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Iddrisu I, Monteagudo-Mera A, Poveda C, Shahzad M, Walton GE, Andrews SC. A review of the effect of iron supplementation on the gut microbiota of children in developing countries and the impact of prebiotics. Nutr Res Rev 2025; 38:229-237. [PMID: 38586996 DOI: 10.1017/s0954422424000118] [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] [Indexed: 04/09/2024]
Abstract
Iron is essential for many physiological functions of the body, and it is required for normal growth and development. Iron deficiency (ID) is the most common form of micronutrient malnutrition and is particularly prevalent in infants and young children in developing countries. Iron supplementation is considered the most effective strategy to combat the risk of ID and ID anaemia (IDA) in infants, although iron supplements cause a range of deleterious gut-related problems in malnourished children. The purpose of this review is to assess the available evidence on the effect of iron supplementation on the gut microbiota during childhood ID and to further assess whether prebiotics offer any benefits for iron supplementation. Prebiotics are well known to improve gut-microbial health in children, and recent reports indicate that prebiotics can mitigate the adverse gut-related effects of iron supplementation in children with ID and IDA. Thus, provision of prebiotics alongside iron supplements has the potential for an enhanced strategy for combatting ID and IDA among children in the developing world. However, further understanding is required before the benefit of such combined treatments of ID in nutritionally deprived children across populations can be fully confirmed. Such enhanced understanding is of high relevance in resource-poor countries where ID, poor sanitation and hygiene, alongside inadequate access to good drinking water and poor health systems, are serious public health concerns.
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Affiliation(s)
- Ishawu Iddrisu
- Rose Ward, Prospect Park Hospital, Berkshire Healthcare NHS Foundation Trust, Reading, RG30 4EJ, UK
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK
- School of Biological Sciences, University of Reading, Whiteknights, Reading, RG6 6EX, UK
| | - Andrea Monteagudo-Mera
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK
| | - Carlos Poveda
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK
| | - Muhammed Shahzad
- Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan
- Faculty of Dentistry, Zarqa University, Zarqa, 13110, Jordan
| | - Gemma E Walton
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading, RG6 6AP, UK
| | - Simon C Andrews
- School of Biological Sciences, University of Reading, Whiteknights, Reading, RG6 6EX, UK
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Detlie TE, Burisch J, Jahnsen J, Bonderup O, Hellström PM, Lindgren S, Frigstad SO. Iron deficiency should not be accepted in patients with inflammatory bowel disease - a Scandinavian expert opinion. Scand J Gastroenterol 2025; 60:430-438. [PMID: 40202208 DOI: 10.1080/00365521.2025.2487907] [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: 01/07/2025] [Revised: 03/10/2025] [Accepted: 03/28/2025] [Indexed: 04/10/2025]
Abstract
AIM In this paper, we aim to explain the reason why iron deficiency (ID) is common in patients with inflammatory bowel disease (IBD), how to better apply diagnostic tools to uncover the state of ID as well as how to interpret the results, and not least, how to treat ID in this group of patients. METHODS This article is an expert review and opinion paper on a topic that is too often forgotten in clinical practice. We have not performed a systematic review, but we present the most important research allocated to the topic to substantiate an expert opinion. RESULTS This position paper summarises the pathophysiology of ID and gives recommendations on the monitoring and treatment of ID in IBD. ID with or without concurrent anaemia (IDA) is the most common systemic complication in patients with IBD, related to both disease activity and severity. It has consequences both for health-related quality of life and future course of disease of the IBD patient. Intravenous iron is an efficacious and well tolerated, but still underused, therapy for ID and IDA. Iron deficiency should be treated before symptoms of anaemia appear and quality of life is impacted. However, there is still limited awareness of how to detect and treat ID in clinical practice. Uncertainty regarding which diagnostic tests to use and how to interpret the results may also be responsible for variations in clinical practice. In addition, opinions on how to correct ID and IDA differ, in relation to both clinical efficacy and safety. CONCLUSION The consequences of ID in patients with IBD are significant. Guidelines on diagnosis, treatment and follow-up of ID should be implemented. IDA is a manifestation of severe ID and preventive strategies focusing on efficient treatment of ID regardless of the level of haemoglobin should therefore be explored.
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Affiliation(s)
- Trond Espen Detlie
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Johan Burisch
- Gastrounit, Medical Division, University Hospital Copenhagen - Amager and Hvidovre Hospital, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, University Hospital Copenhagen - Amager and Hvidovre Hospital, Hvidovre, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jørgen Jahnsen
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ole Bonderup
- Department of Gastroenterology, Silkeborg Regional Hospital, Silkeborg, Denmark
| | - Per M Hellström
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Stefan Lindgren
- Department of Clinical Sciences, Lund University, Lund, Sweden
- Department of Gastroenterology, Skane University Hospital Malmö, Lund, Sweden
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Fijn R, Ablij HC, Knoester PD, Witte AMC. Real-world evaluation of an intravenous iron service for the treatment of iron deficiency with or without anemia. Sci Rep 2025; 15:12093. [PMID: 40204729 PMCID: PMC11982194 DOI: 10.1038/s41598-025-85880-9] [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: 04/18/2024] [Accepted: 01/07/2025] [Indexed: 04/11/2025] Open
Abstract
Intravenous (IV) iron is a guideline-recommended treatment for iron deficiency when oral iron is contraindicated, ineffective, or not tolerated, or when rapid iron delivery is necessary. However, evidence suggests that some patients receive less IV iron than needed. This retrospective audit assessed the effectiveness and safety of ferric derisomaltose (FDI), a high-dose IV iron, in 2,468 patients. Efficacy outcomes assessed at 4-12 weeks post-infusion included changes in hemoglobin (Hb) and ferritin, proportion of courses (a course was defined as the treatment episode required to administer one total dose) after which patients were non-anemic (Hb ≥ 130 g/L [men] or ≥ 120 g/L [women]), and response rate (proportion of courses after which patients were non-anemic or Hb increased by ≥ 20 g/L). Safety was assessed through adverse events. Across 2,775 FDI courses, the mean dose was 1,244 mg, but mean estimated iron need was 1,580 mg. At follow-up, mean Hb had increased by 20.9 g/L and mean ferritin by 188.8 µg/L. Patients were non-anemic after 33.4% (n = 494/1,478) of courses and responded after 65.1% (n = 962/1,478) of courses. One patient (n = 1/2,468; 0.04%) had a serious allergic reaction. Patients remained anemic after > 65% of courses, demonstrating the need to optimize dosing based on iron need.
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Affiliation(s)
- Roel Fijn
- Department of Clinical Pharmacy, Alrijne Healthcare Group, Leiden, The Netherlands.
- Department of Hospital Pharmacy, Northwest Hospital Group, Wilhelminalaan 12, 1815 JD, Alkmaar, The Netherlands.
| | - Hans C Ablij
- Department of Internal Medicine & Nephrology, Alrijne Healthcare Group, Leiden, The Netherlands
| | - Pieter D Knoester
- Department of Clinical Pharmacy, Alrijne Healthcare Group, Leiden, The Netherlands
| | - Anne M C Witte
- Department of Gastroenterology & Hepatology, Alrijne Healthcare Group, Leiden, The Netherlands
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Broekaert IJ, Assa A, Borrelli O, Saccomani MD, Homan M, Martin‐de‐Carpi J, Mas E, Miele E, Misak Z, Sila S, Thomson M, Tzivinikos C, Dolinsek J. Approach to anaemia in gastrointestinal disease: A position paper by the ESPGHAN Gastroenterology Committee. J Pediatr Gastroenterol Nutr 2025; 80:510-532. [PMID: 39783775 PMCID: PMC11874238 DOI: 10.1002/jpn3.12454] [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: 02/12/2024] [Revised: 10/31/2024] [Accepted: 12/10/2024] [Indexed: 01/12/2025]
Abstract
Anaemia is a frequent consequence of many gastrointestinal (GI) diseases in children and it can even be the initial presenting symptom of underlying chronic GI disease. The definition of anaemia is age and gender-dependent and it can be classified based on pathophysiology, red cell morphology, and clinical presentation. Although nutritional deficiencies, including GI malabsorption of nutrients and GI bleeding, play a major role, other pathophysiologic mechanisms seen in chronic GI diseases, whether inflammatory (e.g., inflammatory bowel disease) or not (e.g., coeliac disease and dysmotility), are causing anaemia. Drugs, such as proton pump inhibitors, mesalamine, methotrexate and sulfasalazine, are also a potential cause of anaemia. Not uncommonly, due to a combination of factors, such as iron deficiency and a chronic inflammatory state, the underlying pathophysiology may be difficult to decipher and a broad diagnostic work-up is required. The goal of treatment is correction of anaemia by supplementation of iron and vitamins. The first therapeutic step is to treat the underlying cause of anaemia including bleeding control, restoration of intestinal integrity and reduction of inflammatory burden. The route of iron and vitamin supplementation is guided by the severity of anaemia.
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Affiliation(s)
- Ilse Julia Broekaert
- Department of Paediatrics, Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany
| | - Amit Assa
- The Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition, Shaare Zedek Medical CentreThe Hebrew UniversityJerusalemIsrael
| | - Osvaldo Borrelli
- Division of Neurogastroenterology & Motility, Department of Paediatric GastroenterologyGreat Ormond Street HospitalLondonUK
| | | | - Matjaž Homan
- Department of Gastroenterology, Hepatology and Nutrition, University Children's HospitalFaculty of MedicineUniversity of LjubljanaLjubljanaSlovenia
| | - Javier Martin‐de‐Carpi
- Department of Paediatric Gastroenterology, Hepatology and NutritionHospital Sant Joan de DéuBarcelonaSpain
| | - Emmanuel Mas
- Service de Gastroentérologie, Hépatologie, Nutrition et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, and IRSDUniversité de Toulouse, INSERM, INRAE, ENVT, UPSToulouseFrance
| | - Erasmo Miele
- Department of Translational Medical Science, Section of PediatricsUniversity of Naples “Federico II”NaplesItaly
| | - Zrinjka Misak
- Referral Centre for Paediatric Gastroenterology and NutritionChildren's Hospital ZagrebZagrebCroatia
| | - Sara Sila
- Referral Centre for Paediatric Gastroenterology and NutritionChildren's Hospital ZagrebZagrebCroatia
| | - Mike Thomson
- Centre for Paediatric GastroenterologySheffield Children's Hospital NHS Foundation TrustSheffieldUK
| | - Christos Tzivinikos
- Paediatric Gastroenterology Department, Al Jalila Children's Specialty HospitalMohammed Bin Rashid University, Dubai Medical CollegeDubaiUnited Arab Emirates
| | - Jernej Dolinsek
- Department of PaediatricsUniversity Medical Centre MariborMariborSlovenia
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Malireddi A, Abera M, Suresh SB, Ansar M, Boddeti S, Noor K, Khan S. Safety and Efficacy of Ferric Carboxymaltose for Iron Deficiency Anemia in Inflammatory Bowel Disease: A Systematic Review. Cureus 2024; 16:e76065. [PMID: 39835061 PMCID: PMC11743820 DOI: 10.7759/cureus.76065] [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: 09/24/2024] [Accepted: 12/19/2024] [Indexed: 01/22/2025] Open
Abstract
Ulcerative colitis and Crohn's disease, two types of inflammatory bowel disease (IBD), often cause anemia, primarily due to iron deficiency and chronic inflammation. Anemia negatively affects patients' daily functioning and quality of life, causing symptoms including headaches, exhaustion, and dyspnea. In IBD, iron deficiency arises from reduced intake, chronic blood loss, and impaired absorption. While oral iron supplements are commonly used, their poor absorption and gastrointestinal side effects limit their effectiveness, especially in IBD patients. The European Crohn's and Colitis Organization (ECCO) recommends intravenous iron, such as ferric carboxymaltose (FCM), as iron deficiency anemia in IBD can be managed using a safe and efficient substitute. With regard to treating iron deficiency anemia in patients with IBD, the purpose of this study is to investigate the safety and effectiveness of intravenous ferric carboxymaltose. We conducted a thorough search of medical databases, such as the Cochrane library, PubMed, and ResearchGate, to gather relevant literature. Using the databases, we found a total of 297 relevant articles. The identified studies have been screened, eligibility criteria have been introduced, and 14 research studies were selected for inclusion. This review adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, with quality assessments conducted using the Cochrane risk of bias 2 scale for randomized tests and the Newcastle-Ottawa scale for observational examination. We reviewed 14 research articles involving 2,493 patients. Among these, five were randomized controlled trials (RCTs), and the remaining nine were observational studies. The primary outcomes assessed were the therapeutic response (defined as hemoglobin ≥2 g/dL rise or normalization, improvement in iron profile parameters) and any adverse effects after FCM is administered to IBD patients. FCM was found to be highly effective in improving hemoglobin and iron profile parameters, with a generally good safety profile. Ferric carboxymaltose was the most efficient and well-tolerated intravenous (IV) iron formulation, proving safer and more effective than other iron therapies in patients suffering from IBD. However, severe hypophosphatemia can lead to serious complications, including heart failure, pulmonary failure, rhabdomyolysis, fractures, and osteomalacia, which may worsen its long-term impact. Therefore, the risk of hypophosphatemia associated with prolonged FCM use requires careful monitoring and further research to ensure its long-term safety and assess its effects on patients' quality of life.
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Affiliation(s)
| | - Mahlet Abera
- Internal Medicine, Saint Paul Millennium Medical College, Addis Ababa, ETH
| | - Suchith B Suresh
- Internal Medicine, Montefiore St. Luke's Cornwall, Newburgh, USA
| | - Mehwish Ansar
- General Surgery, Wirral University Teaching Hospital, Wirral, GBR
- General Surgery, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Sruthi Boddeti
- Obstetrics and Gynecology, Tirumala Jyothi Hospital, Visakhapatnam, USA
| | - Khutaija Noor
- Foundation of Clinical Research, Harvard Medical School, Boston, USA
- Neuropsychiatry, PsychCare Consultant Research, Saint Louis, USA
- Internal Medicine, Shadan Institute of Medical Sciences, Peeramcheru, IND
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
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Han J, Song HJ, Kang MS, Jun H, Kim HU, Kang KS, Lee D. Micronutrient Deficiency and Muscular Status in Inflammatory Bowel Disease. Nutrients 2024; 16:3763. [PMID: 39519597 PMCID: PMC11547367 DOI: 10.3390/nu16213763] [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: 09/01/2024] [Revised: 10/04/2024] [Accepted: 10/26/2024] [Indexed: 11/16/2024] Open
Abstract
Micronutrient deficiencies are common in inflammatory bowel disease (IBD). The aim of this study was to evaluate micronutrient deficiencies and identify muscular status of patients with IBD. From June 2019 to October 2021, a total of 105 patients with IBD were enrolled prospectively. To obtain objective data, micronutrients were measured in the patients' serum, and body composition analysis was performed using bioelectrical impedance analysis. There were 51 patients with ulcerative colitis (UC) and 54 with Crohn's disease (CD), while the gender ratio (M: F) was 54:51. The average age was 37 ± 18 years, which was significantly lower in patients with CD than UC (29 ± 16 vs. 45 ± 16, p < 0.001). Iron and magnesium were lower in patients with CD compared to UC, respectively (63.3 ± 42.5 vs. 82.8 ± 44.0 µg/dL, p = 0.024, 2.08 ± 0.15 vs. 2.15 ± 0.19 mg/dL, p = 0.036). Vitamin D levels showed insufficiency in patients with UC and deficiency (below 20 ng/mL) in patients with CD (20.1 ± 10.6 vs. 19.0 ± 9.9 ng/mL, p = 0.567). In the UC and CD patient groups, skeletal muscle index (SMI) and adjusted skeletal muscle mass were lower in patients with CD compared to UC (SMI: 32.8 ± 4.7 vs. 35.8 ± 5.5%, p < 0.004, adjusted skeletal muscle: 7.0 ± 1.5 vs. 8.2 ± 1.9 kg/m2, p < 0.001). In conclusion, decreased trace elements, specifically iron, magnesium, and vitamin D, as well as skeletal muscle mass were observed to be prominent in patients with CD as compared to UC.
