Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model
Background and Aims: Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier funct...
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Frontiers Media S.A.
2021-08-01
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| Շարք: | Frontiers in Medicine |
| Խորագրեր: | |
| Առցանց հասանելիություն: | https://www.frontiersin.org/articles/10.3389/fmed.2021.649818/full |
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| author | Chun-Yan Yeung Chun-Yan Yeung Chun-Yan Yeung Jen-Shiu Chiang Chiau Mei-Lein Cheng Wai-Tao Chan Wai-Tao Chan Wai-Tao Chan Chuen-Bin Jiang Chuen-Bin Jiang Chuen-Bin Jiang Szu-Wen Chang Szu-Wen Chang Szu-Wen Chang Chia-Yuan Liu Chia-Yuan Liu Chia-Yuan Liu Ching-Wei Chang Ching-Wei Chang Ching-Wei Chang Hung-Chang Lee Hung-Chang Lee Hung-Chang Lee |
| author_facet | Chun-Yan Yeung Chun-Yan Yeung Chun-Yan Yeung Jen-Shiu Chiang Chiau Mei-Lein Cheng Wai-Tao Chan Wai-Tao Chan Wai-Tao Chan Chuen-Bin Jiang Chuen-Bin Jiang Chuen-Bin Jiang Szu-Wen Chang Szu-Wen Chang Szu-Wen Chang Chia-Yuan Liu Chia-Yuan Liu Chia-Yuan Liu Ching-Wei Chang Ching-Wei Chang Ching-Wei Chang Hung-Chang Lee Hung-Chang Lee Hung-Chang Lee |
| author_sort | Chun-Yan Yeung |
| collection | DOAJ |
| description | Background and Aims: Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier function is primarily regulated by the tight-junction (TJ) proteins. In this study, we try to establish an animal model by raising mice fed VD-deficient diet and to investigate the effects of VD-deficient diet on gut integrity and zonulin expression.Methods: Male C57BL/6 mice were administered either VD-deficient [VDD group, 25(OH)2D3 0 IU/per mouse] or VD-sufficient [VDS group, 25(OH)2D3 37.8 IU/per mouse] special diets for 7 weeks. Body weight and diet intake were recorded weekly. Serum VD levels were detected. After sacrifice, jejunum and colon specimens were collected. The villus length and crypt depth of the jejunum as well as mucosa thickness of the colon were measured. Various serum pro-inflammatory cytokines and intestinal TJ proteins were assessed. The serum level of zonulin and the mRNA expression of jejunum zonulin were also investigated.Results: We found that mice fed a VDD diet had a lower serum level of VD after 7 weeks (p < 0.001). VDD mice gained significant less weight (p = 0.022) and took a similar amount of diet (p = 0.398) when compared to mice raised on a VDS diet. Significantly decreased colon mucosa thickness was found in VDD mice compared with the VDS group (p = 0.022). A marked increase in serum pro-inflammatory cytokine levels was demonstrated in VDD mice. All relative levels of claudin (CLD)-1 (p = 0.007), CLD-3 (p < 0.001), CLD-7 (p < 0.001), and zonulin-1 (ZO-1, p = 0.038) protein expressions were significantly decreased in the VDD group when compared to the VDS group. A significant upregulation of mRNA expression of jejunum zonulin (p = 0.043) and elevated serum zonulin (p = 0.001) were found in the VDD group.Conclusions: We successfully demonstrated that VDD could lead to impaired barrier properties. We assume that sufficient VD could maintain intestinal epithelial integrity and prevent mucosal barrier dysfunction. VD supplementation may serve as part of a therapeutic strategy for human autoimmune and infectious diseases with intestinal barrier dysfunction (leaky gut) in the future. To our knowledge, this is the first study to demonstrate that VDD could lead to a significant upregulation in mRNA expression of the jejunum zonulin level and also a marked elevation of serum zonulin in a mouse model. |
| first_indexed | 2024-12-13T19:27:18Z |
| format | Article |
| id | doaj.art-901b780c649d4a70a3ad787a2c4e1a65 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-13T19:27:18Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-901b780c649d4a70a3ad787a2c4e1a652022-12-21T23:34:00ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-08-01810.3389/fmed.2021.649818649818Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse ModelChun-Yan Yeung0Chun-Yan Yeung1Chun-Yan Yeung2Jen-Shiu Chiang Chiau3Mei-Lein Cheng4Wai-Tao Chan5Wai-Tao Chan6Wai-Tao Chan7Chuen-Bin Jiang8Chuen-Bin Jiang9Chuen-Bin Jiang10Szu-Wen Chang11Szu-Wen Chang12Szu-Wen Chang13Chia-Yuan Liu14Chia-Yuan Liu15Chia-Yuan Liu16Ching-Wei Chang17Ching-Wei Chang18Ching-Wei Chang19Hung-Chang Lee20Hung-Chang Lee21Hung-Chang Lee22Department of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children's Hospital, Taipei, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children's Hospital, Taipei, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City, TaiwanDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children's