Tingting Zhao, Zhiyue Wen, Li Cui

Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China

Correspondence: Li Cui, Shanghai Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, People’s Republic of China, Tel +86- 13918901989, Email lcui@sjtu.edu.cn

Introduction: Ulcerative colitis (UC) is a chronic disease that requires pharmacological therapy to achieve remission. This study aimed to evaluate the effect of glucosamine selenium (GASe) on chronic colitis and reveal the underlying regulatory mechanisms.
Methods: We evaluated the cumulative toxicity of GASe by gavage in mice for 40 days. Dextran sulfate sodium (DSS; 2.5%) was added to drinking water to induce chronic colitis, and GASe was administered to mice with chronic DSS colitis. 16S rRNA sequencing was performed to investigate the influence of GASe on gut microbiota, followed by diversity and LDA Effect Size (LEfSe) analyses. Differentially expressed genes (DEGs) associated with chronic DSS colitis were identified based on the expression profiling from the Gene Expression Omnibus (GEO) database and were subjected to functional enrichment analysis. Next, the effects of GASe on pyroptosis and chemokine signaling pathways were studied in vitro and in vivo.
Results: GASe had no significant toxicity in mice, and administration of low-GASe and high-GASe increased the length of the colon, inhibited the expression of IL-12, IL-6, and TNF-α, and improved colonic tissue structure. Low-GASe improved the diversity of the gut microbiota and mainly affected the Burkholderiaceae family, Paenalcaligenes genus, and Erysipelatoclostridium genus. Low-GASe and high-GASe suppressed the pyroptosis-related proteins NLRP3, GSDMD, and caspase-1. Furthermore, we identified 114 DEGs from the GSE87466 and GSE53306 datasets and these DEGs were mainly enriched in the chemokine signaling pathway and some inflammatory pathways. Further experiments showed that administration of GASe inhibited the chemokine signaling pathway in chronic DSS colitis mice and NCM460 cells.
Discussion: This study reveals abnormalities in the gut microbiota, pyroptosis, and chemokine signaling pathways involved in chronic colitis and may provide GASe as an alternative supplement for chronic colitis management.

Keywords: ulcerative colitis, glucosamine, selenium, 16S rRNA sequencing, differential expressed genes, chemokine