Gut microbiota derived Bifidobacterium pseudolongum alleviates endometritis caused by dysbiosis and Escherichia coli infection.

Endometritis is a prevalent uterine inflammatory disease that significantly compromises fertility; however, the host-microbial mechanisms governing disease susceptibility remain poorly defined. Although the gut microbiota is increasingly recognized as a central regulator of systemic and extraintestinal immunity, its role in uterine inflammation has received little attention. Here, we investigated whether gut microbiota dysbiosis modulates susceptibility to endometritis and sought to identify the microbial mediators underlying this relationship. Antibiotic-induced dysbiosis markedly exacerbated uterine inflammation and tissue injury in mice, whereas fecal microbiota transplantation (FMT) re-established microbial homeostasis and substantially ameliorated uterine pathology. 16S rRNA sequencing identified Bifidobacterium pseudolongum as a commensal species depleted during dysbiosis and restored following FMT. Monocolonization with B. pseudolongum conferred protection against dysbiosis-associated uterine inflammation, evidenced by diminished IL-1β, TNF-αand IL-10 production, reduced HMGB1 and HABP2 levels, restored epithelial tight junction protein expression-including ZO-1, Claudin-3, and Occludin, and attenuated neutrophil and macrophage infiltration. Beyond the dysbiosis model, B. pseudolongum demonstrated both prophylactic and therapeutic efficacy in murine models of Escherichia coli- and LPS-induced endometritis, suppressing inflammatory responses, limiting tissue damage, preserving epithelial barrier integrity, and reducing immune cell infiltration. In vitro assays showed that culture supernatants of B. pseudolongum inhibited E. coli growth under cell-free conditions, indicating a potential antimicrobial activity in vitro. Taken together, these findings support a gut-uterus immunological axis in which B. pseudolongum attenuates infection-driven uterine inflammation through the coordinated modulation of immune responses, epithelial barrier maintenance, and antimicrobial defense. Our study positions B. pseudolongum as a compelling microbiota-based candidate for the prevention and treatment of endometritis.