C-X-C Motif Chemokine Ligand 1 Promotes Colitis by Modulating the Gut Microbiota

Abstract

Introduction: C-X-C motif chemokine ligand 1 (CXCL1) is a potent neutrophil chemoattractant that plays a pivotal role in recruiting neutrophils during inflammatory conditions. This study explored the role of CXCL1 in modulating the gut microbiota, influencing neutrophil infiltration, and contributing to the development of colitis. Methods: We employed quantitative PCR to assess CXCL1 expression in colon samples. A mouse model of dextran sulfate sodium (DSS)-induced colitis was utilized to explore the progression of colitis in wild-type (WT) and CXCL1-deficient (CXCL1/) mice. Results: Colitis attenuation was evident in CXCL1/ mice. Significant alterations were observed in the gut microbiome, as revealed by 16S rRNA gene sequencing. Furthermore, CXCL1/ mice exhibited reduced gut permeability and diminished endotoxin levels in peripheral blood following DSS treatment compared to WT mice. In response to DSS treatment, WT mice showed a clear increase in neutrophil infiltration, while CXCL1/ mice exhibited lower levels of infiltration. Fecal microbiota transplantation (FMT) using stools from CXCL1/ mice alleviated DSS-induced colitis. Interestingly, FMT from patients with colitis increased CXCL1 and Ly6G expression in the colons of gutsterilized mice. Clinical data analysis revealed elevated CXCL1 and CD15 expression in patients with colitis, with a positive correlation between the severity of colitis and the expression of CXCL1 and CD15. Conclusion: These findings shed light on the pivotal role of CXCL1 in promoting colitis by modulating the gut microbiota.