Jieduquyuziyin prescription (JP) is an empirical formula used to treat systemic lupus erythematosus (SLE). While JP has been shown to have synergistic and attenuated effects when combined with glucocorticoids (GCs) for SLE treatment, the precise mechanism remains unclear. This study utilized MRL/lpr mice to demonstrate the synergistic and attenuated effects of JP when combined with prednisone. Furthermore, a co-housing experiment was conducted to investigate whether JP-regulated gut microbiota had synergistic and attenuated effects in prednisone-treated MRL/lpr mice. The study found that JP exhibited synergistic effects only when combined with 5 mg/kg body weight prednisone, while its attenuated effects were observed with both 5 and 10 mg/kg body weight prednisone. Co-housing resulted in the transmission of gut microbiota between prednisone-treated and JP-treated MRL/lpr mice. However, co-housing did not enhance the therapeutic efficacy of prednisone
instead, it attenuated prednisone's adverse effects on liver inflammation (IL-6 and TNF-α) and serum cholesterol in MRL/lpr mice. The attenuated effects of JP may be associated with specific genera such as