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Affiliation(s)
- Joonhee Han
- Department of Internal Medicine, Jeju National University Hospital, Jeju National University College of Medicine, Jeju 63241, Republic of Korea; (J.H.); (H.J.); (H.U.K.)
| | - Hyun Joo Song
- Department of Internal Medicine, Jeju National University Hospital, Jeju National University College of Medicine, Jeju 63241, Republic of Korea; (J.H.); (H.J.); (H.U.K.)
| | - Min Sook Kang
- Department of Food & Nutrition Service Team, Jeju National University Hospital, Jeju 63241, Republic of Korea;
| | - Hogyung Jun
- Department of Internal Medicine, Jeju National University Hospital, Jeju National University College of Medicine, Jeju 63241, Republic of Korea; (J.H.); (H.J.); (H.U.K.)
| | - Heung Up Kim
- Department of Internal Medicine, Jeju National University Hospital, Jeju National University College of Medicine, Jeju 63241, Republic of Korea; (J.H.); (H.J.); (H.U.K.)
| | - Ki Soo Kang
- Department of Pediatrics, Jeju National University Hospital, Jeju National University College of Medicine, Jeju 63241, Republic of Korea;
| | - Donghyoun Lee
- Department of Surgery, Jeju National University Hospital, Jeju National University College of Medicine, Jeju 63241, Republic of Korea;
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Chaber R, Helwich E, Lauterbach R, Mastalerz-Migas A, Matysiak M, Peregud-Pogorzelski J, Styczyński J, Szczepański T, Jackowska T. Diagnosis and Treatment of Iron Deficiency and Iron Deficiency Anemia in Children and Adolescents: Recommendations of the Polish Pediatric Society, the Polish Society of Pediatric Oncology and Hematology, the Polish Society of Neonatology, and the Polish Society of Family Medicine. Nutrients 2024; 16:3623. [PMID: 39519457 PMCID: PMC11547346 DOI: 10.3390/nu16213623] [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: 09/23/2024] [Revised: 10/11/2024] [Accepted: 10/16/2024] [Indexed: 11/16/2024] Open
Abstract
Background/Objectives. Iron deficiency is one of the most common nutritional deficiencies worldwide and is the leading cause of anemia in the pediatric population (microcytic, hypochromic anemia due to iron deficiency). Moreover, untreated iron deficiency can lead to various systemic consequences and can disrupt the child's development. Methods/Results. Therefore, a team of experts from the Polish Pediatric Society, the Polish Society of Pediatric Oncology and Hematology, the Polish Neonatology Society, and the Polish Society of Family Medicine, based on a review of the current literature, their own clinical experience, and critical discussion, has developed updated guidelines for the diagnosis, prevention, and treatment of iron deficiency in children from birth to 18 years of age. These recommendations apply to the general population and do not take into account the specifics of individual conditions and diseases.
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Affiliation(s)
- Radosław Chaber
- Department of Pediatrics, Institute of Medical Sciences, University of Rzeszow, 35-310 Rzeszow, Poland
- Clinic of Pediatric Oncology and Hematology, State Hospital 2, 35-301 Rzeszow, Poland
| | - Ewa Helwich
- Department of Neonatology and Neonatal Intensive Care, Institute of Mother and Child, 04-370 Warsaw, Poland;
| | - Ryszard Lauterbach
- Clinic of Neonatology, Department of Gynecology and Obstetrics, Jagiellonian University Hospital, 31-501 Cracow, Poland;
| | | | - Michał Matysiak
- Department of Oncology, Children’s Hematology, Clinical Transplantology and Pediatrics, University Clinical Center, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Jarosław Peregud-Pogorzelski
- Department of Pediatrics, Oncology and Pediatric Immunology, Pomeranian Medical University, 70-204 Szczecin, Poland;
| | - Jan Styczyński
- Department of Pediatric Haematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Jurasz University Hospital 1, 85-094 Bydgoszcz, Poland;
| | - Tomasz Szczepański
- Department of Pediatric Haematology and Oncology, Medical University of Silesia, 41-800 Katowice, Poland;
| | - Teresa Jackowska
- Department of Pediatrics, Centre of Postgraduate Medical Education, 01-809 Warsaw, Poland;
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8
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Wang S, Wang J, Meng X, Yang S, Wu L, Chen K, Li Z, Xiao J, Yu X, Chen X, Feng J, Gong R. Exploring causal association between malnutrition, nutrients intake and inflammatory bowel disease: a Mendelian randomization analysis. Front Nutr 2024; 11:1406733. [PMID: 39206309 PMCID: PMC11349745 DOI: 10.3389/fnut.2024.1406733] [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: 03/25/2024] [Accepted: 07/30/2024] [Indexed: 09/04/2024] Open
Abstract
Background Malnutrition has emerged as main side effects of inflammatory bowel disease (IBD) which might also affect the prognosis of IBD. However, whether these associations are causal remains unclear. We aimed to identify the causality of IBD on malnutrition and explore the causal relationship of malnutrition and nutrients intake on IBD by using Mendelian randomization (MR). Methods Single nucleotide polymorphisms associated with IBD, malnutrition and nutrients intake were obtained from previous researches of genome-wide association studies (GWAS) (p < 0.00000005). MR analysis was conducted to evaluate the causality with different methods based on OR and their 95% CIs. Meanwhile, heterogeneity, pleiotropy and MR-PRESSO were used for instrumental variables evaluation. Results The results of MR analysis revealed that IBD, both Crohn disease (CD) and ulcerative colitis (UC), could directly impact the incidence of malnutrition (p-value <0.01). CD is directly related to nutrients such as sugar, fat, VA, VC, VD and zinc, while UC is correlated with carbohydrate, fat, VB12, VC, VD, VE, iron, zinc and magnesium. However, our results suggested that malnutrition could not affect the risk of IBD directly (p > 0.05). Further analysis showed similar results that nutrients intake had no direct effect on IBD, neither CD or UC. Conclusion Our results indicated that IBD increases the risk of malnutrition, however, malnutrition and nutrients intake might not directly affect the progression of IBD.
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Affiliation(s)
- Shi Wang
- Department of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jing Wang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xinyao Meng
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shimin Yang
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Luyao Wu
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ke Chen
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zejian Li
- Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Xiao
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaosi Yu
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xuyong Chen
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jiexiong Feng
- Department of Pediatric Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Rui Gong
- Health Management Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignass A, Ehehalt R, Germer CT, Grunert PC, Helwig U, Horisberger K, Herrlinger K, Kienle P, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) (Version 4.1) – living guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1229-1318. [PMID: 39111333 DOI: 10.1055/a-2309-6123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Minden, Deutschland
| | - Axel Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | | | - P C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | - Karoline Horisberger
- Universitätsmedizin Johannes Gutenberg, Universität Klinik f. Allgemein-,Visceral- und Transplantationschirurgie, Mainz, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Christian Maaser
- Gastroenterologie, Ambulanzzentrum Lüneburg, Lüneburg, Deutschland
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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10
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Martinelli M, Fioretti MT, Aloi M, Alvisi P, Arrigo S, Banzato C, Bramuzzo M, Campanozzi A, Civitelli F, Knafelz D, Lionetti P, Marseglia A, Musto F, Norsa L, Palumbo G, Renzo S, Romano C, Sansotta N, Strisciuglio C, Miele E. Diagnosis and management of anemia in pediatric inflammatory bowel diseases: Clinical practice guidelines on behalf of the SIGENP IBD Working group. Dig Liver Dis 2024; 56:1257-1269. [PMID: 38503658 DOI: 10.1016/j.dld.2024.02.016] [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: 06/02/2023] [Revised: 02/22/2024] [Accepted: 02/22/2024] [Indexed: 03/21/2024]
Abstract
Anemia is one of the most frequent extra-intestinal manifestations of inflammatory bowel disease. Insidious onset, variability of symptoms and lack of standardized screening practices may increase the risk of underestimating its burden in children with IBD. Despite its relevance and peculiarity in everyday clinical practice, this topic is only dealt with in a few documents specifically for the pediatric field. The aim of the current guidelines is therefore to provide pediatric gastroenterologists with a practical update to support the clinical and therapeutic management of children with IBD and anemia. A panel of 19 pediatric gastroenterologists and 1 pediatric hematologist with experience in the field of pediatric IBD was agreed by IBD Working group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) to produce the present article outlining practical clinical approaches to the pediatric patient with IBD and anemia. The levels of evidence and recommendations have been defined for each part of the statement according to the GRADE system.
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Affiliation(s)
- Massimo Martinelli
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"
| | - Maria Teresa Fioretti
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II"
| | - Marina Aloi
- Women's and Children's Health Department, Pediatric Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Patrizia Alvisi
- Pediatric Gastroenterology Unit, Maggiore Hospital, Bologna, Italy
| | - Serena Arrigo
- Pediatric Gastroenterology and Endoscopy Unit, IRCCS Giannina Gaslini, Genova, Italy
| | - Claudia Banzato
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Pediatric Division, University of Verona, Verona, Italy
| | - Matteo Bramuzzo
- Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste, Italy
| | - Angelo Campanozzi
- Department of Medical and Surgical Sciences, Section of Pediatrics, University of Foggia, Italy
| | - Fortunata Civitelli
- Department of Gender diseases, Child and Adolescent health, Pediatric unit, Sant' Eugenio Hospital, Rome, Italy
| | - Daniela Knafelz
- Hepatology and Gastroenterology Unit, Bambino Gesù Hospital, Rome, Italy
| | - Paolo Lionetti
- University of Florence-Gastroenterology and Nutrition Unit, Meyer Children's Hospital, IRCCS, Florence
| | - Antonio Marseglia
- Fondazione IRCCS Casa Sollievo della Sofferenza, Division of Pediatrics, San Giovanni Rotondo, Italy
| | - Francesca Musto
- Women's and Children's Health Department, Pediatric Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Lorenzo Norsa
- Pediatric Department Vittore Buzzi Children's Hospital, University of Milan, Italy
| | - Giuseppe Palumbo
- Department of Haematology, Bambino Gesù Hospital, 00165 Rome, Italy
| | - Sara Renzo
- University of Florence-Gastroenterology and Nutrition Unit, Meyer Children's Hospital, IRCCS, Florence
| | - Claudio Romano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, University of Messina, Messina, Italy
| | - Naire Sansotta
- Paediatric Hepatology Gastroenterology and Transplantation, Papa Giovanni XXIII Hospital, Bergamo, Italy
| | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialistic Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Erasmo Miele
- Department of Translational Medical Science, Section of Pediatrics, University of Naples "Federico II".
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11
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Lepp HL, Amrein K, Dizdar OS, Casaer MP, Gundogan K, de Man AME, Rezzi S, van Zanten ARH, Shenkin A, Berger MM. LLL 44 - Module 3: Micronutrients in Chronic disease. Clin Nutr ESPEN 2024; 62:285-295. [PMID: 38875118 DOI: 10.1016/j.clnesp.2024.05.009] [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: 03/16/2024] [Revised: 04/26/2024] [Accepted: 05/15/2024] [Indexed: 06/16/2024]
Abstract
Micronutrients (MN), i.e. trace elements and vitamins, are essential organic molecules, which are required in the diet in relatively small amounts in any form of nutrition (oral, enteral, parenteral). The probability of MN depletion or deficiencies should be considered in all chronic illnesses, especially in those that can interfere with intake, digestion, or intestinal absorption. Low socio-economic status and food deprivation are recognized as the most prevalent reasons for MN deficiencies world-wide. Elderly multimorbid patients with multimodal therapy, as well as patients with long-lasting menu restrictions, are at high risk for both disease related malnutrition as well as multiple MN deficiencies, needing careful specific follow-up. The importance of monitoring MN blood levels along with CRP is essential for optimal care. Drug interactions are also highlighted. In patients with chronic conditions depending on medical nutrition therapy, the provision of adequate dietary reference intakes (DRI) of MN doses and monitoring of their adequacy belongs to standard of care.
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Affiliation(s)
- Hanna-Liis Lepp
- North Estonia Medical Centre Foundation, Department of Clinical Nutrition, Tallinn, Estonia.
| | - Karin Amrein
- Medical University of Graz, Department of Internal Medicine, Division of Endocrinology and Diabetology, Austria.
| | - Oguzhan S Dizdar
- Department of Internal Medicine and Clinical Nutrition Unit, University of Health Sciences Kayseri City Training and Research Hospital, Kayseri, Turkey.
| | - Michael P Casaer
- KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Intensive Care Medicine, Leuven, Belgium.
| | - Kursat Gundogan
- Division of Intensive Care Medicine, Department of Internal Medicine, Erciyes University School of Medicine, Kayseri, Turkey.
| | - Angélique M E de Man
- Amsterdam UMC, Location Vrije Universiteit, Department of Intensive Care, The Netherlands; Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
| | - Serge Rezzi
- Swiss Nutrition and Health Foundation, Epalinges, Switzerland.
| | - Arthur R H van Zanten
- Amsterdam UMC, Location Vrije Universiteit, Department of Intensive Care, The Netherlands; Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
| | - Alan Shenkin
- Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, UK.
| | - Mette M Berger
- Faculty of Biology & Medicine, Lausanne University, Lausanne, Switzerland.
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12
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Fiorino G, Colombel JF, Katsanos K, Mearin F, Stein J, Andretta M, Antonacci S, Arenare L, Citraro R, Dell’Orco S, Degli Esposti L, Ramirez de Arellano Serna A, Morin NT, Koutroubakis IE. Iron therapy supplementation in inflammatory bowel disease patients with iron deficiency anemia: findings from a real-world analysis in Italy. Eur J Gastroenterol Hepatol 2024; 36:563-570. [PMID: 38477856 PMCID: PMC10965121 DOI: 10.1097/meg.0000000000002740] [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: 05/22/2023] [Accepted: 09/30/2023] [Indexed: 03/14/2024]
Abstract
BACKGROUND This real-world analysis evaluated iron therapy supplementation in inflammatory bowel disease patients with iron-deficiency anemia, considering disease progression and healthcare resource consumption. METHODS A retrospective observational study was conducted using administrative databases of a pool of Italian healthcare entities, covering about 9.3 million beneficiaries. Between January 2010 and September 2017, adult patients were enrolled in the presence of either hospitalization or active exemption code for ulcerative colitis/Crohn's disease, or one vedolizumab prescription. Iron-deficiency anemia was identified by at least one prescription for iron and/or hospitalization for iron-deficiency anemia and/or blood transfusion (proxy of diagnosis). Patients were divided in untreated and iron-treated during 12-month follow-up and analyzed before and after propensity score matching. Disease progression, was evaluated through inflammatory bowel disease-related hospitalizations and surgeries, and healthcare resource utilization was assessed. RESULTS Overall, 1753 patients were included, 1077 (61.4%) treated with iron therapy and 676 (38.6%) untreated. After propensity score matching, 655 patients were included in each group. In unbalanced cohorts, disease progression was significantly reduced in patients receiving iron therapy compared to the untreated (11.0% vs. 15.7%, P < 0.01), and this trend was maintained also after applying propensity score matching. The overall mean cost/patient was significantly lower in iron-treated than untreated (4643€ vs. 6391€, P < 0.01). CONCLUSION The findings of this real-world analysis suggest that iron therapy was associated with significant benefits in inflammatory bowel disease patients with iron-deficiency anemia, in terms of both disease progression and healthcare resource utilization.
