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Leibovitzh H, Fliss Isakov N, Werner L, Thurm T, Hirsch A, Cohen NA, Maharshak N. A Mushroom Based Prebiotic Supplement Pilot Study Among Patients with Crohn's Disease. J Diet Suppl 2025:1-14. [PMID: 40313234 DOI: 10.1080/19390211.2025.2498127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2025]
Abstract
Data on a mushroom based prebiotic supplementation in patients with Crohn's disease (CD) in western population is scarce. In this pilot trial, we aimed to assess the clinical efficacy and fecal microbial compositional and functional alterations associated with 'Mycodigest,' a commercial prebiotic supplement composed of three mushroom extracts. Patients with mild to moderate CD were recruited to a single center, randomized, double-blind, placebo-controlled pilot induction trial. Clinical efficacy using the Harvey-Bradshaw index and biochemical response using C-reactive protein and fecal calprotectin were assessed at week 8 post-intervention. Fecal samples were assessed by DNA shotgun metagenomic sequencing. A multivariable linear mixed effects model was used to assess alteration in fecal microbiome composition and function pre- and post-'Mycodigest' intervention. Clinical response was higher in the 'Mycodigest' intervention (N = 10) compared to the placebo (N = 6) group (80 vs. 16.7%, respectively, p = 0.035). There were no differences in terms of biochemical response within each group pre- and post-intervention. Post-'Mycodigest' intervention, 25 species were found to be differentially abundant compared to baseline, including increase in short chain fatty acid producing bacteria, such as Parabacteroides distasonis (Beta coefficient 0.92, 95% Confidence interval [CI] 0.36-1.47) and Faecalimonas umbilicata (Beta coefficient 0.57, 95% CI 0.23-0.90). Two microbial pathways related to the metabolism of isoprenoid compounds were increased post-'Mycodigest' intervention. Mushroom based prebiotic supplementation in subjects with CD resulted in clinical improvement which may be related to post-intervention favorable compositional and functional microbial alterations.
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Affiliation(s)
- Haim Leibovitzh
- Department of Gastroenterology and Liver Diseases, IBD Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Naomi Fliss Isakov
- Department of Gastroenterology and Liver Diseases, IBD Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Department of Health, Faculty of Medicine, School of Public Health, Tel Aviv University, Tel Aviv, Israel
| | - Lael Werner
- Department of Gastroenterology and Liver Diseases, IBD Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Tamar Thurm
- Department of Gastroenterology and Liver Diseases, IBD Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Ayal Hirsch
- Department of Gastroenterology and Liver Diseases, IBD Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Nathaniel Aviv Cohen
- Department of Gastroenterology and Liver Diseases, IBD Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
| | - Nitsan Maharshak
- Department of Gastroenterology and Liver Diseases, IBD Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
- Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel
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Truyens M, Lernout H, De Vos M, Laukens D, Lobaton T. Unraveling the fatigue puzzle: insights into the pathogenesis and management of IBD-related fatigue including the role of the gut-brain axis. Front Med (Lausanne) 2024; 11:1424926. [PMID: 39021817 PMCID: PMC11252009 DOI: 10.3389/fmed.2024.1424926] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2024] [Accepted: 06/17/2024] [Indexed: 07/20/2024] Open
Abstract
A significant percentage of patients with an inflammatory bowel disease (IBD) encounter fatigue which can profoundly diminish patients' quality of life, particularly during periods of disease remission when gastrointestinal symptoms have receded. Various contributing risk factors have been identified including active inflammation, anemia, psychological, lifestyle and drug-related factors. While addressing these risk factors has been suggested as the initial approach to managing fatigue, a considerable number of patients still experience persisting symptoms, the primary causes of which remain incompletely understood. Recent insights suggest that dysfunction of the gut-brain axis may play a pathogenic role. This review provides an overview of established risk factors for fatigue, alongside emerging perspectives on the role of the gut-brain axis, and potential treatment strategies.
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Affiliation(s)
- Marie Truyens
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
| | - Hannah Lernout
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- VIB Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium
| | - Martine De Vos
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
| | - Debby Laukens
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- VIB Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium
- Ghent Gut Inflammation Group (GGIG), Ghent University, Ghent, Belgium
| | - Triana Lobaton
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium
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3
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Campelo MDS, Mota LB, Câmara Neto JF, Barbosa MLL, Gonzaga MLDC, Leal LKAM, Bastos MDSR, Soares SDA, Ricardo NMPS, Cerqueira GS, Ribeiro MENP. Agaricus blazei Murill extract-loaded in alginate/poly(vinyl alcohol) films prepared by Ca 2+ cross-linking for wound healing applications. J Biomed Mater Res B Appl Biomater 2023; 111:1035-1047. [PMID: 36455230 DOI: 10.1002/jbm.b.35212] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 11/08/2022] [Accepted: 11/23/2022] [Indexed: 12/02/2022]
Abstract
This work aimed the development and evaluation of the wound healing activity of films based on sodium alginate, polyvinyl alcohol (PVA) and Ca2+ loaded with Agaricus blazei Murill hydroalcoholic extract (AbE). Firstly, AbE was prepared using a previously standardized methodology. The films were prepared by casting technique and cross-linked with Ca2+ using CaCl2 as cross-linking agent. The physicochemical, morphological and water vapor barrier properties of the films were analyzed and the pre-clinical efficacy was investigated against the cutaneous wound model in mice. The films showed barrier properties to water vapor promising for wound healing. AbE showed physical and chemical interactions between both polymers, noticed by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and thermal analysis. The delivery of AbE in alginate/PVA films enhanced the antioxidant and wound healing properties of these polymers. Consequently, a reduction of malondialdehyde levels was observed, as well as an increase of the epidermis/dermis thickness and enhancement in collagen I deposition. Thus, these formulations are promising biomaterials for wound care and tissue repairing.
