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

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 gut-sterilized 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. <b><i>Conclusion:</i></b> These findings shed light on the pivotal role of CXCL1 in promoting colitis by modulating the gut microbiota.