P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis
Abstract Background Inflammatory bowel disease (IBD) is a non‐specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulce...
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.1227 |
| _version_ | 1797838626220933120 |
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| author | Peijie Zhong Hang Wu Yuanqiao Ma Xiaoxiao Xu Yizhuo Jiang Chaolei Jin Qiaozhen Zhu Xinlei Liu Zhimin Suo Junpeng Wang |
| author_facet | Peijie Zhong Hang Wu Yuanqiao Ma Xiaoxiao Xu Yizhuo Jiang Chaolei Jin Qiaozhen Zhu Xinlei Liu Zhimin Suo Junpeng Wang |
| author_sort | Peijie Zhong |
| collection | DOAJ |
| description | Abstract Background Inflammatory bowel disease (IBD) is a non‐specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulcerative colitis (UC), the two primary types of IBD. The P2X4 receptor has been demonstrated to have a crucial role in preventing infection, inflammation, and organ damage. However, it remains unclear whether the P2X4 receptor affects IBD and the underlying mechanisms. Methods Colitis was induced in mice administrated with dextran sodium sulphate (DSS). 16S rDNA sequencing was used to analyze the gut microbiota in knockout and wild‐type mice. Clinical and histopathological parameters were monitored throughout the disease progression. Results Gene Expression Omnibus analysis showed the downregulation of P2RX4 (P2rx4) expression in colonic tissues from patients or mice with IBD. However, its expression at the protein levels was upregulated on day 4 or 6 and then downregulated on day 7 in C57BL/6 mice treated with DSS. Gene ablation of P2rx4 aggravated DSS‐induced colitis accompanying gut microbiota dysbiosis in mice. Moreover, P2X4 receptor‐positive modulator ivermectin alleviated colitis and corrected dysregulated microbiota in wild‐type C57BL/6 mice. Further antibiotic‐treated gut microbiota depletion, cohousing experiment, and fecal microbiota transplantation proved that gut microbiota dysbiosis was associated with the aggravation of colitis in the mouse model initiated by P2rx4. Conclusions Our findings elaborate on an unrevealed etiopathophysiological mechanism by which microbiota dysbiosis induced by the P2X4 receptor influences the development of colitis, indicating that the P2X4 receptor represents a promising target for treating patients with CD and UC. |
| first_indexed | 2024-04-09T15:43:55Z |
| format | Article |
| id | doaj.art-2a2a8d3751d84fa895784138a28e9fcf |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-04-09T15:43:55Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-2a2a8d3751d84fa895784138a28e9fcf2023-04-27T05:12:30ZengWileyClinical and Translational Medicine2001-13262023-04-01134n/an/a10.1002/ctm2.1227P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitisPeijie Zhong0Hang Wu1Yuanqiao Ma2Xiaoxiao Xu3Yizhuo Jiang4Chaolei Jin5Qiaozhen Zhu6Xinlei Liu7Zhimin Suo8Junpeng Wang9Infection and Immunity Institute and Translational Medical Center, Huaihe HospitalHenan UniversityKaifengChinaInfection and Immunity Institute and Translational Medical Center, Huaihe HospitalHenan UniversityKaifengChinaInfection and Immunity Institute and Translational Medical Center, Huaihe HospitalHenan UniversityKaifengChinaInfection and Immunity Institute and Translational Medical Center, Huaihe HospitalHenan UniversityKaifengChinaInfection and Immunity Institute and Translational Medical Center, Huaihe HospitalHenan UniversityKaifengChinaInfection and Immunity Institute and Translational Medical Center, Huaihe HospitalHenan UniversityKaifengChinaInfection and Immunity Institute and Translational Medical Center, Huaihe HospitalHenan UniversityKaifengChinaInfection and Immunity Institute and Translational Medical Center, Huaihe HospitalHenan UniversityKaifengChinaInfection and Immunity Institute and Translational Medical Center, Huaihe HospitalHenan UniversityKaifengChinaInfection and Immunity Institute and Translational Medical Center, Huaihe HospitalHenan UniversityKaifengChinaAbstract Background Inflammatory bowel disease (IBD) is a non‐specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulcerative colitis (UC), the two primary types of IBD. The P2X4 receptor has been demonstrated to have a crucial role in preventing infection, inflammation, and organ damage. However, it remains unclear whether the P2X4 receptor affects IBD and the underlying mechanisms. Methods Colitis was induced in mice administrated with dextran sodium sulphate (DSS). 16S rDNA sequencing was used to analyze the gut microbiota in knockout and wild‐type mice. Clinical and histopathological parameters were monitored throughout the disease progression. Results Gene Expression Omnibus analysis showed the downregulation of P2RX4 (P2rx4) expression in colonic tissues from patients or mice with IBD. However, its expression at the protein levels was upregulated on day 4 or 6 and then downregulated on day 7 in C57BL/6 mice treated with DSS. Gene ablation of P2rx4 aggravated DSS‐induced colitis accompanying gut microbiota dysbiosis in mice. Moreover, P2X4 receptor‐positive modulator ivermectin alleviated colitis and corrected dysregulated microbiota in wild‐type C57BL/6 mice. Further antibiotic‐treated gut microbiota depletion, cohousing experiment, and fecal microbiota transplantation proved that gut microbiota dysbiosis was associated with the aggravation of colitis in the mouse model initiated by P2rx4. Conclusions Our findings elaborate on an unrevealed etiopathophysiological mechanism by which microbiota dysbiosis induced by the P2X4 receptor influences the development of colitis, indicating that the P2X4 receptor represents a promising target for treating patients with CD and UC.https://doi.org/10.1002/ctm2.1227gut microbiotagut permeabilityinflammatory bowel diseasesP2X4 receptor |
| spellingShingle | Peijie Zhong Hang Wu Yuanqiao Ma Xiaoxiao Xu Yizhuo Jiang Chaolei Jin Qiaozhen Zhu Xinlei Liu Zhimin Suo Junpeng Wang P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis Clinical and Translational Medicine gut microbiota gut permeability inflammatory bowel diseases P2X4 receptor |
| title | P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis |
| title_full | P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis |
| title_fullStr | P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis |
| title_full_unstemmed | P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis |
| title_short | P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis |
| title_sort | p2x4 receptor modulates gut inflammation and favours microbial homeostasis in colitis |
| topic | gut microbiota gut permeability inflammatory bowel diseases P2X4 receptor |
| url | https://doi.org/10.1002/ctm2.1227 |
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