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Affiliation(s)
- Matheus da Silva Campelo
- Laboratório de Polímeros e Inovação de Materiais, Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, Brazil.,Centro de Estudos Farmacêuticos e Cosméticos, Departamento de Farmácia, Universidade Federal do Ceará, Fortaleza, Brazil
| | - Lucas Barroso Mota
- Laboratório de Polímeros e Inovação de Materiais, Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, Brazil
| | - João Francisco Câmara Neto
- Laboratório de Polímeros e Inovação de Materiais, Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, Brazil
| | - Maria Lucianny Lima Barbosa
- Núcleo de Estudos em Microscopia e Processamento de Imagens, Departamento de Morfologia, Universidade Federal do Ceará, Fortaleza, Brazil
| | - Maria Leônia da Costa Gonzaga
- Laboratório de Polímeros e Inovação de Materiais, Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, Brazil.,Laboratório de Tecnologia de Embalagens de Alimentos, Embrapa Agroindústria Tropical, Fortaleza, Brazil
| | | | | | - Sandra de Aguiar Soares
- Laboratório de Polímeros e Inovação de Materiais, Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, Brazil
| | - Nágila Maria Pontes Silva Ricardo
- Laboratório de Polímeros e Inovação de Materiais, Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, Brazil
| | - Gilberto Santos Cerqueira
- Núcleo de Estudos em Microscopia e Processamento de Imagens, Departamento de Morfologia, Universidade Federal do Ceará, Fortaleza, Brazil
| | - Maria Elenir Nobre Pinho Ribeiro
- Laboratório de Polímeros e Inovação de Materiais, Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará, Fortaleza, Brazil.,Núcleo de Estudos em Microscopia e Processamento de Imagens, Departamento de Morfologia, Universidade Federal do Ceará, Fortaleza, Brazil
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Wen C, Geervliet M, de Vries H, Fabà L, den Hil PJRV, Skovgaard K, Savelkoul HFJ, Schols HA, Wells JM, Tijhaar E, Smidt H. Agaricus subrufescens fermented rye affects the development of intestinal microbiota, local intestinal and innate immunity in suckling-to-nursery pigs. Anim Microbiome 2023; 5:24. [PMID: 37041617 PMCID: PMC10088699 DOI: 10.1186/s42523-023-00244-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Accepted: 03/23/2023] [Indexed: 04/13/2023] Open
Abstract
BACKGROUND Agaricus subrufescens is considered as one of the most important culinary-medicinal mushrooms around the world. It has been widely suggested to be used for the development of functional food ingredients to promote human health ascribed to the various properties (e.g., anti-inflammatory, antioxidant, and immunomodulatory activities). In this context, the interest in A. subrufescens based feed ingredients as alternatives for antibiotics has also been fuelled during an era of reduced/banned antibiotics use. This study aimed to investigate the effects of a fermented feed additive -rye overgrown with mycelium (ROM) of A. subrufescens-on pig intestinal microbiota, mucosal gene expression and local and systemic immunity during early life. Piglets received ROM or a tap water placebo (Ctrl) perorally every other day from day 2 after birth until 2 weeks post-weaning. Eight animals per treatment were euthanized and dissected on days 27, 44 and 70. RESULTS The results showed ROM piglets had a lower inter-individual variation of faecal microbiota composition before weaning and a lower relative abundance of proteobacterial genera in jejunum (Undibacterium and Solobacterium) and caecum (Intestinibacter and Succinivibrionaceae_UCG_001) on day 70, as compared to Ctrl piglets. ROM supplementation also influenced gut mucosal gene expression in both ileum and caecum on day 44. In ileum, ROM pigs showed increased expression of TJP1/ZO1 but decreased expression of CLDN3, CLDN5 and MUC2 than Ctrl pigs. Genes involved in TLR signalling (e.g., TICAM2, IRAK4 and LY96) were more expressed but MYD88 and TOLLIP were less expressed in ROM pigs than Ctrl animals. NOS2 and HIF1A involved in redox signalling were either decreased or increased in ROM pigs, respectively. In caecum, differentially expressed genes between two groups were mainly shown as increased expression (e.g., MUC2, PDGFRB, TOLLIP, TNFAIP3 and MYD88) in ROM pigs. Moreover, ROM animals showed higher NK cell activation in blood and enhanced IL-10 production in ex vivo stimulated MLN cells before weaning. CONCLUSIONS Collectively, these results suggest that ROM supplementation in early life modulates gut microbiota and (local) immune system development. Consequently, ROM supplementation may contribute to improving health of pigs during the weaning transition period and reducing antibiotics use.
