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Baldi S, Sarikaya D, Lotti S, Cuffaro F, Fink D, Colombini B, Sofi F, Amedei A. From traditional to artificial intelligence-driven approaches: Revolutionizing personalized and precision nutrition in inflammatory bowel disease. Clin Nutr ESPEN 2025; 68:106-117. [PMID: 40345659 DOI: 10.1016/j.clnesp.2025.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2025] [Accepted: 05/02/2025] [Indexed: 05/11/2025]
Abstract
Inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn's disease, is a chronic inflammatory condition with global prevalence and varying incidence. The IBD pathogenesis involves intricate interactions among genetic, host and environmental factors, leading to dysregulated immune responses and chronic intestinal inflammation. Alongside elevated levels of inflammatory cytokines and altered miRNAs expression, more studies highlight significant dysbiosis in both fecal and ileal microbiota of IBD patients. This dysbiosis is characterized by an increase in pro-inflammatory and mucin-degrading bacteria (e.g., Fusobacterium spp., Escherichia spp.) and a decline in short-chain fatty acids (SCFAs) -producing microbes (e.g., Roseburia spp., Faecalibacterium spp.) which play a protective role in gut health. Diet emerges as a key environmental factor influencing IBD onset and progression and recent advancements in"omics" technologies, such as genomics, transcriptomics, and metabolomics, provide a deeper understanding of the molecular interactions between genes, gut microbiota (GM) and nutrition. Finally, new technologies like artificial intelligence (AI), further enhance findings by enabling data integration and personalized dietary strategies. In this scenario, this review aims to summarize accumulating data on the effects of dietary interventions in IBD patients and introduce the role of artificial intelligence (AI) in facilitating precision dietary approaches to improve IBD management.
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Affiliation(s)
- Simone Baldi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Dilara Sarikaya
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Sofia Lotti
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Francesca Cuffaro
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Dorian Fink
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Barbara Colombini
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Francesco Sofi
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Unit of Clinical Nutrition, Careggi University Hospital, 50134 Florence, Italy
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Florence, Italy.
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Yu W, Huang P, Jin Y, Wu F, Zhang C, Jing L, Chen Y, Xu H, Xiong J, Zhang R, Zhao K, Li X. Vitamin D enhances the therapeutic effect of TNF-α antibodies through lipid metabolism in overweight IBD patients. Cell Mol Life Sci 2025; 82:176. [PMID: 40285831 PMCID: PMC12033164 DOI: 10.1007/s00018-025-05626-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 02/03/2025] [Accepted: 02/15/2025] [Indexed: 04/29/2025]
Abstract
The inhibitory effects of the tumor necrosis factor-α (TNF-α) antibody infliximab (IFX) on colitis are well established. Since IFX dosing is weight-based and associated with various side effects, there is a growing interest in identifying combination therapies that can enhance its efficacy, particularly in overweight inflammatory bowel disease (IBD) patients, to maximize the anti-inflammatory effect while minimizing the required dose. Our research revealed that overweight IBD patients present decreased vitamin D levels in the intestinal epithelium alongside elevated TNF-α levels. In mice fed a high-fat diet (HFD) for four weeks, treatment with the vitamin D analog palicalcitol (PAL) reduced lipid synthesis and TNF-α production in intestinal epithelial cells (IECs). In a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis model, PAL treatment mitigated TNF-α-induced damage to the intestinal epithelial barrier and reduced the activation of Th1 and Th17 cells in the lamina propria, thereby reducing colitis development in HFD-fed mice. Notably, the combination of IFX and PAL was more effective than IFX alone in treating colitis in these mice. Overall, our findings suggest that vitamin D inhibits TNF-α production by reducing lipid synthesis in IECs, thereby enhancing IFX therapy in overweight IBD patients.
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Affiliation(s)
- Wei Yu
- Institute of Clinical Medicine Research, Zhejiang Provincial People'S Hospital(Affiliated People'S Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Pengpeng Huang
- Institute of Clinical Medicine Research, Zhejiang Provincial People'S Hospital(Affiliated People'S Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Yanling Jin
- Institute of Clinical Medicine Research, Zhejiang Provincial People'S Hospital(Affiliated People'S Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Fang Wu
- Department of General, Cancer Center, Division of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Cuiping Zhang
- Department of Pathology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, Shandong, China
| | - Lili Jing
- Immunology and Pathology Teaching and Research Office, Shandong College of Traditional Chinese Medicine, Yantai, 264199, Shandong, China
| | - Ying Chen
- Institute of Clinical Medicine Research, Zhejiang Provincial People'S Hospital(Affiliated People'S Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Han Xu
- Institute of Clinical Medicine Research, Zhejiang Provincial People'S Hospital(Affiliated People'S Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Jiapin Xiong
- Institute of Clinical Medicine Research, Zhejiang Provincial People'S Hospital(Affiliated People'S Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Rong Zhang
- Institute of Clinical Medicine Research, Zhejiang Provincial People'S Hospital(Affiliated People'S Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Ke Zhao
- Institute of Clinical Medicine Research, Zhejiang Provincial People'S Hospital(Affiliated People'S Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China
| | - Xue Li
- Institute of Clinical Medicine Research, Zhejiang Provincial People'S Hospital(Affiliated People'S Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China.
- Department of Urology, Zhejiang Provincial People'S Hospital (Affiliated People'S Hospital), Hangzhou Medical College, Hangzhou, 310013, Zhejiang, China.
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Ravindra K, Kaur M, Mor S. Impacts of microplastics on gut health: Current status and future directions. Indian J Gastroenterol 2025:10.1007/s12664-025-01744-0. [PMID: 40268833 DOI: 10.1007/s12664-025-01744-0] [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: 11/06/2024] [Accepted: 01/14/2025] [Indexed: 04/25/2025]
Abstract
BACKGROUND AND OBJECTIVES Microplastics are pervasive environmental pollutants, attracting significant concern due to their potential adverse effects on ecosystems and human health. This study hypothesizes that microplastics may significantly impact gastrointestinal (GI) health through various mechanisms. The objective of this systematic review is to explore the effects of microplastics on GI health, focusing on animal models such as mice, fish and earthworms. METHODS A systematic review approach was employed, analyzing studies that investigate the impact of microplastics on the gut microbiota, gut barrier integrity and GI inflammation. The review includes a synthesis of findings from multiple animal models. RESULTS The review reveals consistent evidence that microplastics can disrupt the gut microbiota, impair the gut barrier, and induce inflammatory responses in the GI tract. Statistical analysis shows a significant correlation between microplastic exposure and GI health deterioration across various animal models. CONCLUSIONS The findings underscore the harmful effects of microplastics on GI health, emphasizing the urgent need for policy interventions to reduce plastic pollution. Implementing measures to limit the production and usage of disposable plastics is crucial for mitigating the risks posed by microplastic contamination to promote environmental sustainability and safeguard human well-being.
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Affiliation(s)
- Khaiwal Ravindra
- Department of Community Medicine and School of Public Health, Post Graduate Institute of Medical Education and Research, Chandigarh, 160 012, India.
| | - Manpreet Kaur
- Department of Environment Studies, Panjab University, Chandigarh, 160 014, India
| | - Suman Mor
- Department of Environment Studies, Panjab University, Chandigarh, 160 014, India
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Wang Y, Zhao Z, Wang R, Hu X. Genetic Links between Gastrointestinal Disorders and Kidney Stone Disease: Insights from a Genome-Wide Cross-Trait Analysis. KIDNEY360 2025; 6:616-626. [PMID: 39752564 PMCID: PMC12045493 DOI: 10.34067/kid.0000000689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 12/19/2024] [Indexed: 04/25/2025]
Abstract
Key Points Positive genetic links and shared genetic architecture exist between gastrointestinal disorders and kidney stone disease. Ion homeostasis and response to vitamin D bridge two types of disorders. Genetically predicted irritable bowel syndrome, gastroesophageal reflux, and Crohn's disease were associated with higher risk of kidney stone disease. Background Epidemiological associations between kidney stone disease (KSD) and gastrointestinal disorders have been reported, and intestinal homeostasis plays a critical role in stone formation. However, the underlying intrinsic link is not adequately understood. This study aims to investigate the genetic associations between these two types of diseases. Methods We obtained summary statistics from large-scale genome-wide association studies of KSD and gastrointestinal diseases, including gastroesophageal reflux disease, peptic ulcer disease, inflammatory bowel disease and its subtypes, irritable bowel syndrome, and diverticular disease (N =311,254–720,199). Their overall genetic correlations were first estimated. We then detected the shared genetic architecture, including pleiotropic single nucleotide polymorphisms, loci, genes, and biological processes, through cross-trait analyses. In addition, bidirectional Mendelian randomization analysis was performed to look for their causal relationships. Results We found significantly positive genetic correlations between KSD and all five gastrointestinal diseases. The cross-trait analysis identified 3184 potential pleiotropic single nucleotide polymorphisms, and 33 of which were pleiotropic loci shared by the two disorders. Gene-level analyses revealed eight pleiotropic causal genes, primarily enriched in biological pathways involving ion homeostasis and response to vitamin D. In the Mendelian randomization analysis, we detected causal effects from gastroesophageal reflux disease, irritable bowel syndrome, and Crohn's disease to KSD, while no reverse causality was observed. Conclusions Our study demonstrated the positive genetic links between KSD and gastrointestinal diseases and reported pleiotropic variants, loci, and genes, implicating potential biological mechanisms in the pathogenesis of stone disease. These findings further support the role of the gut-kidney axis and provide a genetic basis for the prevention, coregulation, and treatment of these diseases.
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Affiliation(s)
- Yicun Wang
- Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China and Institute of Urology, Capital Medical University, Beijing, China
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Li H, Li WC, Hu XR. Association between vitamin C, D, and K intake and inflammatory bowel disease risk: findings from 2009 to 2010 NHANES. BMC Gastroenterol 2025; 25:177. [PMID: 40097943 PMCID: PMC11912713 DOI: 10.1186/s12876-025-03747-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 02/28/2025] [Indexed: 03/19/2025] Open
Abstract
BACKGROUND Micronutrient deficiency is commonly observed in patients with inflammatory bowel disease (IBD), yet the role of certain dietary trace elements in the risk of IBD development remains unclear. OBJECTIVES This study aimed to investigate the relationship between vitamin C, D, and K intake and IBD risk. METHODS This study included 3,591 participants from the 2009-2010 National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression were conducted to assess associations between vitamin C, D, and K intake and IBD risk while controlling for multiple confounders. Subgroup analyses were employed to test the robustness of the associations across participants with various characteristics. Additionally, restricted cubic spline (RCS) analysis was conducted to investigate potential nonlinear relationships. RESULTS In the fully adjusted model, each 1 mcg increase in vitamin D intake was linked to an approximately 51% decrease in IBD risk (adjusted OR = 0.49, 95% CI: 0.25-0.98, p = 0.045). The benefit appeared stronger in women, individuals without hypertension, and non-smokers. No statistically significant associations were found between vitamin C or vitamin K intake and IBD risk. However, among individuals without diabetes, each 1 mcg increase in vitamin K intake was associated with an approximate 67% reduction in IBD risk (adjusted OR = 0.33, 95% CI: 0.12-0.94, p = 0.039). RCS analysis suggested a linear relationship between dietary micronutrient intake and IBD risk (vitamin D: p for nonlinearity = 0.127, p for overall = 0.015; vitamin C: p for nonlinearity = 0.984, p for overall = 0.937; vitamin K: p for nonlinearity = 0.736, p for overall = 0.434). CONCLUSION Increased vitamin D intake may reduce the risk of IBD, with more pronounced benefits in certain subgroups, highlighting the potential of vitamin D supplementation as a novel therapeutic approach for IBD prevention and management. Future well-designed studies should further test the therapeutic effects of vitamin D supplementation and investigate the associations of other dietary trace elements with IBD risk to better inform prevention and treatment approaches.
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Affiliation(s)
- Hui Li
- The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523000, China
| | - Wen-Chao Li
- The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523000, China
| | - Xia-Rong Hu
- The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), Dongguan, 523000, China.
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Akinrinde AS, Adeoye BO, Samuel ES, Mustapha OA. Protective effect of cholecalciferol against cobalt-induced neurotoxicity in rats: ZO-1/iFABP, ChAT/AchE and antioxidant pathways as potential therapeutic targets. Biol Trace Elem Res 2025; 203:1555-1570. [PMID: 38836989 DOI: 10.1007/s12011-024-04258-6] [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: 04/02/2024] [Accepted: 05/30/2024] [Indexed: 06/06/2024]
Abstract
Cobalt (Co) toxicity has been reported to produce central nervous system and gastrointestinal abnormalities. This study assessed the therapeutic effect of cholecalciferol (Cho) supplementation against damages caused by sub-acute (14-day) cobalt chloride (CoCl2) exposure in the brain and intestines. Thirty-five male Wistar rats were divided equally into five groups: Group I (control) received no treatment; Group II received oral CoCl2 (100 mg/kg) only; Groups III, IV, and V received 1000, 3000 and 6000 IU/kg of cholecalciferol, respectively by oral gavage, and concurrently with CoCl2. Cobalt-treated rats showed neuronal vacuolation and presence of pyknotic nuclei in the cerebral cortex and hippocampus, depletion of Purkinje cells in the cerebellum, as well as inflammation and congestion in the intestinal mucosa. Cobalt also increased brain and intestinal hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations, while simultaneously reducing glutathione (GSH) content, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities. Further, CoCl2 induced increases in brain acetylcholinesterase (AchE) activity and serum zonulin (ZO-1) levels. Conversely, Cho administration suppressed CoCl2-induced damages in the brain and intestines by reducing lipid peroxidation and increasing the activities of antioxidant enzymes. Remarkably, Cho produced stimulation of brain choline acetyltransferase (ChAT) and suppression of AchE activity, along with dose-dependent reduction in serum levels of ZO-1, intestinal fatty acid-binding protein (iFABP) and nitric oxide. In conclusion, the protective role of cholecalciferol against cobalt-induced toxicity occurred via modulation of cholinergic, intestinal permeability and antioxidant pathways. The results may prove significant in the context of the role of gut-brain connections in neuroprotection.