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Affiliation(s)
- Gionata Fiorino
- Gastroenterology and Digestive Endoscopy, Vita-Salute San Raffaele University, Milan
- Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, Rome, Italy
| | | | - Kostas Katsanos
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina, Ioannina, Greece
| | - Fermín Mearin
- Servicio de Aparato Digestivo, Teknon Medical Center, Barcelona, Spain
| | - Jürgen Stein
- Department of Gastroenterology and Clinical Nutrition, DGD Clinics Sachsenhausen, Frankfurt, Germany
| | | | | | - Loredana Arenare
- U.O.C. Farmaceutica Territoriale e Integrativa, ASL Latina, Latina
| | - Rita Citraro
- Dipartimento di Scienze della Salute, Università Magna Grecia di Catanzaro, U.O. Farmacologia Clinica e Farmacovigilanza, Azienda Ospedaliero-Universitaria “Mater Domini”, Catanzaro
| | | | - Luca Degli Esposti
- CliCon S.r.l. Società Benefit Health, Economics & Outcomes Research, Bologna, Italy
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13
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.2). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:769-858. [PMID: 38718808 DOI: 10.1055/a-2271-0994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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14
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Kaur T, Upadhyay J, Nandave M, Alsayari A, Alshehri SA, Pukale S, Wahab S, Ahmad W, Rashid S, Ansari MN. Exploring progress in iron supplement formulation approaches for treating iron deficiency anemia through bibliometric and thematic analysis. Heliyon 2024; 10:e29058. [PMID: 38623202 PMCID: PMC11016621 DOI: 10.1016/j.heliyon.2024.e29058] [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: 10/24/2023] [Revised: 03/04/2024] [Accepted: 03/28/2024] [Indexed: 04/17/2024] Open
Abstract
Anemia is a severe health issue that affects around one-third of the global population. Therefore, the present study aims to conduct a bibliometric analysis to investigate the research trends regarding advancements on iron formulations in treating iron deficiency anemia via oral or parenteral route. This study adopts thematic and bibliometric methods on existing research on novel iron formulations. It also provides perspective into the existing understanding on treatment strategies for iron deficiency anemia. This study is conducted on 543 papers on various ferrous and ferric formulations used in the treatment of iron deficiency anemia. The study period is from 1977 to 2022, and the papers are identified from the Scopus database. The bibliometric analysis was carried out using the R tool's Bibliometrix package. The study discusses performance analysis, including annual publications, geographic analysis, relevant affiliations, journal analysis, and citation analysis. In addition, the conceptual structure, including the co-occurrence network, thematic map, thematic evolution, intellectual structure highlighting co-citation analysis, and social structure depicting the collaboration network and collaboration world map, are presented. The results showed increased research on formulation strategies for the treatment of iron deficiency anemia from 2010 onwards. The top 5 contributing countries are the USA, Italy, India, Germany, and the UK, and peer-reviewed journals from the area of nutrition. The most trending areas of study are iron deficiency anemia in pregnancy, chronic kidney diseases, inflammatory bowel diseases, and various intravenous formulations used in its treatment. The authors from Europe collaborate the most with authors from other countries. The study concludes that a safer and more effective iron formulation is needed to reduce the prevalence of anemia. The findings of the study are helpful in advancing research on innovative formulations for treating iron deficiency anemia. The insights from the study are helpful to policymakers in designing specific health policies and investing more in research and development of novel formulations for the treatment of iron deficiency anemia.
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Affiliation(s)
- Tarnjot Kaur
- Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Bidholi Campus, Dehradun 248007, Uttarakhand, India
| | - Jyoti Upadhyay
- Department of Pharmaceutical Sciences, School of Health Sciences and Technology, UPES, Bidholi Campus, Dehradun 248007, Uttarakhand, India
| | - Mukesh Nandave
- Department of Pharmacology, Delhi Pharmaceutical Sciences and Research University New Delhi, 110017, India
| | - Abdulrhman Alsayari
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
| | - Saad Ali Alshehri
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
| | - Sudeep Pukale
- Lupin Research Park, Nande, Maharashtra 412115, India
| | - Shadma Wahab
- Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia
| | - Wasim Ahmad
- Department of Pharmacy, Mohammed Al-Mana College for Medical Sciences, Dammam 34222, Saudi Arabia
| | - Summya Rashid
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia
| | - Mohd Nazam Ansari
- Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, 11942, Saudi Arabia
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15
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Tian QB, Chen SJ, Xiao LJ, Xie JQ, Zhao HB, Zhang X. Potential effects of nutrition-induced alteration of gut microbiota on inflammatory bowel disease: A review. J Dig Dis 2024; 25:78-90. [PMID: 38450936 DOI: 10.1111/1751-2980.13256] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 01/27/2024] [Accepted: 02/06/2024] [Indexed: 03/08/2024]
Abstract
Inflammatory bowel disease (IBD), mainly comprising ulcerative colitis and Crohn's disease, is a group of gradually progressive diseases bringing significant mental anguish and imposes serious economic burdens. Interplay of genetic, environmental, and immunological factors have been implicated in its pathogenesis. Nutrients, as crucial environmental determinants, mainly encompassing carbohydrates, fats, proteins, and micronutrients, are closely related to the pathogenesis and development of IBD. Nutrition is essential for maintaining the dynamic balance of intestinal eco-environments to ensure intestinal barrier and immune homeostasis, while this balance can be disrupted easily by maladjusted nutrition. Research has firmly established that nutrition has the potential to shape the composition and function of gut microbiota to affect the disease course. Unhealthy diet and eating disorders lead to gut microbiota dysbiosis and further destroy the function of intestinal barrier such as the disruption of membrane integrity and increased permeability, thereby triggering intestinal inflammation. Notably, appropriate nutritional interventions, such as the Mediterranean diet, can positively modulate intestinal microecology, which may provide a promising strategy for future IBD prevention. In this review, we provide insights into the interplay between nutrition and gut microbiota and its effects on IBD and present some previously overlooked lines of evidence regarding the role of derived metabolites in IBD processes, such as trimethylamine N-oxide and imidazole propionate. Furthermore, we provide some insights into reducing the risk of onset and exacerbation of IBD by modifying nutrition and discuss several outstanding challenges and opportunities for future study.
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Affiliation(s)
- Qi Bai Tian
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan Province, China
| | - Shui Jiao Chen
- Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Li Jun Xiao
- Guangdong Corps Hospital of Chinese People's Armed Police Forces, Guangzhou, Guangdong Province, China
| | - Jia Qi Xie
- Hunan Food and Drug Vocational College, Changsha, Hunan Province, China
| | - Hong Bo Zhao
- School of Minerals Processing and Bioengineering, Central South University, Changsha, Hunan Province, China
| | - Xian Zhang
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan Province, China
- Hunan Provincial Key Laboratory of Clinical Epidemiology, Central South University, Changsha, Hunan Province, China
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16
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Vestergaard MV, Allin KH, Poulsen GJ, Lee JC, Jess T. Characterizing the pre-clinical phase of inflammatory bowel disease. Cell Rep Med 2023; 4:101263. [PMID: 37939713 PMCID: PMC10694632 DOI: 10.1016/j.xcrm.2023.101263] [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: 03/08/2023] [Revised: 07/21/2023] [Accepted: 10/10/2023] [Indexed: 11/10/2023]
Abstract
Understanding the biological changes that precede a diagnosis of inflammatory bowel disease (IBD) could facilitate pre-emptive interventions, including risk factor modification, but this pre-clinical phase of disease remains poorly characterized. Using measurements from 17 hematological and biochemical parameters taken up to 10 years before diagnosis in over 20,000 IBD patients and population controls, we address this at massive scale. We observe widespread significant changes in multiple biochemical and hematological parameters that occur up to 8 years before diagnosis of Crohn's disease (CD) and up to 3 years before diagnosis of ulcerative colitis. These changes far exceed previous expectations regarding the length of this pre-diagnostic phase, revealing an opportunity for earlier intervention, especially in CD. In summary, using a nationwide, case-control dataset-obtained from the Danish registers-we provide a comprehensive characterization of the hematological and biochemical changes that occur in the pre-clinical phase of IBD.
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Affiliation(s)
- Marie Vibeke Vestergaard
- Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Kristine H Allin
- Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark; Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark
| | - Gry J Poulsen
- Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - James C Lee
- Genetic Mechanisms of Disease Laboratory, The Francis Crick Institute, London, UK; Institute of Liver and Digestive Health, Division of Medicine, Royal Free Hospital, University College London, London, UK
| | - Tine Jess
- Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark; Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.
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17
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Liu H, Chen S, Lin Y, Jiang W, Zhao Y, Lu S, Miao L, Ge X. Ferrous Ion Alleviates Lipid Deposition and Inflammatory Responses Caused by a High Cottonseed Meal Diet by Modulating Hepatic Iron Transport Homeostasis and Controlling Ferroptosis in Juvenile Ctenopharyngodon idellus. Antioxidants (Basel) 2023; 12:1968. [PMID: 38001821 PMCID: PMC10669718 DOI: 10.3390/antiox12111968] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 10/28/2023] [Accepted: 10/31/2023] [Indexed: 11/26/2023] Open
Abstract
To investigate the mechanisms through which ferrous ion (Fe2+) addition improves the utilization of a cottonseed meal (CSM) diet, two experimental diets with equal nitrogen and energy content (low-cottonseed meal (LCM) and high-cottonseed meal (HCM) diets, respectively) containing 16.31% and 38.46% CSM were prepared. Additionally, the HCM diet was supplemented with graded levels of FeSO4·7H2O to establish two different Fe2+ supplementation groups (HCM + 0.2%Fe2+ and HCM + 0.4%Fe2+). Juvenile Ctenopharyngodon idellus (grass carps) (5.0 ± 0.5 g) were fed one of these four diets (HCM, LCM, HCM + 0.2%Fe2+ and HCM + 0.4%Fe2+ diets) for eight weeks. Our findings revealed that the HCM diet significantly increased lipid peroxide (LPO) concentration and the expression of lipogenic genes, e.g., sterol regulatory element binding transcription factor 1 (srebp1) and stearoyl-CoA desaturase (scd), leading to excessive lipid droplet deposition in the liver (p < 0.05). However, these effects were significantly reduced in the HCM + 0.2%Fe2+ and HCM + 0.4%Fe2+ groups (p < 0.05). Plasma high-density lipoprotein (HDL) concentration was also significantly lower in the HCM and HCM + 0.2%Fe2+ groups compared to the LCM group (p < 0.05), whereas low-density lipoprotein (LDL) concentration was significantly higher in the HCM + 0.2%Fe2+ and HCM + 0.4%Fe2+ groups than in the LCM group (p < 0.05). Furthermore, the plasma levels of liver functional indices, including alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glucose (GLU), were significantly lower in the HCM + 0.4%Fe2+ group (p < 0.05). Regarding the expression of genes related to iron transport regulation, transferrin 2 (tfr2) expression in the HCM group and Fe2+ supplementation groups were significantly suppressed compared to the LCM group (p < 0.05). The addition of 0.4% Fe2+ in the HCM diet activated hepcidin expression and suppressed ferroportin-1 (fpn1) expression (p < 0.05). Compared to the LCM group, the expression of genes associated with ferroptosis and inflammation, including acyl-CoA synthetase long-chain family member 4b (acsl4b), lysophosphatidylcholine acyltransferase 3 (lpcat3), cyclooxygenase (cox), interleukin 1β (il-1β), and nuclear factor kappa b (nfκb), were significantly increased in the HCM group (p < 0.05), whereas Fe2+ supplementation in the HCM diet significantly inhibited their expression (p < 0.05) and significantly suppressed lipoxygenase (lox) expression (p < 0.05). Compared with the HCM group without Fe2+ supplementation, Fe2+ supplementation in the HCM diet significantly upregulated the expression of genes associated with ferroptosis, such as heat shock protein beta-associated protein1 (hspbap1), glutamate cysteine ligase (gcl), and glutathione peroxidase 4a (gpx4a) (p < 0.05), and significantly decreased the expression of the inflammation-related genes interleukin 15/10 (il-15/il-10) (p < 0.05). In conclusion, FeSO4·7H2O supplementation in the HCM diet maintained iron transport and homeostasis in the liver of juvenile grass carps, thus reducing the occurrence of ferroptosis and alleviating hepatic lipid deposition and inflammatory responses caused by high dietary CSM contents.
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Affiliation(s)
- Hengchen Liu
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; (H.L.); (S.C.); (W.J.); (Y.Z.); (X.G.)
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China; (Y.L.); (S.L.)
| | - Shiyou Chen
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; (H.L.); (S.C.); (W.J.); (Y.Z.); (X.G.)
| | - Yan Lin
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China; (Y.L.); (S.L.)
| | - Wenqiang Jiang
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; (H.L.); (S.C.); (W.J.); (Y.Z.); (X.G.)
| | - Yongfeng Zhao
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; (H.L.); (S.C.); (W.J.); (Y.Z.); (X.G.)
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China; (Y.L.); (S.L.)
| | - Siyue Lu
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China; (Y.L.); (S.L.)
| | - Linghong Miao
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; (H.L.); (S.C.); (W.J.); (Y.Z.); (X.G.)
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China; (Y.L.); (S.L.)
| | - Xianping Ge
- Wuxi Fisheries College, Nanjing Agricultural University, Wuxi 214081, China; (H.L.); (S.C.); (W.J.); (Y.Z.); (X.G.)
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi 214081, China; (Y.L.); (S.L.)
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18
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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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19
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Valvano M, Capannolo A, Cesaro N, Stefanelli G, Fabiani S, Frassino S, Monaco S, Magistroni M, Viscido A, Latella G. Nutrition, Nutritional Status, Micronutrients Deficiency, and Disease Course of Inflammatory Bowel Disease. Nutrients 2023; 15:3824. [PMID: 37686856 PMCID: PMC10489664 DOI: 10.3390/nu15173824] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 08/25/2023] [Accepted: 08/28/2023] [Indexed: 09/10/2023] Open
Abstract
During the disease course, most Inflammatory Bowel Disease patients present a condition of malnutrition, undernutrition, or even overnutrition. These conditions are mainly due to suboptimal nutritional intake, alterations in nutrient requirements and metabolism, malabsorption, and excessive gastrointestinal losses. A suboptimal nutritional status and low micronutrient serum levels can have a negative impact on both induction and maintenance of remission and on the quality of life of Inflammatory Bowel Disease patients. We performed a systematic review including all the studies evaluating the connection between nutrition, nutrition status (including undernutrition and overnutrition), micronutrient deficiency, and both disease course and therapeutic response in Inflammatory Bowel Disease patients. This systematic review was performed using PubMed/MEDLINE and Scopus. Four main clinical settings concerning the effect of nutrition on disease course in adult Inflammatory Bowel Disease patients were analyzed (induction of remission, maintenance of remission, risk of surgery, post-operative recurrence, and surgery-related complications). Four authors independently reviewed abstracts and manuscripts for eligibility. 6077 articles were found; 762 duplicated studies were removed. Out of 412 full texts analyzed, 227 were included in the review. The evidence summarized in this review showed that many nutritional aspects could be potential targets to induce a better control of symptoms, a deeper remission, and overall improve the quality of life of Inflammatory Bowel Disease patients.