Hospital, Taipei, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City, TaiwanDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children's Hospital, Taipei, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City, TaiwanDepartment of Hepatology and Gastroenterology, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City, TaiwanDepartment of Hepatology and Gastroenterology, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children's Hospital, Taipei, TaiwanDepartment of Medical Research, MacKay Memorial Hospital, Taipei, TaiwanDepartment of Medicine, MacKay Medical College, New Taipei City, TaiwanBackground and Aims: Vitamin D (VD) plays an important role not only in mineral balance and skeletal maintenance but also in immune modulation. VD status was found correlated with the pathophysiology and severity of inflammatory bowel diseases and other autoimmune disorders. Epithelial barrier function is primarily regulated by the tight-junction (TJ) proteins. In this study, we try to establish an animal model by raising mice fed VD-deficient diet and to investigate the effects of VD-deficient diet on gut integrity and zonulin expression.Methods: Male C57BL/6 mice were administered either VD-deficient [VDD group, 25(OH)2D3 0 IU/per mouse] or VD-sufficient [VDS group, 25(OH)2D3 37.8 IU/per mouse] special diets for 7 weeks. Body weight and diet intake were recorded weekly. Serum VD levels were detected. After sacrifice, jejunum and colon specimens were collected. The villus length and crypt depth of the jejunum as well as mucosa thickness of the colon were measured. Various serum pro-inflammatory cytokines and intestinal TJ proteins were assessed. The serum level of zonulin and the mRNA expression of jejunum zonulin were also investigated.Results: We found that mice fed a VDD diet had a lower serum level of VD after 7 weeks (p < 0.001). VDD mice gained significant less weight (p = 0.022) and took a similar amount of diet (p = 0.398) when compared to mice raised on a VDS diet. Significantly decreased colon mucosa thickness was found in VDD mice compared with the VDS group (p = 0.022). A marked increase in serum pro-inflammatory cytokine levels was demonstrated in VDD mice. All relative levels of claudin (CLD)-1 (p = 0.007), CLD-3 (p < 0.001), CLD-7 (p < 0.001), and zonulin-1 (ZO-1, p = 0.038) protein expressions were significantly decreased in the VDD group when compared to the VDS group. A significant upregulation of mRNA expression of jejunum zonulin (p = 0.043) and elevated serum zonulin (p = 0.001) were found in the VDD group.Conclusions: We successfully demonstrated that VDD could lead to impaired barrier properties. We assume that sufficient VD could maintain intestinal epithelial integrity and prevent mucosal barrier dysfunction. VD supplementation may serve as part of a therapeutic strategy for human autoimmune and infectious diseases with intestinal barrier dysfunction (leaky gut) in the future. To our knowledge, this is the first study to demonstrate that VDD could lead to a significant upregulation in mRNA expression of the jejunum zonulin level and also a marked elevation of serum zonulin in a mouse model.https://www.frontiersin.org/articles/10.3389/fmed.2021.649818/fullvitamin Dgut integritytight junctionzonulinleaky gut |
| spellingShingle | Chun-Yan Yeung Chun-Yan Yeung Chun-Yan Yeung Jen-Shiu Chiang Chiau Mei-Lein Cheng Wai-Tao Chan Wai-Tao Chan Wai-Tao Chan Chuen-Bin Jiang Chuen-Bin Jiang Chuen-Bin Jiang Szu-Wen Chang Szu-Wen Chang Szu-Wen Chang Chia-Yuan Liu Chia-Yuan Liu Chia-Yuan Liu Ching-Wei Chang Ching-Wei Chang Ching-Wei Chang Hung-Chang Lee Hung-Chang Lee Hung-Chang Lee Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model Frontiers in Medicine vitamin D gut integrity tight junction zonulin leaky gut |
| title | Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model |
| title_full | Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model |
| title_fullStr | Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model |
| title_full_unstemmed | Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model |
| title_short | Effects of Vitamin D-Deficient Diet on Intestinal Epithelial Integrity and Zonulin Expression in a C57BL/6 Mouse Model |
| title_sort | effects of vitamin d deficient diet on intestinal epithelial integrity and zonulin expression in a c57bl 6 mouse model |
| topic | vitamin D gut integrity tight junction zonulin leaky gut |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.649818/full |
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