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Affiliation(s)
- A S Akinrinde
- Gastrointestinal and Environmental Toxicology Laboratory, Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria.
| | - B O Adeoye
- Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
| | - E S Samuel
- Gastrointestinal and Environmental Toxicology Laboratory, Department of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan, Nigeria
| | - O A Mustapha
- Neuroscience Unit, Department of Veterinary Anatomy, College of Veterinary Medicine, Federal University of Agriculture Abeokuta, Abeokuta, Ogun state, Nigeria
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Li P, Zou M, Peng Z. Assessing the impact of 25-hydroxyvitamin concentrations on mortality in chronic diarrhea: a cross-sectional analysis. Front Med (Lausanne) 2025; 12:1508439. [PMID: 40027892 PMCID: PMC11868106 DOI: 10.3389/fmed.2025.1508439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 01/20/2025] [Indexed: 03/05/2025] Open
Abstract
Background The aim of this study was to assess the relationship between serum 25-hydroxyvitamin levels and all-cause mortality in patients with chronic diarrhea. Methods We carried out a cross-sectional study using information drawn from the National Health and Nutrition Examination Survey (NHANES). To assess mortality outcomes, we compared our data with records from the National Death Index as of December 31, 2011. The NHANES data were used to determine mortality outcome. We used a Cox regression model-based approach to analyze the relationship between serum 25-hydroxyvitamin concentrations and mortality in chronic diarrhea patients. Results A total of 2,972 participants with chronic diarrhea were included in our study, 488 cases of all-cause mortality were recorded. The study showed an L-shaped relationship between 25-hydroxyvitamin concentrations and all-cause mortality with a threshold of 73.40 nmol/L. On the left side of the threshold, each 1-unit increase in 25-hydroxyvitamin concentrations was associated with a 2.2% reduction in the risk of all-cause mortality (HR 0.978; 95% CI: 0.969, 0.987); however, on the right side of the threshold, there was no significant correlation between 25(OH)D concentrations and all-cause mortality. Conclusion Serum 25-hydroxyvitamin D levels showed an L-shaped association with all-cause mortality in patients with chronic diarrhea, with 73.40 nmol/L as the potential threshold. However, because this was a cross-sectional study, only an association, not a causal relationship, can be inferred. Further prospective studies are needed to confirm these findings and explore the potential impact of vitamin D supplementation on mortality outcomes.
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Affiliation(s)
- Pengyu Li
- School of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Menglong Zou
- The First Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, China
| | - Ziming Peng
- Fangchenggang Hospital of Traditional Chinese Medicine, Fangchenggang, Guangxi, China
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Vallejos OP, Bueno SM, Kalergis AM. Probiotics in inflammatory bowel disease: microbial modulation and therapeutic prospects. Trends Mol Med 2025:S1471-4914(24)00338-1. [PMID: 39814640 DOI: 10.1016/j.molmed.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 12/06/2024] [Accepted: 12/10/2024] [Indexed: 01/18/2025]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder that represents a significant public health challenge worldwide. This multifactorial condition results from complex interactions among genetic, environmental, immune, and microbial factors. Some beneficial microbes, known as probiotics, have been identified as promising therapeutic agents for inflammatory conditions, such as IBD. In this review, we explore the potential of probiotics as a therapeutic strategy for managing IBD. Probiotics have shown promise due to their ability to modulate the gut microbiota, regulate histamine levels, and enhance vitamin D metabolism, thereby promoting a tolerant immune profile and reducing inflammation. While the exact mechanisms underlying these benefits remain incompletely understood, probiotics represent a novel and emerging approach for alleviating the exacerbated inflammation characteristic of this disorder.
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Affiliation(s)
- Omar P Vallejos
- Millennium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Susan M Bueno
- Millennium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
| | - Alexis M Kalergis
- Millennium Institute of Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
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Zhang D, Zhu Z, He Z, Duan S, Yi Q, Qiu M, Dai X, Su G, Li K, Xu L, Liu D, Wu Y, Gao Y, Li R, Guo S. Kuiyangling Enema Alleviates Ulcerative Colitis Mice by Reducing Levels of Intestinal NETs and Promoting HuR/VDR Signaling. J Inflamm Res 2025; 18:381-403. [PMID: 39802513 PMCID: PMC11725280 DOI: 10.2147/jir.s492818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Accepted: 12/21/2024] [Indexed: 01/16/2025] Open
Abstract
Purpose Kuiyangling is a traditional Chinese medicine formula used for the treatment of ulcerative colitis, but the specific mechanism remains unclear. Imbalance in NETs regulation is one of the important factors contributing to the onset of ulcerative colitis (UC). The HuR/VDR signaling pathway plays a significant role in restoring the intestinal mucosal barrier in UC. The aim of this study is to explore the mechanism of Kuiyangling in the treatment of ulcerative colitis. Methods A mouse model of ulcerative colitis using 3% DSS water was considered, and model, normal, Kuiyangling medium- (5 g·kg-1) and high-dose (10 g·kg-1), and mesalazine (50 mg·kg-1) groups were created. Measurements of colon length, spleen index, histopathological variances, subcellular structure observations, ROS content, and NET-related proteins (PAD4, MPO, citH3) were obtained through HE staining, electron microscopy, live imaging, and Western blotting assays. Immunohistochemistry and immunofluorescence analyses were conducted to assess the levels of HuR/VDR protein complex, ZO-1, Occludin, Claudin-7, and intestinal NETs. An ELISA kit was utilized to determine cytokine levels, LC-MS was performed to analyze the composition of Kuiyangling, and next-generation sequencing was conducted for detection of the intestinal mucosal transcriptome. Results Kuiyangling reduced DAI, splenic index, and ROS content; maintained mucosal structure; decreased inflammation; and increased colon length and body mass index. Western blotting indicated that Kuiyangling reduced PAD4,MPO, and citH3 levels. Kuiyangling decreased NETs and increased the expression levels of ZO-1, Occludin, and Claudin-7, as well as up-regulating HuR, VDR, and HuR/VDR proteins. Kuiyangling reduced IL-1β, IL-6, and TNF-α levels while increasing TGF-β, IL-10, and IL-37 levels. Kuiyangling reduced inflammatory response proteins and elevated the levels of anti-inflammatory and intestinal barrier proteins, possibly inhibiting the TNF and oxidative phosphorylation signaling pathways. Conclusion Kuiyangling enema in treating ulcerative colitis in mice, associated with a reduction in intestinal NETs and enhancement of HuR-mediated intestinal barrier signaling pathways.
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Affiliation(s)
- Dong Zhang
- Gastroenterology Department, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
- Gastroenterology Department, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
| | - Zeming Zhu
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China
| | - Zhangyou He
- Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China
| | - Siwei Duan
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China
| | - Qincheng Yi
- Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China
| | - Min Qiu
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China
| | - Xingzhen Dai
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China
| | - Guang Su
- Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China
| | - Kexin Li
- Gastroenterology Department, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
- Gastroenterology Department, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
| | - Lin Xu
- Gastroenterology Department, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
- Gastroenterology Department, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
| | - Donghou Liu
- Gastroenterology Department, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
- Gastroenterology Department, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
| | - Yabin Wu
- Gastroenterology Department, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
- Gastroenterology Department, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
| | - Yong Gao
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China
| | - Ruliu Li
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, 510000, People’s Republic of China
| | - Shaoju Guo
- Gastroenterology Department, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
- Gastroenterology Department, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, Guangdong Province, 518000, People’s Republic of China
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Sendani AA, Farmani M, Kazemifard N, Ghavami SB, Sadeghi A. Molecular mechanisms and therapeutic effects of natural products in inflammatory bowel disease. CLINICAL NUTRITION OPEN SCIENCE 2024; 58:21-42. [DOI: 10.1016/j.nutos.2024.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
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Chen Y, Liu X, Yuan J, Dong S, Nie M, Jiang W, Wu D, Liu M, Liu T, Wu C, Gao C, Zhang J, Jiang R. Vitamin D accelerates the subdural hematoma clearance through improving the meningeal lymphatic vessel function. Mol Cell Biochem 2024; 479:3129-3140. [PMID: 38294731 DOI: 10.1007/s11010-023-04918-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 12/18/2023] [Indexed: 02/01/2024]
Abstract
Subdural hematoma (SDH) drains into the extracranial lymphatic system through the meningeal lymphatic vessels (mLVs) but the formation of SDH impairs mLVs. Because vitamin D (Vit D) can protect the endothelial cells, we hypothesized that Vit D may enhance the SDH clearance. SDH was induced in Sprague-Dawley rats and treated with Vit D or vehicle. Hematoma volume in each group was measured by H&E staining and hemoglobin quantification. Evans blue (EB) quantification and red blood cells injection were used to evaluated the drainage of mLVs. Western blot analysis and immunofluorescence were conducted to assess the expression of lymphatic protein markers. We also examined the inflammatory factors levels in subdural space by ELISA. Vit D treatment significantly reduced SDH volume and improved the drainage of SDH to cervical lymph nodes. The structure of mLVs in SDH rats were protected by Vit D, and the expressions of LYVE1, PROX1, FOXC2, and VE-cadherin were increased after Vit D treatment. The TNF-α, IL-6, and IL-8 levels were reduced in Vit D group. In vitro, Vit D also increased the VE-cadherin expression levels under inflammation. Vit D protects the structure of mLVs and enhances the absorption of SDH, partly by the anti-inflammatory effect of Vit D.
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Affiliation(s)
- Yupeng Chen
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China
| | - Xuanhui Liu
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China
| | - Jiangyuan Yuan
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China
| | - Shiying Dong
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China
| | - Meng Nie
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China
| | - Weiwei Jiang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China
| | - Di Wu
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China
| | - Mingqi Liu
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China
| | - Tao Liu
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China
| | - Chenrui Wu
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China
| | - Chuang Gao
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China.
| | - Jianning Zhang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China.
| | - Rongcai Jiang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
- Ministry of Education, Tianjin Neurological Institute, Key Laboratory of Post Neuro-injury Neuro-repair and Regeneration in Central Nervous System, Tianjin Medical University General Hospital, 154 Anshan Road, Helping District, Tianjin, 300052, China.
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12
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Choi J, Lee J, Kim WK. Alterations in the gut microbiota of Eimeria infected broiler chickens fed diets supplemented with varying levels of dietary calcium and phosphorus, along with 25-hydroxycholecalciferol. Poult Sci 2024; 103:104223. [PMID: 39216268 PMCID: PMC11402547 DOI: 10.1016/j.psj.2024.104223] [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: 06/03/2024] [Revised: 08/06/2024] [Accepted: 08/11/2024] [Indexed: 09/04/2024] Open
Abstract
The purpose of the study was to investigate the effects of the reduced dietary calcium (Ca) and phosphorus (P) level and supplementation of 25-hydroxycholecalciferol (25-OHD3) on the expression of vitamin D receptor (VDR) and antimicrobial peptides and gut microbiota of broiler chickens with/without Eimeria challenge. A total of 576 fourteen-day-old broiler chicks were randomly allocated according to a 2 × 2 × 2 factorial design with main effects including Eimeria challenging (125,000 Eimeria acervulina, 25,000 Eimeria maxima, and 25,000 Eimeria tenella), dietary Ca and P levels (0.84% Ca and 0.42% available P or 0.64% Ca and 0.22% available P), and supplementation of 25-OHD3 (3,000 IU/kg) of 6 replicates. Three-way ANOVA was performed, and the effects of 3 main factors and their interactions were investigated. The reduced dietary Ca and P level downregulated cathelicidins 3 (CATH3) in the upper jejunum in the Eimeria challenging condition (interaction; P < 0.05). The reduced dietary Ca and P level decreased the relative mRNA expression of jejunal avian beta defensin 5 (AvBD5) in the Eimeria challenging condition (interaction; P < 0.05). The reduced dietary Ca and P level tended to decrease the relative mRNA expression of jejunal AvBD9 in the Eimeria challenging condition (interaction; P = 0.051). The reduced dietary Ca and P level decreased observed features (alpha diversity parameter for richness) in the upper jejunal microbiota in the Eimeria challenging condition (interaction; P < 0.05). The supplementation of 25-OHD3 decreased the relative abundance of the phylum Bacteroidetes (P < 0.05) and increased the relative abundance of the family Ruminococcaceae (P < 0.05) in the cecal digesta. The supplementation of 25-OHD3 decreased the serum endotoxin level in the Eimeria challenging condition (interaction; P < 0.05). Therefore, the reduced dietary Ca and P level modulated the upper jejunal microbiota via modulating the expression of antimicrobial peptides, and the supplementation of 25-OHD3 favorably modulated the cecal microbiota in broiler chickens with/without Eimeria challenge.
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Affiliation(s)
- Janghan Choi
- Department of Poultry Science, University of Georgia, Athens, GA 30602, USA; US National Poultry Research Center, USDA-ARS, Athens, GA 30605, USA
| | - Jihwan Lee
- Department of Poultry Science, University of Georgia, Athens, GA 30602, USA
| | - Woo Kyun Kim
- Department of Poultry Science, University of Georgia, Athens, GA 30602, USA.
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13
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Sheng T, Wang L, Yan S, Wei Q, Geng X, Lan W, Chen Y, Liu Y, Li N. Involvement of gut microbiota recovery and autophagy induction in Youhua Kuijie formula's protection against experimental ulcerative colitis. Exp Anim 2024; 73:357-369. [PMID: 38599877 PMCID: PMC11534492 DOI: 10.1538/expanim.23-0166] [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: 11/28/2023] [Accepted: 04/01/2024] [Indexed: 04/12/2024] Open
Abstract
Ulcerative colitis (UC) is characterized by overactive inflammatory response, impaired intestinal mucosal barrier and disrupted gut microbiota. Youhua Kuijie formula is a classic empirical prescription based on the pathogenesis of UC. The present study was designed to verify the protective effect of Youhua Kuijie formula on DSS-induced UC in mice and uncover the related mechanism. Youhua Kuijie formula were orally administrated to UC mice induced by DSS dissolved in drinking water for ten days. The protective effect of Youhua Kuijie formula was evidenced by reduced pathological symptoms accompanied by palliative inflammatory response and relatively intact intestinal barrier. The data from 16S rRNA gene sequencing and GC-MS untargeted metabolomics indicated that the supplement of Youhua Kuijie formula restructured gut microbiota community structure, and thereby modulated the metabolic profiles in UC mice. The analysis of pathway enrichment analysis suggested the major alterations in metabolic pathway were related to protein digestion and absorption. Besides, the results of the following experiments suggested that Youhua Kuijie formula treatment increased adenosine monophosphate-activated protein kinase (AMPK) activation, decreased mechanistic target of rapamycin (mTOR) phosphorylation, and thereby reversing autophagy deficiency in the intestinal tract of UC mice. Collectively, our results demonstrated that the regulation of AMPK/mTOR was involved in Youhua Kuijie formula administration mediated protective effect on UC.
