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Ahmadi A, Shokoohizadeh L, Sheikhesmaili F, Nikkhoo B, Mohammadi A, Mirzaei MK, Alikhani MY, Yousefimashouf R. The role of vitamin D in treated and refractory ulcerative colitis patients: a case-control study. BMC Gastroenterol 2024; 24:454. [PMID: 39695960 DOI: 10.1186/s12876-024-03558-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 12/10/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Ulcerative colitis is a form of chronic inflammatory bowel disease (IBD) marked by ongoing inflammation of the mucosal lining that extends from the rectum to the upper part of the colon. Vitamin D regulates immune responses in several autoimmune and inflammatory diseases, including ulcerative colitis. Therefore, the study aims to investigate the role of vitamin D in the pathogenesis and treatment of ulcerative colitis. METHODS This case-control study included 94 participants who were divided into four groups. Group 1: people with ulcerative colitis who responded to treatment (n = 24). Group 2: family members of patients who responded to treatment and did not have the disease (n = 24). Group 3: People with ulcerative colitis who are resistant to treatment (n = 23). Group 4: family members of treatment-resistant patients who does not have the disease (n = 23). Groups 1 and 3 were considered as patient groups (n = 47) and groups 2 and 4 as control groups (n = 47). Blood samples were taken and analyzed for complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum vitamin D levels. RESULTS The mean age of treatment-responsive patients (group 1) was 45.88 ± 18.51 years, while treatment-resistant patients (group 3) averaged 41.30 ± 13.01 (P = 0.33) years. Serum Vitamin D levels were 24.96 ± 9.66 ng/mL in group 1 and 27.70 ± 12.28 ng/mL in group 3, showing no significant correlation with ulcerative colitis (P = 0.41). All groups had a BMI within the normal range, and mean CRP levels varied significantly across groups. Hemoglobin was significantly lower in group 3 compared to group 1 (P = 0.029), but ESR results showed no significant relationship with ulcerative colitis. Vitamin D levels were highest in patients with lower BMI, and no significant relationships were found between Vitamin D and other risk factors, although extensive colitis was associated with higher Vitamin D levels compared to distal colitis. CONCLUSION In this study, there was no significant association between ulcerative colitis and serum levels of vitamin D. However, the small number of patients may limit the conclusions that can be drawn regarding the role of vitamin D in the treatment of ulcerative colitis. Future studies should aim for larger cohorts to provide more definitive insights into this important issue.
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Affiliation(s)
- Amjad Ahmadi
- Infectious Disease Research Center, Avicenna Institute of Clinical Sciences, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Leili Shokoohizadeh
- Infectious Disease Research Center, Avicenna Institute of Clinical Sciences, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Farshad Sheikhesmaili
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Bahram Nikkhoo
- Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Asadollah Mohammadi
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mohammadali Khan Mirzaei
- Institute of Virology, Helmholtz Munich, German Research Centre for Environmental Health, Neuherberg, Germany
- Chair of Prevention of Microbial Infectious Diseases, Central Institute of Disease Prevention, School of Life Sciences, Technical University of Munich, Freising, Germany
| | - Mohammad Yousef Alikhani
- Infectious Disease Research Center, Avicenna Institute of Clinical Sciences, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran.
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
| | - Rasoul Yousefimashouf
- Department of Microbiology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
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Kang J, Wu X, Li Y, Zhao S, Wang S, Yu D. Association between inflammatory bowel disease and osteoporosis in European and East Asian populations: exploring causality, mediation by nutritional status, and shared genetic architecture. Front Immunol 2024; 15:1425610. [PMID: 39136019 PMCID: PMC11317921 DOI: 10.3389/fimmu.2024.1425610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 06/24/2024] [Indexed: 08/15/2024] Open
Abstract
Background While previous research has established an association between inflammatory bowel disease (IBD) and osteoporosis (OP), the nature of this association in different populations remains unclear. Objective Our study used linkage disequilibrium scores(LDSC) regression analysis and Mendelian randomization(MR) to assess the genetic correlation and causal relationship between IBD and OP in European and East Asian populations. Methods We performed separate genetic correlation and causal analyses for IBD and OP in European and East Asian populations, used the product of coefficients method to estimate the mediating effect of nutritional status on the causal relationship, and used multi-trait analysis to explore the biological mechanisms underlying the IBD-nutrition-OP causal pathway. Results Our analysis revealed a significant genetic correlation and causal relationship between IBD and OP in the European population. Conversely, no such correlation or causal relationship was observed in the East Asian population. Mediation analysis revealed a significant mediating effect of nutritional status on the causal pathway between IBD and OP in the European population. Multi-trait analysis of the IBD-nutrition-OP causal pathway identified MFAP2, ATP13A2, SERPINA1, FTO and VCAN as deleterious variants. Conclusion Our findings establish a genetic correlation and causal relationship between IBD and OP in the European population, with nutritional status playing a crucial mediating role.
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Affiliation(s)
- Jian Kang
- Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Xize Wu
- Graduate School, Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Yue Li
- Department of Cardiology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Shuangli Zhao
- Orthopedics and Traumatology, The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Shixuan Wang
- Orthopedics and Traumatology, The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
| | - Dongdong Yu
- Orthopedics and Traumatology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China
- Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang, China
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Guo Y, Li Y, Tang Z, Geng C, Xie X, Song S, Wang C, Li X. Compromised NHE8 Expression Is Responsible for Vitamin D-Deficiency Induced Intestinal Barrier Dysfunction. Nutrients 2023; 15:4834. [PMID: 38004229 PMCID: PMC10674576 DOI: 10.3390/nu15224834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/15/2023] [Accepted: 11/16/2023] [Indexed: 11/26/2023] Open
Abstract
Objectives: Vitamin D (VitD) and Vitamin D receptor (VDR) are suggested to play protective roles in the intestinal barrier in ulcerative colitis (UC). However, the underlying mechanisms remain elusive. Evidence demonstrates that Na+/H+ exchanger isoform 8 (NHE8, SLC9A8) is essential in maintaining intestinal homeostasis, regarded as a promising target for UC therapy. Thus, this study aims to investigate the effects of VitD/VDR on NHE8 in intestinal protection. Methods: VitD-deficient mice, VDR-/- mice and NHE8-/- mice were employed in this study. Colitis mice were established by supplementing DSS-containing water. Caco-2 cells and 3D-enteroids were used for in vitro studies. VDR siRNA (siVDR), VDR over-expression plasmid (pVDR), TNF-α and NF-κb p65 inhibitor QNZ were used for mechanical studies. The expression of interested proteins was detected by multiple techniques. Results: In colitis mice, paricalcitol upregulated NHE8 expression was accompanied by restoring colonic mucosal injury. In VitD-deficient and VDR-/- colitis mice, NHE8 expression was compromised with more serious mucosal damage. Noteworthily, paricalcitol could not prevent intestinal barrier dysfunction and histological destruction in NHE8-/- mice. In Caco-2 cells and enteroids, siVDR downregulated NHE8 expression, further promoted TNF-α-induced NHE8 downregulation and stimulated TNF-α-induced NF-κb p65 phosphorylation. Conversely, QNZ blocked TNF-α-induced NHE8 downregulation in the absence or presence of siVDR. Conclusions: Our study indicates depressed NHE8 expression is responsible for VitD-deficient-induced colitis aggravation. These findings provide novel insights into the molecular mechanisms of VitD/VDR in intestine protection in UC.
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Affiliation(s)
- Yaoyu Guo
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China; (Y.G.); (Y.L.); (X.X.); (S.S.)
| | - Yanni Li
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China; (Y.G.); (Y.L.); (X.X.); (S.S.)
| | - Zeya Tang
- Department of Outpatient, West China Hospital, Sichuan University, Chengdu 610041, China;
| | - Chong Geng
- Laboratory of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China;
| | - Xiaoxi Xie
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China; (Y.G.); (Y.L.); (X.X.); (S.S.)
| | - Shuailing Song
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China; (Y.G.); (Y.L.); (X.X.); (S.S.)
| | - Chunhui Wang
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China; (Y.G.); (Y.L.); (X.X.); (S.S.)
| | - Xiao Li
- Department of Gastroenterology and Hepatology, West China Hospital, Sichuan University, Chengdu 610041, China; (Y.G.); (Y.L.); (X.X.); (S.S.)
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Jabłońska B, Mrowiec S. Nutritional Status and Its Detection in Patients with Inflammatory Bowel Diseases. Nutrients 2023; 15:1991. [PMID: 37111210 PMCID: PMC10143611 DOI: 10.3390/nu15081991] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 04/15/2023] [Accepted: 04/19/2023] [Indexed: 04/29/2023] Open
Abstract
Malnutrition is an important issue in patients with inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC). It is caused by altered digestion and absorption within the small bowel, inadequate food intake, and drug-nutrient interactions in patients. Malnutrition is an essential problem because it is related to an increased risk of infections and poor prognosis in patients. It is known that malnutrition is also related to an increased risk of postsurgery complications in IBD patients. Basic nutritional screening involves anthropometric parameters with body mass index (BMI) and others (fat mass, waist-to-hip ratio, muscle strength), medical history concerning weight loss, and biochemical parameters (including the Prognostic Nutritional Index). Besides standard nutritional screening tools, including the Subjective Global Assessment (SGA), Nutritional Risk Score 2002 (NRS 2002), and Malnutrition Universal Screening Tool (MUST), specific nutritional screening tools are used in IBD patients, such as the Saskatchewan Inflammatory Bowel Disease-Nutrition Risk Tool (SaskIBD-NR Tool and IBD-specific Nutritional Screening Tool). There is a higher risk of nutrient deficiencies (including iron, zinc, magnesium) and vitamin deficiencies (including folic acid, vitamin B12 and D) in IBD patients. Therefore, regular evaluation of nutritional status is important in IBD patients because many of them are undernourished. An association between plasma ghrelin and leptin and nutritional status in IBD patients has been observed. According to some authors, anti-tumor necrosis factor (anti-TNFα) therapy (infliximab) can improve nutritional status in IBD patients. On the other hand, improvement in nutritional status may increase the response rate to infliximab therapy in CD patients. Optimization of nutritional parameters is necessary to improve results of conservative and surgical treatment and to prevent postoperative complications in patients with IBDs. This review presents basic nutritional screening tools, anthropometric and laboratory parameters, dietary risk factors for IBDs, common nutrient deficiencies, associations between anti-TNFα therapy and nutritional status, selected features regarding the influence of nutritional status, and surgical outcome in IBD patients.
