Unveiling the Super Tactics of Bile Acid Sniper for Mastitis in Cows

Mastitis in dairy cows has become one of the key diseases restricting the sustainable and healthy development of the global dairy industry. It not only greatly hinders the prosperity and development of the dairy industry, but also profoundly affects the quality and safety of dairy products, causing a huge economic burden on animal husbandry and posing a major threat to public health and safety. According to reports, about one-third of dairy cows worldwide suffer from various types of mastitis, and 30% of cows suffer from clinical mastitis at least once during lactation. The etiology of bovine mastitis is complex, and pathogenic microbial infection is the main cause of its occurrence. Staphylococcus aureus (Saureus) is one of the important pathogenic bacteria that cause mastitis in cows. S. aureus is a pathogen that can cause serious diseases in various humans and animals, and is also the main pathogenic bacteria that cause mastitis. It can repeatedly infect breast tissue, induce inflammation and cell apoptosis in the breast, and release exotoxins to cause systemic symptoms. More and more evidence suggests that S. aureus may be resistant to most antibiotics, and in recent years, methicillin-resistant Staphylococcus aureus (MRSA) has emerged. Therefore, S. aureus induced mastitis requires safer and more effective prevention and control strategies.

Previous studies have found that deoxycholic acid (DCA) plays an important role in many diseases, but its effect on mastitis has not been reported. In order to investigate the effect and mechanism of DCA on S. aureus induced mouse mastitis, this study constructed a S. aureus induced mouse mastitis model and intraperitoneally injected DCA (0.01, 0.02, 0.03 mg/g), Collect breast tissue and detect the protective effect and mechanism of DCA on mastitis. The results showed that DCA can effectively alleviate the pathological damage of mouse breast tissue induced by S. aureus in a dose-dependent manner; Meanwhile, it can inhibit the expression levels of inflammatory mediators induced by S. aureus, including tumor necrosis factor TNF - α, interleukin IL-1 β, and the activity of myeloperoxidase MPO; DCA can reduce MDA and iron ion concentration, while upregulating GSH and GPX4 expression, indicating that DCA can inhibit iron death induced by S. aureus; Western blot results showed that DCA can upregulate TGR5 receptors, thereby inhibiting the NF - κ B signaling pathway. The above results indicate that DCA exerts anti mastitis effects by regulating the TGR5-NF - κ B signaling pathway to inhibit S. aureus induced inflammatory response and ferroptosis.

1.DCA can alleviate pathological changes in mouse mammary gland tissue induced by S. aureus (Figure 1)，The mammary gland tissue of mice in the S. aureus treatment group underwent significant changes, manifested as damaged acinar structure and infiltration of a large number of inflammatory cells in the acini (Figure 1B). After intraperitoneal injection of DCA treatment, the mammary gland tissue gradually showed a recovery trend with increasing concentration of DCA, specifically manifested as a tendency towards normal mammary gland acinar structure and a significant decrease in the number of inflammatory cells (Figure 1C-E).

2.DCA alleviated the increase in MPO activity induced by S. aureus in mouse mammary tissue (Figure 2)，The activity of myeloperoxidase (MPO) is used as an indicator to evaluate the degree of neutrophil infiltration.

3.DCA reduced the expression of inflammatory cytokines in mouse mammary gland tissue induced by S. aureus.With S Compared with the aureus group, the concentrations of TNF - α and IL-1 β in the mammary gland tissue of mice treated with DCA decreased with increasing DCA dose (Figure 3).

4. DCA inhibited S The activation of NF - κ B signaling pathway in mouse mammary gland tissue induced by Staphylococcus aureus alleviates the inflammatory response induced by S. aureus stimulation (Figure 4).

5. DCA alleviated the changes in iron death related indicators in breast tissue induced by S. aureus.After treatment with different concentrations of DCA, the MDA and iron ion concentrations in breast tissue were significantly lower than those in the S. aureus group; The concentration of GSH was significantly higher in the S.au reus group than in the S.au reus group (Figure 5).

This experiment found that under the stimulation of S. aureus, I κ B and p65 proteins in mouse breast tissue were significantly phosphorylated, indicating the activation of the NF - κ B signaling pathway and the exacerbation of inflammatory response. After DCA treatment, the expression of I κ B and p65 phosphorylated proteins in the NF - κ B signaling pathway was significantly inhibited, effectively blocking further activation of the inflammatory pathway and reducing S. aureus induced breast inflammation. In summary, DCA can alleviate mammary gland inflammation induced by S. aureus in mice by regulating the TGR5-NF - κ B signaling pathway.

Original text: Dong Ziting, Liang Chaohui, Sun Qingsong, etc The therapeutic effect and mechanism of deoxycholic acid (DCA) on Staphylococcus aureus induced mastitis in mice [J]. Chinese Journal of Veterinary Medicine, 2025, 45 (02): 274-280. DOI: 10.16303/j.cnki. 1005-4545.2025.02.14

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