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Affiliation(s)
- Tianjiao Sheng
- Graduate school, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshandong Road, Shenyang, Liaoning, 110847, P.R. China
- Department of Traditional Chinese Medicine, General Hospital of Northern Theater Command, No.83 Wenhua Road, Shenyang, Liaoning, 110016, P.R. China
| | - Lei Wang
- Department of anorectum, Hulunbuir Zhong Meng Hospital, No. 58 Xidajie Road, Hulunbuir, 021000, P.R. China
| | - Simeng Yan
- Department of 1st Area of Officers' Ward, General Hospital of Northern Theater Command, No.83 Wenhua Road, Shenyang, Liaoning, 110016, P.R. China
| | - Qiuyu Wei
- Graduate school, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshandong Road, Shenyang, Liaoning, 110847, P.R. China
| | - Xiao Geng
- Department of Traditional Chinese Medicine, General Hospital of Northern Theater Command, No.83 Wenhua Road, Shenyang, Liaoning, 110016, P.R. China
| | - Weiru Lan
- The third department of Anorectal hemorrhoids and Fistula, Liaoning University of Traditional Chinese Medicine Affiliated Third Hospital, No. 35, 11th Wei Road, Shenyang, Liaoning, 110003, P.R. China
| | - Yan Chen
- Graduate school, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshandong Road, Shenyang, Liaoning, 110847, P.R. China
| | - Yuedong Liu
- Graduate school, Liaoning University of Traditional Chinese Medicine, No. 79 Chongshandong Road, Shenyang, Liaoning, 110847, P.R. China
| | - Na Li
- Department of Anorectal Surgery, Xianyang Central Hospital, No. 78 Renmin East Road, Xianyang, Shaanxi, 712000, P.R. China
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14
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Qin X, Jin L, Chen T, He B, Tan P. Association between serum vitamin D, uric acid, C-reactive protein, and disease severity in ulcerative colitis: A retrospective study. Medicine (Baltimore) 2024; 103:e40019. [PMID: 39465814 PMCID: PMC11479401 DOI: 10.1097/md.0000000000040019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 09/20/2024] [Indexed: 10/29/2024] Open
Abstract
Ulcerative colitis (UC) is an inflammatory disease of the intestinal mucosa, and immunodeficiency is the main cause. Vitamin D (VD) has been shown to regulate many immune diseases, and studies have found that the level of uric acid (UA) and C-reactive protein (CRP) may also affect the severity of UC. This study aimed to investigate the correlation between VD levels and disease severity in UC patients. To determine serum VD levels in patients with UC of different ages and genders in China, and to study its correlation with UC, and to analyze its correlation with serum UA levels and CRP, so as to provide guidance for the prevention, diagnosis, and treatment of UC. One hundred three UC patients (64 males and 39 females, aged 16-75 years) were diagnosed with varying severity (mild, moderate, and severe). Serum VD levels, UA levels, and CRP levels were measured by electrochemiluminescence. The serum VD level of patients with severe UC was significantly lower than that of patients with mild UC. Gender was significantly correlated with serum UA, CRP, and disease severity in UC patients. Serum VD levels may affect the disease severity of UC patients, and patients with low serum VD content may have more severe disease. Gender affects serum UA, CRP, and disease severity. Males have significantly higher serum UA and CRP levels than females, while disease severity is generally lower than that of females. However, the mechanism of abnormal serum vitamin and trace element levels in UC patients remains to be further studied.
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Affiliation(s)
- Xiang Qin
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Li Jin
- Zhejiang Key TCM Laboratory for Chinese Resource Innovation and Transformation, School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Tianzhu Chen
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Beihui He
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
| | - Panli Tan
- The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, China
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15
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Khavkin AI, Novikova VP, Kondratyeva EI, Loshkova EV, Yankina GN. Vitamin D and Bone Metabolism in Celiac Disease. The Possibilities of Dietary Correction. PEDIATRIC PHARMACOLOGY 2024; 21:375-384. [DOI: 10.15690/pf.v21i4.2790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
The review describes the state of the vitamin D system and bone metabolism in celiac disease, the mechanisms of the influence of vitamin D on the state of the intestinal mucosa, and risk factors that contribute to pathological changes in bones in celiac disease. Studies are presented that evaluate bone mineral density, bone metabolism, and vitamin D status in patients with celiac disease. The results of a discussion on the effect of calcium and vitamin D supplements on the course of celiac disease and the condition of bone tissue in this disease are presented.
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Affiliation(s)
- Anatoly I. Khavkin
- Research Clinical Institute of Childhood; National Research Institute of Belgorog State University
| | | | | | - Elena V. Loshkova
- Research Clinical Institute of Childhood; Siberian State Medical University
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16
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Wang L, Nabi F, Zhang X, Zhou G, Shah QA, Li S, Lu Y, Mu S, Zhu X, Lin Z, Li J. Effects of Lactobacillus plantarum on Broiler Health: Integrated Microbial and Metabolomics Analysis. Probiotics Antimicrob Proteins 2024:10.1007/s12602-024-10336-x. [PMID: 39090454 DOI: 10.1007/s12602-024-10336-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/24/2024] [Indexed: 08/04/2024]
Abstract
Given China's prohibition on the utilization of antibiotics as feed additives in 2020, we aim to investigate nutrition additives that are both efficient and safe. Lactobacillus, a well-recognized beneficial probiotic, has explicitly been investigated for its effects on health status of the host and overall impact on food industry. To evaluate effects of Lactobacillus plantarum (LW) supplementation on broiler chicken, we conducted comprehensive multi-omics analysis, growth performance evaluation, RT-qPCR analysis, and immunofluorescence. The findings revealed that LW supplementation resulted in a substantial progress in growth performance (approximately 205 g increase in final body weight in comparison to the control group (p < 0.01)). Additionally, LW exhibited promising potential for enhancing antioxidant properties of serum and promoting gut integrity and growth as evidenced by improved antioxidant indices (p < 0.01), intestinal villus morphology (p < 0.01), and enhanced gut barrier function (p < 0.01). Meanwhile, the multi-omics analysis, including 16S rRNA sequencing and liquid chromatography-tandem mass spectrometry, revealed an enrichment of beneficial microbes in the gut of broilers that were supplemented with LW, while simultaneously depleting harmful microorganisms. Moreover, a noteworthy modification was observed in gut metabolic profiling subsequent to the execution of the probiotic strategy. Specifically, variations were noticed in the levels of metabolites and metabolic pathways such as parathyroid hormone synthesis, inflammatory mediator regulation of TRP channels, oxidative phosphorylation, and mineral absorption. Taken together, our findings validate that LW administration produces valuable effects on the health and growth performance of broilers owing to its capability to boost the gut microbiota homeostasis and intestinal metabolism. Present findings signify the potential of LW as a dietary additive to promote growth and development in broiler chickens.
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Affiliation(s)
- Lei Wang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Fazul Nabi
- Faculty of Veterinary and Animal Sciences, Lasbela University of Agriculture, Water and Marine Sciences, Uthal, 90150, Pakistan
| | - Xiaohu Zhang
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Guangyu Zhou
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Qurban Ali Shah
- Faculty of Veterinary and Animal Sciences, Lasbela University of Agriculture, Water and Marine Sciences, Uthal, 90150, Pakistan
| | - Siyuan Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Yaozhong Lu
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Siyang Mu
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Xiaohui Zhu
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Zhengrong Lin
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China
| | - Jiakui Li
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People's Republic of China.
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17
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Yang C, Yi B, Yang S, Li A, Liu J, Wang J, Liu J, Li Z, Liao Q, Zhang W, Zhang H. VDR restores the expression of PINK1 and BNIP3 in TECs of streptozotocin-induced diabetic mice. Life Sci Alliance 2024; 7:e202302474. [PMID: 38697845 PMCID: PMC11066303 DOI: 10.26508/lsa.202302474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Revised: 04/24/2024] [Accepted: 04/25/2024] [Indexed: 05/05/2024] Open
Abstract
Defective mitophagy in renal tubular epithelial cells is one of the main drivers of renal fibrosis in diabetic kidney disease. Our gene sequencing data showed the expression of PINK1 and BNIP3, two key molecules of mitophagy, was decreased in renal tissues of VDR-knockout mice. Herein, streptozotocin (STZ) was used to induce renal interstitial fibrosis in mice. VDR deficiency exacerbated STZ-induced renal impairment and defective mitophagy. Paricalcitol (pari, a VDR agonist) and the tubular epithelial cell-specific overexpression of VDR restored the expression of PINK1 and BNIP3 in the renal cortex and attenuated STZ-induced kidney fibrosis and mitochondrial dysfunction. In HK-2 cells under high glucose conditions, an increased level of α-SMA, COL1, and FN and a decreased expression of PINK1 and BNIP3 with severe mitochondrial damage were observed, and these alterations could be largely reversed by pari treatment. ChIP-qPCR and luciferase reporter assays showed VDR could positively regulate the transcription of Pink1 and Bnip3 genes. These findings reveal that VDR could restore mitophagy defects and attenuate STZ-induced fibrosis in diabetic mice through regulation of PINK1 and BNIP3.
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Affiliation(s)
- Cheng Yang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China
| | - Bin Yi
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China
| | - Shikun Yang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China
| | - Aimei Li
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China
| | - Jishi Liu
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China
| | - Jianwen Wang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China
| | - Jun Liu
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China
| | - Zhi Li
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China
| | - Qin Liao
- Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Wei Zhang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China
| | - Hao Zhang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China
- Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China
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18
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Yang CT, Yen HH, Su PY, Chen YY, Huang SP. High prevalence of vitamin D deficiency in Taiwanese patients with inflammatory bowel disease. Sci Rep 2024; 14:14091. [PMID: 38890510 PMCID: PMC11189481 DOI: 10.1038/s41598-024-64930-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Accepted: 06/14/2024] [Indexed: 06/20/2024] Open
Abstract
Vitamin D deficiency is common in patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the prevalence and risk factors of vitamin D deficiency in a Taiwanese IBD cohort. Vitamin D levels were checked in adult patients with IBD who were treated at Changhua Christian Hospital, a medical center in central Taiwan, from January 2017 to December 2023. The risk factors for vitamin D deficiency were evaluated. 106 adult IBD patients were included, including 20 patients with Crohn's disease and 86 with ulcerative colitis. The median age at diagnosis was 39.2 years. The mean vitamin D level was 22.2 ± 8 ng/mL. Forty-five patients (42.5%) had vitamin D deficiency (vitamin D level < 20 ng/mL). Comparing patients with normal vitamin D levels and those with vitamin D deficiency after multivariate adjustment, female sex and early age at diagnosis were identified as statistically significant risk factors. We found a prevalence of 42.5% of vitamin D deficiency in the Taiwanese IBD population. Understanding this issue is essential for teaching patients and doctors about vitamin D deficiency screening and improving patient outcomes.
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Affiliation(s)
- Chen-Ta Yang
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
| | - Hsu-Heng Yen
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan.
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan.
| | - Pei-Yuan Su
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
| | - Yang-Yuan Chen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
- Department of Hospitality Management, MingDao University, Changhua, 500, Taiwan
| | - Siou-Ping Huang
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, 400, Taiwan
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, 500, Taiwan
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19
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Zhan ZS, Zheng ZS, Shi J, Chen J, Wu SY, Zhang SY. Unraveling colorectal cancer prevention: The vitamin D - gut flora - immune system nexus. World J Gastrointest Oncol 2024; 16:2382-2391. [DOI: 10.4251/wjgo.v16.i6.2382] [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] [Received: 12/26/2023] [Revised: 03/02/2024] [Accepted: 04/11/2024] [Indexed: 06/13/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers diagnosed in the world. Although environmental and genetic factors play a major role in the pathogenesis of CRC, extensive research has suggested that vitamin D may play a pivotal role in the development of CRC. Vitamin D, primarily obtained through sunlight exposure, dietary sources, and supplements, has long been recognized for its essential functions in maintaining health, including immune regulation. This article delves into the intricate relationship between vitamin D, the immune system, gut flora, and the prevention of CRC. It presents a synthesis of epidemiological data, experimental studies, and clinical trials, highlighting the mechanisms by which vitamin D influences immune cell function, cytokine production, and inflammation. By enhancing the immune system’s surveillance and anti-tumor activity, vitamin D may offer a promising avenue for CRC prevention. Furthermore, this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain. Additionally, the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC, emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms, encompassing antineoplastic mechanisms, influences on the immune system, and modulation of the gut microbiome.
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Affiliation(s)
- Zhi-Song Zhan
- Department of Dentistry, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
| | - Zu-Shun Zheng
- Department of Physical Examination, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
| | - Jing Shi
- Department of Anesthesiology, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
| | - Juan Chen
- Department of Clinical Laboratory, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
| | - Si-Yi Wu
- Department of Surgery, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
| | - Shi-Yan Zhang
- Department of Clinical Laboratory, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
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20
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Zhan ZS, Zheng ZS, Shi J, Chen J, Wu SY, Zhang SY. Unraveling colorectal cancer prevention: The vitamin D - gut flora - immune system nexus. World J Gastrointest Oncol 2024; 16:2394-2403. [PMID: 38994172 PMCID: PMC11236262 DOI: 10.4251/wjgo.v16.i6.2394] [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] [Received: 12/26/2023] [Revised: 03/02/2024] [Accepted: 04/11/2024] [Indexed: 06/14/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers diagnosed in the world. Although environmental and genetic factors play a major role in the pathogenesis of CRC, extensive research has suggested that vitamin D may play a pivotal role in the development of CRC. Vitamin D, primarily obtained through sunlight exposure, dietary sources, and supplements, has long been recognized for its essential functions in maintaining health, including immune regulation. This article delves into the intricate relationship between vitamin D, the immune system, gut flora, and the prevention of CRC. It presents a synthesis of epidemiological data, experimental studies, and clinical trials, highlighting the mechanisms by which vitamin D influences immune cell function, cytokine production, and inflammation. By enhancing the immune system's surveillance and anti-tumor activity, vitamin D may offer a promising avenue for CRC prevention. Furthermore, this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain. Additionally, the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC, emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms, encompassing antineoplastic mechanisms, influences on the immune system, and modulation of the gut microbiome.