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Affiliation(s)
- Beata Jabłońska
- Department of Digestive Tract Surgery, Medical University of Silesia, 40-752 Katowice, Poland
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Lomer MCE, Wilson B, Wall CL. British Dietetic Association consensus guidelines on the nutritional assessment and dietary management of patients with inflammatory bowel disease. J Hum Nutr Diet 2023; 36:336-377. [PMID: 35735908 PMCID: PMC10084145 DOI: 10.1111/jhn.13054] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 06/07/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND Despite increased awareness of diet and nutrition being integral to the management of patients with inflammatory bowel disease (IBD), there are gaps in the knowledge of IBD healthcare providers regarding nutrition. Furthermore, high quality evidence on nutritional assessment and dietary management of IBD is limited. A Delphi consensus from a panel of experts allows for best-practice guidelines to be developed, especially where high quality evidence is limited. The aim was to develop guidelines for the nutritional assessment and dietary management of IBD using an eDelphi online consensus agreement platform. METHODS Seventeen research topics related to IBD and nutrition were systematically reviewed. Searches in Cochrane, Embase®, Medline® and Scopus® electronic databases were performed. GRADE was used to develop recommendations. Experts from the IBD community (healthcare professionals and patients with IBD) were invited to vote anonymously on the recommendations in a custom-built online platform. Three rounds of voting were carried out with updated iterations of the recommendations and evaluative text based on feedback from the previous round. RESULTS From 23,824 non-duplicated papers, 167 were critically appraised. Fifty-five participants completed three rounds of voting and 14 GRADE statements and 42 practice statements achieved 80% consensus. Comprehensive guidance related to nutrition assessment, nutrition screening and dietary management is provided. CONCLUSIONS Guidelines on the nutritional assessment and dietary management of IBD have been developed using evidence-based consensus to improve equality of care. The statements and practice statements developed demonstrate the level of agreement and the quality and strength of the guidelines.
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Affiliation(s)
- Miranda C E Lomer
- Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Department of Nutritional Sciences, King's College London, London, UK
| | - Bridgette Wilson
- Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Department of Nutritional Sciences, King's College London, London, UK
| | - Catherine L Wall
- Department of Nutritional Sciences, King's College London, London, UK.,Department of Medicine, University of Otago, Christchurch, New Zealand
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Chen D, Tang H, Li Y, Yang H, Wang H, Tan B, Qian J. Vitamin D3 and Lactobacillus rhamnosus GG/p40 Synergize to Protect Mice From Colitis by Promoting Vitamin D Receptor Expression and Epithelial Proliferation. Inflamm Bowel Dis 2022; 29:620-632. [PMID: 36562589 DOI: 10.1093/ibd/izac238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND While vitamin D (VitD) levels are negatively correlated with inflammatory bowel disease (IBD) activity, VitD supplementation does not reduce IBD severity. The probiotic Lactobacillus rhamnosus GG (LGG), which secretes p40, can upregulate colonic VitD receptor (VDR) expression. We therefore evaluated synergy between VitD3 and LGG/p40 in the treatment of mouse colitis. METHODS A dextran sulfate sodium (DSS) colitis model was established in Vdr+/+ and Vdr-/- mice, and mice were treated with VitD3, LGG, or p40 alone or in combination for 7 to 14 days. Colitis severity was assessed by weight loss, disease activity index (DAI), colon length, histology, and inflammatory cytokine expression together with VDR expression, proliferation, and apoptosis. In vitro, VDR expression and cell viability were assessed in HCT116 cells after stimulation with p40. RESULTS Total and nuclear VDR protein expression were lower in DSS-treated Vdr+/+ mice compared with control mice (P < .05). Compared with the DSS group, VitD3 + LGG alleviated colitis as assessed by significantly improved DAI and histological scores, increased colon length, decreased colonic Tnf, and increased Il10 expression together with increased colonic VDR gene and protein expression and increased Ki-67 proliferation index (P < .05). In Vdr-/- mice, VitD3 + LGG had no effect on DSS colitis. In Vdr+/+ mice, VitD3 + p40 also reduced colitis severity according to clinicopathological and immunological metrics and increased VDR expression and epithelial proliferation (P < .05). In HCT116 cells, p40 stimulation increased VDR protein expression and viability (P < .05). CONCLUSIONS VitD3 and LGG/p40 synergistically improve the severity of colitis by increasing colonic VDR expression and promoting colonic epithelial proliferation.
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Affiliation(s)
- Dan Chen
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of Gastroenterology, Beijing Hospital, National Center of Gerontology.,Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China
| | - Hao Tang
- Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Chinaand
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongying Wang
- State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bei Tan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Tulewicz-Marti EM, Lewandowski K, Rydzewska G. Bone Metabolism Alteration in Patients with Inflammatory Bowel Disease. J Clin Med 2022; 11:jcm11144138. [PMID: 35887903 PMCID: PMC9316624 DOI: 10.3390/jcm11144138] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/04/2022] [Accepted: 07/13/2022] [Indexed: 02/01/2023] Open
Abstract
Background: Metabolic bone disease is a common disorder, but there is a lack of data on it in patients with inflammatory bowel disease (IBD). Methods: In this prospective, one-centre study, we assessed bone mineral and vitamin D alterations in 187 IBD patients (119 with Crohn’s disease (CD) and 68 with ulcerative colitis (UC)). Results: While 81.3% of the patients had vitamin D deficiency, 14.2% of them had a severe deficiency. Elevated serum PTH concentrations were found in 14.9% of the patients. Only in 4.1% of cases was there an elevated level of a serum marker for bone formation (osteocalcin), whereas in 14.4% of cases, the bone resorption marker (CTX) was raised. The concentration of phosphate in urine was higher in the CD than in the UC group (51.20 vs. 31.25; p = 0.003). PTH was negatively associated with vitamin D level. Among the patients receiving corticosteroids, the CTX and CRP median levels were higher (0.49 vs. 0.38; p = 0.013 and 6.45 vs. 2.2; p = 0.029, respectively) compared with the group who did not receive them. Urine phosphate levels were lower (48.60 vs. 26.00; p = 0.005), as were osteocalcin (15.50 vs. 23.80; p < 0.001), and PTH (29.05 vs. 36.05; p = 0.018). Conclusions: Bone mineral alterations were common in patients with IBD, mostly in the CD patients. This may be associated with poor absorption, making CD patients vulnerable to changes in bone mineralization. Vitamin D supplementation remains crucial, especially when taking corticosteroids.
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Affiliation(s)
- Edyta Maria Tulewicz-Marti
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (K.L.); (G.R.)
- Correspondence:
| | - Konrad Lewandowski
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (K.L.); (G.R.)
| | - Grażyna Rydzewska
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Subdivision, Central Clinical Hospital of the Ministry of Interior and Administration, 02-507 Warsaw, Poland; (K.L.); (G.R.)
- Collegium Medicum, Jan Kochanowski University, 25-317 Kielce, Poland
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Chen X, Jiang L, Han W, Bai X, Ruan G, Guo M, Zhou R, Liang H, Yang H, Qian J. Artificial Neural Network Analysis-Based Immune-Related Signatures of Primary Non-Response to Infliximab in Patients With Ulcerative Colitis. Front Immunol 2022; 12:742080. [PMID: 34992592 PMCID: PMC8724249 DOI: 10.3389/fimmu.2021.742080] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 11/10/2021] [Indexed: 12/23/2022] Open
Abstract
Infliximab (IFX) is an effective medication for ulcerative colitis (UC) patients. However, one-third of UC patients show primary non-response (PNR) to IFX. Our study analyzed three Gene Expression Omnibus (GEO) datasets and used the RobustRankAggreg (RRA) algorithm to assist in identifying differentially expressed genes (DEGs) between IFX responders and non-responders. Then, an artificial intelligence (AI) technology, artificial neural network (ANN) analysis, was applied to validate the predictive value of the selected genes. The results showed that the combination of CDX2, CHP2, HSD11B2, RANK, NOX4, and VDR is a good predictor of patients' response to IFX therapy. The range of repeated overall area under the receiver-operating characteristic curve (AUC) was 0.850 ± 0.103. Moreover, we used an independent GEO dataset to further verify the value of the six DEGs in predicting PNR to IFX, which has a range of overall AUC of 0.759 ± 0.065. Since protein detection did not require fresh tissue and can avoid multiple biopsies, our study tried to discover whether the key information, analyzed by RNA levels, is suitable for protein detection. Therefore, immunohistochemistry (IHC) staining of colonic biopsy tissues from UC patients treated with IFX and a receiver-operating characteristic (ROC) analysis were used to further explore the clinical application value of the six DEGs at the protein level. The IHC staining of colon tissues from UC patients confirmed that VDR and RANK are significantly associated with IFX efficacy. Total IHC scores lower than 5 for VDR and lower than 7 for RANK had an AUC of 0.828 (95% CI: 0.665-0.991, p = 0.013) in predicting PNR to IFX. Collectively, we identified a predictive RNA model for PNR to IFX and explored an immune-related protein model based on the RNA model, including VDR and RANK, as a predictor of IFX non-response, and determined the cutoff value. The result showed a connection between the RNA and protein model, and both two models were available. However, the composite signature of VDR and RANK is more conducive to clinical application, which could be used to guide the preselection of patients who might benefit from pharmacological treatment in the future.