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Affiliation(s)
- Caifang Wen
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
- Laboratory of Food Chemistry, Wageningen University & Research, Wageningen, The Netherlands
| | - Mirelle Geervliet
- Cell Biology and Immunology Group, Wageningen University & Research, Wageningen, The Netherlands
| | - Hugo de Vries
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
- Host-Microbe Interactomics Group, Wageningen University & Research, Wageningen, The Netherlands
| | - Lluís Fabà
- Research and Development, Trouw Nutrition, Amersfoort, The Netherlands
| | - Petra J Roubos-van den Hil
- Research and Development, Trouw Nutrition, Amersfoort, The Netherlands
- DSM Food and Beverages - Fresh Dairy, Wageningen, The Netherlands
| | - Kerstin Skovgaard
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark
| | - Huub F J Savelkoul
- Cell Biology and Immunology Group, Wageningen University & Research, Wageningen, The Netherlands
| | - Henk A Schols
- Laboratory of Food Chemistry, Wageningen University & Research, Wageningen, The Netherlands
| | - Jerry M Wells
- Host-Microbe Interactomics Group, Wageningen University & Research, Wageningen, The Netherlands
| | - Edwin Tijhaar
- Cell Biology and Immunology Group, Wageningen University & Research, Wageningen, The Netherlands
| | - Hauke Smidt
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands.
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5
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Hobbs C. The Health and Clinical Benefits of Medicinal Fungi. ADVANCES IN BIOCHEMICAL ENGINEERING/BIOTECHNOLOGY 2023; 184:285-356. [PMID: 37468715 DOI: 10.1007/10_2023_230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/21/2023]
Abstract
The human uses of mushrooms and cultured mycelium products for nutrition and medicine are detailed and supported by available human studies, which in many cases are clinical trials published in peer-reviewed journals. The major medically active immunomodulating compounds in the cell walls-chitin, beta-glucans, and glycoproteins, as well as lower weight molecules-nitrogen-containing compounds, phenolics, and terpenes-are discussed in relation to their current clinical uses. The nutritional content and foods derived from mushrooms, particularly related to their medical benefits, are discussed. High-quality major nutrients such as the high amounts of complete protein and prebiotic fibers found in edible and medicinal fungi and their products are presented. Mushrooms contain the highest amount of valuable medicinal fiber, while dried fruiting bodies of some fungi have up to 80% prebiotic fiber. These fibers are particularly complex and are not broken down in the upper gut, so they can diversify the microbiome and increase the most beneficial species, leading to better immune regulation and increasing normalizing levels of crucial neurotransmitters like serotonin and dopamine. Since the growth of medicinal mushroom products is expanding rapidly worldwide, attention is placed on reviewing important aspects of mushroom and mycelium cultivation and quality issues relating to adulteration, substitution, and purity and for maximizing medicinal potency. Common questions surrounding medicinal mushroom products in the marketplace, particularly the healing potential of fungal mycelium compared with fruiting bodies, extraction methods, and the use of fillers in products, are all explored, and many points are supported by the literature.
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Affiliation(s)
- Christopher Hobbs
- Institute for Natural Products Research, University of Massachusetts, Amherst, MA, USA.
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6
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Caseiro C, Dias JNR, de Andrade Fontes CMG, Bule P. From Cancer Therapy to Winemaking: The Molecular Structure and Applications of β-Glucans and β-1, 3-Glucanases. Int J Mol Sci 2022; 23:3156. [PMID: 35328577 PMCID: PMC8949617 DOI: 10.3390/ijms23063156] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/11/2022] [Accepted: 03/11/2022] [Indexed: 02/04/2023] Open
Abstract
β-glucans are a diverse group of polysaccharides composed of β-1,3 or β-(1,3-1,4) linked glucose monomers. They are mainly synthesized by fungi, plants, seaweed and bacteria, where they carry out structural, protective and energy storage roles. Because of their unique physicochemical properties, they have important applications in several industrial, biomedical and biotechnological processes. β-glucans are also major bioactive molecules with marked immunomodulatory and metabolic properties. As such, they have been the focus of many studies attesting to their ability to, among other roles, fight cancer, reduce the risk of cardiovascular diseases and control diabetes. The physicochemical and functional profiles of β-glucans are deeply influenced by their molecular structure. This structure governs β-glucan interaction with multiple β-glucan binding proteins, triggering myriad biological responses. It is then imperative to understand the structural properties of β-glucans to fully reveal their biological roles and potential applications. The deconstruction of β-glucans is a result of β-glucanase activity. In addition to being invaluable tools for the study of β-glucans, these enzymes have applications in numerous biotechnological and industrial processes, both alone and in conjunction with their natural substrates. Here, we review potential applications for β-glucans and β-glucanases, and explore how their functionalities are dictated by their structure.
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Affiliation(s)
- Catarina Caseiro
- CIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal; (C.C.); (J.N.R.D.)
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
| | - Joana Nunes Ribeiro Dias
- CIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal; (C.C.); (J.N.R.D.)
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
| | | | - Pedro Bule
- CIISA—Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal; (C.C.); (J.N.R.D.)
- Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal
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7
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Edible Mushrooms and Beta-Glucans: Impact on Human Health. Nutrients 2021; 13:nu13072195. [PMID: 34202377 PMCID: PMC8308413 DOI: 10.3390/nu13072195] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Revised: 06/16/2021] [Accepted: 06/22/2021] [Indexed: 12/19/2022] Open
Abstract
Mushroom cell walls are rich in β-glucans, long or short-chain polymers of glucose subunits with β-1,3 and β-1,6 linkages, that are responsible for the linear and branching structures, respectively. β-glucans from cereals, at variance, have no 1,6 linkages nor branching structures. Both immunomodulatory and anti-inflammatory effects of mushrooms have been described using purified β-glucans or fungi extracts on cellular and experimental models; their potential clinical use has been tested in different conditions, such as recurrent infections of the respiratory tract or complications of major surgery. Another promising application of β-glucans is on cancer, as adjuvant of conventional chemotherapy. β-glucans may protect the cardiovascular system, ameliorating glucose, lipid metabolism, and blood pressure: these activities, observed for oat and barley β-glucans, require confirmation in human studies with mushroom β-glucans. On the other hand, mushrooms may also protect the cardiovascular system via a number of other components, such as bioactive phenolic compounds, vitamins, and mineral elements. The growing knowledge on the mechanism(s) and health benefits of mushrooms is encouraging the development of a potential clinical use of β-glucans, and also to further document their role in preserving health and prevent disease in the context of healthy lifestyles.
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8
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Davis SP, Bolin LP, Crane PB, Wei H, Crandell J. Non-pharmacological interventions to manage fatigue in adults with inflammatory bowel disease: A systematic review and meta-analysis. Complement Ther Clin Pract 2020; 41:101229. [PMID: 32836107 DOI: 10.1016/j.ctcp.2020.101229] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Revised: 08/03/2020] [Accepted: 08/08/2020] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND PURPOSE The prevalence of fatigue is higher in adults with inflammatory bowel disease (IBD). There is limited information on the effectiveness of non-pharmacological interventions to manage fatigue. The purposes of this review is to evaluate the effectiveness of these interventions to manage fatigue in adults with IBD. MATERIALS AND METHODS A systematic review was conducted based on the PRISMA guidelines. Comprehensive Meta-Analysis software was used to compute metaanalysis. RESULTS Eleven studies were included in the review. The interventions to manage fatigue included problem-solving therapy, solution-focused therapy, cognitive behavioral therapy, psychoeducational intervention, exercise advice with omega-3 supplements, electro-acupuncture, and AndoSan. The pooled evidence from the metaanalysis demonstrated that non-pharmacological interventions could decrease IBDFatigue (SMD = 0.33, 95% CI [0.10, 0.55], p = 0.005). CONCLUSION The pooled data indicate that non-pharmacological interventions are helpful in managing IBD-Fatigue. Additionally, the non-pharmacological interventions reviewed could be utilized to promote self-management in IBD.
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Affiliation(s)
- Suja P Davis
- School of Nursing, UNC-CH, CB#7460, Chapel Hill, NC, 27599, USA.
| | - Linda P Bolin
- Department of Nursing Science, College of Nursing, East Carolina University, 2205 W 5th St, Greenville, NC, 27889, USA.
| | - Patricia B Crane
- Carol Grotnes Belk Endowed Chair, 9201, University City Blvd, Charlotte, NC, USA.
| | - Holly Wei
- College of Nursing, East Carolina University, 2205 W 5th St, Greenville, NC, 27889, USA.
| | - Jamie Crandell
- School of Nursing, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
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9
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Hetland G, Johnson E, Bernardshaw SV, Grinde B. Can medicinal mushrooms have prophylactic or therapeutic effect against COVID-19 and its pneumonic superinfection and complicating inflammation? Scand J Immunol 2020; 93:e12937. [PMID: 32657436 PMCID: PMC7404338 DOI: 10.1111/sji.12937] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 06/04/2020] [Accepted: 07/06/2020] [Indexed: 12/18/2022]
Abstract
Medicinal mushrooms have documented effects against different diseases, including infections and inflammatory disorders. The related Basidiomycota Agaricus blazei Murill (AbM), Hericium erinaceus (HE), and Grifola frondosa (GF) have been shown to exert antimicrobial activity against viral agents, Gram‐positive and Gram‐negative bacteria, and parasites in vitro and in vivo. Since the mechanism is immunomodulatory and not antibiotical, the mushrooms should be active against multi‐drug resistant microbes as well. Moreover, since these Basidiomycota also have anti‐inflammatory properties, they may be suited for treatment of the severe lung inflammation that often follows COVID‐19 infection. An AbM‐based mushroom extract (Andosan™), also containing HE and GF, has been shown to significantly reduce bacteraemia and increase survival in mice with pneumococcal sepsis, and to improve symptoms and quality of life in IBD patients via an anti‐inflammatory effect. Hence, such mushroom extracts could have prophylactic or therapeutic effect against the pneumonic superinfection and severe lung inflammation that often complicates COVID‐19 infection. Here, we review antimicrobial and anti‐inflammatory properties of AbM, HE and GF mushrooms, which could be used for the battle against COVID‐19.