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Affiliation(s)
- Zhi-Song Zhan
- Department of Dentistry, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
| | - Zu-Shun Zheng
- Department of Physical Examination, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
| | - Jing Shi
- Department of Anesthesiology, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
| | - Juan Chen
- Department of Clinical Laboratory, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
| | - Si-Yi Wu
- Department of Surgery, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
| | - Shi-Yan Zhang
- Department of Clinical Laboratory, Fuding Hospital, Fujian University of Traditional Chinese Medicine, Fuding 355200, Fujian Province, China
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dos Santos Miranda Lobato A, da Silva JAR, de Carvalho Rodrigues TCG, Silva AGME, da Cruz AV, Ferreira APD, Costa MM, Cunha AMQ, Lourenço-Costa VV, Barbosa AVC, Prates JAM, de Brito Lourenço-Júnior J. Impact of rearing systems in the Eastern Amazon on cholesterol, β-carotene and vitamin E homologues in steer. Front Vet Sci 2024; 11:1331913. [PMID: 38818497 PMCID: PMC11138155 DOI: 10.3389/fvets.2024.1331913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 03/21/2024] [Indexed: 06/01/2024] Open
Abstract
Introduction The quality of meat, with a focus on compounds important for human health, is directly related to the rearing systems in which the animals are produced. The search for a balanced diet, with an emphasis on low cholesterol and adequate levels of vitamins, aligns with society's emphasis on healthy eating, directly correlated with the importance of the offer made by producers for the cattle's diet. Objective and methodology The objective was to verify the impact of different rearing systems, in the Eastern Amazon, during the rainy season, on the concentrations of vitamins (A, E) and cholesterol in the muscle (Longissimus lumborum) of crossbred Nelore cattle, castrated, aged between 24 and 36 months, and weighing between 410 and 628 kg. Twelve animals, from each of the three pasture rearing systems: native pasture in flooded areas of Monte Alegre; native pasture in a flooded area of Santa Cruz do Arari; and pasture cultivated on dry land in São Miguel do Guamá, all located in Pará, Brazil-were sampled in commercial slaughterhouses. Results A notable influence was observed in the concentrations of β-carotene (p < 0.01), α-Tocopherol (p = 0.02), β-Tocopherol (p < 0.01) and the combined sum of β-Tocotrienol and γ-Tocopherol (p < 0.01), as well as δ-Tocopherol (p < 0.01) when contrasting extensive with intensive systems (confinement). However, there was a difference in the content of vitamins and cholesterol between the isolated extensive systems, or between the four rearing systems (p > 0.05). Extensive systems, mainly in Monte Alegre, demonstrated greater amounts of α-Tocopherol and δ-Tocopherol. Conclusion On the other hand, the intensive system exhibited higher levels of other investigated compounds, clarifying the nutritional variations generated by different livestock rearing practices in the region. Therefore, the results obtained are innovative in the Eastern Amazon, Brazil, in addition to inspiring the development of new research to meet other demands in this field, and achieve additional results, such as determining which meat, coming from cattle in production systems in the country, presents the better compositional quality of vitamins and lipids.
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Affiliation(s)
- Adriny dos Santos Miranda Lobato
- Postgraduate Program in Animal Science (PPGCAN), Institute of Veterinary Medicine, Federal University of Para (UFPA), Castanhal, Brazil
| | | | | | - André Guimarães Maciel e Silva
- Postgraduate Program in Animal Science (PPGCAN), Institute of Veterinary Medicine, Federal University of Para (UFPA), Castanhal, Brazil
| | - Andrea Viana da Cruz
- Postgraduate Program in Animal Science (PPGCAN), Institute of Veterinary Medicine, Federal University of Para (UFPA), Castanhal, Brazil
| | - Ana Paula Damasceno Ferreira
- Postgraduate Program in Animal Science (PPGCAN), Institute of Veterinary Medicine, Federal University of Para (UFPA), Castanhal, Brazil
| | - Mónica Mendes Costa
- Faculty of Veterinary Medicine, Centre for Interdisciplinary Research in Animal Health (CIISA), University of Lisbon, Lisbon, Portugal
- Laboratório Associado para Ciência Animal e Veterinária (AL4AnimalS), Faculdade de Medicina Veterinária, Universidade de Lisboa, Lisbon, Portugal
| | | | | | | | - José António Mestre Prates
- Faculty of Veterinary Medicine, Centre for Interdisciplinary Research in Animal Health (CIISA), University of Lisbon, Lisbon, Portugal
- Laboratório Associado para Ciência Animal e Veterinária (AL4AnimalS), Faculdade de Medicina Veterinária, Universidade de Lisboa, Lisbon, Portugal
| | - José de Brito Lourenço-Júnior
- Postgraduate Program in Animal Science (PPGCAN), Institute of Veterinary Medicine, Federal University of Para (UFPA), Castanhal, Brazil
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22
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Xu D, Peng Z, Li Y, Hou Q, Peng Y, Liu X. Progress and Clinical Applications of Crohn's Disease Exclusion Diet in Crohn's Disease. Gut Liver 2024; 18:404-413. [PMID: 37842728 PMCID: PMC11096903 DOI: 10.5009/gnl230093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 07/07/2023] [Accepted: 07/24/2023] [Indexed: 10/17/2023] Open
Abstract
Crohn's disease is a chronic intestinal inflammatory disorder of unknown etiology. Although the pharmacotherapies for Crohn's disease are constantly updating, nutritional support and adjuvant therapies have recently gained more attention. Due to advancements in clinical nutrition, various clinical nutritional therapies are used to treat Crohn's disease. Doctors treating inflammatory bowel disease can now offer several diets with more flexibility than ever. The Crohn's disease exclusion diet is a widely used diet for patients with active Crohn's disease. The Crohn's disease exclusion diet requires both exclusion and inclusion. Periodic exclusion of harmful foods and inclusion of wholesome foods gradually improves a patient's nutritional status. This article reviews the Crohn's disease exclusion diet, including its structure, mechanisms, research findings, and clinical applications.
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Affiliation(s)
- Duo Xu
- Departments of Gastroenterology, Xiangya Hospital of Central South University, Changsha, China
| | - Ziheng Peng
- Departments of Gastroenterology, Xiangya Hospital of Central South University, Changsha, China
| | - Yong Li
- Departments of Gastroenterology, Xiangya Hospital of Central South University, Changsha, China
| | - Qian Hou
- Departments of Clinical Nutrition, Xiangya Hospital of Central South University, Changsha, China
| | - Yu Peng
- Departments of Gastroenterology, Xiangya Hospital of Central South University, Changsha, China
- Hunan Key Laboratory of Organ Fibrosis, Changsha, China
- Hunan International Scientific and Technological Cooperation Base of Artificial Intelligence Computer Aided Diagnosis and Treatment for Digestive Disease, Changsha, China
| | - Xiaowei Liu
- Departments of Gastroenterology, Xiangya Hospital of Central South University, Changsha, China
- Hunan International Scientific and Technological Cooperation Base of Artificial Intelligence Computer Aided Diagnosis and Treatment for Digestive Disease, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China
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23
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Cui J, Wang S, Zhai Z, Song X, Qiu T, Yu L, Zhai Q, Zhang H. Induction of autism-related behavior in male mice by early-life vitamin D deficiency: association with disruption of the gut microbial composition and homeostasis. Food Funct 2024; 15:4338-4353. [PMID: 38533674 DOI: 10.1039/d4fo00279b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/28/2024]
Abstract
Vitamin D deficiency (VDD) during early life emerges as a potential risk factor for autism spectrum disorder (ASD). Individuals with autism commonly exhibit lower vitamin D (VD) levels compared to the general population, and VD deficiency is prevalent during pregnancy and lactation. Moreover, gastrointestinal comorbidity, prevalent in ASD patients, correlates closely with disruptions in the gut microbiota and altered intestinal permeability. Therefore, it is fascinating and significant to explore the effects of maternal VD deficiency during pregnancy and lactation on the maturation of the gut microbiota of the offspring and its relevance to autism spectrum disorders. In this study, we established maternal pregnancy and lactation VD-deficient mouse models, employed shotgun macrogenomic sequencing to unveil alterations in the gut microbiome of offspring mice, and observed autism-related behaviours. Furthermore, fecal microbial transplantation (FMT) reversed repetitive and anxious behaviours and alleviated social deficits in offspring mice by modulating the gut microbiota and increasing short-chain fatty acid levels in the cecum, along with influencing the concentrations of claudin-1 and occludin in the colon. Our findings confirm that VDD during pregnancy and lactation is a risk factor for autism in the offspring, with disturbances in the structure and function of the offspring's gut microbiota contributing at least part of the effect. The study emphasises the importance of nutrition and gut health early in life. Simultaneously, this study further demonstrates the effect of VDD on ASD and provides potential ideas for early prevention and intervention of ASD.
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Affiliation(s)
- Jingjing Cui
- Wuxi School of Medicine, Jiangnan University, Wuxi, 214002, Jiangsu, China.
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Affiliated Women's Hospital of Jiangnan University, Wuxi, 214002, Jiangsu, China.
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China.
| | - Shumin Wang
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China.
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
| | - Zidan Zhai
- Wuxi School of Medicine, Jiangnan University, Wuxi, 214002, Jiangsu, China.
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Affiliated Women's Hospital of Jiangnan University, Wuxi, 214002, Jiangsu, China.
| | - Xiaoyue Song
- Department of Toxicology, School of Public Health, Anhui Medical University/Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, Anhui, China.
| | - Ting Qiu
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Affiliated Women's Hospital of Jiangnan University, Wuxi, 214002, Jiangsu, China.
| | - Leilei Yu
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China.
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China.
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu 214122, China.
| | - Heng Zhang
- Department of Child Health Care, Wuxi Maternity and Child Health Care Hospital, Affiliated Women's Hospital of Jiangnan University, Wuxi, 214002, Jiangsu, China.
- Department of Toxicology, School of Public Health, Anhui Medical University/Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Hefei 230032, Anhui, China.
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Zeng L, Zhang X, Shen Q, He L, Liu X, Zeng X, Wu Q, Ma I, Zheng S, Cheng L, Li L, Yao P. Exposure to Progestin 17-OHPC Induces Gastrointestinal Dysfunction through Claudin-1 Suppression in Female Mice with Increased Anxiety-Like Behaviors. Neuroendocrinology 2024; 114:623-638. [PMID: 38583420 PMCID: PMC11232951 DOI: 10.1159/000538692] [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: 10/20/2023] [Accepted: 03/28/2024] [Indexed: 04/09/2024]
Abstract
INTRODUCTION Progestin, commonly used in oral contraception and preventing preterm birth, elicits various off-target side effects on brain and gastrointestinal (GI) functions, yet the precise mechanisms remain elusive. This study aims to probe progestin's impact on GI function and anxiety-like behaviors in female mice. METHODS Colon stem cells were utilized to explore the mechanism underlying progestin 17-hydroxyprogesterone caproate (17-OHPC)-mediated suppression of claudin-1 (CLDN1), crucial for epithelial integrity. Chromatin immunoprecipitation and luciferase assays identified potential progestin-response elements on the CLDN1 promoter, with subsequent assessment of oxidative stress and pro-inflammatory cytokine release. Manipulation of vitamin D receptor (VDR) or estrogen receptor β (ERβ) expression elucidated their roles in 17-OHPC-mediated effects. Intestine-specific VDR deficient mice were generated to evaluate 17-OHPC's impact on GI dysfunction and anxiety-like behaviors in female mice. Additionally, gene expression was analyzed in various brain regions, including the amygdala, hypothalamus, and hippocampus. RESULTS Exposure to 17-OHPC suppressed CLDN1 expression via epigenetic modifications and VDR dissociation from the CLDN1 promoter. Furthermore, 17-OHPC intensified oxidative stress and pro-inflammatory cytokine release. VDR knockdown partly mimicked, while overexpression of either VDR or ERβ partly restored 17-OHPC-mediated effects. Intestinal VDR deficiency partly mirrored 17-OHPC-induced GI dysfunction, with minimal impact on 17-OHPC-mediated anxiety-like behaviors. CONCLUSIONS 17-OHPC suppresses CLDN1 expression through VDR, contributing to GI dysfunction in female mice, distinct from 17-OHPC-induced anxiety-like behaviors. This study reveals a new mechanism and potential negative impact of progestin exposure on the GI tract, alongside inducing anxiety-like behaviors in female mice.
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Affiliation(s)
- Liqin Zeng
- Department of Gynecology, Sun Yat-Sen University Affiliated No. 8 Hospital, Guangzhou, PR China
| | | | - Qingjun Shen
- Department of Gynecology, Sun Yat-Sen University Affiliated No. 8 Hospital, Guangzhou, PR China
| | - Li He
- Hainan Women and Children’s Medical Center, Haikou, PR China
| | - Xiaohan Liu
- Department of Gynecology, Sun Yat-Sen University Affiliated No. 8 Hospital, Guangzhou, PR China
| | - Xiangyue Zeng
- Hainan Women and Children’s Medical Center, Haikou, PR China
| | - Qiaozhu Wu
- Department of Gynecology, Sun Yat-Sen University Affiliated No. 8 Hospital, Guangzhou, PR China
| | - Irene Ma
- Hainan Women and Children’s Medical Center, Haikou, PR China
| | - Shuangyun Zheng
- Department of Gynecology, Sun Yat-Sen University Affiliated No. 8 Hospital, Guangzhou, PR China
| | - Liqin Cheng
- Department of Gynecology, Sun Yat-Sen University Affiliated No. 8 Hospital, Guangzhou, PR China
| | - Ling Li
- Hainan Women and Children’s Medical Center, Haikou, PR China
| | - Paul Yao
- Department of Gynecology, Sun Yat-Sen University Affiliated No. 8 Hospital, Guangzhou, PR China
- Hainan Women and Children’s Medical Center, Haikou, PR China
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Singhal B, Chauhan S, Soni N, Gurjar V, Joshi V, Kaur P, Ratre P, Kumari R, Mishra PK. Modulatory Effects of Vitamin D: A Possible Approach to Mitigate Air Pollution Related Pregnancy Complications. J Reprod Infertil 2024; 25:79-101. [PMID: 39157803 PMCID: PMC11327426 DOI: 10.18502/jri.v25i2.16004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 05/18/2024] [Indexed: 08/20/2024] Open
Abstract
Approximately 99% of people on the planet breathe air that exceeds the World Health Organization's permitted threshold for pollution. South Asia is home to the world's most polluted cities. Population-based studies have suggested that women's reproductive health outcomes are worsening due to air pollution. Preeclampsia, miscarriage, gestational diabetes, high blood pressure, and unfavorable birth outcomes, including preterm birth, low birth weight, or even stillbirth are all linked to exposure to air pollution during pregnancy. It is estimated that 0.61 million deaths in India alone were related to indoor air pollution. Females frequently cook in the household using solid fuel as a primary combustion source. Women in the regions with the highest population density are disproportionately affected by high levels of poor-quality indoor air. Recently, it has been proposed that air pollution has a distinct role in the onset of vitamin D deficiency. Numerous studies have explored associations between low vitamin D level and various female reproductive health conditions since the discovery of the vitamin D receptor. It is worthy to note that some of these reproductive health conditions positively correlate with the severity of air pollution. In this study, the evidence has been synthesized on vitamin D's protective properties and dietary and pharmaceutical interventions have been discussed to show their beneficial effects in decreasing the long-term negative impacts of air pollution on women's health.