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Affiliation(s)
- Xuanfu Chen
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Lingjuan Jiang
- Medical Research Center, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Wei Han
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, China
| | - Xiaoyin Bai
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Gechong Ruan
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Mingyue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Runing Zhou
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Haozheng Liang
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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9
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McGing JJ, Radford SJ, Francis ST, Serres S, Greenhaff PL, Moran GW. Review article: The aetiology of fatigue in inflammatory bowel disease and potential therapeutic management strategies. Aliment Pharmacol Ther 2021; 54:368-387. [PMID: 34228817 DOI: 10.1111/apt.16465] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 09/30/2020] [Accepted: 05/20/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Fatigue is the inability to achieve or maintain an expected work output resulting from central or peripheral mechanisms. The prevalence of inflammatory bowel disease (IBD) fatigue can reach 86% in active disease, persisting in 50%-52% of patients with mild to inactive disease. Fatigue is the commonest reason for work absence in IBD, and patients often report fatigue burden to be greater than that of primary disease symptoms. Relatively few evidence-based treatment options exist, and the aetiology is poorly understood. AIM To review the available data and suggest a possible aetiology of IBD fatigue and to consider the efficacy of existing management strategies and highlight potential future interventions. METHODS We reviewed fatigue-related literature in IBD using PubMed database. RESULTS Disease related factors such as inflammation and pharmacological treatments negatively impact skeletal muscle and brain physiology, likely contributing to fatigue symptoms. Secondary factors such as malnutrition, anaemia, sleep disturbance and psychological comorbidity are potential determinants. Immune profile, faecal microbiota composition and physical fitness differ significantly between fatigued and non-fatigued patients, suggesting these may be aetiological factors. Solution-focused therapy, high-dosage thiamine supplementation and biological therapy may reduce fatigue perception in IBD. The effect of physical activity interventions is inconclusive. CONCLUSIONS A multimodal approach is likely required to treat IBD fatigue. Established reversible factors like anaemia, micronutrient deficiencies and active disease should initially be resolved. Psychosocial intervention shows potential efficacy in reducing fatigue perception in quiescent disease. Restoring physical deconditioning by exercise training intervention may further improve fatigue burden.
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Affiliation(s)
- Jordan J McGing
- School of Medicine, University of Nottingham, Nottingham, UK.,Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Shellie Jean Radford
- School of Medicine, University of Nottingham, Nottingham, UK.,National Institute of Health Research Nottingham Biomedical Research Centre (NIHR), Nottingham University Hospitals and University of Nottingham, Nottingham, UK
| | - Susan T Francis
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK.,National Institute of Health Research Nottingham Biomedical Research Centre (NIHR), Nottingham University Hospitals and University of Nottingham, Nottingham, UK
| | - Sébastien Serres
- School of Life Sciences, University of Nottingham, Nottingham, UK
| | - Paul L Greenhaff
- National Institute of Health Research Nottingham Biomedical Research Centre (NIHR), Nottingham University Hospitals and University of Nottingham, Nottingham, UK.,MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, Nottingham, UK
| | - Gordon W Moran
- School of Medicine, University of Nottingham, Nottingham, UK.,National Institute of Health Research Nottingham Biomedical Research Centre (NIHR), Nottingham University Hospitals and University of Nottingham, Nottingham, UK
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10
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Economu L, Chang YM, Priestnall SL, Kathrani A. The effect of assisted enteral feeding on treatment outcome in dogs with inflammatory protein-losing enteropathy. J Vet Intern Med 2021; 35:1297-1305. [PMID: 33931908 PMCID: PMC8163126 DOI: 10.1111/jvim.16125] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 03/26/2021] [Accepted: 03/31/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The effect of assisted enteral feeding on treatment outcome in dogs with protein-losing enteropathy (PLE) is unknown. OBJECTIVES To determine if dogs with inflammatory PLE that had an enteral feeding tube placed had better outcome vs dogs with inflammatory PLE without a feeding tube. ANIMALS Fifty-seven dogs with inflammatory PLE. METHODS A retrospective study at a UK referral hospital identified dogs with inflammatory PLE using a standard diagnostic criterion. Positive outcome was defined as survival greater than 6 months or death unrelated to PLE and negative outcome as death related to PLE within 6 months of diagnosis. Several variables were assessed to identify factors for positive outcome using logistic regression. RESULTS Thirty-five (61%) and 22 (39%) dogs had a positive and negative outcome at 6 months, respectively. Of the 21 dogs that had a feeding tube placed within 5 days of gastrointestinal biopsy, 16 (76%) had a positive outcome and 5 (24%) had a negative outcome. Dogs treated with dietary treatment alone (P = .002) and dogs with an enteral feeding tube (P = .006) were significantly associated with a positive outcome. When stratified by treatment, assisted enteral feeding was significantly associated with a positive outcome in dogs treated with concurrent immunosuppressive treatment (P = .006), but there was insufficient data to evaluate dogs treated with dietary treatment alone. CONCLUSIONS AND CLINICAL IMPORTANCE Assisted enteral feeding in dogs with inflammatory PLE could be associated with improved treatment outcome, especially in those receiving immunosuppressive treatment, and should be considered in the treatment plan of these dogs.
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Affiliation(s)
| | - Yu-Mei Chang
- Research Support Office, Royal Veterinary College, Hatfield, United Kingdom
| | - Simon L Priestnall
- Pathobiology and Population Sciences, Royal Veterinary College, Hatfield, United Kingdom
| | - Aarti Kathrani
- Department of Clinical Science and Services, Royal Veterinary College, Hatfield, United Kingdom
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Abstract
Abstract
Objective Vitamin D has been widely studied as a mediator of the immune response, becoming evident the prevalence of hypovitaminosis D in patients with Crohn's disease. This work aims at evaluating the serum levels of vitamin D in patients suffering from Crohn's disease in a southeast region of Brazil.
Methods It is a prospective study, with statistical analysis of the values of serum vitamin D measured between April 2014 and April 2015 in patients with Crohn's disease. Individuals with mild anal complaints, without any colorectal involvement, comprised the control group.
Results One hundred and four patients whose average age was 40.6 years were evaluated, being 56 (53.8%) female and 48 (46.2%) male. The average serum vitamin D level was 21.6 ng/mL, with standard deviation 13.85. The control group was comprised by 66 individuals, whose average age was 48.9 years. With 38 (57.6%) female and 28 (42.4%) male. In this group the average serum vitamin D level was 40.9 ng/mL. Statistical significance was demonstrated with p < 0.0001.
Conclusion There was high prevalence of hypovitaminosis D in patients with Chron's disease, when compared to the control group. Hypovitaminosis D was not evidenced in patients in the latter group.
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Soltys K, Stuchlikova M, Hlavaty T, Gaalova B, Budis J, Gazdarica J, Krajcovicova A, Zelinkova Z, Szemes T, Kuba D, Drahovska H, Turna J, Stuchlik S. Seasonal changes of circulating 25-hydroxyvitamin D correlate with the lower gut microbiome composition in inflammatory bowel disease patients. Sci Rep 2020; 10:6024. [PMID: 32265456 PMCID: PMC7138827 DOI: 10.1038/s41598-020-62811-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 03/18/2020] [Indexed: 12/24/2022] Open
Abstract
Higher probability of the development of Crohn's disease (CD) and ulcerative colitis (UC) as a possible consequence of the north-south gradient has been recently suggested. Living far north or south of the equator is manifested in fluctuation of vitamin D (vitD) levels depending on the season in both healthy and affected individuals. In the present study we investigate the possible link between the seasonal serum vitD level to the microbial composition of the lower gut of Inflammatory Bowel disease (IBD) patients using 16S rRNA sequencing. Decrease of serum vitD level in winter/spring season in a cohort of 35 UC patients and 39 CD patients was confirmed. Low gut microbiota composition of patients with IBD correlated with the serum level of 25(OH)D that directly coupled to seasonal variability of the sunshine in the central European countries. It is supposed to be related to increased abundance of Actinobacteria and Proteobacteria in UC and Actinobacteria, Fusobacteria, Firmicutes and Bacteroidetes in CD. In summer/autumn period, we observed a reduction in abundance of bacterial genera typical for inflammation like Eggerthella lenta, Fusobacterium spp., Bacteroides spp., Collinsella aerofaciens, Helicobacter spp., Rhodococcus spp., Faecalibacterium prausnitzii; and increased abundance of Pediococcus spp. and Clostridium spp. and of Escherichia/Shigella spp.
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Affiliation(s)
- Katarina Soltys
- Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 84215, Bratislava, Slovakia.
- Comenius University Science Park, Comenius University in Bratislava, Ilkovicova 8, 84104, Bratislava, Slovakia.