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Affiliation(s)
- Geir Hetland
- Department of Immunology and Transfusion Medicine, Oslo University Hospital (OUH), Oslo, Norway.,Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Egil Johnson
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Gastrointestinal and Pediatric Surgery, Oslo University Hospital, Oslo, Norway
| | | | - Bjørn Grinde
- Norwegian Institute of Public Health, Oslo, Norway
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10
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Hetland G, Tangen JM, Mahmood F, Mirlashari MR, Nissen-Meyer LSH, Nentwich I, Therkelsen SP, Tjønnfjord GE, Johnson E. Antitumor, Anti-Inflammatory and Antiallergic Effects of Agaricus blazei Mushroom Extract and the Related Medicinal Basidiomycetes Mushrooms, Hericium erinaceus and Grifola frondosa: A Review of Preclinical and Clinical Studies. Nutrients 2020; 12:nu12051339. [PMID: 32397163 PMCID: PMC7285126 DOI: 10.3390/nu12051339] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 04/23/2020] [Accepted: 05/04/2020] [Indexed: 02/07/2023] Open
Abstract
Since the 1980s, medicinal effects have been documented in scientific studies with the related Basidiomycota mushrooms Agaricus blazei Murill (AbM), Hericium erinaceus (HE) and Grifola frondosa (GF) from Brazilian and Eastern traditional medicine. Special focus has been on their antitumor effects, but the mushrooms' anti-inflammatory and antiallergic properties have also been investigated. The antitumor mechanisms were either direct tumor attack, e.g., apoptosis and metastatic suppression, or indirect defense, e.g., inhibited tumor neovascularization and T helper cell (Th) 1 immune response. The anti-inflammatory mechanisms were a reduction in proinflammatory cytokines, oxidative stress and changed gut microbiota, and the antiallergic mechanism was amelioration of a skewed Th1/Th2 balance. Since a predominant Th2 milieu is also found in cancer, which quite often is caused by a local chronic inflammation, the three conditions-tumor, inflammation and allergy-seem to be linked. Further mechanisms for HE were increased nerve and beneficial gut microbiota growth, and oxidative stress regulation. The medicinal mushrooms AbM, HE and GF appear to be safe, and can, in fact, increase longevity in animal models, possibly due to reduced tumorigenesis and oxidation. This article reviews preclinical and clinical findings with these mushrooms and the mechanisms behind them.
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Affiliation(s)
- Geir Hetland
- Department of Immunology and Transfusion Medicine, Oslo University Hospital, 0407 Oslo, Norway; (M.R.M.); (L.S.H.N.-M.); (I.N.)
- Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway; (G.E.T.); (E.J.)
- Correspondence:
| | - Jon-Magnus Tangen
- National CBRNE Medical Advisory Centre, Oslo University Hospital, 0407 Oslo, Norway;
| | - Faiza Mahmood
- Department of Immunology and Transfusion Medicine, Akershus University Hospital, 1478 Lørenskog, Norway;
| | - Mohammad Reza Mirlashari
- Department of Immunology and Transfusion Medicine, Oslo University Hospital, 0407 Oslo, Norway; (M.R.M.); (L.S.H.N.-M.); (I.N.)
| | - Lise Sofie Haug Nissen-Meyer
- Department of Immunology and Transfusion Medicine, Oslo University Hospital, 0407 Oslo, Norway; (M.R.M.); (L.S.H.N.-M.); (I.N.)
| | - Ivo Nentwich
- Department of Immunology and Transfusion Medicine, Oslo University Hospital, 0407 Oslo, Norway; (M.R.M.); (L.S.H.N.-M.); (I.N.)
| | | | - Geir Erland Tjønnfjord
- Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway; (G.E.T.); (E.J.)
- Department of Haematology, Oslo University Hospital, 0424 Oslo, Norway
- KG Jebsen Centre for B-cell Malignancies, Institute of Clinical Medicine, University of Oslo, 0315 Oslo, Norway
| | - Egil Johnson
- Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway; (G.E.T.); (E.J.)
