacilli-based teat disinfectant was found to be superior to the commercial disinfectant in reducing somatic cell count. Oral supplementation of probiotics for the treatment of IMI have not been effectively in polygastric animals such as ruminants, especially since the enteromammary pathway is poorly operative in these species. This is probably why probiotics for the bovine MG have been administered through the teat canal. Therefore, profiling microbiome dynamics in different conditions of mastitis and associated microbial genomic features contributes to developing microbiome-based diagnostics and therapeutics for bovine mastitis.

Conclusion and Future prospects

Strategies to optimize mammary gland defenses can be an effective way to prevent the establishment of new IMI and to limit the use of antimicrobials. The choice of measures to control mastitis must be applicable throughout the herd. Great effort is still needed in longitudinal studies exploring the dynamics of the bovine udder microbiota of various compartments of the udder interact with each other, with mastitis pathogens, and the immune system. Metagenomic and metatranscriptomic investigations are required to develop a holistic understanding of genetic diversity and functionality of various bacterial groups within the udder ecosystem. Moreover, novel molecular techniques can also provide an exciting opportunity for investigating the role of traditionally neglected components of the udder microbiome, including fungi, protozoa, and viruses, in modulating mastitis susceptibility. Mechanistic investigations of BoLA gene polymorphisms links, genomic investigation of SCS of milch breeds is also necessary for development of mastitis resistance herd. A cost effective, new technological interventions suitable for a herd are still the need of the hour for effective mastitis control to provide good quality milk with low SCC.

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References

Ahmed Dawod. 2022. Impacts of Climatic Factors on Milk Yield Performance and Mastitis Incidence in Holstein Cattle Reared under Subtropical Condition. Journal of Current Veterinary Research, 4:1: 106-117

Bouchard, D. S., B. Seridan, T. Saraoui, L. Rault, P. Germon, C. Gonzalez-Moreno, F. M. Nader-Macias, D. Baud, P. François, and V. Chuat. 2015. Lactic acid bacteria isolated from bovine mammary microbiota: potential allies against bovine mastitis. PLoS One 10:e0144831.

Cobirka M, Tancin V, Slama P. Epidemiology and classification of mastitis. Animals. (2020) 10:2212. doi: 10.3390/ani10122212

Dang AK, Prasad S, De K, Pal S, Mukherjee J, Sandeep IVR (2013). Effect of supplementation of vitamin E, copper and zinc on the in vitro phagocytic activity and lymphocyte proliferation index of peripartum Sahiwal (Bos indicus) cows. J Anim Physiol Anim Nutr. 97:315–32. doi: 10.1111/j.1439-0396.2011.01272.x

Derakhshani, H.; Fehr, K.B.; Sepehri, S.; Francoz, D.; De Buck, J.; Barkema, H.W.; Plaizier, J.C.; Khafipour, E. (2018). Invited review: Microbiota of the bovine udder: Contributing factors and potential implications for udder health and mastitis susceptibility. J. Dairy Sci., 101, 10605–10625

Derakhshani, H.; Plaizier, J.C.; De Buck, J.; Barkema, H.W.; Khafipour, E. (2020). Composition and co-occurrence patterns of the microbiota of different niches of the bovine mammary gland: Potential associations with mastitis susceptibility, udder inflammation, and teat-end hyperkeratosis. Anim. Microbiome, 2, 1–17.

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Zigo F, Vasil M, Ondrasovicc ova S, Vyrostkova J, Bujok J and Pecka-Kielb E (2021) Maintaining Optimal Mammary Gland Health and Prevention of Mastitis. Front. Vet. Sci. 8:607311. doi: 10.3389/fvets.2021.607311

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