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 84215, Bratislava, Slovakia.
| | - Martina Stuchlikova
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 84215, Bratislava, Slovakia
- National Transplant Organization, Limbova 14, 83303, Bratislava, Slovakia
| | - Tibor Hlavaty
- Department of Internal Medicine, Faculty of Medicine, Division of Gastroenterology, Comenius University in Bratislava and University hospital Bratislava, Ruzinovska 6, 826 06, Bratislava, Slovakia
| | - Barbora Gaalova
- Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 84215, Bratislava, Slovakia
| | - Jaroslav Budis
- Department of Computer Science, Faculty of Mathematics, Physics and Informatics, Comenius University in Bratislava, Mlynska dolina F1, 842 48, Bratislava, Slovakia
| | - Juraj Gazdarica
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 84215, Bratislava, Slovakia
| | - Anna Krajcovicova
- Department of Internal Medicine, Faculty of Medicine, Division of Gastroenterology, Comenius University in Bratislava and University hospital Bratislava, Ruzinovska 6, 826 06, Bratislava, Slovakia
| | - Zuzana Zelinkova
- Department of Gastroenterology, St Michael Hospital, Bratislava, Slovakia
| | - Tomas Szemes
- Comenius University Science Park, Comenius University in Bratislava, Ilkovicova 8, 84104, Bratislava, Slovakia
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 84215, Bratislava, Slovakia
| | - Daniel Kuba
- National Transplant Organization, Limbova 14, 83303, Bratislava, Slovakia
| | - Hana Drahovska
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 84215, Bratislava, Slovakia
| | - Jan Turna
- Comenius University Science Park, Comenius University in Bratislava, Ilkovicova 8, 84104, Bratislava, Slovakia
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 84215, Bratislava, Slovakia
| | - Stanislav Stuchlik
- Comenius University Science Park, Comenius University in Bratislava, Ilkovicova 8, 84104, Bratislava, Slovakia
- Department of Molecular Biology, Faculty of Natural Sciences, Comenius University in Bratislava, Ilkovicova 6, 84215, Bratislava, Slovakia
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Hidalgo DF, Boonpheng B, Phemister J, Hidalgo J, Young M. Inflammatory Bowel Disease and Risk of Osteoporotic Fractures: A Meta-Analysis. Cureus 2019; 11:e5810. [PMID: 31720198 PMCID: PMC6823062 DOI: 10.7759/cureus.5810] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Introduction Inflammatory bowel disease (IBD) and its complications have been well-established. The literature shows an association between IBD and decreased bone mineral density in the adult population. However, most studies have reported an association between IBD and osteoporosis, while the risk of fractures has not been well-studied. The aim of this meta-analysis is to summarize the best available evidence regarding IBS and osteoporotic fractures. Methods A review of the literature using the MEDLINE and EMBASE databases was performed during November 2017. We included cross-sectional and cohort studies that reported the relative risks, odds ratios, and hazard ratios comparing the risk of developing osteoporotic fractures among patients with IBD patients, both ulcerative colitis (UC) and Crohn's disease (CD), versus patients without IBD as controls. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using the generic inverse-variance method. Results After a review of the literature, seven studies fulfilled the eligibility criteria established during the analysis. A significant association was found between IBD and osteoporosis, with a pooled OR of 1.32 (95% CI, 1.2 - 1.4). Low heterogeneity among the studies was found, I2=42.3. No publication bias was found using the Egger regression test p=0.18. Sensitivity analysis showed that the inclusion of data on children by Kappelman et al. (2007) did not change the results. Conclusion A significant association between IBD and the risk of developing osteoporotic fractures was observed in this study. There is a 32% increased risk, which is consistent with different cohort studies previously done.
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Affiliation(s)
- Diego F Hidalgo
- Geriatrics, Jackson Memorial Hospital / University of Miami, Miami, USA
| | | | | | - Jessica Hidalgo
- Internal Medicine, San Francisco De Quito University, Quito, ECU
| | - Mark Young
- Gastroenterology, East Tennessee State University, Johnson City, USA
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Li XX, Liu Y, Luo J, Huang ZD, Zhang C, Fu Y. Vitamin D deficiency associated with Crohn's disease and ulcerative colitis: a meta-analysis of 55 observational studies. J Transl Med 2019; 17:323. [PMID: 31547829 PMCID: PMC6757415 DOI: 10.1186/s12967-019-2070-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Accepted: 09/17/2019] [Indexed: 12/13/2022] Open
Abstract
PURPOSE To investigate the association of serum levels of 25(OH)D and 1,25(OH)2D3 in healthy and non-healthy controls with Crohn's disease (CD) and ulcerative colitis (UC). METHODS Three electronic databases: PubMed, EMbase and EBSCOhost CINAHL, were searched for observational studies to measure the relationship between serum levels of vitamin D (VitD) and CD (or UC). RESULTS Fifty-five studies were included in the meta-analysis. We found that mean serum 25(OH)D levels in patients with CD were significantly lower than those in healthy controls (MD: - 3.17 ng/mL; 95% CI - 4.42 to - 1.93). Results from the meta-analysis examining 1,25(OH)2D3 levels in Crohn's patients revealed higher levels in the CD group than in healthy (MD: 3.47 pg/mL; 95% CI - 7.72 to 14.66) and UC group (MD: 5.05 pg/mL; 95% CI - 2.42 to 12.52). Serum 25(OH)D levels were lower in the UC group than in the healthy control group (MD: - 2.52 ng/mL; 95% CI - 4.02 to - 1.02). In studies investigating the level of 1,25(OH)2D3 in UC and healthy control groups, the level of 1,25(OH)2D3 in the UC groups were found to be higher than that in the control groups (MD: 3.76 pg/mL; 95% CI - 8.36 to 15.57). However, the 1,25(OH)2D3 level in patients with UC was lower than that in CD groups (MD: - 6.71 pg/mL; 95% CI - 15.30 to 1.88). No significant difference was noted between CD patients and UC patients in terms of average serum 25(OH)D levels. CONCLUSIONS This study found that VitD levels were inversely related to CD and UC. Serum levels of 25(OH)D were lower in patients with CD and UC than in healthy people, and more than half of the patients had insufficient vitamin D levels. The serum level of 1,25(OH)2D3 in both the CD and UC groups was higher than that in healthy people.
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Affiliation(s)
- Xi-Xi Li
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China.,Zhejiang Chinese Medical University, No. 548, Binwen Road, Zhengjiang, 310053, China
| | - Yang Liu
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China
| | - Jie Luo
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China
| | - Zhen-Dong Huang
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China
| | - Chao Zhang
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China.
| | - Yan Fu
- Department of General Surgery, Taihe Hospital, Hubei University of Medicine, No. 32, South Renmin Road, Shiyan, 442000, China.
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Vitamin D in inflammatory bowel disease: From biology to clinical implications. Complement Ther Med 2019; 47:102189. [PMID: 31779998 DOI: 10.1016/j.ctim.2019.08.023] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 08/27/2019] [Accepted: 08/28/2019] [Indexed: 12/30/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic immune-mediated inflammatory disorder of the gastrointestinal tract consisting two principal categories, ulcerative colitis (UC) and Crohn's disease (CD). The precise etiology of IBD remains unknown. Vitamin D is an important micronutrient that plays a critical biological role in various processes in human tissues. However, the relationship between disruption of the gut microbiota and the development of IBD is unclear. Some studies suggest that IBD is the cause of disrupted gut microbiota while others propose that gut microbiota itself can lead to development of IBD. Regardless of this complexity, it has emerged that vitamin D is an immunoregulatory factor that plays a significant role in the pathogenesis of IBD by affecting the gut microbiome and the inflammatory response. It has been reported that 38.1% of CD patients and 31.6% of UC patients suffer from vitamin D deficiency (VDD). In this review, we aimed to evaluate the association between VDD and IBD, summarizing recent clinical studies examining the effect of low vitamin D and the role of vitamin D supplementation on IBD clinical outcomes.
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Ben Jemaa S, Chtourou L, Akrout R, Chaabouni K, Chaabouni T, Fourati HM, Amouri A, Tahri N, Ayedi F, Baklouti S. Bone Mineral Density and Bone Remodeling in Tunisian Patients with Inflammatory Bowel Disease. Open Rheumatol J 2019. [DOI: 10.2174/1874312901913010022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background:A high prevalence of osteopenia and osteoporosis is observed in patients with Inflammatory Bowel Disease (IBD).Objective:The aim of our study was to investigate the prevalence of bone loss, bone remodeling and risk factors in Tunisian patient with IBD.Patients and Methods:The study included 40 patients with IBD and 32 age- and sex-matched healthy controls subjects. All participants underwent bone densitometry by dual energy X-ray absorptiometry at the femoral neck and lumbar spine. Serum levels of 25-hydroxy vitamin D (25(OH)D), parathyroid hormone (PTH), osteocalcin(OC), and urinary degradation products of C-terminal telopeptide of type I collagen (CTXI) were measured in all participants to assess the bone metabolism status.Results:Twelve (30%) patients were normal, 32.5% were osteopenic and 37.5% were osteoporotic. Osteoporosis was more frequent in IBD patients than controls (p=0.0001). Age and inflammation were associated with low bone mineral density (BMD). Mean calcium, phosphorus and alkaline phosphatase levels were similar in both groups. Median 25(OH) D levels were significantly lower in IBD patients compared with controls (p=0.0001). Median urinary CTXI levels were significantly higher in IBD patients compared with healthy controls (p=0.007). No significant differences between IBD patients and controls concerning the median serum OC and PTH levels were found.Conclusion:In our study, there is a high prevalence of low BMD in IBD patients and an increase in bone resorption without a change of bone formation. Low BMI and hypovitaminoses D were identified as risk factors for low BMD.