- Department of Gastrointestinal and Pediatric Surgery, Oslo University Hospital, 0407 Oslo, Norway
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11
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Farrell D, Artom M, Czuber‐Dochan W, Jelsness‐Jørgensen LP, Norton C, Savage E, Cochrane IBD Group. Interventions for fatigue in inflammatory bowel disease. Cochrane Database Syst Rev 2020; 4:CD012005. [PMID: 32297974 PMCID: PMC7161727 DOI: 10.1002/14651858.cd012005.pub2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is an umbrella term used to describe a group of chronic, progressive inflammatory disorders of the digestive tract. Crohn's disease and ulcerative colitis are the two main types. Fatigue is a common, debilitating and burdensome symptom experienced by individuals with IBD. The subjective, complex nature of fatigue can often hamper its management. The efficacy and safety of pharmacological or non-pharmacological treatments for fatigue in IBD is not yet established through systematic review of studies. OBJECTIVES To assess the efficacy and safety of pharmacological and non-pharmacological interventions for managing fatigue in IBD compared to no treatment, placebo or active comparator. SEARCH METHODS A systematic search of the databases Embase, MEDLINE, Cochrane Library, CINAHL, PsycINFO was undertaken from inception to July 2018. A top-up search was run in October 2019. We also searched the Cochrane IBD Group Specialized Register, the Cochrane Central Register of Controlled Trials, ongoing trials and research registers, conference abstracts and reference lists for potentially eligible studies. SELECTION CRITERIA Randomised controlled trials of pharmacological and non-pharmacological interventions in children or adults with IBD, where fatigue was assessed as a primary or secondary outcome using a generic or disease-specific fatigue measure, a subscale of a larger quality of life scale or as a single-item measure, were included. DATA COLLECTION AND ANALYSIS Two authors independently screened search results and four authors extracted and assessed bias independently using the Cochrane 'Risk of bias' tool. The primary outcome was fatigue and the secondary outcomes included quality of life, adverse events (AEs), serious AEs and withdrawal due to AEs. Standard methodological procedures were used. MAIN RESULTS We included 14 studies (3741 participants): nine trials of pharmacological interventions and five trials of non-pharmacological interventions. Thirty ongoing studies were identified, and five studies are awaiting classification. Data on fatigue were available from nine trials (1344 participants). In only four trials was managing fatigue the primary intention of the intervention (electroacupuncture, physical activity advice, cognitive behavioural therapy and solution-focused therapy). Electroacupuncture Fatigue was measured with Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) (scores range from 0 to 52). The FACIT-F score at week eight was 8.00 points higher (better) in participants receiving electroacupuncture compared with no treatment (mean difference (MD) 8.00, 95% CI 6.45 to 9.55; 1 RCT; 27 participants; low-certainty evidence). Results at week 16 could not be calculated. FACIT-F scores were also higher with electroacupuncture compared to sham electroacupuncture at week eight (MD 5.10, 95% CI 3.49 to 6.71; 1 RCT; 30 participants; low-certainty evidence) but not at week 16 (MD 2.60, 95% CI 0.74 to 4.46; 1 RCT; 30 participants; low-certainty evidence). No adverse events were reported, except for one adverse event in the sham electroacupuncture group. Cognitive behavioural therapy (CBT) and solution-focused therapy Compared with a fatigue information leaflet, the effects of CBT on fatigue are very uncertain (Inflammatory Bowel Disease-Fatigue (IBD-F) section I: MD -2.16, 95% CI -6.13 to 1.81; IBD-F section II: MD -21.62, 95% CI -45.02 to 1.78; 1 RCT, 18 participants, very low-certainty evidence). The efficacy of solution-focused therapy on fatigue is also very uncertain, because standard summary data were not reported (1 RCT, 98 participants). Physical activity advice One 2 x 2 factorial trial (45 participants) found physical activity advice may reduce fatigue but the evidence is very uncertain. At week 12, compared to a control group receiving no physical activity advice plus omega 3 capsules, FACIT-F scores were higher (better) in the physical activity advice plus omega 3 group (FACIT-F MD 6.40, 95% CI -1.80 to 14.60, very low-certainty evidence) and the physical activity advice plus placebo group (FACIT-F MD 9.00, 95% CI 1.64 to 16.36, very low-certainty evidence). Adverse events were predominantly gastrointestinal and similar across physical activity groups, although more adverse events were reported in the no physical activity advice plus omega 3 group. Pharmacological interventions Compared with placebo, adalimumab 40 mg, administered every other week ('eow') (only for those known to respond to adalimumab induction therapy), may reduce fatigue in patients with moderately-to-severely active Crohn's disease, but the evidence is very uncertain (FACIT-F MD 4.30, 95% CI 1.75 to 6.85; very low-certainty evidence). The adalimumab 40 mg eow group was less likely to experience serious adverse events (OR 0.56, 95% CI 0.33 to 0.96; 521 participants; moderate-certainty evidence) and withdrawal due to adverse events (OR 0.48, 95%CI 0.26 to 0.87; 521 participants; moderate-certainty evidence). Ferric maltol may result in a slight increase in fatigue, with better SF-36 vitality scores reported in the placebo group compared to the treatment group following 12 weeks of treatment (MD -9.31, 95% CI -17.15 to -1.47; 118 participants; low-certainty evidence). There may be little or no difference in adverse events (OR 0.55, 95% CI 0.26 to 1.18; 120 participants; low-certainty evidence) AUTHORS' CONCLUSIONS: The effects of interventions for the management of fatigue in IBD are uncertain. No firm conclusions regarding the efficacy and safety of interventions can be drawn. Further high-quality studies, with a larger number of participants, are required to assess the potential benefits and harms of therapies. Future studies should assess interventions specifically designed for fatigue management, targeted at selected IBD populations, and measure fatigue as the primary outcome.