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Affiliation(s)
| | | | - Nikita Soni
- - Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, India
| | - Vikas Gurjar
- - Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, India
| | - Vibhor Joshi
- - Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, India
| | - Prasan Kaur
- - Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, India
| | - Pooja Ratre
- - Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, India
| | - Roshani Kumari
- - Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, India
| | - Pradyumna Kumar Mishra
- - Division of Environmental Biotechnology, Genetics & Molecular Biology (EBGMB), ICMR-National Institute for Research in Environmental Health (NIREH), Bhopal, India
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Schreiber L, Ghimire S, Hiergeist A, Renner K, Althammer M, Babl N, Peuker A, Schoenhammer G, Hippe K, Gessner A, Albrecht C, Pielmeier F, Büttner-Herold M, Bruns H, Hoffmann P, Herr W, Holler E, Peter K, Kreutz M, Matos C. Strain specific differences in vitamin D3 response: impact on gut homeostasis. Front Immunol 2024; 15:1347835. [PMID: 38495883 PMCID: PMC10943696 DOI: 10.3389/fimmu.2024.1347835] [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: 12/01/2023] [Accepted: 02/15/2024] [Indexed: 03/19/2024] Open
Abstract
Vitamin D3 regulates a variety of biological processes irrespective of its well-known importance for calcium metabolism. Epidemiological and animal studies indicate a role in immune regulation, intestinal barrier function and microbiome diversity. Here, we analyzed the impact of different vitamin D3- containing diets on C57BL/6 and BALB/c mice, with a particular focus on gut homeostasis and also investigated effects on immune cells in vitro. Weak regulatory effects were detected on murine T cells. By trend, the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 suppressed IFN, GM-CSF and IL-10 cytokine secretion in T cells of C57BL/6 but not BALB/c mice, respectively. Using different vitamin D3-fortified diets, we found a tissue-specific enrichment of mainly CD11b+ myeloid cells but not T cells in both mouse strains e.g. in spleen and Peyer's Patches. Mucin Reg3γ and Batf expression, as well as important proteins for gut homeostasis, were significantly suppressed in the small intestine of C57BL76 but not BALB/c mice fed with a high-vitamin D3 containing diet. Differences between both mouse stains were not completely explained by differences in vitamin D3 receptor expression which was strongly expressed in epithelial cells of both strains. Finally, we analyzed gut microbiome and again an impact of vitamin D3 was detected in C57BL76 but not BALB/c. Our data suggest strain-specific differences in vitamin D3 responsiveness under steady state conditions which may have important implications when choosing a murine disease model to study vitamin D3 effects.
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Affiliation(s)
- Laura Schreiber
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Sakhila Ghimire
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Andreas Hiergeist
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
| | - Kathrin Renner
- Department of Otorhinolaryngology, University Hospital Regensburg, Regensburg, Germany
| | - Michael Althammer
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Nathalie Babl
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Alice Peuker
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Gabriele Schoenhammer
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Katrin Hippe
- Department of Pathology, University of Regensburg, Regensburg, Germany
| | - Andre Gessner
- Institute of Clinical Microbiology and Hygiene, University Hospital Regensburg, Regensburg, Germany
| | | | | | - Maike Büttner-Herold
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Heiko Bruns
- Department of Internal Medicine 5, Hematology and Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany
| | - Petra Hoffmann
- Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany
| | - Wolfgang Herr
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Ernst Holler
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Katrin Peter
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Marina Kreutz
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
| | - Carina Matos
- Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany
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Hu JJ, Lin YS, Zhang JC, Wang YH. Vitamin D Improves Klebsiella-Induced Severe Pneumonia in Rats by Regulating Intestinal Microbiota. Infect Drug Resist 2024; 17:475-484. [PMID: 38348232 PMCID: PMC10860834 DOI: 10.2147/idr.s442330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 01/17/2024] [Indexed: 02/15/2024] Open
Abstract
Background In the context of progressively uncontrolled drug resistance of bacteria, the difficulty of treating Klebsiella (KP)-induced pneumonia increases. Searching for drugs other than antibiotics has become an urgent task. Vitamin D (VD), meanwhile, is shown to be capable of treating pneumonia. Therefore, we aimed to explore the effects and mechanisms of VD on KP-infected rats. Methods Male Sprague Dawley rats were divided into the Control, VD, KP and KP+VD groups. A rat pneumonia model was induced using an intratracheal drop of 2.4×108 CFU/mL KP. VD treatment was performed by gavage using 5 μg/kg. Subsequently, the survival of the rats was recorded, and the lungs, bronchoalveolar lavage fluid, and feces of the rats were collected 4 days after KP infection. Next, the water content of lung tissues was measured by the wet-to-dry weight ratio. Histopathological changes of lung tissues were observed by Hematoxylin and Eosin staining and the levels of inflammatory factors (TNF-α, IL-1β, MCP1) were detected using ELISA. The feces of rats in each group were also subjected to 16S rDNA gene analysis of intestinal microbiota. Results Compared with the KP group, the KP+VD group showed a significant increase in survival, a significant decrease in water content and bacterial counts in the lungs, a significant improvement in lung injury, and a significant decline in the levels of TNF-α, IL-1β, and MCP1. According to the 16S rDNA sequencing, VD altered the structure of the intestinal bacterial community in the KP-infected rats and made the species richness similar to that of healthy rats. Additionally, the abundance of Anaeroglobus was significantly increased in the KP+VD group. Conclusion VD modulates intestinal microbiota to increase the resistance of rats to pneumonia caused by Klebsiella infection.
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Affiliation(s)
- Jia-Jia Hu
- Medical Intensive Care Unit, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Yu-Sen Lin
- Medical Intensive Care Unit, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Jing-Cong Zhang
- Medical Intensive Care Unit, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Yan-Hong Wang
- Medical Intensive Care Unit, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
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Matias JN, Lima VM, Nutels GS, Laurindo LF, Barbalho SM, de Alvares Goulart R, Araújo AC, Suzuki RB, Guiguer EL. The use of vitamin D for patients with inflammatory bowel diseases. INT J VITAM NUTR RES 2024; 94:54-70. [PMID: 36017738 DOI: 10.1024/0300-9831/a000764] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
As vitamin D (VD) plays an essential role in inflammatory bowel diseases (IBD), this systematic review aimed to update the participation of this vitamin in the prevention or remission of these diseases. This review has included studies in MEDLINE-PubMed, EMBASE, and Cochrane databases. The authors have followed PRISMA (Preferred Reporting Items for a Systematic Review and Meta-analysis) guidelines. According to the inclusion and exclusion criteria, twenty-two randomized clinical trials were selected. In total, 1,209 patients were included in this systematic review: 1034 received only VD and 175 received VD in combination with calcium. The average doses of VD supplementation were from oral 400 IU daily to 10,000 IU per kilogram of body weight. Single injection of 300,000 IU of VD was also used. Several studies have shown the crucial role that VD plays in the therapeutic approach of IBD due to its effects on the immune system. It effectively decreased inflammatory cytokines such as TNF-α and IFN-γ (p<0.05) and provided a reduction in disease activity assessed through different scores such as Crohn's Disease Activity Index (CDAI) (p<0.05) and Ulcerative Colitis Disease Activity Index (UCDAI) (p<0.05). Unfortunately, the available clinical trials are not standardized for of doses and routes of administration. Existing meta-analyses are biased because they compare studies using different doses or treatments in combination with different drugs or supplements such as calcium. Even though VD has crucial effects on inflammatory processes, there is still a need for standardized studies to establish how the supplementation should be performed and the doses to be administered.
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Affiliation(s)
- Júlia Novaes Matias
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
| | - Vinícius Marinho Lima
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
| | - Giovanna Soares Nutels
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
| | - Lucas Fornari Laurindo
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
| | - Sandra Maria Barbalho
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília, São Paulo, Brazil
| | - Ricardo de Alvares Goulart
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília, São Paulo, Brazil
| | - Adriano Cressoni Araújo
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília, São Paulo, Brazil
| | - Rodrigo Buzinaro Suzuki
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
- Department of Parasitology, Marília Medical School (Famema), Marília, São Paulo, Brazil
| | - Elen Landgraf Guiguer
- Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Marília, São Paulo, Brazil
- Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Marília, São Paulo, Brazil
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Xiang L, Du T, Zhang J, Zhang Y, Zhou Y, Zhao Y, Zhou Y, Ma L. Vitamin D 3 supplementation shapes the composition of gut microbiota and improves some obesity parameters induced by high-fat diet in mice. Eur J Nutr 2024; 63:155-172. [PMID: 37740812 DOI: 10.1007/s00394-023-03246-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Accepted: 09/01/2023] [Indexed: 09/25/2023]
Abstract
PURPOSE Individuals with vitamin D (VD) insufficiency have a greater tendency to develop obesity and have increased systemic inflammation. Gut microbiota are involved in the regulation of host inflammation and energy metabolism, which plays a role in the pathogenesis of obesity. Thus, we aimed to evaluate the effects of different doses of VD3 on body weight, serum lipids, inflammatory factors, and intestinal barrier function in obese mice and to explore the regulatory effect of VD3 on gut microbiota in obese mice. METHODS Male C57BL/6 J mice received a normal chow diet (NCD, 10% fat) or high-fat diet (HFD, 60% fat) to induce obesity within 10 weeks. Then, HFD mice were supplemented with 5650, 8475, or 11,300 IU VD3/kg diet for 8 weeks. Finally, 16 s rRNA analysis was performed to analyze gut microbiota composition in cecal contents. In addition, body weight, serum lipids, inflammatory factors, and intestinal barrier function were analyzed. RESULTS VD3 supplementation reduced body weight and the levels of TG, TC, HDL-C, TNF-α, IL-1β and LPS, and increased ZO-1 in HFD-fed mice. Moreover, it increased α-diversity, reduced F/B ratio and altered microbiota composition by increasing relative abundance of Bacteroidetes, Proteobacteria, Desulfovibrio, Dehalobacterium, Odoribacter, and Parabacteroides and reducing relative abundance of Firmicutes and Ruminococcus. There were significant differences between HFD and NCD groups in several metabolic pathways, including endotoxin biosynthesis, tricarboxylic acid cycle, lipid synthesis and metabolism, and glycolysis. CONCLUSIONS Low, medium, and high doses of VD3 inhibited weight gain, reduced levels of blood lipids and inflammatory factors, and improved endotoxemia and gut barrier function in obese mice. It also increased the α-diversity of gut microbiota in obese mice and reduced the relative abundance of some intestinal pathogenic bacteria, increased the relative abundance of some beneficial bacteria, and corrected the intestinal flora disorder of obese mice, with the low- and high-dose groups showing better effects than the medium-dose group.
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Affiliation(s)
- Lian Xiang
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Tingwan Du
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Jingjing Zhang
- Department of Clinical Nutrition, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Yuanfan Zhang
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Yanqiu Zhou
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Yueying Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China
| | - Yong Zhou
- Department of Medical Cell Biology and Genetics, School of Basic Medical Science, Southwest Medical University, Luzhou, China.
| | - Ling Ma
- Department of Nutrition and Food Hygiene, School of Public Health, Southwest Medical University, Luzhou, China.
- Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou, China.
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Hu Y, Wang Y, Chen Y, Li C, Long Y, Wu C. Co-administration of 1,25-dihydroxyvitamin D3 and infliximab improves colitis in mice by modulating Treg differentiation. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES 2024; 27:1172-1179. [PMID: 39055880 PMCID: PMC11266739 DOI: 10.22038/ijbms.2024.74640.16209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 02/10/2024] [Indexed: 07/28/2024]
Abstract
Objectives The combination of TNF-α inhibitors and vitamin D in colitis remains to be elucidated. In the present study, we revealed the benefit of infliximab (IFX) and vitamin D in a mouse model of Ulcerative colitis (UC). Materials and Methods A dextran sulfate sodium-induced colitis model was used. The therapeutic effect of the combination was evaluated by symptom and histopathology analysis. The synergistic mechanism was explored by detecting the regulatory effect of the combined therapy on Regulatory T cell (Treg) differentiation. Results IFX and 1,25-dihydroxyvitamin D3 (VitD3) synergistically prevented the development of colitis by improving clinical signs, pathological and hematological manifestation, and inhibiting intestinal inflammation (decreasing TNF-α, IL-1β, and IL-6). Co-administration of IFX (2.5 mg/kg) with VitD3 or IFX (5.0 mg/kg) with VitD3 was more effective than administration of IFX (2.5 mg/kg, 5.0 mg/kg). There was no difference in therapeutic effect between IFX (5.0 mg/kg) and VitD3+ IFX (2.5 mg/kg) groups or between the VitD3+IFX (5.0 mg/kg) and VitD3+ Azathioprine (AZA) groups. VitD3 or combination therapy showed more powerful regulation of splenetic Treg differentiation and IL-10 production than IFX alone. Moreover, VitD3 alone or in combination induced higher levels of Foxp3 and IL-10 than IFX in colon tissue. In ulcerative colitis patients, serum VitD3 levels positively correlated with Treg levels. Conclusion VitD3 and IFX synergistically inhibit colitis based on their powerful regulation of Treg differentiation. VitD3 combined with IFX is an alternative therapy for patients who are intolerant to standard doses of IFX or combination of IFX and AZA.
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Affiliation(s)
- Yan Hu
- Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, China, 230022
- Department of Gastroenterology, Anhui Children’s Hospital, 39 Wangjiang East road, Hefei, China, 230051
| | - Yang Wang
- Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, China, 230022
| | - Ying Chen
- Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, China, 230022
| | - ChuanYing Li
- Department of Gastroenterology, Anhui Children’s Hospital, 39 Wangjiang East road, Hefei, China, 230051
| | - Yun Long
- Department of Gastroenterology, Anhui Children’s Hospital, 39 Wangjiang East road, Hefei, China, 230051
| | - Cheng Wu
- Department of Gastroenterology, Anhui Children’s Hospital, 39 Wangjiang East road, Hefei, China, 230051
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Yang J, Chen X, Liu T, Shi Y. Potential role of bile acids in the pathogenesis of necrotizing enterocolitis. Life Sci 2024; 336:122279. [PMID: 37995935 DOI: 10.1016/j.lfs.2023.122279] [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: 09/01/2023] [Revised: 11/13/2023] [Accepted: 11/15/2023] [Indexed: 11/25/2023]
Abstract
Necrotizing enterocolitis (NEC) is one of the most common acute gastrointestinal diseases in preterm infants. Recent studies have found that NEC is not only caused by changes in the intestinal environment but also by the failure of multiple systems and organs, including the liver. The accumulation of bile acids (BAs) in the ileum and the disorder of ileal BA transporters are related to the ileum injury of NEC. Inflammatory factors such as tumor necrosis factor (TNF)-α and interleukin (IL)-18 secreted by NEC also play an important role in regulating intrahepatic BA transporters. As an important link connecting the liver and intestinal circulation, the bile acid metabolic pathway plays an important role in the regulation of intestinal microbiota, cell proliferation, and barrier protection. In this review, we focus on how bile acids explore the dynamic changes of bile acid metabolism in necrotizing enterocolitis and the potential therapeutic value of targeting the bile acid signaling pathways.
