The Protective Effects and Underlying Mechanisms of Taraxacum kok-saghyz Polysaccharides Against Intestinal Dysbiosis-Induced Mastitis Were Elucidated Using a Murine Model of the “Gut–Mammary” Axis

The gut-mammary axis represents a promising therapeutic target for mastitis. Although plant-derived polysaccharides exhibit immunomodulatory properties, their capacity to modulate this axis-and specifically to ameliorate dysbiosis-induced mastitis-remains unexplored. Here, we investigated the therapeutic potential of <i>Taraxacum kok-saghyz</i> leaf-derived polysaccharides (TKP-L) against mastitis in a murine model of gut dysbiosis, with dysbiosis induced by fecal microbiota transplantation (FMT) from donor cows. Pregnant mice (<i>n</i> = 60) with antibiotic-depleted microbiota received FMT suspensions prepared from the feces of healthy dairy cows or cows with clinical mastitis (based on somatic cell count). Mice were randomly divided into five groups: Control (vehicle), M-FMT (mastitis-cow FMT, disease model), H-FMT (healthy-cow FMT), TKP-L (M-FMT + oral TKP-L, 500 mg/kg/day), and Ciprofloxacin (M-FMT + ciprofloxacin, positive Control). After FMT establishment, TKP-L or ciprofloxacin was administered for 14 days. We assessed histopathology, pro-inflammatory mediators (IL-6, IL-1β, TNF-α, MPO), tight junction proteins (occludin, ZO-1, Claudin-3), and bacterial translocation using GFP-<i>E. coli</i>, and gut/milk microbiota via 16S rRNA sequencing. Compared to the M-FMT group, TKP-L treatment significantly alleviated mammary inflammation and pathology, inhibited pro-inflammatory cytokine expression, and enhanced the expression of tight junction proteins in both intestinal and mammary tissues, correlating with reduced bacterial translocation to the mammary gland. Microbiota analysis showed that TKP-L restored microbial homeostasis in the gut and milk, concurrently increasing the relative abundance of beneficial bacteria such as Limosilactobacillus. TKP-L alleviates gut dysbiosis-induced mastitis in mice by concurrently modulating the gut-mammary axis through microbial remodeling, enhancement of epithelial barriers, and anti-inflammatory actions. These findings highlight TKP-L as a promising gut microbiota-targeting candidate for mastitis intervention.