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Affiliation(s)
- Dawn Farrell
- Institute of Technology TraleeDepartment of Nursing and Healthcare SciencesTraleeCounty KerryIreland
| | - Micol Artom
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery and Palliative Care57 Waterloo RoadLondonUKSE1 8WA
| | - Wladyslawa Czuber‐Dochan
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery and Palliative Care57 Waterloo RoadLondonUKSE1 8WA
| | | | - Christine Norton
- King's College LondonFlorence Nightingale Faculty of Nursing, Midwifery and Palliative Care57 Waterloo RoadLondonUKSE1 8WA
| | - Eileen Savage
- University College CorkSchool of Nursing and Midwifery, Brookfield Health Sciences ComplexCorkIreland
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Lu YP, Liao JH, Guo ZJ, Cai ZX, Chen MY. Genome Survey and Transcriptome Analysis on Mycelia and Primordia of Agaricus blazei. BIOMED RESEARCH INTERNATIONAL 2020; 2020:1824183. [PMID: 32025516 PMCID: PMC6983287 DOI: 10.1155/2020/1824183] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Revised: 09/14/2019] [Accepted: 09/26/2019] [Indexed: 12/13/2022]
Abstract
Agaricus blazei, a type of edible straw-rotting mushroom with somewhat sweet taste and fragrance of almonds, has attracted considerable scientific and practical attention. High-throughput Illumina PE150 and PacBio RSII platform were employed to generate a genomic sequence. De novo assembly generated 36 contigs with 38,686,133 bp in size, containing 10,119 putative predicted genes. Additionally, we also studied transcriptional regulation of the mycelia and the primordia for exploration of genes involved in fruiting body formation. Expression profiling analysis revealed that 2,164 genes were upregulated in mycelia and 1,557 in primordia. Functional enrichment showed that differentially expressed genes associated with response to stress, ribosome biogenesis, arginine biosynthesis, and steroid biosynthesis pathway were more active in fruiting body. The genome and transcriptome analysis of A. blazei provide valuable sequence resources and contribute to our understanding of genes related to the biosynthesis pathway of polysaccharide and benzaldehyde, as well as the fruiting body formation.
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Affiliation(s)
- Yuan-Ping Lu
- Institute of Edible Fungi, Fujian Academy of Agricultural Sciences, Fuzhou 350014, Fujian Province, China
| | - Jian-Hua Liao
- Institute of Edible Fungi, Fujian Academy of Agricultural Sciences, Fuzhou 350014, Fujian Province, China
| | - Zhong-Jie Guo
- Institute of Edible Fungi, Fujian Academy of Agricultural Sciences, Fuzhou 350014, Fujian Province, China
| | - Zhi-Xin Cai
- Institute of Edible Fungi, Fujian Academy of Agricultural Sciences, Fuzhou 350014, Fujian Province, China
| | - Mei-Yuan Chen
- Institute of Edible Fungi, Fujian Academy of Agricultural Sciences, Fuzhou 350014, Fujian Province, China
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Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial. Nutrients 2019; 11:nu11102339. [PMID: 31581605 PMCID: PMC6836217 DOI: 10.3390/nu11102339] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Revised: 09/06/2019] [Accepted: 09/19/2019] [Indexed: 11/24/2022] Open
Abstract
Since Agaricus blazei Murill (AbM) extract reduced specific IgE and ameliorated a skewed Th1/Th2 balance in a mouse allergy model, it was tested in blood donors with self-reported, IgE-positive, birch pollen allergy and/or asthma. Sixty recruited donors were randomized in a placebo-controlled, double-blinded study with pre-seasonal, 7-week, oral supplementation with the AbM-based extract AndosanTM. Before and after the pollen season, questionnaires were answered for allergic rhino-conjunctivitis, asthma, and medication; serum IgE was measured, and Bet v 1-induced basophil activation was determined by CD63 expression. The reported general allergy and asthma symptoms and medication were significantly reduced in the AbM compared to the placebo group during pollen season. During the season, there was significant reduction in specific IgE anti-Bet v 1 and anti-t3 (birch pollen extract) levels in the AbM compared with the placebo group. While the maximal allergen concentrations needed for eliciting basophil activation before the season, changed significantly in the placebo group to lower concentrations (i.e., enhanced sensitization) after the season, these concentrations remained similar in the AndosanTM AbM extract group. Hence, the prophylactic effect of oral supplementation before the season with the AbM-based AndosanTM extract on aeroallergen-induced allergy was associated with reduced specific IgE levels during the season and basophils becoming less sensitive to allergen activation.
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Johnson E, Therkelsen SP, Nentwich I, Nissen-Meyer LSH, Hetland G. IgE-sensitization to food and inhalant allergens in IBD patients compared with normal blood donors at Oslo University Hospital, Norway. Scand J Gastroenterol 2019; 54:1107-1110. [PMID: 31524013 DOI: 10.1080/00365521.2019.1663445] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objectives: Crohn's disease (CD) and ulcerative colitis (UC) have been regarded as autoimmune Th-1/Th-17- and Th-2-associated conditions, respectively. The aim of the study was to examine possible differences in allergen sensitization between these diseases and relative to normal blood donors (BD). Materials and methods: Plasma from 29 UC and 37 CD patients with moderate disease activity and 100 healthy age- and gender-matched BD, were analyzed for specific IgE to 22 food- and 28 inhalation allergens using EUROLINE atopy screen. Results: There was significantly higher proportion of allergen sensitized patients in UC compared to BD. Corresponding mean percentages for UC, CD and BD were 8.5, 8.9 (p = .2) and 5.9 (p = .04). There was no intergroup difference in sensitization to food allergens. Most prominent result was the double level of sensitization to inhalants in CD (15%) compared to BD (8%) (p = .03). Overall highest levels of sensitization to inhalants were for grass pollens. Interestingly, the number of allergens (n = 50) the subjects were sensitized to, was significantly lower among UC (n = 20; 40%) (p = .0005) than CD (n = 31; 62%) and BD (n = 38; 76%). Conclusions: The percentage of individuals sensitized to inhalants in CD and to inhalants and foods in UC, were higher than corresponding results in BD. However, whereas allergen positive reactions in CD were comparable to those in BD, they were reduced in UC because of the few UC reactions to food allergens. This contrasts previous data and the study also points to sensitization to inhalants as a potential factor in the complex pathogenesis of IBD.