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A New Model Based on 25-Hydroxyvitamin D3 for Predicting Active Crohn's Disease in Chinese Patients. Mediators Inflamm 2018; 2018:3275025. [PMID: 30647532 PMCID: PMC6311756 DOI: 10.1155/2018/3275025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Revised: 10/06/2018] [Accepted: 10/10/2018] [Indexed: 02/08/2023] Open
Abstract
Background The association between vitamin D3 and activity of Crohn's disease (CD) is unclear in Chinese patients. In this study, we aimed to evaluate the correlations between serum levels of 25-hydroxyvitamin D3 (25(OH)D3) and disease activity and predict active disease based on vitamin D status. Methods Between January 2014 and December 2017, 346 CD patients from the First Affiliated Hospital of Sun Yat-sen University were recruited and categorized into a group with 25(OH)D3 ≤ 20 ng/ml and a group with 25(OH)D3 > 20 ng/ml. The clinical characteristics, medication, and health-care needs were compared between the groups. The correlations among 25(OH)D3 and routine serum biomarkers and disease activity were examined. The predictive efficiency of 25(OH)D3 and other biomarkers for active diseases was also explored using receiver-operating characteristic (ROC) curve analysis. A new predictive model, −(5∗25(OH)D3 + 2∗Hb) + ESR, and a nomogram were established using Logistic Regression. Results Patients with 25(OH)D3 ≤ 20 ng/ml had higher serum levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and platelets (PLT) and lower levels of hemoglobin (Hb) and albumin (ALB). Serum levels of 25(OH)D3 were inversely correlated with the score of Crohn's Disease Activity Index (CDAI) (rs = −0.608). ROC analysis showed a better predictive value of −25(OH)D3 and the new model with areas under curve (AUC) of 0.804 and 0.879, respectively, than those of CRP (0.693) and ESR (0.713) in disease activity. A nomogram for prediction was established with a c-index of 0.882. Conclusions Serum levels of 25(OH)D3 negatively correlated with CD activity in Chinese patients. The new model and a nomogram based on 25(OH)D3 showed a better efficiency in predicting disease activity in CD patients but warrants further study.
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Branco JC, Cardoso MF, Anapaz V, Lourenço LC, Oliveira AM, Rodrigues CG, Santos L, Reis JA. Vitamin D Deficiency in a Portuguese Cohort of Patients with Inflammatory Bowel Disease: Prevalence and Relation to Disease Activity. GE-PORTUGUESE JOURNAL OF GASTROENTEROLOGY 2018; 26:155-162. [PMID: 31192283 DOI: 10.1159/000488744] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Revised: 03/18/2018] [Indexed: 12/28/2022]
Abstract
Background and Aims Vitamin D deficiency is more common in inflammatory bowel disease (IBD) patients than in the general population. However, there are conflicting data about predictive factors of vitamin D deficiency and its potential association with disease activity. The aims of this study were to determine the prevalence and predictive factors of vitamin D deficiency and to evaluate a possible association with disease activity. Methods A prospective observational study was conducted, including patients with IBD from January to July 2016. The Endocrine Society guidelines were considered for defining levels of serum 25-hydroxyvitamin D (25-OH-D) as follows: deficient (< 20 ng/mL, < 10 ng/mL being severe deficiency), insufficient (21-29 ng/mL), and adequate (> 30 ng/mL). Results A total of 152 patients (52% men; 47.2 ± 17.3 years) were included, of whom 70% had Crohn's disease (CD). Thirty-seven percent of patients were on immunosuppressors and 17% were on biologics. The majority were outpatients (88.2%). Mean 25-OH-D levels were 17.1 ± 8 ng/mL (CD: 16.7 ± 8 ng/mL vs. ulcerative colitis: 17.6 ± 7 ng/mL, p = 0.1). Inadequate levels were present in 90.8% of patients (deficiency: 68.4%; insufficiency: 22.4%). A significant negative correlation between 25-OH-D levels and age (r = -0.2, p = 0.04), C-reactive protein (CRP) levels (r = -0.22, p = 0.004), and Harvey-Bradshaw index (HBi) (r = -0.32, p = 0.001) was found. Patients with severe deficiency showed a higher CRP (0.6 vs. 1.4 mg/dL, p = 0.03), erythrocyte sedimentation rate (ESR) (22 vs. 31 mm/h, p = 0.03), and HBi (2 vs. 5, p < 0.001) and lower hemoglobin (13.6 vs. 12.7 g/dL, p = 0.02). There was no association between vitamin D deficiency and gender, type, extent, and duration of disease, surgery, and other measures of disease activity, such as ESR, hemoglobin (these 2 items except for severe deficiency), fecal calprotectin, or Truelove and Witts classification. Conclusions There is a high prevalence of inadequate levels of vitamin D in IBD patients, particularly deficiency (68.4%). There seems to exist an association between lower levels of vitamin D and higher disease activity, especially in CD.
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Affiliation(s)
- Joana C Branco
- Serviço de Gastrenterologia, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal
| | - Mariana F Cardoso
- Serviço de Gastrenterologia, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal
| | - Vera Anapaz
- Serviço de Gastrenterologia, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal
| | - Luís Carvalho Lourenço
- Serviço de Gastrenterologia, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal
| | - Ana Maria Oliveira
- Serviço de Gastrenterologia, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal
| | | | - Liliana Santos
- Serviço de Gastrenterologia, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal
| | - Jorge A Reis
- Serviço de Gastrenterologia, Hospital Professor Doutor Fernando Fonseca, Amadora, Portugal
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Tan B, Li P, Lv H, Yang H, Li Y, Li J, Wang O, Qian JM. Treatment of vitamin D deficiency in Chinese inflammatory bowel disease patients: A prospective, randomized, open-label, pilot study. J Dig Dis 2018. [PMID: 29542862 DOI: 10.1111/1751-2980.12590] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To assess the necessity and efficacy of vitamin D (VitD) supplementation in Chinese ulcerative colitis (UC) and Crohn's disease (CD) patients with vitamin D insufficiency/deficiency. METHODS UC and CD patients were randomly assigned into one of the three arms for 12 months: arm A (VitD3 150 000 IU once per 3 months plus elemental calcium 200 mg thrice daily), arm B (elemental calcium 200 mg thrice daily) and arm C (vehicle control group), in addition to conventional treatment. Improvement in 25-hydroxyvitamin D [25(OH)D] level was the primary outcome of the study. Secondary outcomes were changes in bone mineral density (BMD) and disease activity. RESULTS Sixty-five UC and 59 CD patients completed the study. The difference in the pre-and post-treatment 25(OH)D [Δ25(OH)D] of arm A was significantly higher than in arm B or C (UC: 17.47 ± 13.01 ng/mL vs 5.30 ± 6.28 ng/mL or 2.02 ± 6.19 ng/mL, P < 0.001; CD: 12.47 ± 9.15 ng/mL vs 4.73 ± 6.97 ng/mL or 1.36 ± 4.75 ng/mL, P < 0.01). There was no significant difference between pre- and post-treatment BMD and disease activity in arm A compared to those in arms B and C (P > 0.05). Although the Mayo score and Crohn's disease activity index decreased by conventional treatment, serum 25(OH)D did not improve in arm C without vitamin D supplementation (P > 0.05). CONCLUSION VitD supplementation is necessary to treat hypovitaminosis D in UC and CD patients, even with background amelioration of disease activity.
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Affiliation(s)
- Bei Tan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Pan Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Hong Lv
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Ou Wang
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Jia Ming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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Fat-soluble Vitamin Deficiencies and Inflammatory Bowel Disease: Systematic Review and Meta-Analysis. J Clin Gastroenterol 2017; 51:878-889. [PMID: 28858940 DOI: 10.1097/mcg.0000000000000911] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Vitamin deficiency is frequently associated with inflammatory bowel disease (IBD). Supplementation of vitamins could thus serve as an adjunctive therapy. The present meta-analysis reviews the deficiencies and alterations in serum fat-soluble vitamins (A, D, E, and K) reported in IBD patients. MATERIALS AND METHODS PubMed database search was performed to identify all primary studies up to January 2015 that evaluated the serum concentrations of fat-soluble vitamin levels in IBD patients compared with healthy individuals. We estimated pooled mean differences between groups and estimated their relations with some compounding variables (age, disease duration, C-reactive protein, albumin), using a meta-regression analysis. RESULTS Nineteen case-control studies met selection criteria. In patients with Crohn's disease (CD), vitamin A, D, E, K status was lower than in controls [D=212 μg/L.92; 95% confidence interval (CI), 95.36-330.48 μg/L, P=0.0002; D=6.97 nmol/L, 95% CI, 1.61-12.32 nmol/L, P=0.01; D=4.72 μmol/L, 95% CI, 1.60-7.84 μmol/L, P=0.003; D=1.46 ng/mL, 95% CI, 0.48-2.43 ng/mL, P=0.003, respectively]. Patients with ulcerative colitis had lower levels of vitamin A than controls (D=223.22 μg/L, 95% CI, 44.32-402.12 μg/L, P=0.01). Patients suffering from CD for a longer time had lower levels of vitamins A (95% CI=7.1-67.58 y, P=0.02) and K (95% CI, 0.09-0.71 y, P=0.02). Meta-regression analysis demonstrated statistically significant associations between the levels of inflammatory biomarkers: C-reactive protein (P=0.03, 95% CI, -9.74 to -0.6 mgl/L) and albumin (P=0.0003, 95% CI, 402.76-1361.98 g/dL), and vitamin A status in CD patients. CONCLUSION Our meta-analysis shows that the levels of fat-soluble vitamins are generally lower in patients with inflammatory bowel diseases and their supplementation is undoubtedly indicated.