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Affiliation(s)
- Jiahui Yang
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
| | - Xiaoyu Chen
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
| | - Tianjing Liu
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
| | - Yongyan Shi
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
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Wang HQ, Zhao MX, Hong SC, He X, Tao L, Tong CC, Jing Guan, Xu DX, Chen X. 1,25(OH) 2D 3 alleviates oxidative stress and inflammation through up-regulating HMGCS2 in DSS-induced colitis. Int Immunopharmacol 2023; 125:111131. [PMID: 38149572 DOI: 10.1016/j.intimp.2023.111131] [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: 09/09/2023] [Revised: 10/16/2023] [Accepted: 10/23/2023] [Indexed: 12/28/2023]
Abstract
BACKGROUND Previous study found that supplements with active vitamin D3 alleviated experimental colitis. The objective of this study was to investigate the possible role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a ketone synthase, on vitamin D3 protecting against experimental colitis. METHODS HMGCS2 and vitamin D receptor (VDR) were measured in UC patients. The effects of vitamin D deficiency (VDD) and exogenous 1,25(OH)2D3 supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)-treated mice. DSS-induced oxidative stress and inflammation were analyzed in HT-29 cells. HMGCS2 was detected in 1,25(OH)2D3-pretreated HT-29 cells and mouse intestines. HMGCS2 was silenced to investigate the role of HMGCS2 in 1,25(OH)2D3 protecting against experimental colitis. RESULTS Intestinal HMGCS2 downregulation was positively correlated with VDR reduction in UC patients. The in vivo experiments showed that VDD exacerbated DSS-induced colitis. By contrast, 1,25(OH)2D3 supplementation ameliorated DSS-induced colon damage, oxidative stress and inflammation. HMGCS2 was up-regulated after 1,25(OH)2D3 supplementation both in vivo and in vitro. Transfection with HMGCS2-siRNA inhibited antioxidant and anti-inflammatory effects of 1,25(OH)2D3 in DSS-treated HT-29 cells. CONCLUSION 1,25(OH)2D3 supplementation up-regulates HMGCS2, which is responsible for 1,25(OH)2D3-mediated protection against oxidative stress and inflammation in DSS-induced colitis. These findings provide a potential therapeutic strategy for alleviating colitis-associated oxidative stress and inflammation.
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Affiliation(s)
- Hong-Qian Wang
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Digestive Diseases of Anhui Province, Hefei, China
| | - Meng-Xue Zhao
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Digestive Diseases of Anhui Province, Hefei, China
| | - Shao-Cheng Hong
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Digestive Diseases of Anhui Province, Hefei, China
| | - Xue He
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Digestive Diseases of Anhui Province, Hefei, China
| | - Li Tao
- Department of Gastroenterology, Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Cheng-Cheng Tong
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Digestive Diseases of Anhui Province, Hefei, China
| | - Jing Guan
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Digestive Diseases of Anhui Province, Hefei, China
| | - De-Xiang Xu
- Department of Toxicology, Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China.
| | - Xi Chen
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China; Key Laboratory of Digestive Diseases of Anhui Province, Hefei, China.
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Fan L, Xia Y, Wang Y, Han D, Liu Y, Li J, Fu J, Wang L, Gan Z, Liu B, Fu J, Zhu C, Wu Z, Zhao J, Han H, Wu H, He Y, Tang Y, Zhang Q, Wang Y, Zhang F, Zong X, Yin J, Zhou X, Yang X, Wang J, Yin Y, Ren W. Gut microbiota bridges dietary nutrients and host immunity. SCIENCE CHINA. LIFE SCIENCES 2023; 66:2466-2514. [PMID: 37286860 PMCID: PMC10247344 DOI: 10.1007/s11427-023-2346-1] [Citation(s) in RCA: 68] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Accepted: 04/05/2023] [Indexed: 06/09/2023]
Abstract
Dietary nutrients and the gut microbiota are increasingly recognized to cross-regulate and entrain each other, and thus affect host health and immune-mediated diseases. Here, we systematically review the current understanding linking dietary nutrients to gut microbiota-host immune interactions, emphasizing how this axis might influence host immunity in health and diseases. Of relevance, we highlight that the implications of gut microbiota-targeted dietary intervention could be harnessed in orchestrating a spectrum of immune-associated diseases.
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Affiliation(s)
- Lijuan Fan
- Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Yaoyao Xia
- Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Youxia Wang
- Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Dandan Han
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Yanli Liu
- College of Animal Science and Technology, Northwest A&F University, Xi'an, 712100, China
| | - Jiahuan Li
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Jie Fu
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Leli Wang
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China
| | - Zhending Gan
- Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Bingnan Liu
- Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Jian Fu
- Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Congrui Zhu
- Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Zhenhua Wu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Jinbiao Zhao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Hui Han
- Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Hao Wu
- State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China
| | - Yiwen He
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China
- Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, College of Life Sciences, Hunan Normal University, Changsha, 410081, China
| | - Yulong Tang
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China
| | - Qingzhuo Zhang
- Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China
| | - Yibin Wang
- College of Animal Science and Technology, Northwest A&F University, Xi'an, 712100, China
| | - Fan Zhang
- College of Animal Science and Technology, Northwest A&F University, Xi'an, 712100, China
| | - Xin Zong
- College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
| | - Jie Yin
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China.
| | - Xihong Zhou
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China.
| | - Xiaojun Yang
- College of Animal Science and Technology, Northwest A&F University, Xi'an, 712100, China.
| | - Junjun Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
| | - Yulong Yin
- Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, 410125, China.
- College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China.
| | - Wenkai Ren
- Guangdong Laboratory of Lingnan Modern Agriculture, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
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Bersanelli M, Cortellini A, Leonetti A, Parisi A, Tiseo M, Bordi P, Michiara M, Bui S, Cosenza A, Ferri L, Giudice GC, Testi I, Rapacchi E, Camisa R, Vincenzi B, Caruso G, Rauti AN, Arturi F, Tucci M, Santo V, Ricozzi V, Burtet V, Sgargi P, Todeschini R, Zustovich F, Stucci LS, Santini D, Buti S. Systematic vitamin D supplementation is associated with improved outcomes and reduced thyroid adverse events in patients with cancer treated with immune checkpoint inhibitors: results from the prospective PROVIDENCE study. Cancer Immunol Immunother 2023; 72:3707-3716. [PMID: 37638980 PMCID: PMC10576732 DOI: 10.1007/s00262-023-03522-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 08/10/2023] [Indexed: 08/29/2023]
Abstract
BACKGROUND Hypovitaminosis D can have a negative prognostic impact in patients with cancer. Vitamin D has a demonstrated role in T-cell-mediated immune activation. We hypothesized that systematic vitamin D repletion could impact clinical outcomes in patients with cancer receiving immune-checkpoint inhibitors (ICIs). METHODS We planned a prospective observational study (PROVIDENCE) to assess serum vitamin D levels in patients with advanced cancer receiving ICIs (cohort 1 at treatment initiation, cohort 2 during treatment) and the impact of systematic repletion on survival and toxicity outcomes. In an exploratory analysis, we compared the clinical outcomes of cohort 1 with a control cohort of patients followed at the participating centers who did not receive systematic vitamin D repletion. RESULTS Overall, 164 patients were prospectively recruited in the PROVIDENCE study. In cohort 1, consisting of 101 patients with 94.1% hypovitaminosis (≤ 30 ng/ml) at baseline, adequate repletion with cholecalciferol was obtained in 70.1% at the three months re-assessment. Cohort 2 consisted of 63 patients assessed for vitamin D at a median time of 3.7 months since immunotherapy initiation, with no patients having adequate levels (> 30 ng/ml). Even in cohort 2, systematic supplementation led to adequate levels in 77.8% of patients at the three months re-assessment. Compared to a retrospective control group of 238 patients without systematic vitamin D repletion, PROVIDENCE cohort 1 showed longer overall survival (OS, p = 0.013), time to treatment failure (TTF, p = 0.017), and higher disease control rate (DCR, p = 0.016). The Inverse Probability of Treatment Weighing (IPTW) fitted multivariable Cox regression confirmed the significantly decreased risk of death (HR 0.55, 95%CI: 0.34-0.90) and treatment discontinuation (HR 0.61, 95%CI: 0.40-0.91) for patients from PROVIDENCE cohort 1 in comparison to the control cohort. In the context of longer treatment exposure, the cumulative incidence of any grade immune-related adverse events (irAEs) was higher in the PROVIDENCE cohort 1 compared to the control cohort. Nevertheless, patients from cohort 1 experienced a significantly decreased risk of all grade thyroid irAEs than the control cohort (OR 0.16, 95%CI: 0.03-0.85). CONCLUSION The PROVIDENCE study suggests the potential positive impact of early systematic vitamin D supplementation on outcomes of patients with advanced cancer receiving ICIs and support adequate repletion as a possible prophylaxis for thyroid irAEs.
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Affiliation(s)
- Melissa Bersanelli
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
- Gruppo Oncologico Italiano Di Ricerca Clinica (GOIRC), Parma, Italy
| | - Alessio Cortellini
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Alvaro del Portillo N° 200, 00128, Rome, Italy.
- Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College London, London, UK.
| | - Alessandro Leonetti
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
- Gruppo Oncologico Italiano Di Ricerca Clinica (GOIRC), Parma, Italy
| | - Alessandro Parisi
- Department of Oncology, Università Politecnica Delle Marche-AOU Delle Marche, 60121, Ancona, Italy
| | - Marcello Tiseo
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
- Gruppo Oncologico Italiano Di Ricerca Clinica (GOIRC), Parma, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Paola Bordi
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Maria Michiara
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Simona Bui
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Agnese Cosenza
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Leonarda Ferri
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Giulia Claire Giudice
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Irene Testi
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Elena Rapacchi
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Roberta Camisa
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Bruno Vincenzi
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Alvaro del Portillo N° 200, 00128, Rome, Italy
| | - Giuseppe Caruso
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | | | - Federica Arturi
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Marco Tucci
- Department of Interdisciplinary Medicine (DIM), University of Bari "Aldo Moro", Bari, Italy
| | - Valentina Santo
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Alvaro del Portillo N° 200, 00128, Rome, Italy
| | - Valentina Ricozzi
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Alvaro del Portillo N° 200, 00128, Rome, Italy
| | - Vanessa Burtet
- UOC Farmacia Ospedaliera, Aulss N.1 Dolomiti, Belluno Hospital, Belluno, Italy
| | - Paolo Sgargi
- Cancer Registry of Parma Province, University Hospital of Parma, Parma, Italy
| | | | - Fable Zustovich
- UOC Oncologia, Aulss N.1 Dolomiti, Belluno Hospital, Belluno, Italy
| | | | - Daniele Santini
- Oncologia Medica A, Policlinico Umberto 1, La Sapienza Università Di Roma, Rome, Italy
| | - Sebastiano Buti
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
- Gruppo Oncologico Italiano Di Ricerca Clinica (GOIRC), Parma, Italy
- Department of Medicine and Surgery, University of Parma, Parma, Italy
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Lee D, Kim S, Koo Y, Chae Y, Wang J, Kim S, Yun T, Yang MP, Kang BT, Kim H. Expression of vitamin D receptor, CYP24A1, and CYP27B1 in normal and inflamed canine pancreases. Front Vet Sci 2023; 10:1265203. [PMID: 37808100 PMCID: PMC10551448 DOI: 10.3389/fvets.2023.1265203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 09/05/2023] [Indexed: 10/10/2023] Open
Abstract
Vitamin D plays a role in anti-inflammatory processes, and the alteration of its metabolism is associated with the inflammatory processes of pancreatitis. This study was performed to evaluate the expression of the vitamin D receptor (VDR) and the two major enzymes that regulate vitamin D metabolism, 1α-hydroxylase (CYP27B1) and 24-hydroxylase (CYP24A1), in the canine pancreas and to compare their degrees of immunoreactivity between normal and inflamed pancreases. Five normal and inflamed pancreatic tissues each were obtained from six dogs. The expression of VDR, CYP24A1, and CYP27B1 were determined immunohistochemically, and the degree of immunostaining was assessed semiquantitatively. The VDR was expressed in the ducts, acini, and islets of Langerhans of normal pancreases and in the ducts and acini of inflamed ones. There was a significant difference in the immunoreactivity score for VDR in the islets of Langerhans between normal (median, 3 [interquartile range, 2-7.5] score) and inflamed pancreatic tissues (0 [0-0.5] score, p = 0.03). CYP24A1 was expressed in the ducts and islets of Langerhans in both normal and inflamed pancreases, whereas CYP27B1 was expressed in the ducts and acini in only some normal and inflamed pancreatic tissues. This study showed that VDR expression decreased in inflamed pancreases and demonstrated CYP24A1 and CYP27B1 expression in the canine pancreas for the first time. These findings indicate that the pancreas could regulate the metabolism and biological activity of vitamin D and suggest that a decrease in these might be related to the pathophysiology of pancreatitis.
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Affiliation(s)
- Dohee Lee
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Sanggu Kim
- Laboratory of Veterinary Pathology and Platelet Signaling, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Yoonhoi Koo
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Yeon Chae
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Juwon Wang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Soochong Kim
- Laboratory of Veterinary Pathology and Platelet Signaling, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Taesik Yun
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Mhan-Pyo Yang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Byeong-Teck Kang
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
| | - Hakhyun Kim
- Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea
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Song WX, Yu ZH, Ren XF, Chen JH, Chen X. Role of micronutrients in inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2023; 31:711-731. [DOI: 10.11569/wcjd.v31.i17.711] [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] [Received: 08/08/2023] [Revised: 08/28/2023] [Accepted: 09/01/2023] [Indexed: 09/08/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an autoimmune intestinal disease that includes ulcerative colitis, Crohn's disease, and indeterminate colitis. Patients with IBD are often at risk for malnutrition, including micronutrient deficiencies, due to dietary restrictions and poor intestinal absorption. Micronutrients, including vitamins and minerals, play an important role in the human body's metabolism and maintenance of tissue functions. This article reviews the role of micronutrients in IBD. Micronutrients can affect the occurrence and progression of IBD by regulating immunity, intestinal flora, oxidative stress, intestinal barrier function, and other aspects. Monitoring and timely supplementation of micronutrients are important to delay progression and improve clinical symptoms in IBD patients.