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Affiliation(s)
- Marco Valvano
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
- Division of Gastroenterology, Galliera Hospital, 16128 Genoa, Italy;
| | - Annalisa Capannolo
- Diagnostic and Surgical Endoscopy Unit, San Salvatore Academic Hospital, 67100 L’Aquila, Italy;
| | - Nicola Cesaro
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | | | - Stefano Fabiani
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | - Sara Frassino
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | - Sabrina Monaco
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | - Marco Magistroni
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | - Angelo Viscido
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
| | - Giovanni Latella
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L’Aquila, Piazzale Salvatore Tommasi 1, 67100 L’Aquila, Italy; (N.C.); (S.F.); (S.F.); (S.M.); (M.M.); (A.V.); (G.L.)
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20
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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21
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Fiorino G, Colombel JF, Katsanos K, Mearin F, Stein J, Andretta M, Antonacci S, Arenare L, Citraro R, Dell’Orco S, Degli Esposti L, Ramirez de Arellano Serna A, Morin N, Koutroubakis IE. Iron deficiency anemia impacts disease progression and healthcare resource consumption in patients with inflammatory bowel disease: a real-world evidence study. Therap Adv Gastroenterol 2023; 16:17562848231177153. [PMID: 37274300 PMCID: PMC10236249 DOI: 10.1177/17562848231177153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 05/04/2023] [Indexed: 06/06/2023] Open
Abstract
BACKGROUND Iron deficiency anemia (IDA) is a common extraintestinal manifestation of inflammatory bowel disease (IBD), affecting around one-third of patients. OBJECTIVE To compare IBD progression and healthcare resource utilization in patients with and without a co-diagnosis of IDA in a real-world setting. DESIGN A retrospective comparative study was conducted using Italian entities' administrative databases, covering 9.3 million health-assisted individuals. METHODS Adult IBD patients diagnosed with ulcerative colitis and/or Crohn's disease were enrolled between January 2010 and September 2017. Within 12 months from IBD diagnosis, IDA was identified by at least one prescription for iron and/or IDA hospitalization and/or blood transfusion (proxy of diagnosis). IBD population was divided according to the presence/absence of IDA. Given the nonrandom patients' allocation, propensity score matching (PSM) was applied to abate potential unbalances between the groups. Before and after PSM, IBD progression (in terms of IBD-related hospitalizations and surgeries), and healthcare resource costs were assessed. RESULTS Overall, 13,475 IBD patients were included, with an average age at diagnosis of 49.9 years, and a 53.9% percentage of male gender. Before PSM, 1753 (13%) patients were IBD-IDA, and 11,722 (87%) were IBD-non-IDA. Post-PSM, 1753 IBD-IDA patients were matched with 3506 IBD-non-IDA. Before PSM, IBD progression was significantly higher in IBD-IDA (12.8%) than in IBD-non-IDA (6.5%) (p < 0.001). After PSM, IBD progression and IBD-related hospitalizations were significantly (p < 0.001) more frequent in IBD-IDA patients (12.8% and 12.0%, respectively) compared to IBD-non-IDA (8.7% and 7.7%). Consistently, healthcare expenditures resulted significantly higher among IDA patients (p < 0.001), with an overall mean annual cost of €5317 compared to €2798 for patients without IDA. These results were confirmed after PSM matching, as the mean annual total cost/patient in IBD-IDA versus IBD-non-IDA were €3693 and €3046, respectively (p < 0.001). CONCLUSION In a real-life setting, IDA co-diagnosis in IBD patients was associated with disease progression and higher related economic burden.
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Affiliation(s)
- Gionata Fiorino
- Gastroenterology and Digestive Endoscopy,
Vita-Salute San Raffaele University, Milan, Italy
- Gastroenterology and Digestive Endoscopy, San
Camillo-Forlanini Hospital, Rome, Italy
| | | | | | | | - Jürgen Stein
- DGD Kliniken Frankfurt Sachsenhausen,
Frankfurt/Main, Germany
| | | | | | | | - Rita Citraro
- Azienda Ospedaliero-Universitaria Mater
Domini, Catanzaro, Italy
| | | | - Luca Degli Esposti
- CliCon S.r.l. Società Benefit Health,
Economics & Outcomes Research, Bologna, Italy
| | | | | | - Ioannis E. Koutroubakis
- Department of Gastroenterology, University
Hospital Heraklion, P.O. BOX 1352, Heraklion, Crete 71110, Greece
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22
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Zhu L, Li G, Liang Z, Qi T, Deng K, Yu J, Peng Y, Zheng J, Song Y, Chang X. Microbiota-assisted iron uptake promotes immune tolerance in the intestine. Nat Commun 2023; 14:2790. [PMID: 37188703 PMCID: PMC10185671 DOI: 10.1038/s41467-023-38444-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 04/28/2023] [Indexed: 05/17/2023] Open
Abstract
Iron deficiencies are the most common nonenteric syndromes observed in patients with inflammatory bowel disease, but little is known about their impacts on immune tolerance. Here we show that homeostasis of regulatory T cells in the intestine was dependent on high cellular iron levels, which were fostered by pentanoate, a short-chain fatty acid produced by intestinal microbiota. Iron deficiencies in Treg caused by the depletion of Transferrin receptor 1, a major iron transporter, result in the abrogation of Treg in the intestine and lethal autoimmune disease. Transferrin receptor 1 is required for differentiation of c-Maf+ Treg, major constituents of intestinal Treg. Mechanistically, iron enhances the translation of HIF-2α mRNA, and HIF-2α in turn induces c-Maf expression. Importantly, microbiota-produced pentanoate promotes iron uptake and Treg differentiation in the intestine. This subsequently restores immune tolerance and ameliorated iron deficiencies in mice with colitis. Our results thus reveal an association between nutrient uptake and immune tolerance in the intestine.
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Affiliation(s)
- Lizhen Zhu
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
- Research Center for Industries of the Future (RCIF), Westlake University, Hangzhou, Zhejiang, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
| | - Geng Li
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
- Research Center for Industries of the Future (RCIF), Westlake University, Hangzhou, Zhejiang, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
| | - Zhixin Liang
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
- Research Center for Industries of the Future (RCIF), Westlake University, Hangzhou, Zhejiang, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
| | - Tuan Qi
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
- Research Center for Industries of the Future (RCIF), Westlake University, Hangzhou, Zhejiang, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
| | - Kui Deng
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
- Research Center for Industries of the Future (RCIF), Westlake University, Hangzhou, Zhejiang, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
| | - Jiancheng Yu
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
- Research Center for Industries of the Future (RCIF), Westlake University, Hangzhou, Zhejiang, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
| | - Yue Peng
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
- Research Center for Industries of the Future (RCIF), Westlake University, Hangzhou, Zhejiang, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
| | - Jusheng Zheng
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China
- Research Center for Industries of the Future (RCIF), Westlake University, Hangzhou, Zhejiang, China
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China
| | - Yan Song
- School of Medicine, University of California San Diego, La Jolla, CA, US
| | - Xing Chang
- Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
- Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
- Research Center for Industries of the Future (RCIF), Westlake University, Hangzhou, Zhejiang, China.
- Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang, China.
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23
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Han SY, Yun G, Cha HM, Lee MK, Lee H, Kang EK, Hong SP, Teahan KA, Park M, Hwang H, Lee SS, Kim M, Choi IS. A Natural Virucidal and Microbicidal Spray Based on Polyphenol-Iron Sols. ACS APPLIED BIO MATERIALS 2023; 6:1981-1991. [PMID: 37083357 PMCID: PMC10152399 DOI: 10.1021/acsabm.3c00195] [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: 03/14/2023] [Accepted: 04/09/2023] [Indexed: 04/22/2023]
Abstract
Numerous disinfection methods have been developed to reduce the transmission of infectious diseases that threaten human health. However, it still remains elusively challenging to develop eco-friendly and cost-effective methods that deactivate a wide range of pathogens, from viruses to bacteria and fungi, without doing any harm to humans or the environment. Herein we report a natural spraying protocol, based on a water-dispersible supramolecular sol of nature-derived tannic acid (TA) and Fe3+, which is easy-to-use and low-cost. Our formulation effectively deactivates viruses (influenza A viruses, SARS-CoV-2, and human rhinovirus) as well as suppressing the growth and spread of pathogenic bacteria (Escherichia coli, Salmonella typhimurium, Staphylococcus aureus, and Acinetobacter baumannii) and fungi (Pleurotus ostreatus and Trichophyton rubrum). Its versatile applicability in a real-life setting is also demonstrated against microorganisms present on the surfaces of common household items (e.g., air filter membranes, disposable face masks, kitchen sinks, mobile phones, refrigerators, and toilet seats).
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Affiliation(s)
| | - Gyeongwon Yun
- Department of Chemistry,
KAIST, Daejeon 34141, Korea
| | - Hyeon-Min Cha
- Infectious Diseases Therapeutic Research Center,
KRICT, Daejeon 34114, Korea
- Graduate School of New Drug Discovery and Development,
Chungnam National University, Daejeon 34134,
Korea
| | - Myoung Kyu Lee
- Infectious Diseases Therapeutic Research Center,
KRICT, Daejeon 34114, Korea
| | - Hojae Lee
- Department of Chemistry, Hallym
University, Chuncheon 24252, Korea
| | | | - Seok-Pyo Hong
- Department of Chemistry,
KAIST, Daejeon 34141, Korea
| | - Kirsty A. Teahan
- School of Chemistry and Institute for Life Sciences,
Highfield Campus, University of Southampton, Southampton SO17
1BJ, United Kingdom
| | - Minjeong Park
- Hansol RootOne, Inc., 165
Myeoncheon-ro, Dangjin 31803, Korea
| | - Hansol Hwang
- Hansol RootOne, Inc., 165
Myeoncheon-ro, Dangjin 31803, Korea
| | - Seung Seo Lee
- School of Chemistry and Institute for Life Sciences,
Highfield Campus, University of Southampton, Southampton SO17
1BJ, United Kingdom
| | - Meehyein Kim
- Infectious Diseases Therapeutic Research Center,
KRICT, Daejeon 34114, Korea
- Graduate School of New Drug Discovery and Development,
Chungnam National University, Daejeon 34134,
Korea
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24
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Chen OCW, Siebel S, Colaco A, Nicoli ER, Platt N, Shepherd D, Newman S, Armitage AE, Farhat NY, Seligmann G, Smith C, Smith DA, Abdul-Sada A, Jeyakumar M, Drakesmith H, Porter FD, Platt FM. Defective iron homeostasis and hematological abnormalities in Niemann-Pick disease type C1. Wellcome Open Res 2023; 7:267. [PMID: 37065726 PMCID: PMC10090865 DOI: 10.12688/wellcomeopenres.17261.2] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/22/2023] [Indexed: 04/05/2023] Open
Abstract
Background: Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the accumulation of multiple lipids in the late endosome/lysosomal system and reduced acidic store calcium. The lysosomal system regulates key aspects of iron homeostasis, which prompted us to investigate whether there are hematological abnormalities and iron metabolism defects in NPC1. Methods: Iron-related hematological parameters, systemic and tissue metal ion and relevant hormonal and proteins levels, expression of specific pro-inflammatory mediators and erythrophagocytosis were evaluated in an authentic mouse model and in a large cohort of NPC patients. Results: Significant changes in mean corpuscular volume and corpuscular hemoglobin were detected in Npc1 -/- mice from an early age. Hematocrit, red cell distribution width and hemoglobin changes were observed in late-stage disease animals. Systemic iron deficiency, increased circulating hepcidin, decreased ferritin and abnormal pro-inflammatory cytokine levels were also found. Furthermore, there is evidence of defective erythrophagocytosis in Npc1 -/- mice and in an in vitro NPC1 cellular model. Comparable hematological changes, including low normal serum iron and transferrin saturation and low cerebrospinal fluid ferritin were confirmed in NPC1 patients. Conclusions: These data suggest loss of iron homeostasis and hematological abnormalities in NPC1 may contribute to the pathophysiology of this disease.
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Affiliation(s)
- Oscar C W Chen
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Stephan Siebel
- Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20892, USA
| | - Alexandria Colaco
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Elena-Raluca Nicoli
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Nick Platt
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Dawn Shepherd
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Stephanie Newman
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Andrew E Armitage
- MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, Oxfordshire, OX3 9DS, UK
| | - Nicole Y Farhat
- Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20892, USA
| | - George Seligmann
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Claire Smith
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - David A Smith
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Alaa Abdul-Sada
- Chemistry Department, School of Life Sciences, University of Sussex, Brighton, Sussex, BN1 9QJ, UK
| | - Mylvaganam Jeyakumar
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Hal Drakesmith
- MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, Oxfordshire, OX3 9DS, UK
| | - Forbes D Porter
- Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20892, USA
| | - Frances M Platt
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
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25
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Fang X, Kang L, Qiu YF, Li ZS, Bai Y. Yersinia enterocolitica in Crohn’s disease. Front Cell Infect Microbiol 2023; 13:1129996. [PMID: 36968108 PMCID: PMC10031030 DOI: 10.3389/fcimb.2023.1129996] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 02/13/2023] [Indexed: 03/11/2023] Open
Abstract
Increasing attention is being paid to the unique roles gut microbes play in both physiological and pathological processes. Crohn’s disease (CD) is a chronic, relapsing, inflammatory disease of the gastrointestinal tract with unknown etiology. Currently, gastrointestinal infection has been proposed as one initiating factor of CD. Yersinia enterocolitica, a zoonotic pathogen that exists widely in nature, is one of the most common bacteria causing acute infectious gastroenteritis, which displays clinical manifestations similar to CD. However, the specific role of Y. enterocolitica in CD is controversial. In this Review, we discuss the current knowledge on how Y. enterocolitica and derived microbial compounds may link to the pathogenesis of CD. We highlight examples of Y. enterocolitica-targeted interventions in the diagnosis and treatment of CD, and provide perspectives for future basic and translational investigations on this topic.
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Affiliation(s)
| | | | | | | | - Yu Bai
- *Correspondence: Zhao-Shen Li, ; Yu Bai,
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Novichkova E, Nayak S, Boussiba S, Gopas J, Zilberg D, Khozin-Goldberg I. Dietary Application of the Microalga Lobosphaera incisa P127 Reduces Severity of Intestinal Inflammation, Modulates Gut-Associated Gene Expression, and Microbiome in the Zebrafish Model of IBD. Mol Nutr Food Res 2023; 67:e2200253. [PMID: 36683256 DOI: 10.1002/mnfr.202200253] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2022] [Revised: 11/30/2022] [Indexed: 01/24/2023]
Abstract
SCOPE Microalgae are an emerging nutritional resource of biomolecules with potential to alleviate gut inflammation. The study explores the anti-inflammatory and immunomodulatory potential of the microalga Lobosphaera incisa P127, which accumulates a rare omega-6 LC-PUFA dihomo-ɣ-linolenic acid (DGLA) under nitrogen starvation. The therapeutic potential of dietary supplementation with P127 is investigated in the zebrafish model of IBD (TNBS-induced colitis). METHODS AND RESULTS Guts are sampled from zebrafish fed experimental diets for 4 weeks, before and 24 h after TNBS challenge. Diets containing 15% non-starved (Ns) and 7.5% and 15% N-starved (St) algal biomass significantly attenuate the severity of gut injury and goblet cell depletion. In contrast, diets containing 7.5% Ns and DGLA ethyl ester have no effect on gut condition. Fish fed 15% St, high-DGLA biomass, have the fewest individuals with pathological alterations in the gut. Dietary inclusion of Ns and St distinctly modulates gut-associated expression of the immune and inflammatory genes. Fish fed 15% Ns biomass display a coordinated boost in immune gene expression and show major changes in the gut microbiome prior challenge. CONCLUSION Dietary inclusion of L. incisa biomass at two physiological states, ameliorates TNBS-induced gut inflammation, suggesting the synergistic beneficial effects of biomass components not limited to DGLA.
