P102 Neuron-specific gene-2 aggravates colitis and colon tumorigenesis by controlling microbial composition

Abstract

Abstract Background Previous studies have shown that Neuron Specific Gene-2 (NSG-2) plays a role in exacerbating murine colitis and colitis-associated tumorigenesis. This study aimed to elucidate the role of Nsg-2 in the pathogenesis of intestinal inflammation by controlling microbial composition. Methods The effect of NSG-2 in acute murine colitis was evaluated using both wild-type (WT) and Nsg-2 knock-out (KO) mice. The effect of NSG-2 on colitis-associated tumorigenesis was evaluated using an azoxymethane (AOM) and 3% dextran sodium sulfate (DSS)-induced murine model. The co-housing method was used to assess the role of microbiome in colitis and colitis-associated tumorigenesis. Microbial composition was analyzed using 16S rRNA between the two groups before and after co-housing. Results DSS-treated WT mice showed severe colitis compared to DSS-treated Nsg-2 -/- mice. In addition, WT mice exposed to AOM/DSS exhibited higher tumor burdens than Nsg-2-/- mice. After co-housing using WT and Nsg-2 -/- mice, the severity of colitis and colitis-associated tumorigenesis was not different between the two groups, suggesting that microbiome may play a key role in Nsg-2-related aggravation of colitis and tumorigenesis. The microbial taxonomy differed between the two groups in 16S rRNA analysis of stools collected before and after co-housing. Before co-housing, Nsg-2-/- mice showed higher α-diversity than WT mice. Significant differences exist in the Sangeribacter Muris and Lactobacillus Taiwanensis proportion between the two groups. PCoA of beta diversity showed that the microbiome profiles between the two groups were separated before co-housing. However, after co-housing, the difference between the two groups significantly decreased. Conclusion Nsg-2 intensifies colitis resulting in colon tumorigenesis through microbial interaction, which suggests that Nsg-2 may have the potential as a therapeutic target for intestinal inflammation.