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Abstract
Vitamin D3 is beneficial in ameliorating or preventing inflammation and carcinogenesis. Here, we evaluated if vitamin D3 has a preventive effect on colitis-associated carcinogenesis. Administration of azoxymethane (AOM), followed with dextran sulfate sodium (DSS), was used to simulate colitis-associated colon cancer in mice. The supplement of vitamin D3 at different dosages (15, 30, 60 IU·g·w), started before AOM or immediately after DSS treatment (post 60), was sustained to the end of the experiment. Dietary vitamin D3 significantly reduced the number of tumors and tumor burden in a dose-dependent manner. Of note, vitamin D3 in high doses showed significant preventive effects on carcinogenesis regardless of administration before or after AOM-DSS treatment. Cell proliferation decreased in vitamin D3 groups compared with the control group after inhibition of expression of β-catenin and its downstream target gene cyclin D1 in the colon. In vitro, vitamin D3 reduced the transcriptional activity and nuclear level of β-catenin, and it also increased E-cadherin expression and its binding affinity for β-catenin. Moreover, repression of E-cadherin was rescued by supplemental vitamin D3 in mouse colons. Taken together, our results indicate that vitamin D3 effectively suppressed colonic carcinogenesis in the AOM-DSS mouse model. Our findings further suggest that upregulation of E-cadherin contributes to the preventive effect of vitamin D3 on β-catenin activity.
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Zheng SZ, Zhang DG, Wu H, Jiang LJ, Jin J, Lin XQ, Ding R, Jiang Y. The association between vitamin D receptor polymorphisms and serum 25-hydroxyvitamin D levels with ulcerative colitis in Chinese Han population. Clin Res Hepatol Gastroenterol 2017; 41:110-117. [PMID: 27771345 DOI: 10.1016/j.clinre.2016.09.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Revised: 08/18/2016] [Accepted: 09/02/2016] [Indexed: 02/04/2023]
Abstract
There is now growing evidence suggesting that Vitamin D is playing a critical role in modulating the innate and adaptive immune responses. Several polymorphisms have been identified in the vitamin D receptor (VDR) gene but their association with ulcerative colitis (UC) susceptibility remained controversy. In the current study, we examined the association between VDR polymorphisms and serum level of 25-hydroxyvitamin D [25(OH)D] with UC in Chinese Han population. Polymorphisms of FokI (rs2228570)/BsmI (rs1544410)/ApaI (rs7975232)/TaqI (rs731236) in the VDR gene were assessed in a case-control study comprising 404 UC patients and 612 controls. Moreover, 25(OH)D levels were measured by electro-chemiluminescence immunoassay in 75 UC patients and 120 controls. Our results suggested that BsmI polymorphism frequency was significantly lower in UC patients (P=0.028), and the frequency of AAC haplotype formed by BsmI, ApaI and TaqI was also significantly lower in UC patients (P=0.012). Moreover, FokI polymorphism was more frequently observed in patients with mild and moderate UC as compared to those with severe UC (P=0.001, P<0.001, respectively). Average 25(OH)D level was lower in UC patients than in controls (19.3±6.8 vs. 21.8±7.3ng/mL, P=0.017), and was significantly correlated with hemoglobin (β=0.49, P<0.001), C-reactive protein (β=-0.36, P<0.001), severity of UC (β=-0.21, P=0.025) and FokI polymorphism (β=-0.20, P=0.031) in UC patients. Interestingly, there was a significant correlation between FokI polymorphism and vitamin D deficiency (<20ng/mL) in UC patients (P=0.006). Together, these results supported that VDR polymorphisms and 25(OH)D level were significantly correlated with UC risk and severity in Chinese Han population.
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Affiliation(s)
- Shu-Zi Zheng
- Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Da-Guan Zhang
- Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Hao Wu
- Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Li-Jia Jiang
- Department of Gastroenterology, the Wenzhou Central Hospital, Wenzhou, China
| | - Jie Jin
- Department of Gastroenterology, the Wenzhou Central Hospital, Wenzhou, China
| | - Xiu-Qing Lin
- Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ran Ding
- Department of Gastroenterology, Wenzhou Renmin Hospital, Wenzhou, China
| | - Yi Jiang
- Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
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Liu T, Shi Y, Du J, Ge X, Teng X, Liu L, Wang E, Zhao Q. Vitamin D treatment attenuates 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis. Sci Rep 2016; 6:32889. [PMID: 27620138 PMCID: PMC5020649 DOI: 10.1038/srep32889] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2016] [Accepted: 08/16/2016] [Indexed: 02/06/2023] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) have different immunological mechanisms, while both of them are potential targets of vitamin D treatment. In this study, we have tried to address the role of vitamin D in CD and UC using two mouse models. Mice of C57B6L were given vitamin D before the induction of colitis. Our results showed that vitamin D attenuated 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis but not oxazolone-induced colitis. Vitamin D could preserve the local histology, alleviate inflammation, suppress apoptosis, maintain tight junction function and decrease permeability. Interestingly, it has more of an effect on local structure preservation and inflammation inhibition in CD than in UC mice. Vitamin D blocked the increase of helper T-cell type 1 (Th1)- and helper T-cell type 17 (Th17)-related cytokines in TNBS-induced colitis. But the increase of helper T-cell type 2 (Th2)- and regulatory T cells (Treg)-related cytokines was augmented at the same time in oxazolone-induced colitis which counteracted each other. Our study helps elucidate the differential protective effects of vitamin D on CD and UC patients, as reported in literature.
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Affiliation(s)
- Tianjing Liu
- Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Shenyang, Liaoning 110004, P. R. China.,Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Shenyang, Liaoning 110004, P. R. China
| | - Yongyan Shi
- Department of Neonatology, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Shenyang, Liaoning 110004, P. R. China
| | - Jie Du
- Institute of Metabolic Disease Research and Drug Development, China Medical University, 77 Puhe Road, Shenyang, Liaoning 110004, P. R. China
| | - Xin Ge
- Institute of Metabolic Disease Research and Drug Development, China Medical University, 77 Puhe Road, Shenyang, Liaoning 110004, P. R. China
| | - Xu Teng
- Department of Gastroenterology, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Shenyang, Liaoning 110004, P. R. China
| | - Lu Liu
- Department of Gastroenterology, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Shenyang, Liaoning 110004, P. R. China
| | - Enbo Wang
- Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Shenyang, Liaoning 110004, P. R. China
| | - Qun Zhao
- Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Shenyang, Liaoning 110004, P. R. China.,Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, NO. 36 Sanhao Street, Shenyang, Liaoning 110004, P. R. China
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24
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Wang JJ, Wang QM. Clinical significance of serum 25OHD level in patients with Crohn's disease. Shijie Huaren Xiaohua Zazhi 2016; 24:2737-2742. [DOI: 10.11569/wcjd.v24.i17.2737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
AIM: To detect serum 25OHD levels in patients with Crohn's disease, and to analyze the relationship between serum 25OHD level and clinical parameters of Crohn's disease.
METHODS: Forty-five outpatients or inpatients with Crohn's disease (CD group) and 40 normal controls (NC group) were included in the study. Serum 25OHD levels were measured in all subjects by electrochemiluminescence. Correlation analysis was performed to identify the association between serum 25OHD levels and clinical indices of Crohn's disease. Afterwards, we analyzed the influence of related clinical indices on the level of serum 25OHD.
RESULTS: Serum 25OHD level was significantly lower in the CD group than in the NC group (12.17 ng/mL ± 6.12 ng/mL vs 19.56 ng/mL ± 5.69 ng/mL, P < 0.05, t = 5.738). The detection rate of 25OHD deficiency was significantly higher in the CD group than that of the NC group (86.7% vs 62.5%, P < 0.05, χ2 = 6.649). Serum 25OHD level was correlated with BMI (P < 0.05, r = 0.508), CRP (P < 0.05, r = -0.713), ESR (P < 0.05, r = -0.389), duration of exposure to sunshine < 30 min/d (P < 0.05, r = 0.362), active disease (P < 0.05, r = 0.384) and use of remicade (P < 0.05, r = 0.475). Serum 25OHD level was significantly lower in patients with Crohn's disease whose duration of exposure to sunshine was < 30 min/d than in those with a duration of exposure to sunshine > 30 min/d (10.33 ng/mL ± 5.75 ng/mL vs 14.47 ng/mL ± 5.91 ng/mL, P < 0.05, t = 2.371), in patients who did not use remicade than in those who used remicade (8.51 ng/mL ± 3.95 ng/mL vs 14.19 ng/mL ± 6.21 ng/mL, P < 0.05, t = 3.302), and in patients with active disease than in those with an inactive stage (9.36 ng/mL ± 4.43 ng/mL vs 14.05 ng/mL ± 6.44 ng/mL, P < 0.05, t = 2.693).
CONCLUSION: Patients with Crohn's disease have significantly lower serum 25OHD level than healthy people. Disease activity, duration of exposure to sunshine and use of remicade can affect serum 25OHD levels in patients with Crohn's disease.