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Affiliation(s)
- Wen-Xuan Song
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Zi-Han Yu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xiang-Feng Ren
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Ji-Hua Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xin Chen
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin 300052, China
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Liu H, Lu N, Cui M, Zhang M. Role of epigenetic modifications mediated by vitamins and trace elements in inflammatory bowel disease. Epigenomics 2023; 15:839-843. [PMID: 37694343 DOI: 10.2217/epi-2023-0226] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/12/2023] Open
Abstract
Graphical abstract [Formula: see text] Numerous environmental factors frequently emerge as primary determinants of inflammatory bowel disease (IBD). Diet is a major component of environmental factors, and the consumption of vitamins (A, B, C and D) and trace elements (calcium, iron, zinc and selenium) exerts an impact on the progression of IBD through epigenetic modifications. Intake of vitamins A, B, C and D, as well as excessive amounts of iron and calcium, can modulate the condition of IBD by regulating the levels of DNA methylation, histone acetylation and miRNA. Zinc and selenium alleviate the progression of IBD by regulating the levels of promoter methylation or histone ubiquitination, respectively. Graphical Abstract was adapted from 'Epigenetic levels (layout)', by BioRender.com. Retrieved from https://app.biorender.com/biorender-templates.
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Affiliation(s)
- Hao Liu
- Department of Clinical Medicine, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, 712046, China
| | - Ning Lu
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, China
| | - Manli Cui
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, China
| | - Mingxin Zhang
- Department of Gastroenterology, the First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, China
- The Second Affiliated Hospital of Chinese Medicine, Xianyang, Shaanxi, 712099, China
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夏 雨, 周 娟, 赵 红, 游 洁. [Mechanism of action and exogenous supplementation of vitamin D in Crohn's disease]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2023; 25:870-876. [PMID: 37668037 PMCID: PMC10484078 DOI: 10.7499/j.issn.1008-8830.2212064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 06/29/2023] [Indexed: 09/06/2023]
Abstract
Vitamin D can not only regulate calcium and phosphorus metabolism, but also exert an immunoregulatory effect. Vitamin D deficiency is common in patients with Crohn's disease (CD). Studies have shown that vitamin D is associated with CD and other autoimmune diseases and can improve the condition of patients with CD and promote their recovery by regulating intestinal immunity, repairing the intestinal mucosal barrier, inhibiting intestinal fibrosis, enhancing the response to infliximab, and regulating intestinal microbiota. Exogenous vitamin D supplementation can induce disease remission while increasing the serum level of vitamin D. However, only a few randomized, double-blind, and placebo-controlled trials have investigated the therapeutic effect of vitamin D in CD, and the optimal form of vitamin D supplementation, the specific dosage of vitamin D supplementation, and the optimal serum maintenance concentration of vitamin D remain to be clarified. This article mainly discusses the mechanism of action of vitamin D in CD and the beneficial effect of exogenous vitamin D supplementation on CD.
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Affiliation(s)
- 雨 夏
- 南华大学衡阳医学院/湖南省儿童医院研究生协作培养基地， 湖南衡阳421001
| | | | | | - 洁玉 游
- 南华大学衡阳医学院/湖南省儿童医院研究生协作培养基地， 湖南衡阳421001
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Matthews SW, Plantinga A, Burr R, Cain KC, Savidge T, Kamp K, Heitkemper MM. Exploring the Role of Vitamin D and the Gut Microbiome: A Cross-Sectional Study of Individuals with Irritable Bowel Syndrome and Healthy Controls. Biol Res Nurs 2023; 25:436-443. [PMID: 36624571 PMCID: PMC10404909 DOI: 10.1177/10998004221150395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction with multifaceted pathophysiology. Prior studies have demonstrated higher rates of vitamin D deficiency in individuals with IBS compared to healthy controls (HC), as well as associations of vitamin D concentration with IBS symptoms. A systematic review of 10 mouse and 14 human studies reported a positive association between vitamin D (serum levels and supplementation) and beta diversity of gut microbiome in a variety of conditions. The present retrospective case-control study aimed to compare vitamin D (25(OH)D) plasma concentrations and gut microbiome composition in adult women with IBS (n=99) and HC (n=62). Plasma concentrations of 25(OH)D were assessed using the Endocrine Society Guidelines definition of vitamin D deficiency (25(OH)D <20 ng/ml) and insufficiency (25(OH)D >20-<30 ng/ml). 16S rRNA microbiome gene sequencing data was available for 39 HC and 62 participants with IBS. Genus-level Bifidobacterium and Lactobacillus and phylum-level Firmicutes and Bacteroidetes relative abundances were extracted from microbiome profiles. Results showed vitamin D deficiency in 40.3% (n=25) vs. 41.4% (n=41), and insufficiency 33.9% (n=21) vs. 34.3% (n=34) in the HCs vs. IBS groups, respectively. The odds of IBS did not differ depending on 25(OH)D status (p=0.75 for deficient, p=0.78 for insufficient), and the average plasma vitamin D concentration did not differ between IBS (mean 24.8 ng/ml) and HCs (mean 25.1 ng/ml; p=0.57). We did not find evidence of an association between plasma 25(OH)D concentration and richness, Shannon index, Simpson index or specific bacterial abundances in either HCs or the IBS group.
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Affiliation(s)
| | | | - Robert Burr
- School of Nursing, University of Washington, Seattle, WA, USA
| | - Kevin C. Cain
- Department of Biostatistics and Office for Nursing Research, School of Nursing, University of Washington, Seattle, WA, USA
| | - Tor Savidge
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children’s Microbiome Center, Texas Children’s Hospital, Houston, TX, USA
| | - Kendra Kamp
- School of Nursing, University of Washington, Seattle, WA, USA
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Luo M, Xu Y, Li J, Luo D, Zhu L, Wu Y, Liu X, Wu P. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Open Med (Wars) 2023; 18:20230714. [PMID: 37273916 PMCID: PMC10238812 DOI: 10.1515/med-2023-0714] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 03/14/2023] [Accepted: 04/15/2023] [Indexed: 06/06/2023] Open
Abstract
Liver cirrhosis affects the structures and physiological functions of the intestine. Our previous study revealed that liver injury inhibited 25-hydroxylation of vitamin D (25(OH)-VD). The aim of this study was to investigate the roles and mechanisms of vitamin D in liver cirrhosis-induced intestinal injury. The rat liver cirrhosis model was established through the administration of carbon tetrachloride (CCl4) for 8 weeks. Hematoxylin-eosin staining was performed to unveil the intestinal injury induced by liver cirrhosis. Enzyme-linked immunosorbent and reverse transcription PCR (RT-PCR) analysis were used to determine the levels of 25(OH)-VD, vitamin D receptor, Cytochrome P450 24A1 (CYP24A1), and α-defensin 5 (DEFA5) in rat and human serum of liver cirrhosis. Furthermore, liver cirrhosis rats were treated with low-dose (500 IU/kg) and high-dose (2,000 IU/kg) vitamin D intraperitoneally. The expression levels of TLR4/MyD88/NF-κB signaling pathway were evaluated by RT-PCR and Western blot. In conclusion, we determined the deficiency of vitamin D and down-regulation of DEFA5 and intestinal damage induced by liver cirrhosis. Moreover, vitamin D effectively inhibited liver cirrhosis-induced intestinal inflammation and oxidative stress through the TLR4/MyD88/NF-κB pathway. Vitamin D might be a promising therapeutic strategy for future treatment of liver-induced intestinal injury.
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Affiliation(s)
- Mei Luo
- Infectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, China
| | - Yuanhong Xu
- Clinical Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, China
| | - Jike Li
- Infectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, China
| | - Dongxia Luo
- Infectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, China
| | - Li Zhu
- Hepatology Clinic, Chengdu Public Health Clinical Center, Chengdu, 610061, China
| | - Yanxi Wu
- Infectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, China
| | - Xiaodong Liu
- Clinical Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, China
| | - Pengfei Wu
- Infectious Disease Laboratory, Chengdu Public Health Clinical Center, Chengdu, 610061, China
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Yang J, Shi Y. Paneth cell development in the neonatal gut: pathway regulation, development, and relevance to necrotizing enterocolitis. Front Cell Dev Biol 2023; 11:1184159. [PMID: 37266449 PMCID: PMC10231676 DOI: 10.3389/fcell.2023.1184159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Accepted: 05/09/2023] [Indexed: 06/03/2023] Open
Abstract
Paneth cells (PCs) are intestinal epithelial cells (IECs) that contain eosinophilic granules, which are located in Lieberkühn crypts. An increasing number of animal and human experiments have indicated that PCs are involved in the progression of a variety of intestinal as well as systemic inflammatory responses including necrotizing enterocolitis (NEC). NEC is an enteric acquired disease with high mortality that usually occurs in premature infants and neonates, however the underlying mechanisms remain unclear. In this review, we summarize the features of PCs, including their immune function, association with gut microbiota and intestinal stem cells, and their mechanism of regulating IEC death to explore the possible mechanisms by which PCs affect NEC.
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Yu XL, Wu QQ, He LP, Zheng YF. Role of in vitamin D in irritable bowel syndrome. World J Clin Cases 2023; 11:2677-2683. [PMID: 37214583 PMCID: PMC10198110 DOI: 10.12998/wjcc.v11.i12.2677] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/12/2023] [Accepted: 03/24/2023] [Indexed: 04/25/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder affecting 10%-22% of adults. Its development is closely related to the gut microbiota, and the inflammatory and immune responses triggered by the gut microbiota can lead to IBS. Vitamin D (VD) effectively treats IBS with fewer side effects by improving gut microbiota, immune regulation, and anti-inflammatory effects. In the future, it is necessary to carry out epidemiological studies on the relationship between VD and IBS, clinical studies on the efficacy of supplementing VD to improve IBS, and animal studies on the mechanism of VD improving IBS. Therefore, this paper discussed the relationship between VD and IBS.
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Affiliation(s)
- Xiao-Lan Yu
- School of Medicine, Taizhou University, Jiaojiang 318000, Zhejiang Province, China
| | - Qi-Qi Wu
- School of Medicine, Taizhou University, Jiaojiang 318000, Zhejiang Province, China
| | - Lian-Ping He
- School of Medicine, Taizhou University, Jiaojiang 318000, Zhejiang Province, China
| | - Yong-Feng Zheng
- Department of Anesthesiology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu Province, China
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Giustina A, di Filippo L, Allora A, Bikle DD, Cavestro GM, Feldman D, Latella G, Minisola S, Napoli N, Trasciatti S, Uygur M, Bilezikian JP. Vitamin D and malabsorptive gastrointestinal conditions: A bidirectional relationship? Rev Endocr Metab Disord 2023; 24:121-138. [PMID: 36813995 PMCID: PMC9946876 DOI: 10.1007/s11154-023-09792-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/03/2023] [Indexed: 02/24/2023]
Abstract
This paper is one of the outcomes of the 5th International Conference "Controversies in Vitamin D" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases.
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Affiliation(s)
- Andrea Giustina
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy.
- Division of Endocrinology, IRCCS San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy.
| | - Luigi di Filippo
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Agnese Allora
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Daniel D Bikle
- Veterans Affairs Medical Center, University of California San Francisco, 1700 Owens St, San Francisco, CA, 94158, USA
| | - Giulia Martina Cavestro
- Gastroenterology and Gastrointestinal Endoscopy Unit, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
| | - David Feldman
- Stanford University School of Medicine, Stanford, CA, USA
| | - Giovanni Latella
- Gastroenterology, Hepatology and Nutrition Division, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Salvatore Minisola
- Department of Clinical, Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
| | - Nicola Napoli
- Department of Medicine, Unit of Endocrinology and Diabetes, Università Campus Bio-Medico Di Roma, Rome, Italy
| | | | - Melin Uygur
- Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy
- Department of Endocrinology and Metabolism Disease, RTE University School of Medicine, Rize, Turkey
| | - John P Bilezikian
- Department of Medicine, Vagelos College of Physicians and Surgeons, New York City, NY, USA
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de Oliveira CS, Baptistella MM, Siqueira AP, Carvalho MO, Ramos LF, Souto BS, de Almeida LA, Dos Santos EG, Novaes RD, Nogueira ESC, de Oliveira PF. Combination of vitamin D and probiotics inhibits chemically induced colorectal carcinogenesis in Wistar rats. Life Sci 2023; 322:121617. [PMID: 37003542 DOI: 10.1016/j.lfs.2023.121617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 03/10/2023] [Accepted: 03/20/2023] [Indexed: 04/03/2023]
Abstract
The modulation of inflammatory elements, cell differentiation and proliferation by vitamin D and the role of probiotics in the intestinal microbiota and immunogenic response have sparked interest in the application of both in chemotherapeutics and chemoprevention of colorectal tumors. AIMS The present study aimed to investigate the effects of isolated and/or combined treatment of vitamin D3 and probiotics on colorectal carcinogenesis. MAIN METHODS Pre-neoplastic lesions were induced with 1,2-dimethylhydrazine in the colon of Wistar rats, which were treated with probiotics and/or vitamin D in three different approaches (simultaneous, pre-, and post-treatment). We investigated the frequency of aberrant crypt foci (ACF) and aberrant crypt (AC) in the distal colon, fecal microbiome composition, gene and protein expression through immunohistochemical and RT-PCR assays, and general toxicity through water consumption and weight gain monitoring. KEY FINDINGS Results confirm the systemic safety of treatments, and show a protective effect of vitamin D and probiotics in all approaches studied, as well as in combined treatments, with predominance of different bacterial phyla compared to controls. Treated groups show different levels of Nrf2, GST, COX2, iNOS, β-catenin and PCNA expression. SIGNIFICANCE These experimental conditions explore the combination of vitamin D and probiotics supplementation at low doses over pathways involved in distinct stages of colorectal carcinogenesis, with results supporting its application in prevention and long-term strategies.
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Affiliation(s)
- Carolina S de Oliveira
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil; Postgraduate Program in Biosciences Applied to Health, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Mariane M Baptistella
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil; Postgraduate Program in Biosciences Applied to Health, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Alexia P Siqueira
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Michele O Carvalho
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil; Postgraduate Program in Nutrition and Longevity, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Luiz Fernando Ramos
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Bianca S Souto
- Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Leonardo A de Almeida
- Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Elda G Dos Santos
- Postgraduate Program in Biosciences Applied to Health, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Rômulo D Novaes
- Department of Structural Biology, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Ester S C Nogueira
- Animal Integrative Biology Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil
| | - Pollyanna F de Oliveira
- Human Genetics Laboratory, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil; Postgraduate Program in Nutrition and Longevity, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil; Laboratory of Molecular Biology of Microorganisms, Federal University of Alfenas, Alfenas 37130-001, MG, Brazil.