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Affiliation(s)
- Ekaterina Novichkova
- The French Associates Institute for Agriculture and Biotechnology of Drylands, The Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, Midreshet Ben-Gurion, 8499000, Israel
- The Albert Katz International School for Desert Studies, The Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, Midreshet Ben-Gurion, 8499000, Israel
| | - Sagar Nayak
- The French Associates Institute for Agriculture and Biotechnology of Drylands, The Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, Midreshet Ben-Gurion, 8499000, Israel
- The Jacob Blaustein Center for Scientific Cooperation, The Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, Midreshet Ben-Gurion, 8499000, Israel
| | - Sammy Boussiba
- The French Associates Institute for Agriculture and Biotechnology of Drylands, The Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, Midreshet Ben-Gurion, 8499000, Israel
| | - Jacob Gopas
- Department of Microbiology and Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, 8400501, Israel
| | - Dina Zilberg
- The French Associates Institute for Agriculture and Biotechnology of Drylands, The Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, Midreshet Ben-Gurion, 8499000, Israel
| | - Inna Khozin-Goldberg
- The French Associates Institute for Agriculture and Biotechnology of Drylands, The Jacob Blaustein Institutes for Desert Research, Ben-Gurion University of the Negev, Sede Boqer Campus, Midreshet Ben-Gurion, 8499000, Israel
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Ji X, Ma S, Sun X, Yu D, Song Y, Li R. Analysis of ferroptosis-associated genes in Crohn's disease based on bioinformatics. Front Med (Lausanne) 2023; 9:1058076. [PMID: 36714107 PMCID: PMC9881725 DOI: 10.3389/fmed.2022.1058076] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 12/29/2022] [Indexed: 01/14/2023] Open
Abstract
Background Ferroptosis, a novel mode of apoptosis has recently been shown to be associated with fibrosis, tumor, cardiovascular, and other diseases. In this study, using bioinformatic analysis, we identified ferroptosis genes associated with Crohn's disease (CD) and performed biological function analysis, identified potential drug targets, and provided new directions for the future treatment of CD. Methods Differential expression analysis was performed using the GSE186582 dataset from the Gene Expression Omnibus (GEO) database. Ferroptosis-associated genes were downloaded from the FerrDB database, and overlapping genes associated with CD and ferroptosis were extracted. Then, we performed functional enrichment analysis, constructed a protein-protein interaction network (PPI), identified the correlation between hub genes and immune infiltration, performed external validation using a second and third dataset (GSE102133, GSE95095), and identified potential therapeutic agents. Finally, we validated the protein expression levels of the identified hub genes by immunohistochemical staining in the colon tissues from CD and healthy participants. Results A total of 28 ferroptosis-associated genes associated with CD were identified in our analysis, which included 22 up-regulated and 6 down-regulated genes. Gene Ontology (GO) analysis showed that these genes are essential for the apical plasma membrane and amide transport, and Metascape analysis showed that these genes mainly act on IL-4 and IL-13 signaling pathways. Five hub genes, PTGS2, IL6, IL1B, NOS2, and IDO1, were identified by a protein interaction network, and external validation of these hub genes showed statistically significant differences in expression between the CD patients and normal participants (p < 0.05), and all AUC values were greater than 0.8. Further, we predicted the top 10 drugs used to treat CD. Immune infiltration results suggest that Hub gene is related to T cells, macrophages, dendritic cells, and other immune cells. Finally, the results of immunohistochemical experiments showed that the protein expression of the hub gene was higher in CD colon tissue than in normal subjects (p < 0.05). Conclusion Bioinformatics analysis showed that ferroptosis is closely related to the development of CD, and the prediction of potential drugs provides new targets for the treatment of CD. Moreover, five hub genes identified are potentially new and effective markers for the diagnosis of CD.
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Affiliation(s)
- Xingyu Ji
- Department of Gastroenterology, The First Affiliated Hospital of Jiamusi University, Jiamusi, China,Department of Gastroenterology, Heilongjiang Provincial Hospital, Harbin, China
| | - Su Ma
- Department of Gastroenterology, The First Affiliated Hospital of Jiamusi University, Jiamusi, China,Department of Gastroenterology, Heilongjiang Provincial Hospital, Harbin, China
| | - Xiaomei Sun
- Department of Gastroenterology, Heilongjiang Provincial Hospital, Harbin, China,*Correspondence: Xiaomei Sun,
| | - Dan Yu
- Department of Gastroenterology, Heilongjiang Provincial Hospital, Harbin, China
| | - Ye Song
- Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Rui Li
- Department of Gastroenterology, Heilongjiang Provincial Hospital, Harbin, China
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Bevers N, Van de Vijver E, Aliu A, Rezazadeh Ardabili A, Rosias P, Stapelbroek J, Bertrams Maartens IA, van de Feen C, Escher H, Oudshoorn A, Teklenburg S, Vande Velde S, Winkens B, Raijmakers M, Vreugdenhil A, Pierik MJ, van Rheenen PF. Ferric Carboxymaltose Versus Ferrous Fumarate in Anemic Children with Inflammatory Bowel Disease: The POPEYE Randomized Controlled Clinical Trial. J Pediatr 2022; 256:113-119.e4. [PMID: 36563900 DOI: 10.1016/j.jpeds.2022.12.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 09/29/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022]
Abstract
OBJECTIVE To determine whether intravenous (IV) or oral iron suppletion is superior in improving physical fitness in anemic children with inflammatory bowel disease (IBD). STUDY DESIGN We conducted a clinical trial at 11 centers. Children aged 8-18 with IBD and anemia (defined as hemoglobin [Hb] z-score < -2) were randomly assigned to a single IV dose of ferric carboxymaltose or 12 weeks of oral ferrous fumarate. Primary end point was the change in 6-minute walking distance (6MWD) from baseline, expressed as z-score. Secondary outcome was a change in Hb z-score from baseline. RESULTS We randomized 64 patients (33 IV iron and 31 oral iron) and followed them for 6 months. One month after the start of iron therapy, the 6MWD z-score of patients in the IV group had increased by 0.71 compared with -0.11 in the oral group (P = .01). At 3- and 6-month follow-ups, no significant differences in 6MWD z-scores were observed. Hb z-scores gradually increased in both groups and the rate of increase was not different between groups at 1, 3, and 6 months after initiation of iron therapy (overall P = .97). CONCLUSION In this trial involving anemic children with IBD, a single dose of IV ferric carboxymaltose was superior to oral ferrous fumarate with respect to quick improvement of physical fitness. At 3 and 6 months after initiation of therapy, no differences were discovered between oral and IV therapies. The increase of Hb over time was comparable in both treatment groups. TRIAL REGISTRATION NTR4487 [Netherlands Trial Registry].
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Affiliation(s)
- Nanja Bevers
- Department of Paediatrics, Zuyderland Medical Center, Sittard, The Netherlands.
| | - Els Van de Vijver
- Department of Paediatric Gastroenterology, Hepatology and Nutrition, Antwerp University Hospital, Edegem, Belgium
| | - Arta Aliu
- Department of Paediatrics, Zuyderland Medical Center, Sittard, The Netherlands
| | | | - Philippe Rosias
- Department of Paediatrics, Zuyderland Medical Center, Sittard, The Netherlands
| | | | | | | | - Hankje Escher
- Erasmus Medical Center, Children's Hospital Department of Paediatric Gastroenterology, Rotterdam, The Netherlands
| | | | - Sarah Teklenburg
- Department of Paediatrics, Isala Hospitals, Zwolle, The Netherlands
| | | | - Bjorn Winkens
- Department of Methodology and Statistics, Maastricht University, Maastricht, The Netherlands
| | - Maarten Raijmakers
- Laboratory of Clinical Chemistry and Haematology, Zuyderland Medical Centre, Heerlen, Limburg, The Netherlands
| | - Anita Vreugdenhil
- Department of Paediatrics and NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Marieke J Pierik
- Division of Gastroenterology-Hepatology and NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Patrick F van Rheenen
- University of Groningen, University Medical Centre Groningen - Beatrix Children's Hospital, Department of Paediatric Gastroenterology Hepatology and Nutrition, Groningen, The Netherlands
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Tan YL, Zhao YE. Advances in understanding of effects of dietary nutrients in inflammatory bowel disease patients. Shijie Huaren Xiaohua Zazhi 2022; 30:921-927. [DOI: 10.11569/wcjd.v30.i21.921] [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] [Indexed: 11/08/2022] Open
Abstract
The occurrence of inflammatory bowel disease (IBD) is influenced by environmental factors. Diet, as an important environmental factor, is closely associated with intestinal ecology and plays a critical role in the pathological process of IBD. This review summarizes the role of major dietary nutrients in the pathogenesis of IBD, with an aim to provide clues for the prevention and treatment of IBD.
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Affiliation(s)
- Yan-Li Tan
- Department of Gastroenterology, TongJi Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
| | - Yu-E Zhao
- Department of Gastroenterology, TongJi Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
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Hsiao PY, Weng MT, Chang CH, Huang LY, Tung CC, Leong YL, Shieh MJ, Wong JM, Wei SC. Anemia in inflammatory bowel disease course is associated with patients' worse outcome. J Formos Med Assoc 2022:S0929-6646(22)00426-0. [DOI: 10.1016/j.jfma.2022.11.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 10/03/2022] [Accepted: 11/11/2022] [Indexed: 11/27/2022] Open
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Chen OCW, Siebel S, Colaco A, Nicoli ER, Platt N, Shepherd D, Newman S, Armitage AE, Farhat NY, Seligmann G, Smith C, Smith DA, Abdul-Sada A, Jeyakumar M, Drakesmith H, Porter FD, Platt FM. Defective iron homeostasis and hematological abnormalities in Niemann-Pick disease type C1. Wellcome Open Res 2022; 7:267. [PMID: 37065726 PMCID: PMC10090865 DOI: 10.12688/wellcomeopenres.17261.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/12/2022] [Indexed: 11/20/2022] Open
Abstract
Background: Niemann-Pick disease type C1 (NPC1) is a neurodegenerative lysosomal storage disorder characterized by the accumulation of multiple lipids in the late endosome/lysosomal system and reduced acidic store calcium. The lysosomal system regulates key aspects of iron homeostasis, which prompted us to investigate whether there are hematological abnormalities and iron metabolism defects in NPC1. Methods: Iron-related hematological parameters, systemic and tissue metal ion and relevant hormonal and proteins levels, expression of specific pro-inflammatory mediators and erythrophagocytosis were evaluated in an authentic mouse model and in a large cohort of NPC patients. Results: Significant changes in mean corpuscular volume and corpuscular hemoglobin were detected in Npc1 -/- mice from an early age. Hematocrit, red cell distribution width and hemoglobin changes were observed in late-stage disease animals. Systemic iron deficiency, increased circulating hepcidin, decreased ferritin and abnormal pro-inflammatory cytokine levels were also found. Furthermore, there is evidence of defective erythrophagocytosis in Npc1 -/- mice and in an in vitro NPC1 cellular model. Comparable hematological changes, including low normal serum iron and transferrin saturation and low cerebrospinal fluid ferritin were confirmed in NPC1 patients. Conclusions: These data suggest loss of iron homeostasis and hematological abnormalities in NPC1 may contribute to the pathophysiology of this disease.
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Affiliation(s)
- Oscar C W Chen
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Stephan Siebel
- Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20892, USA
| | - Alexandria Colaco
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Elena-Raluca Nicoli
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Nick Platt
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Dawn Shepherd
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Stephanie Newman
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Andrew E Armitage
- MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, Oxfordshire, OX3 9DS, UK
| | - Nicole Y Farhat
- Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20892, USA
| | - George Seligmann
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Claire Smith
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - David A Smith
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Alaa Abdul-Sada
- Chemistry Department, School of Life Sciences, University of Sussex, Brighton, Sussex, BN1 9QJ, UK
| | - Mylvaganam Jeyakumar
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
| | - Hal Drakesmith
- MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, Oxfordshire, OX3 9DS, UK
| | - Forbes D Porter
- Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, 20892, USA
| | - Frances M Platt
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, Oxfordshire, OX1 3QT, UK
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Ellwanger JH, Ziliotto M, Kulmann-Leal B, Chies JAB. Iron deficiency and soil-transmitted helminth infection: classic and neglected connections. Parasitol Res 2022; 121:3381-3392. [PMID: 36258094 DOI: 10.1007/s00436-022-07697-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 10/14/2022] [Indexed: 10/24/2022]
Abstract
Beyond participating in the oxygen transport by red blood cells, iron is an essential micronutrient and contributes to different physiological pathways and processes, such as cell proliferation, DNA repair, and other homeostatic functions. Iron deficiency affects millions of people, especially children and pregnant women. The consequences of iron deficiency are diverse, including inadequate child development, impaired cognition, and reduced productivity. Several factors contribute to iron deficiency, such as iron-poor diet, genetic factors, and infection with soil-transmitted helminths (STHs), especially roundworms (Ascaris lumbricoides), hookworms (Necator americanus and Ancylostoma duodenale), and whipworms (Trichuris trichiura). This review updates and summarizes the role of STHs as drivers of iron deficiency. Also, the poorly explored connections between STH infection, geophagia (a pica manifestation), immune response, and iron deficiency are discussed, highlighting how iron deficiency may act as a risk factor for infections by STHs, in addition to being a consequence of intestinal parasitic infections. Finally, strategies for control and management of iron deficiency and STH infection are described.
