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Updated: Aug 20, 2025
A Mouse Model of Intestinal Partial Obstruction
Published on: March 5, 2018
Reprogrammed fecal and mucosa-associated intestinal microbiota and weakened mucus layer in intestinal goblet cell-
Ying Liu1, Feifei Fang1, Yilin Xiong1
1Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Abstract:
Dysfunction of the mucus layer allows commensal and pathogenic microorganisms to reach the intestinal epithelium, thereby leading to infection and inflammation. This barrier is synthesized and secreted by host goblet cells. Many factors that influence the function of goblet cells (GCs) have been studied. However, how the microenvironment surrounding GCs influences the mucus layer and microbiota of the colon is unclear. To explore the effect of GC Piezo1 on the mucus layer and microbiota in the colon, we generated an intestinal epithelial Piezo1 conditional knockout mouse model. The fecal-associated microbiota (FAM) and mucosa-associated microbiota (MAM) of the two groups were characterized based on amplicon sequencing of the 16S rRNA gene. Our results showed that GC Piezo1-/- mice developed decreased GC numbers, thinner mucus layer, and increased inflammatory cytokines (e.g., CXCL1, CXCL2, IL-6) on the 7th day. In addition, decreased Spdef and increased DOCK4 were discovered in KO mice. Meanwhile, the diversity and richness were increased in MAM and decreased in FAM in the GC Piezo1-/- group compared with the GC Piezo1+/+ group. We also observed increased abundances of Firmicutes and decreased abundances of Verrucomicrobiota and Actinobacteriota in the MAM of the GC Piezo1-/- group. Additionally, BugBase predicts that potentially pathogenic bacteria may have increased in the inner mucus layer, which is consistent with the higher abundance of Helicobacter hepaticus, Lactobacillus johnsonii, Escherichia-Shigella and Oscillospiraceae in MAM. These results further support the hypothesis that the role of Piezo1 in GCs is important for maintaining the function of the mucus layer and intestinal microbiota balance in the mouse colon.
Insights
Goblet cell Piezo1 is crucial for maintaining the colon's mucus layer and gut microbiota balance. Its absence in mice led to a thinner mucus layer and altered microbial communities, suggesting a role in intestinal health.
Area of Science:
- Gastroenterology and Microbiology
- Cell Biology and Mechanosensation
Background:
- The intestinal mucus layer, secreted by goblet cells (GCs), is a critical barrier against microbial invasion.
- Factors influencing GC function and their impact on the colonic microenvironment, mucus layer, and microbiota remain incompletely understood.
Purpose of the Study:
- To investigate the role of Piezo1, a mechanosensitive ion channel, in colonic GCs regarding mucus layer integrity and gut microbiota composition.
- To elucidate how GC-specific Piezo1 deletion affects the colonic microenvironment and associated microbial communities.
Main Methods:
- Generation of an intestinal epithelial-specific Piezo1 conditional knockout (KO) mouse model (GC Piezo1-/-).
- Characterization of fecal-associated microbiota (FAM) and mucosa-associated microbiota (MAM) using 16S rRNA gene amplicon sequencing.
- Analysis of GC numbers, mucus layer thickness, and inflammatory cytokine expression.
Main Results:
- GC Piezo1-/- mice exhibited reduced GC numbers, a thinner mucus layer, and elevated inflammatory cytokines (CXCL1, CXCL2, IL-6).
- Significant alterations in gut microbiota were observed: increased diversity/richness in MAM, decreased diversity/richness in FAM.
- Changes in bacterial phyla abundance in MAM (increased Firmicutes, decreased Verrucomicrobiota and Actinobacteriota) and predicted increase in potentially pathogenic bacteria.
Conclusions:
- Piezo1 in colonic goblet cells plays a vital role in maintaining mucus layer function and intestinal microbiota homeostasis.
- GC Piezo1 deficiency disrupts the colonic barrier, leading to dysbiosis and potentially promoting a pro-inflammatory environment.
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