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Lv W, Zhang D, He T, Liu Y, Shao L, Lv Z, Pu X, Wang Y, Liu L. Combination of Lactobacillus plantarum improves the effects of tacrolimus on colitis in a mouse model. Front Cell Infect Microbiol 2023; 13:1130820. [PMID: 36992690 PMCID: PMC10040537 DOI: 10.3389/fcimb.2023.1130820] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 02/06/2023] [Indexed: 03/14/2023] Open
Abstract
The gut microbiome has been considered to play an important role in inflammatory bowel disease (IBD). Our previous study reported that tacrolimus-altered gut microbiota elicited immunoregulatory effects in both colonic mucosa and circulation, contributing to an increased allograft survival rate in mice. Here, we aimed to observe the changes in the tacrolimus-induced microbiome in a dextran sulfate sodium (DSS)-induced colitis mouse model and explore the possibility and efficacy of combination therapy with tacrolimus and the microbiome on colitis. Mice were divided into the control, DSS, tacrolimus monotherapy and tacrolimus plus Lactobacillus plantarum 550 (Lacto)-treated groups. The body weight, stool consistency, hematochezia and survival of mice were observed daily. Total RNA from colonic mucosa was extracted and subjected to transcriptome sequencing. Cecal contents were collected and the 16S rRNA sequencing was performed to characterize the gut microbiome and the ultrahigh- performance liquid chromatography-MS/MS (UHPLC-MS/MS) was used for targeted quantification of bile acids. The results confirmed that tacrolimus significantly ameliorated DSS-induced colitis in mice. Beneficial alterations of the gut microbiome characterized by a remarkable expansion of the genus Lactobacillus were induced by tacrolimus treatment. Oral supplementation with Lacto further improved the tacrolimus-mediated suppression of body weight loss in colitis, while the survival time of mice was further prolonged and the inflammation of colonic mucosa was obviously relieved. The immune and inflammation-related signaling pathways, including IFN-γ and IFN-α response, allograft rejection, IL2 STAT5 signaling and the inflammatory response pathways, were further downregulated in the tacrolimus plus Lacto cotreatment group. Cotreatment also improved the diversity of the gut microbiome and rescued the concentration of taurochenodeoxycholic acid (TCDCA) in colitis. The latter was positively correlated with the abundance of Lactobacillus but negatively related to the disease activity index score. Overall, our results indicated that Lactobacillus plantarum promoted the therapeutic effect of tacrolimus in experimental colitis, offering a promising strategy to combine tacrolimus and Lactobacillus in the treatment of colitis patients.
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Affiliation(s)
- Wei Lv
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Di Zhang
- Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China
| | - Tian He
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yingying Liu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Limei Shao
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Zhongping Lv
- Technology Research Institute of Shuxi Condiments of Sichuan Cuisine Co. LTD, Chengdu, Sichuan, China
| | - Xiaoping Pu
- Technology Research Institute of Shuxi Condiments of Sichuan Cuisine Co. LTD, Chengdu, Sichuan, China
| | - Yufang Wang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- *Correspondence: Yufang Wang, ; Ling Liu,
| | - Ling Liu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- *Correspondence: Yufang Wang, ; Ling Liu,
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Guo Y, Li X, Geng C, Song S, Xie X, Wang C. Vitamin D receptor involves in the protection of intestinal epithelial barrier function via up-regulating SLC26A3. J Steroid Biochem Mol Biol 2023; 227:106231. [PMID: 36462760 DOI: 10.1016/j.jsbmb.2022.106231] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 05/13/2022] [Accepted: 07/15/2022] [Indexed: 12/05/2022]
Abstract
BACKGROUND Vitamin D receptor (VDR) and SLC26A3 (DRA) have been identified as pivotal protective factors in maintaining gut homeostasis in IBD patients. However, the specific mechanism underlying the increased intestinal susceptibility to inflammation induced by the loss of VDR and whether DRA participates in the role of VDR regulating intestinal epithelial barrier function are undefined. AIM The current study is undertaken to elucidate the regulatory effects of VDR on DRA and VDR prevents intestinal epithelial barrier dysfunction via up-regulating the expression of DRA. METHODS WT and VDR-/- mice are used as models for intestinal epithelial response. Paracellular permeability is measured by TEER and FD-4 assays. Immunohistochemistry, immunofluorescence, qPCR and immunoblotting are performed to determine the effects of VDR and DRA on gut epithelial barrier function. RESULTS VDR-/- mice exhibits significant hyperpermeability of intestine with greatly decreased levels of ZO-1 and Claudin1 proteins. DRA is located on the intestinal epithelial apical membrane and is tightly modulated by VDR in vivo and in vitro via activating ERK1/2 MAPK signaling pathway. Notably, the current study for the first time demonstrates that VDR maintains intestinal epithelial barrier integrity via up-regulating DRA expression and the lack of DRA induced by VDR knockdown leads to a more susceptive condition for intestine to DSS-induced colitis. CONCLUSION Our study provides evidence and deep comprehension regarding the role of VDR in modulating DRA expression in gut homeostasis and makes novel contributions to better generally understanding the links between VDR, DRA and intestinal epithelial barrier function.
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Affiliation(s)
- Yaoyu Guo
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China
| | - Xiao Li
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China
| | - Chong Geng
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China
| | - Shuailing Song
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaoxi Xie
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China
| | - Chunhui Wang
- Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China.
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Gao H, Zhou H, Zhang Z, Gao J, Li J, Li X. Vitamin D3 alleviates inflammation in ulcerative colitis by activating the VDR-NLRP6 signaling pathway. Front Immunol 2023; 14:1135930. [PMID: 36845152 PMCID: PMC9944717 DOI: 10.3389/fimmu.2023.1135930] [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: 01/02/2023] [Accepted: 01/19/2023] [Indexed: 02/10/2023] Open
Abstract
Inflammation is a key factor in the development of ulcerative colitis (UC). 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, VD3), as the major active ingredient of vitamin D and an anti-inflammatory activator, is closely related to the initiation and development of UC, but its regulatory mechanism remains unclear. In this study, we carried out histological and physiological analyses in UC patients and UC mice. RNA sequencing (RNA-seq), assays for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), chromatin immunoprecipitation (ChIP) assays and protein and mRNA expression were performed to analyze and identify the potential molecular mechanism in UC mice and lipopolysaccharide (LPS)-induced mouse intestinal epithelial cells (MIECs). Moreover, we established nucleotide-binding oligomerization domain (NOD)-like receptor protein nlrp6 -/- mice and siRNA-NLRP6 MIECs to further characterize the role of NLRP6 in anti-inflammation of VD3. Our study revealed that VD3 abolished NOD-like receptor protein 6 (NLRP6) inflammasome activation, suppressing NLRP6, apoptosis-associated speck-like protein (ASC) and Caspase-1 levels via the vitamin D receptor (VDR). ChIP and ATAC-seq showed that VDR transcriptionally repressed NLRP6 by binding to vitamin D response elements (VDREs) in the promoter of NLRP6, impairing UC development. Importantly, VD3 had both preventive and therapeutic effects on the UC mouse model via inhibition of NLRP6 inflammasome activation. Our results demonstrated that VD3 substantially represses inflammation and the development of UC in vivo. These findings reveal a new mechanism by which VD3 affects inflammation in UC by regulating the expression of NLRP6 and show the potential clinical use of VD3 in autoimmune syndromes or other NLRP6 inflammasome-driven inflammatory diseases.
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Affiliation(s)
- Hongliang Gao
- Pathology Center, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang, China
- The Second Department of Gastroenterology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - He Zhou
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, China
| | - Zhiqiang Zhang
- The Second Department of Gastroenterology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Jianshu Gao
- The Second Department of Gastroenterology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Jian Li
- The Second Department of Gastroenterology, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Xinxia Li
- Pathology Center, Xinjiang Medical University Affiliated Tumor Hospital, Urumqi, Xinjiang, China
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Im H, Wang W, Qi Q, Li Q, Wu M, Wu H, Liu Y, Huang Y, Zhu Y, Zheng H, Wu L. Clinical efficacy of moxibustion for ulcerative colitis and its influence on vitamin D receptor. JOURNAL OF ACUPUNCTURE AND TUINA SCIENCE 2023. [DOI: 10.1007/s11726-023-1357-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/19/2023]
Abstract
Abstract
Objective
To observe the clinical efficacy of herbal cake-partitioned moxibustion for ulcerative colitis (UC) and elucidate its mechanism by targeting the vitamin D receptor (VDR) signaling pathway.
Methods
A total of 63 patients with UC were randomly divided into an observation group (30 cases, treated with herbal cake-partitioned moxibustion) and a control group (33 cases, treated with sham herbal cake-partitioned moxibustion). Moxibustion treatment was performed at Qihai (CV6) and bilateral Tianshu (ST25) and Shangjuxu (ST37), 3 times per week for 12 weeks. The total effective rate, visual analog scale (VAS) score for abdominal bloating and pain, and hospital anxiety and depression scale (HADS) score were compared between the two groups. Enzyme-linked immunosorbent assay was used to detect the concentrations of serum C-reactive protein (CRP), 25-hydroxyvitamin D [25(OH)D], and interleukin-12 (IL-12)/interleukin-23 (IL-23) p40. Immunohistochemistry was used to observe the expression levels of VDR and regenerating gene IV (Reg IV) proteins in colonic mucosa. The expression levels of VDR, cytochrome p450 27B1 (CYP27B1), and Reg IV mRNAs were detected by real-time fluorescence quantitive polymerase chain reaction.
Results
After treatment, the total effective rate in the observation group was 86.7%, which was significantly higher than 51.5% in the control group (P<0.05). After treatment, the VAS scores for abdominal bloating and pain in the observation group were significantly decreased (P<0.01), as well as the HADS-depression subscale (HADS-D) and HADS-anxiety subscale (HADS) scores (P<0.05), while only the VAS score for abdominal pain in the control group was reduced (P<0.05), and the improvements of the scores in the observation group were more significant than those in the control group (P<0.05). After treatment, the serum CRP concentrations in both groups and the IL-12/IL-23 p40 concentration in the observation group were significantly decreased (P<0.05), and the concentrations in the observation group were lower than those in the control group (P<0.05). The expression levels of VDR protein and mRNA in the colon in both groups were all increased (P<0.01), and the expression levels of Reg IV protein and mRNA and CYP27B1 mRNA were all decreased in the two groups (P<0.05 or P<0.01); the improvements in the observation group were more notable than those in the control group (P<0.05 or P<0.01).
Conclusion
Herbal cake-partitioned moxibustion can effectively alleviate abdominal pain and diarrhea in patients with UC, improve depression and anxiety disorders, and regulate the expression of related proteins in the VDR signaling pathway. The mechanism may be related to inhibiting intestinal inflammation by reducing the release of the proinflammatory cytokine IL-12/IL-23 p40.
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Sun YH, Tian DD, Zhou JM, Ye Q. Association between vitamin D level and pediatric inflammatory bowel disease: A systematic review and meta-analysis. Front Pediatr 2023; 11:1155004. [PMID: 37168807 PMCID: PMC10164952 DOI: 10.3389/fped.2023.1155004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 04/06/2023] [Indexed: 05/13/2023] Open
Abstract
Background Previous studies have reported that the incidence of pediatric inflammatory bowel disease (IBD) is related to vitamin D, but it is still unclear. This study intends to calculate the relationship between pediatric IBD and vitamin D. Methods A comprehensive literature search from inception to January 2023 was performed in the PubMed, EMBASE, Medline, Web of Science, and Google Scholar databases. Relevant data were extracted as required and used for subsequent calculations. Results Sixteen papers were included, and there was no significant difference between the average vitamin D level in IBD patients and healthy controls. In addition, the overall pooled results showed that C-reactive protein (CRP) was 2.65 higher before vitamin D supplementation than after supplementation [SMD = 2.65, 95% CI = (2.26, 3.04)]. Moreover, patients with IBD in remission were 0.72 higher before vitamin D supplementation than after supplementation [OR = 0.72, 95% CI = (0.52, 1.00)]. Conclusion This study suggested that there was no obvious relationship between pediatric IBD and vitamin D, while vitamin D supplementation can improve disease activity. Therefore, follow-up still needs many prospective studies to confirm the relationship between pediatric IBD and vitamin D.
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Maurya VK, Shakya A, Bashir K, Jan K, McClements DJ. Fortification by design: A rational approach to designing vitamin D delivery systems for foods and beverages. Compr Rev Food Sci Food Saf 2023; 22:135-186. [PMID: 36468215 DOI: 10.1111/1541-4337.13066] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 10/04/2022] [Accepted: 10/10/2022] [Indexed: 12/09/2022]
Abstract
Over the past few decades, vitamin D deficiency has been recognized as a serious global public health challenge. The World Health Organization has recommended fortification of foods with vitamin D, but this is often challenging because of its low water solubility, poor chemical stability, and low bioavailability. Studies have shown that these challenges can be overcome by encapsulating vitamin D within well-designed delivery systems containing nanoscale or microscale particles. The characteristics of these particles, such as their composition, size, structure, interfacial properties, and charge, can be controlled to attain desired functionality for specific applications. Recently, there has been great interest in the design, production, and application of vitamin-D loaded delivery systems. Many of the delivery systems reported in the literature are unsuitable for widespread application due to the complexity and high costs of the processing operations required to fabricate them, or because they are incompatible with food matrices. In this article, the concept of "fortification by design" is introduced, which involves a systematic approach to the design, production, and testing of colloidal delivery systems for the encapsulation and fortification of oil-soluble vitamins, using vitamin D as a model. Initially, the challenges associated with the incorporation of vitamin D into foods and beverages are reviewed. The fortification by design concept is then described, which involves several steps: (i) selection of appropriate vitamin D form; (ii) selection of appropriate food matrix; (iii) identification of appropriate delivery system; (iv) identification of appropriate production method; (vii) establishment of appropriate testing procedures; and (viii) system optimization.
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Affiliation(s)
- Vaibhav Kumar Maurya
- Centre for Food Research and Analysis, National Institute of Food Technology Entrepreneurship and Management, Sonepat, India
| | - Amita Shakya
- Agriculture and Environmental Sciences, National Institute of Food Technology Entrepreneurship and Management, Sonepat, India
| | - Khalid Bashir
- Department of Food Technology, Jamia Hamdard, New Delhi, India
| | - Kulsum Jan
- Department of Food Technology, Jamia Hamdard, New Delhi, India
| | - David Julian McClements
- Department of Food Science, University of Massachusetts, Amherst, Massachusetts, USA.,Department of Food Science & Bioengineering, Zhejiang Gongshang University, Hangzhou, China
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