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Affiliation(s)
- Joel Henrique Ellwanger
- Laboratory of Immunobiology and Immunogenetics (Prédio 43323, Laboratório 212), Department of Genetics, Postgraduate Program in Genetics and Molecular Biology (PPGBM), Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, Campus do Vale, Rio Grande do Sul, Porto Alegre, Brazil.
| | - Marina Ziliotto
- Laboratory of Immunobiology and Immunogenetics (Prédio 43323, Laboratório 212), Department of Genetics, Postgraduate Program in Genetics and Molecular Biology (PPGBM), Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, Campus do Vale, Rio Grande do Sul, Porto Alegre, Brazil
| | - Bruna Kulmann-Leal
- Laboratory of Immunobiology and Immunogenetics (Prédio 43323, Laboratório 212), Department of Genetics, Postgraduate Program in Genetics and Molecular Biology (PPGBM), Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, Campus do Vale, Rio Grande do Sul, Porto Alegre, Brazil
| | - José Artur Bogo Chies
- Laboratory of Immunobiology and Immunogenetics (Prédio 43323, Laboratório 212), Department of Genetics, Postgraduate Program in Genetics and Molecular Biology (PPGBM), Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, Campus do Vale, Rio Grande do Sul, Porto Alegre, Brazil
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Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease. Life (Basel) 2022; 12:life12101623. [PMID: 36295058 PMCID: PMC9604584 DOI: 10.3390/life12101623] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 10/07/2022] [Accepted: 10/08/2022] [Indexed: 11/16/2022] Open
Abstract
Inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are complex diseases whose etiology is associated with genetic and environmental risk factors, among which are diet and gut microbiota. To date, IBD is an incurable disease and the main goal of its treatment is to reduce symptoms, prevent complications, and improve nutritional status and the quality of life. Patients with IBD usually suffer from nutritional deficiency with imbalances of specific micronutrient levels that contribute to the further deterioration of the disease. Therefore, along with medications usually used for IBD treatment, therapeutic strategies also include the supplementation of micronutrients such as vitamin D, folic acid, iron, and zinc. Micronutrient supplementation tailored according to individual needs could help patients to maintain overall health, avoid the triggering of symptoms, and support remission. The identification of individuals’ genotypes associated with the absorption, transport and metabolism of micronutrients can modify future clinical practice in IBD and enable individualized treatment. This review discusses the personalized approach with respect to genetics related to micronutrients commonly used in inflammatory bowel disease treatment.
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Macrophage immunometabolism in inflammatory bowel diseases: From pathogenesis to therapy. Pharmacol Ther 2022; 238:108176. [DOI: 10.1016/j.pharmthera.2022.108176] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 03/11/2022] [Accepted: 03/22/2022] [Indexed: 12/17/2022]
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Singh A, Mishra R, Ranjan R. Gastrointestinal Lesions and Its Associated Factors in Adult Males With Iron Deficiency Anaemia: A Cross-Sectional Study From Tertiary Care Centre of North India. Cureus 2022; 14:e26905. [PMID: 35983390 PMCID: PMC9376560 DOI: 10.7759/cureus.26905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2022] [Indexed: 11/14/2022] Open
Abstract
Background Around 30% of the world's population suffers from iron deficiency anaemia (IDA). The standard evaluation for IDA involves upper and lower endoscopy, which allows for the confirmation of pathology of the gastrointestinal tract (GIT) induced due to IDA through iron malabsorption mechanism or loss of blood. Assessing the prevalence of lesions of GIT of significant nature among males having IDA, was the goal of our study. Methods Our cross-sectional study was conducted for two years and involved 152 males (adults) with confirmed cases of IDA from the Outpatient (OPD) and In-patient (IPD) in the present hospital. Following collecting consent (both informed and written in nature), patient-specific data was collected in a standardized form, and a blood sample was taken for laboratory testing. The analyses were done at a 5% level of significance; an association was considered significant if the p-value < 0.05. Results The average age of the study participants was 59.6 years. The commonest lesions reported were antral gastritis (9.9%) and H. pylori gastritis (7.2%) in upper GI; and haemorrhoid (9.2%) and anal fissure (3.9%) in lower GI. The overall prevalence of any GI lesions was 65.1%. The GI lesions were significantly associated higher among men with age > 50 years (73.7%). The presence of occult blood in stools (p < 0.0001) and parasites in stools (p=0.0001) were significantly related to the presence of GI lesions. Conclusion GI lesions are frequently detected in males with IDA. Whether it is symptomatic male or asymptomatic male with anaemia refractory to iron treatment, GIT should be evaluated in them.
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Cuthbert JJ, Ransome N, Clark AL. Re-defining iron deficiency in patients with heart failure. Expert Rev Cardiovasc Ther 2022; 20:667-681. [DOI: 10.1080/14779072.2022.2100349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Affiliation(s)
- JJ Cuthbert
- Department of Cardiorespiratory Medicine, Centre for Clinical Sciences, Hull York Medical School, University of Hull, Kingston-Upon-Hull, East Riding of Yorkshire, UK
- Department of Cardiology, Hull University Teaching Hospital Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, East Riding of Yorkshire, UK
| | - N Ransome
- Department of Haematology, York and Scarborough Teaching Hospitals NHS Trust, York, UK
| | - AL Clark
- Department of Cardiology, Hull University Teaching Hospital Trust, Castle Hill Hospital, Castle Road, Cottingham, Kingston-Upon-Hull, East Riding of Yorkshire, UK
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Bergamaschi G, Caprioli F, Lenti MV, Elli L, Radaelli F, Rondonotti E, Mengoli C, Miceli E, Ricci C, Ardizzone S, Vecchi M, Di Sabatino A. Pathophysiology and therapeutic management of anemia in gastrointestinal disorders. Expert Rev Gastroenterol Hepatol 2022; 16:625-637. [PMID: 35696485 DOI: 10.1080/17474124.2022.2089114] [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] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Anemia is a common complication of gastrointestinal (GI) disorders, with a prevalence up to 60% in celiac disease (CeD) and inflammatory bowel disease (IBD). Iron deficiency anemia (IDA) is the most prevalent form of anemia in these conditions, but chronic inflammation and vitamin B12 deficiency represent other common contributing mechanisms, especially in IBD. AREAS COVERED We discuss the pathogenesis of anemia in various medical GI disorders, the sometime problematic distinction between IDA, anemia of inflammation (AI) and the association of the two, and therapeutic and preventive measures that can be useful for the management of anemia in GI disorders. Unfortunately, with the exception of IDA and AI in IBD, large RCT concerning the treatment of anemia in GI disorders are lacking. EXPERT OPINION Anemia management strategies in GI disorders are outlined, with a focus on the main prevention, diagnostic, and therapeutic measures. Specific problems and situations such as the role of gluten-free diet for IDA treatment in CeD, the choice between oral and parenteral supplementation of iron or vitamin B12 in carential anemias, the use of endoscopic procedures to stop bleeding in intestinal angiodysplasia and preventive/treatment strategies for NSAID-associated GI bleeding are discussed.
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Affiliation(s)
- Gaetano Bergamaschi
- Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy
| | - Flavio Caprioli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy
| | - Marco Vincenzo Lenti
- Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy.,Department of Internal Medicine, University of Pavia, Pavia, Italy
| | - Luca Elli
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, Milan, Italy
| | | | | | - Caterina Mengoli
- Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy
| | - Emanuela Miceli
- Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy
| | - Chiara Ricci
- Gastroenterology Unit, Spedali Civili di Brescia and Department of Clinical and Experimental Sciences, University of Brescia, Brescia Italy
| | - Sandro Ardizzone
- Sacco, University of MilanGastroenterology and Digestive Endoscopy Unit, Department of Biochemical and Clinical Sciences L , Milano, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine, San Matteo Hospital Foundation, Pavia, Italy.,Department of Internal Medicine, University of Pavia, Pavia, Italy
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Huguet JM, Cortés X, Boscá-Watts MM, Muñoz M, Maroto N, Iborra M, Hinojosa E, Capilla M, Asencio C, Amoros C, Paredes JM. Ferric Carboxymaltose Improves the Quality of Life of Patients with Inflammatory Bowel Disease and Iron Deficiency without Anaemia. J Clin Med 2022; 11:2786. [PMID: 35628914 PMCID: PMC9146412 DOI: 10.3390/jcm11102786] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/11/2022] [Accepted: 05/12/2022] [Indexed: 12/07/2022] Open
Abstract
Background: Iron deficiency (ID) without anaemia is a common comorbidity associated with inflammatory bowel disease (IBD) that has a negative impact on health-related quality of life (HRQoL). Methods: This multicentre, prospective, observational study examined the response to, safety of and impact on HRQoL of a single 500 mg dose of intravenous ferric carboxymaltose (FCM) in patients with IBD and ID without anaemia. The diagnostic criteria for ID were low serum ferritin (<30 µg/L in the absence of inflammatory activity or <100 µg/L with inflammation) and transferrin saturation index (TSAT) < 16%. The effect on iron levels and HRQoL, according to the health status questionnaires SF-12v2 and EQ-5D, was evaluated 1 month after FCM infusion in an outpatient setting. Results: Of the 105 patients who received FCM, 98 patients completed the study. After 1 month, a single dose of FCM significantly increased serum ferritin, serum iron and TSAT. Importantly, patients reported fewer ID symptoms and problems on all EQ-5D dimensions. They also had higher EQ-5D visual analogue scale and SF-12v2 scores after treatment. FCM had similar clinical effects on men and women and on patients with Crohn’s disease (n = 66) and ulcerative colitis (n = 32). Conclusion: A single dose of FCM rapidly restored iron parameters and significantly improved patients’ symptoms and HRQoL at 1 month after treatment.
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Affiliation(s)
- Jose María Huguet
- Gastroenterology Department, Hospital General Universitario de Valencia, 46014 Valencia, Spain;
| | - Xavier Cortés
- Gastroenterology Department, Hospital de Sagunto, 46520 Valencia, Spain;
| | - Marta Maia Boscá-Watts
- Gastroenterology Department, Hospital Clínico Universitario de Valencia, University of Valencia, 46010 Valencia, Spain;
| | - Margarita Muñoz
- Gastroenterology Department, Hospital General Universitario de Castellón, 12004 Castesllon de la Plana, Spain;
| | - Nuria Maroto
- Gastroenterology Department, Hospital de Manises, 46940 Valencia, Spain; (N.M.); (E.H.)
| | - Marisa Iborra
- Gastroenterology Department, Hospital Universitario y Politécnico de La Fe, 46026 Valencia, Spain;
| | - Esther Hinojosa
- Gastroenterology Department, Hospital de Manises, 46940 Valencia, Spain; (N.M.); (E.H.)
| | - María Capilla
- Gastroenterology Department, Hospital General Universitario de Valencia, 46014 Valencia, Spain;
| | - Carmina Asencio
- Gastroenterology Department, Hospital Universitario Doctor Peset, 46017 Valencia, Spain; (C.A.); (J.M.P.)
| | - Cirilo Amoros
- Gastroenterology Department, Hospital Arnau de Vilanova de Valencia, 46015 Valencia, Spain;
| | - Jose María Paredes
- Gastroenterology Department, Hospital Universitario Doctor Peset, 46017 Valencia, Spain; (C.A.); (J.M.P.)
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Sturm A, Atreya R, Bettenworth D, Bokemeyer B, Dignaß A, Ehehalt R, Germer C, Grunert PC, Helwig U, Herrlinger K, Kienle P, Kreis ME, Kucharzik T, Langhorst J, Maaser C, Ockenga J, Ott C, Siegmund B, Zeißig S, Stallmach A. Aktualisierte S3-Leitlinie „Diagnostik und Therapie des Morbus Crohn“ der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) – August 2021 – AWMF-Registernummer: 021-004. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2022; 60:332-418. [PMID: 35263784 DOI: 10.1055/a-1713-3941] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | | | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Axel Dignaß
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Christoph Germer
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Deutschland
| | - Philip C Grunert
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
| | - Ulf Helwig
- Internistische Praxengemeinschaft, Oldenburg, Deutschland
| | | | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Martin E Kreis
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Deutschland
| | - Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | | | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen Mitte - Gesundheit Nord, Bremen, Deutschland
| | - Claudia Ott
- Gastroenterologie Facharztzentrum, Regensburg, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Deutschland
| | - Sebastian Zeißig
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Deutschland
| | - Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Deutschland
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Howaldt S, Domènech E, Martinez N, Schmidt C, Bokemeyer B. Long-Term Effectiveness of Oral Ferric Maltol vs Intravenous Ferric Carboxymaltose for the Treatment of Iron-Deficiency Anemia in Patients With Inflammatory Bowel Disease: A Randomized Controlled Noninferiority Trial. Inflamm Bowel Dis 2022; 28:373-384. [PMID: 33988236 PMCID: PMC8889281 DOI: 10.1093/ibd/izab073] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Iron-deficiency anemia is common in inflammatory bowel disease, requiring oral or intravenous iron replacement therapy. Treatment with standard oral irons is limited by poor absorption and gastrointestinal toxicity. Ferric maltol is an oral iron designed for improved absorption and tolerability. METHODS In this open-label, phase 3b trial (EudraCT 2015-002496-26 and NCT02680756), adults with nonseverely active inflammatory bowel disease and iron-deficiency anemia (hemoglobin, 8.0-11.0/12.0 g/dL [women/men]; ferritin, <30 ng/mL/<100 ng/mL with transferrin saturation <20%) were randomized to oral ferric maltol 30 mg twice daily or intravenous ferric carboxymaltose given according to each center's standard practice. The primary endpoint was a hemoglobin responder rate (≥2 g/dL increase or normalization) at week 12, with a 20% noninferiority limit in the intent-to-treat and per-protocol populations. RESULTS For the intent-to-treat (ferric maltol, n = 125/ferric carboxymaltose, n = 125) and per-protocol (n = 78/88) analyses, week 12 responder rates were 67% and 68%, respectively, for ferric maltol vs 84% and 85%, respectively, for ferric carboxymaltose. As the confidence intervals crossed the noninferiority margin, the primary endpoint was not met. Mean hemoglobin increases at weeks 12, 24, and 52 were 2.5 vs 3.0 g/dL, 2.9 vs 2.8 g/dL, and 2.7 vs 2.8 g/dL with ferric maltol vs ferric carboxymaltose. Treatment-emergent adverse events occurred in 59% and 36% of patients, respectively, and resulted in treatment discontinuation in 10% and 3% of patients, respectively. CONCLUSIONS Ferric maltol achieved clinically relevant increases in hemoglobin but did not show noninferiority vs ferric carboxymaltose at week 12. Both treatments had comparable long-term effectiveness for hemoglobin and ferritin over 52 weeks and were well tolerated.
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Affiliation(s)
| | - Eugeni Domènech
- Gastroenterology and Hepatology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | | | - Carsten Schmidt
- Department of Gastroenterology, Hepatology, Endocrinology, Diabetology, and Infectious Diseases, Klinikum Fulda, Fulda, Germany
| | - Bernd Bokemeyer
- Gastroenterology Practice Minden and University Hospital Schleswig-Holstein, Campus Kiel, Clinic for Internal Medicine I, Kiel, Germany
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Buret AG, Allain T, Motta JP, Wallace JL. Effects of Hydrogen Sulfide on the Microbiome: From Toxicity to Therapy. Antioxid Redox Signal 2022; 36:211-219. [PMID: 33691464 PMCID: PMC8861923 DOI: 10.1089/ars.2021.0004] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 02/24/2021] [Accepted: 02/26/2021] [Indexed: 12/13/2022]
Abstract
Significance: Hydrogen sulfide (H2S), an important regulator of physiology and health, helps resolve inflammation and promotes tissue repair in the gastrointestinal tract. Recent Advances: Gut microbiota live as a multispecies biofilm in close interaction with the upper mucus layer lining the epithelium. The relative abundance, spatial organization, and function of these microorganisms affect a broad range of health outcomes. This article provides a state-of-the-art review of our understanding of the cross talk between H2S, the gut microbiota, and health. H2S can have toxic or therapeutic effects, depending on its concentration and source. When produced at excessive concentrations by local microbiota, H2S may cause mucus disruption and inflammation and contribute to development of cancer. In contrast, low levels of endogenous or exogenous H2S directly stabilize mucus layers, prevent fragmentation and adherence of the microbiota biofilm to the epithelium, inhibit the release of invasive pathobionts, and help resolve inflammation and tissue injury. Although scarce, research findings suggest that dietary H2S obtained from plants or ingestion of the H2S precursor, L-cysteine, may also modulate the abundance and function of microbiota. Critical Issues: A critical issue is the lack of understanding of the metagenomic, transcriptomic, and proteomic alterations that characterize the interactions between H2S and gut microbiota to shape health outcomes. Future Directions: The ambivalent roles of H2S in the gut offer a fertile ground for research on such critical issues. The findings will improve our understanding of how H2S modulates the microbiota to affect body function and will help identify novel therapeutic strategies. Antioxid. Redox Signal. 36, 211-219.