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25
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Sadeghian M, Saneei P, Siassi F, Esmaillzadeh A. Vitamin D status in relation to Crohn's disease: Meta-analysis of observational studies. Nutrition 2016; 32:505-514. [PMID: 26837598 DOI: 10.1016/j.nut.2015.11.008] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2015] [Revised: 11/16/2015] [Accepted: 11/17/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Inconsistent findings have been published regarding vitamin D status among patients with Crohn's disease (CD) and the association with disease severity. We aimed to perform a meta-analysis evaluating serum 25-hydroxy vitamin D and 1,25 dehydroxyvitamin D among CD patients compared with healthy and non-healthy controls, the prevalence of vitamin D deficiency, and the association with disease. METHODS We searched MEDLINE, SCOPUS, EMBASE, and Google Scholar up to March 2015 for observational studies assessing serum vitamin D levels in CD patients. A total of 63 studies were included in the following four meta-analyses: 1) a meta-analysis on the mean difference of 25(OH)D levels in CD patients compared with healthy (number of studies = 27) and non-healthy (n = 25) controls; 2) a meta-analysis on the mean difference of 1,25(OH)2 D3 levels in CD patients compared with healthy (n = 7) and non-healthy (n = 8) controls; 3) a meta-analysis on the prevalence of vitamin D deficiency (n = 34); 4) a meta-analysis on the correlation coefficients between vitamin D status severity of CD (n = 6). Subgroup analysis and meta-regression were used to discover possible sources of between-study heterogeneity. RESULTS It was found that CD patients had lower levels of 25(OH)D compared with healthy (-3.99 ng/mL; 95% confidence interval [CI]: -5.91 to -2.08) but not non-healthy controls (-1.07 ng/mL; 95% CI: -2.84 to 0.70). There was also no significant mean difference for 1,25(OH)2 D3 for both healthy and non-healthy controls. Meta-analysis on the prevalence of vitamin D deficiency showed an overall prevalence of 57.7% (95% CI: 0.502-0.649). An inverse association was observed between serum vitamin D and severity of CD (-0.36; 95% CI: -0.48 to -0.24). Meta-regression showed that mean levels of 25(OH)D were decreased 0.09 for each unit change of latitude among CD patients compared with healthy controls (B = -0.09, P = 0.004, I(2) residual = 86.08%). CONCLUSIONS We found that patients with Crohn's disease had lower serum 25(OH)D concentrations compared with their healthy counterparts, and more than half of them have hypovitaminosis D. Moreover, there was an inverse correlation between circulating 25(OH)D concentrations and severity of Crohn's disease.
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Affiliation(s)
- Mehdi Sadeghian
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Students' Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Parvane Saneei
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Students' Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Fereydoun Siassi
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Esmaillzadeh
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran; Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
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26
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Wędrychowicz A, Zając A, Tomasik P. Advances in nutritional therapy in inflammatory bowel diseases: Review. World J Gastroenterol 2016; 22:1045-1066. [PMID: 26811646 PMCID: PMC4716019 DOI: 10.3748/wjg.v22.i3.1045] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Revised: 07/22/2015] [Accepted: 09/13/2015] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted.
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27
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Dai ZH, Tan B, Yang H, Wang O, Qian JM, Lv H. 1,25-hydroxyvitamin D relieves colitis in rats via down-regulation of toll-like receptor 9 expression. Croat Med J 2015; 56:515-24. [PMID: 26718757 PMCID: PMC4707923 DOI: 10.3325/cmj.2015.56.515] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2015] [Accepted: 11/23/2015] [Indexed: 12/14/2022] Open
Abstract
AIM To investigate the therapeutic and immunoregulatory effects of 1,25-dihydroxyvitamin D (1,25(OH)D3) on 2,4,6-trinitrobenzenesulfonic acid (TNBS) -induced colitis in rats. METHODS Experimental colitis induced by enema administration of TNBS plus ethanol was treated with 5-aminosalicylic acid (5-ASA) and/or 1,25(OH)D3. Disease activity was measured using the disease activation index (DAI), colon macroscopic damage index (CMDI), histological colonic damage score, and myeloperoxidase (MPO) activity. The expression of toll-like receptor 9 (TLR9) in the colon was determined by reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS Rats with TNBS-induced colitis had significantly elevated DAI, CMDI, histological colonic damage score, and MPO activity (all P<0.001) compared to rats without colitis. Treatment with 5-ASA or 1,25(OH)D3 ameliorated colitis by lowering CMDI (P=0.049, P=0.040, respectively), histological colonic damage score (P=0.010, P=0.005, respectively), and MPO activity (P=0.0003, P=0.0013, respectively) compared with the TNBS group. Combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased MPO activity (P=0.003). 1,25(OH)D3 attenuated colitis without causing hypercalcemia or renal insufficiency. TNBS significantly increased the number of TLR9 positive cells compared to control (P<0.010), while 5-ASA, 1,25(OH)D3, and combined treatment with 5-ASA and 1,25(OH)D3 significantly decreased it compared to TNBS group (all P<0.010). In TNBS group a moderate correlation was observed between MPO activity and the number of TLR9-positive cells (r=0.654, P<0.001). CONCLUSION TLR9 expression correlates with the extent of inflammation in TNBS-induced colitis. 1,25(OH)D3 relieves this inflammation possibly by decreasing TLR9 expression.
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Affiliation(s)
| | | | | | | | | | - Hong Lv
- Lv Hong, No. 1 Shuai-fu-yuan, Dong-cheng Districts, Beijing, China,
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28
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Abstract
PURPOSE OF REVIEW Malnutrition, protein-energy, and micronutrient deficiencies are common among patients with inflammatory bowel disease (IBD). The deficiencies are a manifestation of the complicated disease and a cause of morbidity. The present review summarizes recent advances and evidence-based knowledge regarding micronutrients in relation to patients with IBD. RECENT FINDINGS Micronutrient deficiencies occur in more than half of patients with IBD. Most common are deficiencies of iron, B12, vitamin D, vitamin K, folic acid, selenium, zinc, vitamin B6, and vitamin B1. Deficiencies are more common in Crohn's disease than in ulcerative colitis, and more in active disease than at times of remission. Micronutrient deficiency is associated with prolonged and complicated course of disease. Iron deficiency is the most common cause for anemia. Definite diagnosis of B12 deficiency cannot be established by serum levels alone. Vitamin D and vitamin K deficiencies are thought to be associated with heightened inflammatory state. The relationship of these deficiencies with bone disease is controversial. The present review focuses on the significance, epidemiology, treatment options, and recommendations regarding micronutrient deficiencies in IBD. SUMMARY Micronutrient deficiencies are common and have clinical significance. High suspicion for micronutrient deficiencies is advocated so that treatable causes of morbidity are treated appropriately and late and irreversible sequlae are prevented.
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Affiliation(s)
- Roni Weisshof
- Department of Gastroenterology, Rambam Health Care Campus and Bruce Rappaport School of Medicine, Technion Israel Institute of Technology, Haifa, Israel
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29
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Del Pinto R, Pietropaoli D, Chandar AK, Ferri C, Cominelli F. Association Between Inflammatory Bowel Disease and Vitamin D Deficiency: A Systematic Review and Meta-analysis. Inflamm Bowel Dis 2015; 21:2708-17. [PMID: 26348447 PMCID: PMC4615394 DOI: 10.1097/mib.0000000000000546] [Citation(s) in RCA: 174] [Impact Index Per Article: 17.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Vitamin D plays a role in several immune-mediated diseases, but its association with inflammatory bowel disease (IBD) is unclear. We conducted a systematic review and meta-analysis to assess the association between IBD and vitamin D deficiency. METHODS We searched electronic databases from inception to December 2014 for observational studies reporting the presence of vitamin D deficiency (defined as serum 25-hydroxycholecalciferol [25(OH)D] level of ≤20 ng/mL) in IBD patients and having a control group without IBD. Odds ratios (ORs) were combined using a random-effects model. Meta-regression was performed using latitude as a moderator. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS Out of 816 citations, 14 eligible studies were identified, comprising 1891 participants (938 IBD cases and 953 controls). Meta-analysis showed that patients with IBD had 64% higher odds of vitamin D deficiency when compared with controls (OR = 1.64; 95% confidence interval, 1.30-2.08; I = 7%; P < 0.0001). Patients with ulcerative colitis had more than double the odds of vitamin D deficiency when compared with normal controls (OR = 2.28; 95% confidence interval, 1.18-4.41; I = 41%; P = 0.01). Latitude did not influence the association between IBD and vitamin D deficiency (P = 0.34). Generalizability of our results might be limited as we summarized unadjusted ORs, because of nonavailability of adjusted ORs in individual studies. CONCLUSIONS IBD is significantly associated with having higher odds of vitamin D deficiency. Well-designed randomized controlled trials and longitudinal studies are needed to further explain the role of vitamin D in IBD pathogenesis and its therapy.
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Affiliation(s)
- Rita Del Pinto
- University of L’Aquila, Division of Internal Medicine, Department of Life, Health and Environmental Sciences, San Salvatore Hospital, Italy
- Case Western Reserve University, Division of Gastroenterology and Liver Disease, Cleveland, OH
| | - Davide Pietropaoli
- Case Western Reserve University, Division of Gastroenterology and Liver Disease, Cleveland, OH
- University of L’Aquila, Division of Dentistry, Department of Life, Health and Environmental Sciences, San Salvatore Hospital, Italy
| | - Apoorva Krishna Chandar
- Case Western Reserve University, Division of Gastroenterology and Liver Disease, Cleveland, OH
- University Hospitals Case Medical Center, Digestive Health Institute, Cleveland, OH
| | - Claudio Ferri
- University of L’Aquila, Division of Internal Medicine, Department of Life, Health and Environmental Sciences, San Salvatore Hospital, Italy
| | - Fabio Cominelli
- Case Western Reserve University, Division of Gastroenterology and Liver Disease, Cleveland, OH
- University Hospitals Case Medical Center, Digestive Health Institute, Cleveland, OH
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30
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Raffner Basson A, Swart R, Jordaan E, Mazinu M, Watermeyer G. Vitamin D Deficiency Increases the Risk for Moderate to Severe Disease Activity in Crohn's Disease Patients in South Africa, Measured by the Harvey Bradshaw Index. J Am Coll Nutr 2015; 35:163-74. [PMID: 26430776 DOI: 10.1080/07315724.2015.1039665] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Vitamin D has immunoregulatory properties and appears to influence disease outcomes in patients with Crohn's disease (CD). The primary aim of this study was to evaluate the association between vitamin D status and CD activity in South Africa. METHODS In a cross-sectional study performed between September 2011 and January 2013, serum 25-hydroxyvitamin D (25(OH)D) was measured in 186 consecutive patients with CD seen at 2 inflammatory bowel disease (IBD) centers and 199 healthy controls in the Western Cape, South Africa. Lifestyle and clinical variables were identified using an investigator-administered questionnaire, as well as clinical examination and patient case notes. Vitamin D status was evaluated in 2 ways: ≤ 20 ng/mL vs ≥ 21 ng/mL and ≤ 29 ng/mL vs ≥ 30 ng/mL. Disease activity was measured by the Harvey Bradshaw Index (HBI). Various 25(OH)D threshold concentrations for predicting a higher HBI score were also investigated. RESULTS On multiple log-binomial regression analysis, higher HBI scores and not having taken vitamin D supplementation in the 6 months prior to enrollment were identified as risk factors for vitamin D deficiency in patients with CD, defined either as ≤ 20 ng/mL or as ≤ 29 ng/mL (p < 0.03). Compared to patients with HBI < 5, those with HBI ≥ 8 were 2.5 times more likely to have 25(OH)D concentrations ≤ 21 ng/mL (prevalence risk [PR] = 2.5; 95% confidence interval [CI], 1.21-6.30). The risk was similar, though not as high, when defined as ≤ 29 ng/mL (PR = 2.0; 95% CI, 1.13-3.51). When vitamin D deficiency was defined as <20, <30, <40, and <50 ng/mL, the sensitivity and specificity obtained were 44.9% and 78.8%; 75.5% and 62.4%; 86.7% and 44.7%; and 92.9% and 23.5%, respectively (area under the curve = 0.71; p < 0.0001). CONCLUSION Low serum 25(OH)D was associated with increased CD activity in a South African cohort.
