Dataset Information

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

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.

SUBMITTER: Lan J

PROVIDER: S-EPMC11321658 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Lan Jiaoli J Zhang Yuxin Y Jin Cuiyuan C Chen Huan H Su Zexiong Z Wu Jiaxing J Ma Ni N Zhang Xiaoyan X Lu Yiyun Y Chen Yongxin Y Zeng Xiaolu X Zhang Huiqiong H Zheng Guilang G Sun Yueyu Y Wang Chun C Hu Yan Y Wang Yifei Y Liu Yumei Y Zeng Zhaoyang Z Shi Liyun L He Jun J Cao Aihua A Wang Yichao Y Pan Xu X Jin Gulei G Wang Ying Y Jiang Xun X Shen Huiqing H Tang Qing Q Xie Xiaoli X Xiao Yuan Y Zhong Xuemei X Zhang Xuchao X Zeng Liang L Ye Liping L Xie Jing J Geng Lanlan L Li Zhiling Z Wu Xiaohui X Wang Ying Y Mao Ren R Zhang Shaojun S Huang Siyuan S Liu Suling S Zeng Hanshi H Xu Wanfu W Gong Sitang S Guo Yuxiong Y Yang Min M

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20240618 30

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 mucosa ...[more]

PMID: 38889269

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Project description:Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that fall into two main categories: Crohn's disease (CD) and ulcerative colitis (UC). The gastrointestinal tract extends from the mouth to the anus and harbors diverse bacterial communities. Several sequencing-based studies have identified an intestinal enrichment of oral-associated bacteria and demonstrated their ability to induce intestinal inflammation in mice, suggesting that intestinal pathobionts originate from the oral cavity, particularly members of the genus Streptococcus. This study aimed to investigate the composition of the salivary and fecal microbiome of IBD patients (n = 14) compared to healthy controls (n = 12) and to determine the abundance of common bacterial taxa in both niches. Metagenomic DNA was extracted from saliva and fecal samples, and the 16S rRNA gene was targeted for sequencing. Our results revealed that the overall microbial composition of saliva was significantly altered in the IBD patients compared to the control subjects (p = 0.038). At the genus level, Veillonella and Prevotella were highly abundant in IBD (median: 25.4% and 22.2%, respectively) compared to the control group (17.9% and 13.4%, respectively). In contrast, Neisseria, Streptococcus, Haemophilus, and Fusobacterium were associated with a healthy gut state. Regarding the fecal microbiome, the IBD group had a significantly higher abundance of Clostridium sensu stricto 1 and Escherichia-Shigella (both comprising pathogenic bacteria) compared with the control group. Members of both bacterial groups have previously been shown to positively correlate with intestinal inflammation and high expression of pro-inflammatory cytokines that disrupt intestinal barrier integrity. In addition, we demonstrate that the increased abundance of Clostridium sensu stricto 1 and Escherichia-Shigella has also been associated with significant upregulation of certain metabolic pathways in the feces of the IBD group, including bacterial invasion of epithelial cells. Streptococcus was the only common genus detected in both the salivary and fecal microbiome and represented the oral-gut axis in our study. Using culture-based methods, we isolated 57 and 91 Streptococcus strains from saliva as well as 40 and 31 strains from fecal samples of the controls and IBD patients, respectively. The phylogenetic tree of streptococci based on sodA sequences revealed several patient-specific clusters comprising salivary and fecal streptococcal isolates from the same patient and belonging to the same species, suggesting that the oral cavity is an endogenous reservoir for intestinal strains.

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Dataset Information

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Publications

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

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