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Affiliation(s)
- Andre G. Buret
- Host–Parasite Interactions Program, Inflammation Research Network, Biological Sciences, University of Calgary, Calgary, Canada
- Antibe Therapeutics, Inc., Toronto, Canada
| | - Thibault Allain
- Host–Parasite Interactions Program, Inflammation Research Network, Biological Sciences, University of Calgary, Calgary, Canada
| | - Jean-Paul Motta
- Institute of Digestive Health Research, IRSD, INSERM U1220, Toulouse, France
| | - John L. Wallace
- Host–Parasite Interactions Program, Inflammation Research Network, Biological Sciences, University of Calgary, Calgary, Canada
- Antibe Therapeutics, Inc., Toronto, Canada
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Stallhofer J, Veith L, Diegelmann J, Probst P, Brand S, Schnitzler F, Olszak T, Török H, Mayerle J, Stallmach A, Beigel F. Iron Deficiency in Inflammatory Bowel Disease Is Associated With Low Levels of Vitamin D Modulating Serum Hepcidin and Intestinal Ceruloplasmin Expression. Clin Transl Gastroenterol 2022; 13:e00450. [PMID: 35029158 PMCID: PMC8806373 DOI: 10.14309/ctg.0000000000000450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Accepted: 11/04/2021] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Iron deficiency and vitamin D deficiency are common comorbidities in inflammatory bowel disease (IBD). Accumulating evidence indicates that active 1,25-dihydroxyvitamin D (1,25(OH)D) may enhance iron absorption by suppressing hepcidin. We investigated the influence of vitamin D on iron metabolism in patients with IBD and on the expression of genes facilitating intestinal epithelial iron absorption. METHODS Iron parameters and serum levels of 25-hydroxyvitamin D (25(OH)D), 1,25(OH)D, and hepcidin were measured in 104 adult patients with IBD (67 with Crohn's disease and 37 with ulcerative colitis). Genes involved in iron absorption were tested for induction by 1,25(OH)D in Caco-2 cells, which resemble the small intestinal epithelium. RESULTS In multiple regression models controlling for age, sex, body mass index, smoking status, disease activity, and C-reactive protein levels, low 25(OH)D levels were associated with iron deficiency in patients with IBD (β [SE] = -0.064 [0.030], P = 0.029). Vitamin D sufficiency was associated with increased levels of ferritin (β [SE] = 0.25 [0.11], P = 0.024) and transferrin saturation (β [SE] = 8.41 [4.07], P = 0.044). Higher 1,25(OH)D:25(OH)D ratios were associated with lower hepcidin levels (β [SE] = -4.31 [1.67], P = 0.012). Especially in Crohn's disease, increased 1,25(OH)D correlated with higher transferrin saturation (β [SE] = 0.43 [0.18], P = 0.027). Furthermore, 1,25(OH)D strongly induced the expression of the ferroxidase ceruloplasmin in Caco-2 cells. DISCUSSION Low vitamin D levels in IBD correlate with iron deficiency. Vitamin D may ameliorate iron deficiency, potentially by downregulating hepcidin and upregulating ceruloplasmin, enhancing intestinal iron absorption.
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Affiliation(s)
- Johannes Stallhofer
- Department of Medicine II, University Hospital, LMU Munich, Germany
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Lisa Veith
- Department of Medicine II, University Hospital, LMU Munich, Germany
| | - Julia Diegelmann
- Department of Medicine II, University Hospital, LMU Munich, Germany
- Department of Conservative Dentistry and Periodontology, University Hospital, LMU Munich, Germany
| | - Philipp Probst
- Chair of Biometrics and Bioinformatics, IBE, Faculty of Medicine, LMU Munich, Germany
| | - Stephan Brand
- Department of Medicine II, University Hospital, LMU Munich, Germany
- Department of Gastroenterology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | | | - Torsten Olszak
- Department of Medicine II, University Hospital, LMU Munich, Germany
| | - Helga Török
- Department of Medicine II, University Hospital, LMU Munich, Germany
| | - Julia Mayerle
- Department of Medicine II, University Hospital, LMU Munich, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Florian Beigel
- Department of Medicine II, University Hospital, LMU Munich, Germany
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Tolbert MK, Murphy M, Gaylord L, Witzel-Rollins A. Dietary management of chronic enteropathy in dogs. J Small Anim Pract 2022; 63:425-434. [PMID: 34991182 DOI: 10.1111/jsap.13471] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 11/17/2021] [Accepted: 12/17/2021] [Indexed: 12/21/2022]
Abstract
Chronic idiopathic enteropathy is a clinical condition defined by the exclusion of infectious, metabolic or neoplastic causes of gastrointestinal signs and is categorised by a response to treatment including management with diet change, immunosuppressant medication or interventions that directly target the microbiome (e.g. antibiotics, faecal transplantation or probiotics). Animals that fail these therapies are categorised as non-responsive or refractory chronic idiopathic enteropathy. This specific categorisation implies that nutritional intervention is only needed for a subset of patients with enteropathy. However, often dogs with chronic idiopathic enteropathy are malnourished, have nutrient malabsorption or have gastrointestinal inflammation that occurs as a result of a breakdown in tolerance to luminal antigens including microorganism or dietary components. Thus, all dogs with chronic idiopathic enteropathy benefit from a nutritional assessment and targeted nutritional intervention. Among dogs presenting for chronic idiopathic enteropathy, the response rate to diet alone is roughly 50% in the referral population giving the impression that the overall response could be even higher especially when more than one nutritional intervention is attempted and strict adherence is maintained. The objectives of this review article are to outline the nutritional approach to a dog with chronic idiopathic enteropathy, including the nutritional assessment, and to highlight areas for nutritional intervention.
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Affiliation(s)
- M K Tolbert
- Gastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843-4474, USA
| | - M Murphy
- College of Veterinary Medicine, Department of Small Animal Clinical Sciences, University of Tennessee, Knoxville, TN, 37996, USA
| | - L Gaylord
- Whole Pet Provisions, PLLC, Fuquay-Varina, NC, 27526, USA
| | - A Witzel-Rollins
- College of Veterinary Medicine, Department of Small Animal Clinical Sciences, University of Tennessee, Knoxville, TN, 37996, USA
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Peyrin-Biroulet L, Bouguen G, Laharie D, Pellet G, Savoye G, Gilletta C, Michiels C, Buisson A, Fumery M, Trochu JN, Cacoub P, The CARENFER study group MacaigneGillesAmilMorganeAmiotAurélienLocherChristopheKaassisMehdiNahonStéphaneBenamouzigRobertAltweggRomainHeluwaertFredericClaudePierreAndrauPierreVeyrardPaulineDibNinaAndrieuValérieChoukrounGabrielCohen-solalAlainLuporsiElisabethPeoc’hKatell. Iron Deficiency in Patients with Inflammatory Bowel Diseases: A Prospective Multicenter Cross-Sectional Study. Dig Dis Sci 2022; 67:5637-5646. [PMID: 35384624 PMCID: PMC9652270 DOI: 10.1007/s10620-022-07474-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 03/01/2022] [Indexed: 01/05/2023]
Abstract
BACKGROUND Iron deficiency (ID) is a frequent condition in patients with inflammatory bowel disease (IBD). AIM Our aim was to investigate the prevalence of ID in patients with IBD. METHODS This was a prospective multicenter cross-sectional study conducted in 21 gastroenterology departments in France between January and March 2020. All adult patients with confirmed IBD who were admitted to the hospital were eligible for inclusion. ID was defined as ferritinemia ≤ 100 μg/L in patients with signs of inflammation (C-reactive protein (CRP) ≥ 5 mg/L) or ferritinemia < 30 μg/L in the absence of inflammation. RESULTS In total, 1036 IBD (685 Crohn's disease and 351 ulcerative colitis) patients (52.1% women) with a mean age of 41.8 ± 15.5 years were recruited. Approximately half of the patients (504, 51.1%) were in disease remission at the time of enrollment. Systematic monitoring of iron status was performed in 12/21 (57%) participating centers, including measurements of ferritin (12/12, 100%), hemoglobin (11/12, 92%), transferrin saturation (TSAT) (6/12, 50.0%), and serum iron (5/12, 42%). About one-fifth of the patients had been treated with intravenous iron (218, 21.0%), whereas only a small percentage received oral iron (36, 3.5%). ID occurred in 97 patients (23.7% CI 95% 19.8-28.1). Patients with moderate/severe IBD activity (OR: 3.66; CI 95% 24.4-61.2; p = 0.007) or concomitant anemia (OR: 3.66; CI 95% 1.97-6.78; p < 0.001) had an increased likelihood of having ID. CONCLUSION Patients with moderate/severe IBD activity or concomitant anemia are at increased risk of ID. Early detection and management of ID in patients with IBD is recommended.
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Affiliation(s)
- Laurent Peyrin-Biroulet
- grid.29172.3f0000 0001 2194 6418Department of Gastroenterology, University of Lorraine, CHRU-Nancy, 54000 Nancy, France ,grid.29172.3f0000 0001 2194 6418University of Lorraine, Inserm, NGERE, 54000 Nancy, France ,grid.29172.3f0000 0001 2194 6418Inserm NGERE and Department of Gastroenterology, Nancy University Hospital, University of Lorraine, 1 Allée du Morvan, 54511 Vandoeuvre-lès-Nancy, France
| | - Guillaume Bouguen
- grid.411154.40000 0001 2175 0984CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer), CHU Rennes, Univ Rennes, INSERM, 35000 Rennes, France
| | - David Laharie
- grid.42399.350000 0004 0593 7118Service d’Hépato-gastroentérologie et Oncologie Digestive, CHU de Bordeaux, Hôpital Haut-Lévêque, 33000 Bordeaux, France
| | - Gauthier Pellet
- grid.42399.350000 0004 0593 7118Service d’Hépato-gastroentérologie et Oncologie Digestive, CHU de Bordeaux, Hôpital Haut-Lévêque, 33000 Bordeaux, France
| | - Guillaume Savoye
- grid.10400.350000 0001 2108 3034INSERM UMR1073, Université de Rouen, Hôpital Universitaire de Rouen, Rouen, France
| | - Cyrielle Gilletta
- grid.411175.70000 0001 1457 2980Department of Pancreatology and Gastroenterology, University Hospital of Toulouse Rangueil, 31059 Toulouse Cedex 9, France
| | - Christophe Michiels
- grid.31151.37Service d’Hepato-Gastro-Entérologie, CHU Dijon Bourgogne, Dijon, France
| | - Anthony Buisson
- grid.411163.00000 0004 0639 4151Service d’Hépato-Gastroentérologie, Université Clermont Auvergne, Inserm, 3iHP, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Mathurin Fumery
- Department of Gastroenterology, University Hospital of Amiens, and Peritox, University of Picardie, Amiens, France
| | | | - Patrice Cacoub
- grid.411439.a0000 0001 2150 9058Department of Internal Medicine and Clinical Immunology, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, 83 Boulevard de l’Hôpital, 75651 Paris, Cedex 13, France ,Immunology-Immunopathology- Immunotherapy (I3), Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR S 959, Paris, France ,grid.411439.a0000 0001 2150 9058Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Hôpital Pitié-Salpêtrière, AP-HP, Paris, France
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Breton J, Witmer CM, Zhang Y, Downing M, Stevenson J, McDermott J, Siddique SM, Grossman AB. Utilization of an Electronic Medical Record-integrated Dashboard Improves Identification and Treatment of Anemia and Iron Deficiency in Pediatric Inflammatory Bowel Disease. Inflamm Bowel Dis 2021; 27:1409-1417. [PMID: 33165613 DOI: 10.1093/ibd/izaa288] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Iron deficiency (ID) and anemia are one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD), usually complicating the course both in ulcerative colitis and Crohn's disease. Despite their high prevalence and significant impact on patients, this particular aspect is still underestimated by clinicians. Although guidelines have been recently published to address this problem, these recommendations do not address pediatric specific concerns and do not provide guidance as to how implement these guidelines in clinical practice. The aims of this quality improvement (QI) initiative were to improve the rates of detection and treatment of anemia in children with IBD. METHODS After the creation of a multidisciplinary team of skateholders in IBD and anemia, we launched a multifaceted QI strategy that included the development of a pediatric evidence-based care pathway, utilization of an electronic medical record (EMR)-integrated dashboard to track patients, and generation of an automated provider-based monthly report. Data were collected and graphed into statistical process control charts. RESULTS These key strategies resulted in improved rates of ID screening from 31.7% to 63.6%, in increased treatment rates from 38.2% to 49.9%, and in decreased prevalence of anemia from 35.8% to 29.7%, which was reflected by a greater decline in patients with quiescent disease. CONCLUSIONS Quality improvement strategies incorporating the creation of a pediatric evidence-based care pathway with an EMR-supported electronic dashboard were the foundation of a successful intervention in the management of ID and anemia in pediatric IBD. Our positive results demonstrate the potential of QI initiatives using automated technology to assist clinicians in their commitment to provide evidence-based IBD care and enhance patient outcomes.
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Affiliation(s)
- Jessica Breton
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Department of Pediatrics
| | - Char M Witmer
- Division of Hematology, Children's Hospital of Philadelphia, Department of Pediatrics
| | - Yuchen Zhang
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Department of Pediatrics
| | - Maura Downing
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Department of Pediatrics
| | - Jamie Stevenson
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Department of Pediatrics
| | - Janine McDermott
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Department of Pediatrics
| | - Shazia M Siddique
- Division of Gastroenterology, Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
| | - Andrew B Grossman
- Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia, Department of Pediatrics
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McGing JJ, Radford SJ, Francis ST, Serres S, Greenhaff PL, Moran GW. Review article: The aetiology of fatigue in inflammatory bowel disease and potential therapeutic management strategies. Aliment Pharmacol Ther 2021; 54:368-387. [PMID: 34228817 DOI: 10.1111/apt.16465] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 09/30/2020] [Accepted: 05/20/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Fatigue is the inability to achieve or maintain an expected work output resulting from central or peripheral mechanisms. The prevalence of inflammatory bowel disease (IBD) fatigue can reach 86% in active disease, persisting in 50%-52% of patients with mild to inactive disease. Fatigue is the commonest reason for work absence in IBD, and patients often report fatigue burden to be greater than that of primary disease symptoms. Relatively few evidence-based treatment options exist, and the aetiology is poorly understood. AIM To review the available data and suggest a possible aetiology of IBD fatigue and to consider the efficacy of existing management strategies and highlight potential future interventions. METHODS We reviewed fatigue-related literature in IBD using PubMed database. RESULTS Disease related factors such as inflammation and pharmacological treatments negatively impact skeletal muscle and brain physiology, likely contributing to fatigue symptoms. Secondary factors such as malnutrition, anaemia, sleep disturbance and psychological comorbidity are potential determinants. Immune profile, faecal microbiota composition and physical fitness differ significantly between fatigued and non-fatigued patients, suggesting these may be aetiological factors. Solution-focused therapy, high-dosage thiamine supplementation and biological therapy may reduce fatigue perception in IBD. The effect of physical activity interventions is inconclusive. CONCLUSIONS A multimodal approach is likely required to treat IBD fatigue. Established reversible factors like anaemia, micronutrient deficiencies and active disease should initially be resolved. Psychosocial intervention shows potential efficacy in reducing fatigue perception in quiescent disease. Restoring physical deconditioning by exercise training intervention may further improve fatigue burden.
