Tas2r105 ameliorates gut inflammation, possibly through influencing the gut microbiota and metabolites.

IF 5 2区 生物学 Q1 MICROBIOLOGY mSystems Pub Date : 2025-03-13 DOI:10.1128/msystems.01556-24
Xiucai Lan, Liang Ma, Jiaming Ma, Zhipeng Huang, Lingling Liu, Feng Li, Mingbang Wang, Yaomin Hu
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引用次数: 0

Abstract

Inflammatory bowel disease (IBD) is an immune-mediated gastrointestinal disorder that significantly impacts the life quality of people worldwide. Genetic factors play crucial roles in the development of IBD. Tas2rs, members of the G protein-coupled receptor (GPCR) superfamily, are known for their roles in bitter taste perception. However, Tas2rs have also been identified in the gut, where they help sense luminal contents and regulate gastrointestinal hormones. Periodontal Tas2r105 has been shown to modulate innate immunity by interacting with metabolites produced by oral bacteria. In this study, we observed increased Tas2r105 in the inflammatory colons induced by dextran sulfate sodium salt (DSS). We also noted that α-gustducin, the α-subunit of GPCRs, is present in the intestine, and that α-gustducin knockout mice exhibit aggravated colitis. Based on these findings, we hypothesize that Tas2r105 may play a role in immune regulation during IBD pathogenesis. To test this hypothesis, we used Tas2r105 knockout (KO) mice in a colitis model. Our results show that the KO mice had significantly shorter colon length, more severe colon inflammation, and greater destruction of the gut barrier compared with control mice. We also observed increased recruitment of macrophages to the lamina propria mucosa in the KO mice. Microbiological analysis revealed a significant increase in Proteobacteria and Bacteroidota, with a concomitant decrease in Firmicutes after Tas2r105 knockout. Metabolomic analysis showed a significant reduction in lysophosphatidylethanolamine (LPE) levels in the KO mice, which is known to have anti-inflammatory effects. Based on these findings, we speculate that Tas2r105 may help protect the intestine from inflammation by influencing the gut microbiota composition and LPE production.IMPORTANCEIncreased Tas2r105 was detected in the inflamed colon of mice outside the tongue. Tas2r105 deletion aggravated mice colon colitis. Tas2r105 might alleviate mice colitis by downregulating the Proteobacteria and the Bacteroidota abundance in the colon. Lysophosphatidylethanolamine (LPE) might be the key metabolite that mediated the intestinal protection of Tas2r105.

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来源期刊
mSystems
mSystems Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
10.50
自引率
3.10%
发文量
308
审稿时长
13 weeks
期刊介绍: mSystems™ will publish preeminent work that stems from applying technologies for high-throughput analyses to achieve insights into the metabolic and regulatory systems at the scale of both the single cell and microbial communities. The scope of mSystems™ encompasses all important biological and biochemical findings drawn from analyses of large data sets, as well as new computational approaches for deriving these insights. mSystems™ will welcome submissions from researchers who focus on the microbiome, genomics, metagenomics, transcriptomics, metabolomics, proteomics, glycomics, bioinformatics, and computational microbiology. mSystems™ will provide streamlined decisions, while carrying on ASM''s tradition of rigorous peer review.
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