Protective Effect of Clostridium butyricum on Escherichia coli-Induced Endometritis in Mice via Ameliorating Endometrial Barrier and Inhibiting Inflammatory Response

Abstract

Endometritis is a common reproductive disease occurs both in human and animals. Clostridium butyricum is a Gram-positive anaerobic bacterium that can ferment various carbohydrates into butyric acid. In this study, we investigated the effects of <i>C. butyricum</i> on Escherichia coli-induced endometritis and clarified the underlying mechanism. We first verified the protective effect of <i>C. butyricum in vivo</i> by establishing a mouse model of E. coli-induced endometritis. It was determined that <i>C. butyricum</i> pretreatment significantly reversed E. coli-induced uterine histopathological changes. Meanwhile, <i>C. butyricum</i> pretreatment significantly decreased the production of pro-inflammatory mediators and the levels of myeloperoxidase (MPO) and malondialdehyde (MDA). We found that <i>C. butyricum</i> could inhibit TLR4-mediated phosphorylation of NF-κB and the activity of histone deacetylase (HDAC). Furthermore, <i>C. butyricum</i> significantly increased the expression of the tight junction proteins (TJPs) ZO-1, claudin-3, and occludin. Additionally, treatment with <i>C. butyricum</i> culture supernatant dramatically suppressed the degree of inflammation in the uterus, and inactivated <i>C. butyricum</i> did not exert a protective effect. We subsequently investigated butyrate levels in both the uterus and blood and observed a marked augment in the <i>C. butyricum</i> treatment group. Collectively, our data suggest that <i>C. butyricum</i> maintains epithelial barrier function and suppresses inflammatory response during E. coli-induced endometritis and that the protective effect of <i>C. butyricum</i> may be related to the production of butyrate. <b>IMPORTANCE</b> Endometritis is a common reproductive disease both in human and animals. It impairs female fertility by disrupting endometrial function. Antibiotics are widely used to treat endometritis in clinical practice, but the misuse of antibiotics often leads to antibiotic resistance. Therefore, there is an urgent need for new therapeutic agents to treat bacterial endometritis and overcome bacterial resistance. In this study, we found that C. butyricum could protect from E. coli-induced endometritis.