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Affiliation(s)
- Jordan J McGing
- School of Medicine, University of Nottingham, Nottingham, UK.,Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK
| | - Shellie Jean Radford
- School of Medicine, University of Nottingham, Nottingham, UK.,National Institute of Health Research Nottingham Biomedical Research Centre (NIHR), Nottingham University Hospitals and University of Nottingham, Nottingham, UK
| | - Susan T Francis
- Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, UK.,National Institute of Health Research Nottingham Biomedical Research Centre (NIHR), Nottingham University Hospitals and University of Nottingham, Nottingham, UK
| | - Sébastien Serres
- School of Life Sciences, University of Nottingham, Nottingham, UK
| | - Paul L Greenhaff
- National Institute of Health Research Nottingham Biomedical Research Centre (NIHR), Nottingham University Hospitals and University of Nottingham, Nottingham, UK.,MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, National Institute for Health Research (NIHR), Nottingham Biomedical Research Centre, School of Life Sciences, University of Nottingham, Nottingham, UK
| | - Gordon W Moran
- School of Medicine, University of Nottingham, Nottingham, UK.,National Institute of Health Research Nottingham Biomedical Research Centre (NIHR), Nottingham University Hospitals and University of Nottingham, Nottingham, UK
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Shah Y, Patel D, Khan N. Iron deficiency anemia in IBD: an overlooked comorbidity. Expert Rev Gastroenterol Hepatol 2021; 15:771-781. [PMID: 33691543 DOI: 10.1080/17474124.2021.1900730] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 03/05/2021] [Indexed: 12/21/2022]
Abstract
Introduction: Iron Deficiency Anemia (IDA) is a leading cause of anemia in Inflammatory Bowel disease (IBD). IDA affects quality of life (QoL) and lead to developmental and cognitive abnormalities. Diagnosis of IDA in IBD is complicated as biochemical tests available at present cannot help distinguish between IDA and anemia of chronic disease. Soluble transferrin receptor ferritin index has been gaining popularity as it can diagnose IDA in presence of chronic inflammation. ECCO guidelines recommend a Hb increase of >2 g/dL and a TfS of >30% within 4 weeks as adequate therapeutic response. IV iron is preferred over oral iron as it bypasses gastrointestinal tract, rapidly increases haemoglobin, and is not associated with intestinal inflammation. Our aim in this review is to provide apathway for physicians to help them diagnose and appropriately treat IDA in IBD.Areas covered: In this review article, we have discussed current diagnosis and treatment in detail and have proposed new directions on how future research can help manage IDA in IBD effectively.Expert opinion: Understanding the pathogenesis of IDA in IBD will further lead to exploring new potential diagnostic tests and treatment regimens for effective management of IDA in IBD.
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Affiliation(s)
- Yash Shah
- Department of Internal Medicine, Hackensack Meridian Health Ocean Medical Center, Brick Township, NJ, USA
| | - Dhruvan Patel
- Department of Gastroenterology and Hepatology, Mercy Fitzgerald Hospital, Darby, PA, USA
| | - Nabeel Khan
- Department of Gastroenterology and Hepatology, Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA, USA
- Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, USA
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Foteinogiannopoulou K, Karmiris K, Axiaris G, Velegraki M, Gklavas A, Kapizioni C, Karageorgos C, Kateri C, Katsoula A, Kokkotis G, Koureta E, Lamouri C, Markopoulos P, Palatianou M, Pastras P, Fasoulas K, Giouleme O, Zampeli E, Theodoropoulou A, Theocharis G, Thomopoulos K, Karatzas P, Katsanos KH, Kapsoritakis A, Kourikou A, Mathou N, Manolakopoulos S, Michalopoulos G, Michopoulos S, Boubonaris A, Bamias G, Papadopoulos V, Papatheodoridis G, Papaconstantinou I, Pachiadakis I, Soufleris K, Tzouvala M, Triantos C, Tsironi E, Christodoulou DK, Koutroubakis IE. The burden and management of anemia in Greek patients with inflammatory bowel disease: a retrospective, multicenter, observational study. BMC Gastroenterol 2021; 21:269. [PMID: 34187376 PMCID: PMC8240305 DOI: 10.1186/s12876-021-01826-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 05/23/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Anemia is a common extraintestinal manifestation of Inflammatory Bowel Disease (IBD) affecting negatively the patients' quality of life. The aim of this study was to determine the frequency and real-life management of anemia in IBD patients in Greece. METHODS This study was conducted in 17 Greek IBD referral centers. Demographic, clinical, laboratory, IBD and anemia treatment data were collected and analyzed retrospectively. RESULTS A total of 1394 IBD patients [560 ulcerative colitis (UC), 834 Crohn's disease (CD)] were enrolled. Anemia at any time was reported in 687 (49.3%) patients of whom 413 (29.6%) had episodic and 274 (19.7%) had recurrent/persistent anemia. Anemia was diagnosed before IBD in 45 (6.5%), along with IBD in 269 (39.2%) and after IBD in 373 (54.3%) patients. In the multivariate analysis the presence of extraintestinal manifestations (p = 0.0008), IBD duration (p = 0.026), IBD related surgeries and hospitalizations (p = 0.026 and p = 0.004 accordingly) were risk factors of recurrent/persistent anemia. Serum ferritin was measured in 839 (60.2%) IBD patients. Among anemic patients, 535 (77.9%) received treatment. Iron supplementation was administered in 485 (90.6%) patients, oral in 142 (29.3%) and intravenous in 393 (81%). CONCLUSIONS The frequency of anemia in IBD patients, followed at Greek referral centers, is approximately 50%. Development of recurrent/persistent anemia may be observed in 20% of cases and is independently associated with the presence of extraintestinal manifestations, IBD duration, IBD related surgeries and hospitalizations. Anemia treatment is administered in up to [Formula: see text] of anemia IBD patients with the majority of them receiving iron intravenously.
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Affiliation(s)
- Kalliopi Foteinogiannopoulou
- Gastroenterology Department, University Hospital of Heraklion, Medical School University of Crete, P.O. Box 1352, 71110, Heraklion, Crete, Greece.
| | | | - Georgios Axiaris
- Department of Gastroenterology, General Hospital of Athens "Alexandra", Athens, Greece
| | - Magdalini Velegraki
- Department of Gastroenterology, Venizelio General Hospital, Heraklion, Greece
| | - Antonios Gklavas
- 2nd Department of Surgery, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Christina Kapizioni
- Department of Gastroenterology, General Hospital of Piraeus "Tzaneio", Athens, Greece
| | - Charalabos Karageorgos
- Hepato-Gastroenterology/Endoscopy Unit, 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens General Hospital "Heppocratio", Athens, Greece
| | - Christina Kateri
- Department of Gastroenterology, University General Hospital of Larissa, Larissa, Greece
| | - Anastasia Katsoula
- 2nd Internal Medicine Department, General Hospital of Thessaloniki "Ippokratio", Thessaloniki, Greece
| | - Georgios Kokkotis
- Gastroenterology Unit, 3rd Academic Department of Internal Medicine, National and Kapodistrian Univeristy of Athens, "Sotiria" General Hospital, Athens, Greece
| | - Evgenia Koureta
- Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Charikleia Lamouri
- Department of Gastroenterology, University General Hospital of Ioannina, Ioannina, Greece
| | - Panagiotis Markopoulos
- Department of Gastroenterology, "Metaxa" General Anticancer Hospital of Piraeus, Piraeus, Greece
| | - Maria Palatianou
- Department of Gastroenterology, General Hospital of Nikaia Piraeus "Ag. Panteleimon"-General Hospital Dytikis Attikis "Agia Varvara", Athens, Greece
| | - Ploutarchos Pastras
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras, Greece
| | - Konstantinos Fasoulas
- Department of Gastroenterology-Oncology, Theageneio Cancer Hospital of Thessaloniki, Thessaloniki, Greece
| | - Olga Giouleme
- 2nd Internal Medicine Department, General Hospital of Thessaloniki "Ippokratio", Thessaloniki, Greece
| | - Evanthia Zampeli
- Department of Gastroenterology, General Hospital of Athens "Alexandra", Athens, Greece
| | | | - Georgios Theocharis
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras, Greece
| | - Konstantinos Thomopoulos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras, Greece
| | - Pantelis Karatzas
- Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | | | - Andreas Kapsoritakis
- Department of Gastroenterology, University General Hospital of Larissa, Larissa, Greece
| | - Anastasia Kourikou
- Hepato-Gastroenterology/Endoscopy Unit, 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens General Hospital "Heppocratio", Athens, Greece
| | - Nikoleta Mathou
- Department of Gastroenterology, General Hospital of Nea Ionia "Konstantopoulio - Patision", Athens, Greece
| | - Spilios Manolakopoulos
- Hepato-Gastroenterology/Endoscopy Unit, 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens General Hospital "Heppocratio", Athens, Greece
| | | | - Spyridon Michopoulos
- Department of Gastroenterology, General Hospital of Athens "Alexandra", Athens, Greece
| | | | - Giorgos Bamias
- Gastroenterology Unit, 3rd Academic Department of Internal Medicine, National and Kapodistrian Univeristy of Athens, "Sotiria" General Hospital, Athens, Greece
| | | | - George Papatheodoridis
- Department of Gastroenterology, National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece
| | - Ioannis Papaconstantinou
- 2nd Department of Surgery, Aretaieion Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Pachiadakis
- Department of Gastroenterology, 424 General Military Hospital, Thessaloniki, Greece
| | - Konstantinos Soufleris
- Department of Gastroenterology-Oncology, Theageneio Cancer Hospital of Thessaloniki, Thessaloniki, Greece
| | - Maria Tzouvala
- Department of Gastroenterology, General Hospital of Nikaia Piraeus "Ag. Panteleimon"-General Hospital Dytikis Attikis "Agia Varvara", Athens, Greece
| | - Christos Triantos
- Division of Gastroenterology, Department of Internal Medicine, University Hospital of Patras, Patras, Greece
| | - Eftychia Tsironi
- Department of Gastroenterology, "Metaxa" General Anticancer Hospital of Piraeus, Piraeus, Greece
| | | | - Ioannis E Koutroubakis
- Gastroenterology Department, University Hospital of Heraklion, Medical School University of Crete, P.O. Box 1352, 71110, Heraklion, Crete, Greece
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Khasheii B, Mahmoodi P, Mohammadzadeh A. Siderophores: Importance in bacterial pathogenesis and applications in medicine and industry. Microbiol Res 2021; 250:126790. [PMID: 34098495 DOI: 10.1016/j.micres.2021.126790] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/14/2021] [Accepted: 05/24/2021] [Indexed: 12/21/2022]
Abstract
Iron is an essential element for all microorganisms. Siderophores are low-weight, high-affinity iron chelating molecules produced in response to iron deficiency by Gram-positive and Gram-negative bacteria which also known as essential virulence factors of bacteria. Several studies have indicated that defective production and/or function of these molecules as well as iron acquisition systems in pathogens are associated with a reduction in pathogenicity of bacteria. Because of their potential role in various biological pathways, siderophores have been received special attention as secondary metabolites. Siderophores can detect iron levels in a variety of environments with a biosensor function. In medicine, siderophores are used to deliver antibiotics (Trojan horse strategy) to resistant bacteria and to treat diseases such as cancer and malaria. In this review, we discuss the iron acquisition pathways in Gram-positive and -negative bacteria, importance of siderophore production in pathogenesis of bacteria, classification of siderophores, and main applications of siderophores in medicine and industry.
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Affiliation(s)
- Behnoush Khasheii
- Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran
| | - Pezhman Mahmoodi
- Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran.
| | - Abdolmajid Mohammadzadeh
- Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran
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50
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Bastida G, Herrera-de Guise C, Algaba A, Ber Nieto Y, Soares JM, Robles V, Bermejo F, Sáez-González E, Gomollón F, Nos P. Sucrosomial Iron Supplementation for the Treatment of Iron Deficiency Anemia in Inflammatory Bowel Disease Patients Refractory to Oral Iron Treatment. Nutrients 2021; 13:1770. [PMID: 34067320 PMCID: PMC8224651 DOI: 10.3390/nu13061770] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/11/2021] [Accepted: 05/19/2021] [Indexed: 12/12/2022] Open
Abstract
Iron deficiency anemia (IDA) is a common manifestation of Inflammatory Bowel Disease (IBD). Oral iron supplements are the treatment of choice, but are not always well tolerated. Sucrosomial® iron (SI) may represent an alternative. This prospective study assessed the tolerability and effectiveness of SI, and quality of life (QoL) of IDA-IBD patients who were intolerant to oral iron salts. The study included 52 individuals treated with 1 capsule/day for 12 weeks. Tolerability was assessed through a gastrointestinal symptom severity questionnaire. Hemoglobin (Hb) levels and clinical symptoms of IDA were analyzed. QoL was assessed using IBDQ-9 and EuroQoL questionnaires. The percentage of patients with excellent/good health increased from 42.9% to 94.3%. Mean Hb concentration significantly increased at all follow-up visits (p < 0.05). Almost all participants (96.9%) were adherent to the study medication. Patients' QoL improved (IBDQ-9: from 60.9 to 65.5). Patients also improved in mobility (71.8% to 78.1%), usual activities (51.3% to 68.7%), pain/discomfort (41.0% to 53.1%), and extreme depression/anxiety problems (7.7% to 3.2%); they worsened in self-care (100% to 90.6%), but perceived an enhancement in their global health [EQ-VAS score: 61.9 (±26.1) to 66.9 (±20.3)]. SI was well tolerated and improved IDA symptoms, IBD activity, and patients' QoL. In conclusion, SI should be considered in IDA-IBD patients.
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Affiliation(s)
- Guillermo Bastida
- Department of Gastroenterology, CIBEREHD, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain
| | | | - Alicia Algaba
- Department of Gastroenterology, Instituto de Investigación Sanitaria Hospital La Paz (IdiPaz), Hospital Universitario de Fuenlabrada, 28046 Madrid, Spain
| | - Yolanda Ber Nieto
- Department of Gastroenterology, Hospital Universitario San Jorge, 22004 Huesca, Spain
| | - Jose Manuel Soares
- Department of Gastroenterology, Hospital Pedro Hispano, 4454-509 Matosinhos, Portugal
| | - Virginia Robles
- Crohn-Colitis Care Unit, Vall d'Hebron Hospital Universitari, 08035 Barcelona, Spain
| | - Fernando Bermejo
- Department of Gastroenterology, Instituto de Investigación Sanitaria Hospital La Paz (IdiPaz), Hospital Universitario de Fuenlabrada, 28046 Madrid, Spain
| | - Esteban Sáez-González
- Department of Gastroenterology, CIBEREHD, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain
| | - Fernando Gomollón
- IBD Unit, Digestive Diseases Service, Instituto de Investigación Sanitaria de Aragón (IIS), CIBEREHD, Hospital Clínico Universitario "Lozano Blesa", 50009 Zaragoza, Spain
| | - Pilar Nos
- Department of Gastroenterology, CIBEREHD, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain
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