Probiotics alleviate heat stress-induced uterine inflammation, reproductive hormone disruption and fetal growth restriction in mice.

With rising global temperatures, the detrimental effects of heat stress on the reproductive performance of female animals have received increasing attention. In this study, we investigated the effects of heat stress on reproductive function in female mice and explored the therapeutic potential of probiotics in alleviating uterine damage through repair of the intestinal barrier. Seven-week-old female ICR mice were used to establish a systemic heat stress model. Mice in the treatment groups received Enterococcus faecium or Clostridium butyricum during heat stress. The results showed that heat stress induced systemic inflammation, oxidative stress, and elevated endotoxin (LPS) levels, leading to downregulation of tight junction proteins (ZO-1, occludin, and claudin-1) in the colon and uterine tissues. Systemic inflammation increased the levels of the pro-inflammatory cytokines IL-1β and IL-2 while decreasing the levels of the anti-inflammatory cytokines IL-4 and IL-10 in uterine tissue, resulting in uterine inflammatory damage and reproductive hormone dysregulation, thereby exacerbating placental injury and increasing the risk of fetal growth restriction. Treatment with E. faecium or C. butyricum repaired the intestinal barrier and inhibited the TLR4-MyD88 signaling pathway, thereby protecting the uterus from heat stress-induced injury and effectively alleviating uterine inflammation and fetal growth restriction. The 16S rRNA sequencing results demonstrate the regulatory effects of Enterococcus faecium and Clostridium butyricum on intestinal microbiota. Fecal microbiota transplantation (FMT) experiments further demonstrated that oxidative stress and uterine inflammatory damage in heat-stressed mice were alleviated following transplantation of intestinal microbiota from mice treated with E. faecium or C. butyricum. These findings suggest that E. faecium and C. butyricum have potential applications in reducing heat stress-induced reproductive damage in female animals.