{Reference Type}: Journal Article
{Title}: Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.
{Author}: Lan J;Zhang Y;Jin C;Chen H;Su Z;Wu J;Ma N;Zhang X;Lu Y;Chen Y;Zeng X;Zhang H;Zheng G;Sun Y;Wang C;Hu Y;Wang Y;Liu Y;Zeng Z;Shi L;He J;Cao A;Wang Y;Pan X;Jin G;Wang Y;Jiang X;Shen H;Tang Q;Xie X;Xiao Y;Zhong X;Zhang X;Zeng L;Ye L;Xie J;Geng L;Li Z;Wu X;Wang Y;Mao R;Zhang S;Huang S;Liu S;Zeng H;Xu W;Gong S;Guo Y;Yang M;
{Journal}: Adv Sci (Weinh)
{Volume}: 11
{Issue}: 30
{Year}: 2024 Aug 18
{Factor}: 17.521
{DOI}: 10.1002/advs.202309471
{Abstract}: Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.