CXCL1 Promotes Colitis by Modulating the Gut Microbiota

Abstract

The effects of CXCL1 on colitis remain unclear. In the present study, using a dextran sulfate sodium (DSS)-induced colitis mouse model, we explored colitis development in wild-type (WT) and CXCL1-deficient mice (CXCL1-/-). Colitis was suppressed in CXCL1 −/− mice. Sequencing of 16s rRNA genes indicated a significant alteration in the gut microbiome. Gut permeability and endotoxin concentration in the peripheral blood of CXCL1-/- mice decreased compared to those in WT mice after DSS treatment. Neutrophil infiltration was clearly increased in WT mice but was much lower in CXCL1-/- mice after DSS treatment. Fecal microbiota transplantation (FMT) using stools of CXCL1-/- mice suppressed DSS-induced colitis. FMT from patients with colitis enhanced CXCL1 and Ly6G expression levels in colon tissues of gut-sterilized mice. Analysis of clinical data indicates that patients with colitis had higher expression levels of CXCL1 and Ly6G. Moreover, CXCL1 and Ly6G expression levels were positively correlated with the colitis scores. These results demonstrate that CXCL1 promotes colitis by modulating the gut microbiota.

Note:
Funding declaration: This work is supported by grants from the Natural Science Foundation of Shanghai (20ZR1445000), and the Interdisciplinary Program of Shanghai Jiao Tong University (YG2019QNB36 ).

Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical Approval: approved by the Animal Research Committee at Shanghai General Hospital. Written informed consent was obtained from all patients and healthy donors. The study using human samples was approved by the Ethics Committee of Shanghai General Hospital.

Keywords: CXCL1, gut microbiota, colitis, neutrophil, inflammation