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Affiliation(s)
| | | | - Esme Jordaan
- b Statistics and Population Studies Department.,c University of the Western Cape, Bellville, Western Cape, SOUTH AFRICA; Biostatistics Unit, Medical Research Council of South Africa , Parow , Western Cape , SOUTH AFRICA
| | - Mikatako Mazinu
- c University of the Western Cape, Bellville, Western Cape, SOUTH AFRICA; Biostatistics Unit, Medical Research Council of South Africa , Parow , Western Cape , SOUTH AFRICA
| | - Gillian Watermeyer
- d Department of Gastroenterology , Groote Schuur Hospital , Cape Town , Western Cape , SOUTH AFRICA.,e Department of Medicine , University of Cape Town , Cape Town , Western Cape , SOUTH AFRICA
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31
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Lu C, Yang J, Yu W, Li D, Xiang Z, Lin Y, Yu C. Association between 25(OH)D Level, Ultraviolet Exposure, Geographical Location, and Inflammatory Bowel Disease Activity: A Systematic Review and Meta-Analysis. PLoS One 2015; 10:e0132036. [PMID: 26172950 PMCID: PMC4501705 DOI: 10.1371/journal.pone.0132036] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Accepted: 06/09/2015] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND There is no consensus on the vitamin D levels and inflammatory bowel disease (IBD). AIM To conduct a systematic review and meta-analysis to analyze the relationship between IBD and 25(OH)D, sun exposure, and latitude, and to determine whether vitamin D deficiency affects the severity of IBD. METHODS We searched the PubMed, EBSCO, and ClinicalTrials.gov databases to identify all studies that assessed the association between 25(OH)D, sun exposure, latitude, and IBD through November 1, 2014, without language restrictions. Studies that compared 25(OH)D levels between IBD patients and controls were selected for inclusion in the meta-analysis. We calculated pooled standardized mean differences (SMDs) and odds ratios (ORs). RESULTS Thirteen case-control studies investigating CD and 25(OH)D levels were included, and eight studies part of above studies also investigated the relationship between UC and 25(OH)D. Both CD patients (SMD: 0.26 nmol/L, 95% confidence interval [CI]: 0.09-0.42 nmol/L) and UC patients (SMD: 0.5 nmol/L, 95% CI: 0.15-0.85 nmol/L) had lower levels of 25(OH)D than controls. In addition, CD patients and UC patients were 1.95 times (OR, 1.95; 95% CI, 1.48-2.57) and 2.02 times (OR, 2.02; 95% CI, 1.13-3.60) more likely to be 25(OH)D deficient than controls. We also included 10 studies investigating the relationship between CD activity and vitamin D. Results showed that patients with active CD (CD Activity Index ≥ 150) were more likely to have low vitamin D levels. In addition, whether low sun exposure and high latitude were related to a high morbidity of CD need to be provided more evidence. CONCLUSION Our study shows that IBD patients have lower vitamin D levels. For active CD patients, vitamin D levels were low. These findings suggest that vitamin D may play an important role in the development of IBD, although a direct association could not be determined in our study.
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Affiliation(s)
- Chao Lu
- Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Jun Yang
- Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Weilai Yu
- Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Dejian Li
- Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Zun Xiang
- Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Yiming Lin
- Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
| | - Chaohui Yu
- Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China
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Zhu T, Liu TJ, Shi YY, Zhao Q. Vitamin D/VDR signaling pathway ameliorates 2,4,6-trinitrobenzene sulfonic acid-induced colitis by inhibiting intestinal epithelial apoptosis. Int J Mol Med 2015; 35:1213-8. [PMID: 25813397 PMCID: PMC4380119 DOI: 10.3892/ijmm.2015.2150] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Accepted: 03/13/2015] [Indexed: 12/15/2022] Open
Abstract
Increasing epidemiological data have suggested a link between vitamin D deficiency and the incidence of inflammatory bowel disease (IBD). In the present study, we confirmed that vitamin D deficiency, as well as the decreased local expression of vitamin D receptor (VDR), was prevalent in an IBD cohort. The excessive apoptosis of intestinal epithelial cells (IECs) partly accounts for the development of colonic inflammation and eventually results in IBD. Based on the established inhibitory effects of the vitamin D/VDR pathway on IEC apoptosis, we treated mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis with paricalcitol, a vitamin D analog, in order to investigate the mechanisms responsible for the inhibitory effects of the vitamin D/VDR pathway. We observed that following treatment with vitamin D, the mice presented with only minor bodyweight loss, and the mice also showed improved histological scores and decreased intestinal epithelial permeability compared with the vehicle-treated group. The colonic mRNA expression of inflammatory cytokines and chemokines was markedly suppressed, indicating less severe colitis in the vitamin D-treated mice. Subsequently, we investigated p53 upregulated modulator of apoptosis (PUMA) and p53, two major independent pathways of apoptosis, as well as caspase-3. We found that the vitamin D-treated mice had lower expression levels of caspase-3 than the vehicle-treated mice. PUMA expression showed the same tendency; however, the p53 protein level was not altered. The present study indicates that vitamin D attenuates the development of TNBS-induced colitis by inhibiting the apoptosis of IECs. The mechanisms involved include the downregulation of PUMA expression. Our data provide experimental support for the clinical trials of vitamin D intervention in patients with IBD.
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Affiliation(s)
- Tong Zhu
- Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
| | - Tian-Jing Liu
- Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
| | - Yong-Yan Shi
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
| | - Qun Zhao
- Department of Pediatric Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
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Hlavaty T, Krajcovicova A, Payer J. Vitamin D therapy in inflammatory bowel diseases: who, in what form, and how much? J Crohns Colitis 2015; 9:198-209. [PMID: 26046136 DOI: 10.1093/ecco-jcc/jju004] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND The north–south geographical gradient of inflammatory bowel disease (IBD) prevalence, its epidemiology, the genetic association of vitamin D receptor polymorphisms, and results in animal models suggest that vitamin D plays an important role in the pathogenesis of IBD. AIMS The purpose of this review was to critically appraise the effectiveness and safety of vitamin D therapy in patients with IBD. METHODS MEDLINE, Scopus and Google Scholar were searched from inception to May 20, 2014 using the terms ‘Crohn’s disease’, ‘ulcerative colitis’ and ‘vitamin D’. Results: Vitamin D deficiency is common in patients with IBD. Limited clinical data suggest an association between low vitamin D concentration and increased disease activity in both ulcerative colitis (UC) and Crohn’s disease (CD). To date, only two small open label trials and one randomized controlled trial have shown a positive effect of vitamin D supplementation on disease activity in patients with CD; no effect has been shown for UC. An optimal vitamin D supplementation protocol for patients with IBD remains undetermined, but targeting serum 25-hydroxy vitamin D [25(OH)D] levels between 30 and 50 ng/mL appears safe and may have benefits for IBD disease activity. Depending on baseline vitamin D serum concentration, ileal involvement in CD, body mass index, and perhaps smoking status, daily vitamin D doses between 1800–10,000 international units/day are probably necessary. CONCLUSION Increasing preclinical and clinical evidence suggests a role for vitamin D deficiency in the development and severity of IBD. The possible therapeutic role of vitamin D in patients with IBD merits continued investigation.
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Abstract
The emerging role of vitamin D as a regulator of both innate and adaptive immune responses has encouraged the investigation of its role in the pathogenesis of a variety of autoimmune conditions including the inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis. Animal models consistently demonstrate that vitamin D significantly impacts on the modulation of astrointestinal inflammation, while epidemiological and observational data show an inverse relationship between vitamin D status and the onset/progression of Crohn's disease as well as the development of colorectal cancer. As vitamin D supplementation is readily available, at low cost, it is a very attractive potential therapeutic option. The biological plausibility for a role for vitamin D in inflammation modulation, the potential genetic links associated with vitamin D metabolism and the clinical aspects for it in IBD will be discussed.
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Affiliation(s)
- Simon Ghaly
- Centre for Inflammatory Bowel Diseases, Fremantle Hospital and School of Medicine and Pharmacology, University of Western Australia, Level 5, T Block, Alma St, Fremanlte, Western Australia 6159, Australia
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