Protective Effects of Engineered Lactobacillus crispatus on Intrauterine Adhesions in Mice via Delivering CXCL12

Frontiers in Immunology

Xiaorong Deng¹  Yao Kong²  Fei Wu²  Lijuan Hu²  Zhaoxia Liu²  Qin Xiao²  Tingtao Chen³ 

[1] Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China;Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Nanchang University, Nanchang, China;National Engineering Research Center for Bioengineering Drugs and The Technologies, Institute of Translational Medicine, Nanchang University, Nanchang, China;

关键词: Lactobacillus crispatus;    mCXCL12;    pMG36e;    intrauterine adhesions;    high-throughput sequencing;   

DOI  :  10.3389/fimmu.2022.905876

来源: DOAJ

【 摘 要 】

Endometrial injury is the main cause of intrauterine adhesions (IUA), and there is currently no effective prevention and treatment. Immune cells play an important role in damage repair by sensing the change in the microenvironment. Exogenous CXCL12 can promote tissue regeneration and repair by recruiting immune cells, but its effect and possible mechanism on endometrial regeneration and repair have not been reported. In the present study, we constructed an engineered a Lactobacillus crispatus strain by transforming a pMG36e plasmid carrying a CXCL12 gene into the bacterium, and developed two animal models, the intrauterine adhesion mice with or without diabetes to evaluate the positive effects of this strain on the prevention of IUA after accepting intrauterine surgery in normal and diabetic mice. The results showed that vaginal application of L. crispatus-pMG36e-mCXCL12 strains significantly diminished the levels of pro-inflammatory factors interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) in serum and uterine tissues of IUA mice, and resulted in the inhibition of the inflammatory (toll-like receptor 4/nuclear factor-κb, TLR4/NF-κB) and fibrotic (transforming growth factor-β1/smads, TGF-β1/Smads) signalling pathways in the uterine tissues. The high-throughput sequencing results further indicated that treatment with L. crispatus-pMG36e-mCXCL12 strains greatly increased the abundance of Lactobacillus spp. and reduced that of the pathogenic Klebsiella spp. in IUA mice. Furthermore, among intrauterine adhesion mice with diabetes, we obtained similar results to non-diabetic mice, that is, L.crispatus-pMG36e-mCXCL12 significantly improved fibrosis and inflammation in the uterine cavity of diabetic mice, and restored the vaginal microbiota balance in diabetic mice. Therefore, we speculated that vaginal administration of L. crispatus-pMG36e-mCXCL12 strains can effectively alleviate intrauterine adhesions by restoring the microbial balance and reducing inflammation and fibrosis caused by surgery.

【 授权许可】

Unknown