Regulating acid-base balance through Carbonate Buffer Mixture alleviates ruminal dysbiosis-induced mastitis by modulating rumen homeostasis and microbial metabolism

Background: The pathophysiology of mastitis, a serious illness that impacts human health and the growth of the dairy industry, may be linked to gastrointestinal dysbiosis brought on by subacute ruminal acidosis (SARA) brought on by high-concentration diet (HCD) consumption, according to mounting studies However, the effect of the remodeling of the gastrointestinal microbiota by regulating ruminal acid-base balance on mastitis remains unclear. Results: In the current study, we used Carbonate Buffer Mixture (CBM) to regulate acid-base balance in goats. These data demonstrated that CBM alleviated ruminal dysbiosis-induced mastitis along with reduced mammary inflammatory responses and repaired blood-milk barrier integrity, which was further confirmed by ruminal microbiota transplantation (RMT) from CBM-treated goats (MC-RMT) to recipient mice. Consistent with these observations, mice treated with CBM and MC-RMT showed decreased rumen, colon, and liver damage as well as systemic inflammatory markers, indicating lower mucosal and systemic inflammation. Moreover, CBM and MC-RMT improved ruminal dysbiosis, especially enriched Bacteroidota and depleted Firmicutes. Falcarindiol (FAD), a metabolite with anti-inflammatory effects, was enriched in both the donor goats and recipient mice. Supplement of mice with FAD also relieved mastitis symptom and systemic inflammation caused by gut dysbiosis. Mechanically, FAD activated PPARr and subsequently ABCA1, which inhibited NF-kB and NLRP3 activation and inflammatory responses in macrophages. Conclusions: Our findings indicate that CBM improved ruminal dysbiosis-induced mastitis by regulating rumen homostasis and FAD production, which implies that modulation of ruminal microbiota and ruminal-associated metabolites by regulating acid-base balance is a potential strategy for mastitis intervention.