Upregulation of antimicrobial peptide expression in slc26a3-/- mice with colonic dysbiosis and barrier defect
Genetic defects in SLC26A3 (DRA), an intestinal Cl−/HCO3− exchanger, result in congenital chloride diarrhea (CLD), marked by lifelong acidic diarrhea and a high risk of inflammatory bowel disease. Slc26a3−/− mice serve as a model to understand the pathophysiology of CLD and search for treatment opti...
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| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2041943 |
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| author | Archana Kini Bei Zhao Marijana Basic Urmi Roy Aida Iljazovic Ivan Odak Zhenghao Ye Brigitte Riederer Gabriella Di Stefano Dorothee Römermann Christian Koenecke André Bleich Till Strowig Ursula Seidler |
| author_facet | Archana Kini Bei Zhao Marijana Basic Urmi Roy Aida Iljazovic Ivan Odak Zhenghao Ye Brigitte Riederer Gabriella Di Stefano Dorothee Römermann Christian Koenecke André Bleich Till Strowig Ursula Seidler |
| author_sort | Archana Kini |
| collection | DOAJ |
| description | Genetic defects in SLC26A3 (DRA), an intestinal Cl−/HCO3− exchanger, result in congenital chloride diarrhea (CLD), marked by lifelong acidic diarrhea and a high risk of inflammatory bowel disease. Slc26a3−/− mice serve as a model to understand the pathophysiology of CLD and search for treatment options. This study investigates the microbiota changes in slc26a3−/− colon, the genotype-related causes for the observed microbiota alterations, its inflammatory potential, as well as the corresponding host responses. The luminal and the mucosa-adherent cecal and colonic microbiota of cohoused slc26a3−/− and wt littermates were analyzed by 16S rRNA gene sequencing. Fecal microbiota transfer from cohoused slc26a3−/− and wt littermates to germ-free wt mice was performed to analyze the stability and the inflammatory potential of the communities.The cecal and colonic luminal and mucosa-adherent microbiota of slc26a3−/− mice was abnormal from an early age, with a loss of diversity, of short-chain fatty acid producers, and an increase of pathobionts. The transfer of slc26a3−/− microbiota did not result in intestinal inflammation and the microbial diversity in the recipient mice normalized over time. A strong increase in the expression of Il22, Reg3β/γ, Relmβ, and other proteins with antimicrobial functions was observed in slc26a3−/− colon from juvenile age, while the mucosal and systemic inflammatory signature was surprisingly mild. The dysbiotic microbiota, low mucosal pH, and mucus barrier defect in slc26a3−/− colon are accompanied by a stark upregulation of the expression of a panel of antimicrobial proteins. This may explain the low inflammatory burden in the gut of these mice. |
| format | Article |
| id | doaj-art-1c64cba46b194950be690c85e4c2c089 |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-1c64cba46b194950be690c85e4c2c0892025-08-20T02:29:56ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2041943Upregulation of antimicrobial peptide expression in slc26a3-/- mice with colonic dysbiosis and barrier defectArchana Kini0Bei Zhao1Marijana Basic2Urmi Roy3Aida Iljazovic4Ivan Odak5Zhenghao Ye6Brigitte Riederer7Gabriella Di Stefano8Dorothee Römermann9Christian Koenecke10André Bleich11Till Strowig12Ursula Seidler13Department of GastroenterologyMicrobial Immune Regulation Research Group, Helmholtz Center for Infection Research, Braunschweig, GermanyInstitute of Laboratory Animal ScienceMicrobial Immune Regulation Research Group, Helmholtz Center for Infection Research, Braunschweig, GermanyMicrobial Immune Regulation Research Group, Helmholtz Center for Infection Research, Braunschweig, GermanyInstitute of Immunology Hannover Medical School Hannover, GermanyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyInstitute of Immunology Hannover Medical School Hannover, GermanyInstitute of Laboratory Animal ScienceMicrobial Immune Regulation Research Group, Helmholtz Center for Infection Research, Braunschweig, GermanyDepartment of GastroenterologyGenetic defects in SLC26A3 (DRA), an intestinal Cl−/HCO3− exchanger, result in congenital chloride diarrhea (CLD), marked by lifelong acidic diarrhea and a high risk of inflammatory bowel disease. Slc26a3−/− mice serve as a model to understand the pathophysiology of CLD and search for treatment options. This study investigates the microbiota changes in slc26a3−/− colon, the genotype-related causes for the observed microbiota alterations, its inflammatory potential, as well as the corresponding host responses. The luminal and the mucosa-adherent cecal and colonic microbiota of cohoused slc26a3−/− and wt littermates were analyzed by 16S rRNA gene sequencing. Fecal microbiota transfer from cohoused slc26a3−/− and wt littermates to germ-free wt mice was performed to analyze the stability and the inflammatory potential of the communities.The cecal and colonic luminal and mucosa-adherent microbiota of slc26a3−/− mice was abnormal from an early age, with a loss of diversity, of short-chain fatty acid producers, and an increase of pathobionts. The transfer of slc26a3−/− microbiota did not result in intestinal inflammation and the microbial diversity in the recipient mice normalized over time. A strong increase in the expression of Il22, Reg3β/γ, Relmβ, and other proteins with antimicrobial functions was observed in slc26a3−/− colon from juvenile age, while the mucosal and systemic inflammatory signature was surprisingly mild. The dysbiotic microbiota, low mucosal pH, and mucus barrier defect in slc26a3−/− colon are accompanied by a stark upregulation of the expression of a panel of antimicrobial proteins. This may explain the low inflammatory burden in the gut of these mice.https://www.tandfonline.com/doi/10.1080/19490976.2022.2041943Anion exchangeintestinal electrolyte transportinflammatory bowel diseasegut dysbiosisantimicrobial peptides |
| spellingShingle | Archana Kini Bei Zhao Marijana Basic Urmi Roy Aida Iljazovic Ivan Odak Zhenghao Ye Brigitte Riederer Gabriella Di Stefano Dorothee Römermann Christian Koenecke André Bleich Till Strowig Ursula Seidler Upregulation of antimicrobial peptide expression in slc26a3-/- mice with colonic dysbiosis and barrier defect Gut Microbes Anion exchange intestinal electrolyte transport inflammatory bowel disease gut dysbiosis antimicrobial peptides |
| title | Upregulation of antimicrobial peptide expression in slc26a3-/- mice with colonic dysbiosis and barrier defect |
| title_full | Upregulation of antimicrobial peptide expression in slc26a3-/- mice with colonic dysbiosis and barrier defect |
| title_fullStr | Upregulation of antimicrobial peptide expression in slc26a3-/- mice with colonic dysbiosis and barrier defect |
| title_full_unstemmed | Upregulation of antimicrobial peptide expression in slc26a3-/- mice with colonic dysbiosis and barrier defect |
| title_short | Upregulation of antimicrobial peptide expression in slc26a3-/- mice with colonic dysbiosis and barrier defect |
| title_sort | upregulation of antimicrobial peptide expression in slc26a3 mice with colonic dysbiosis and barrier defect |
| topic | Anion exchange intestinal electrolyte transport inflammatory bowel disease gut dysbiosis antimicrobial peptides |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2041943 |
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