The inflammasome maintains intestinal homeostasis via regulation of intestinal glucose transport 4532
Year: 2025
Type: article
Abstract: Description The inflammasome has been shown to protect mice from colitis; however, the precise mechanism is poorly understood. Here we investigated how inflammasome regulates intestinal microbial ecology and whether such a regulation impacts on colitis pathology. While Casp1-/- mice are susceptible to DSS-induced colitis compared to wild-type (WT) mice, co-housed Casp1-/- and WT mice showed similar colitis pathogenesis, underscoring the influence of gut microbiota composition. 16S rRNA analysis of gut microbiota showed distinct microbiota composition of Casp1-/- mice with a higher abundance of Proteobacteria and Bacteroidetes. We and others previously showed that a high-sugar diet promotes the growth of these gut commensal bacteria. As such, we observed higher concentrations of glucose in the intestine of Casp1-/- mice, suggesting that Caspase-1/inflammasome regulates intestinal glucose transport. Consistently, there was reduced expression of glucose transporters, particularly Sglt1 and Glut2, in the intestine of Casp1-/- compared to WT mice. Studies with in vitro cell culture systems showed that IL1b and IL18 induce Sglt1 and Gluts in intestinal epithelial cells. Overall, these findings shed light on a novel mechanism of inflammasome-mediated regulation of intestinal homeostasis involving glucose transporters. Funding Sources Supported by NIH/NIDDK R01 DK125352-01 Topic Categories Mucosal and Regional Immunology (MUC)
Source: The Journal of Immunology
Authors: Hasan Zaki, Kawsar Mustafa
Institution: The University of Texas Southwestern Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4416449740
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