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Affiliation(s)
- Egil Johnson
- Department of Pediatric and Gastrointestinal Surgery, Oslo University Hospital, Ullevål , Oslo , Norway.,Institute of Clinical Medicine, University of Oslo , Oslo , Norway
| | - Stig Palm Therkelsen
- Department of Pediatric and Gastrointestinal Surgery, Oslo University Hospital, Ullevål , Oslo , Norway
| | - Ivo Nentwich
- Department of Immunology and Transfusion Medicine, Oslo University Hospital , Oslo , Norway
| | | | - Geir Hetland
- Institute of Clinical Medicine, University of Oslo , Oslo , Norway.,Department of Immunology and Transfusion Medicine, Oslo University Hospital , Oslo , Norway
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Yarlas A, Rubin DT, Panés J, Lindsay JO, Vermeire S, Bayliss M, Cappelleri JC, Maher S, Bushmakin AG, Chen LA, DiBonaventura M. Burden of Ulcerative Colitis on Functioning and Well-being: A Systematic Literature Review of the SF-36® Health Survey. J Crohns Colitis 2018; 12:600-609. [PMID: 29718244 DOI: 10.1093/ecco-jcc/jjy024] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS This review is the first to evaluate the burden of ulcerative colitis [UC] on patients' quality of life by synthesizing data from studies comparing scores from the SF-36® Health Survey, a generic measure assessing eight quality-of-life domains, between UC patients and matched reference samples. METHODS A systematic review of the published literature identified articles reporting SF-36 domains or physical and mental component summary scores [PCS, MCS] from UC and reference samples. Burden of disease for each SF-36 domain was then summarized across studies by comparing weighted mean differences in scores between patient and reference samples with minimally important difference thresholds. RESULTS Thirty articles met pre-specified inclusion criteria. SF-36 scores were extracted from five samples of patients with active disease, 11 samples with a mixture of disease activity, five samples of patients in clinical remission, and 13 samples of patients following proctocolectomy with ileostomy or ileal pouch-anal anastomosis, along with respective reference samples. Clinically meaningful burden was observed in samples with active or mixed disease activity [deficits: PCS = 5.6, MCS = 5.5] on all SF-36 domains except Physical Functioning. No burden was observed in samples in remission or post-surgical patients [deficits: PCS = 0.8, MCS = 0.4] except for the General Health perception domain. CONCLUSIONS Patients with active UC experience a clinically meaningful burden of disease across most aspects of quality of life. Patients with inactive UC exhibit negligible disease burden and are comparable to the general population on most quality-of-life outcomes. Thus, treatments which effectively induce and maintain remission may restore physical and mental health status.
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Affiliation(s)
| | - David T Rubin
- University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - Julian Panés
- Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain
| | - James O Lindsay
- Centre for Immunobiology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Séverine Vermeire
- Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium
| | | | | | | | | | - Lea Ann Chen
- New York University School of Medicine, New York, NY, USA
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Psychometric validation of the SF-36® Health Survey in ulcerative colitis: results from a systematic literature review. Qual Life Res 2017; 27:273-290. [DOI: 10.1007/s11136-017-1690-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2017] [Indexed: 12/12/2022]
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18
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da Silva de Souza AC, Correa VG, Goncalves GDA, Soares AA, Bracht A, Peralta RM. Agaricus blazei Bioactive Compounds and their Effects on Human Health: Benefits and Controversies. Curr Pharm Des 2017; 23:2807-2834. [DOI: 10.2174/1381612823666170119093719] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2016] [Accepted: 01/03/2017] [Indexed: 01/13/2023]
Affiliation(s)
| | | | | | | | - Adelar Bracht
- Department of Biochemistry, State University of Maringá, Maringa, Brazil
| | - Rosane Marina Peralta
- Post- graduated Program of Biological Sciences, State University of Maringá; Post-graduated Program of Food Science, State University of Maringá; Department of Biochemistry, State University of Maringa, Maringa, Brazil
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Therkelsen SP, Hetland G, Lyberg T, Lygren I, Johnson E. Cytokine Levels After Consumption of a Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSan ™ , in Patients with Crohn's Disease and Ulcerative Colitis in a Randomized Single-Blinded Placebo-Controlled Study. Scand J Immunol 2017; 84:323-331. [PMID: 27588816 DOI: 10.1111/sji.12476] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 08/31/2016] [Indexed: 12/23/2022]
Abstract
Ingestion of the Agaricus blazei Murill-based mushroom extract AndoSan™ has been shown in randomized placebo-controlled studies to improve symptoms in Crohn's disease (CD) and ulcerative colitis (UC) and also fatigue and quality of life in the latter patients. The aim was to examine whether this clinical impact of AndoSan™ intake could be explained by influence on foremost pro-inflammatory cytokines in the patients. Fifty patients with symptomatic UC and CD were randomized and blinded for oral daily intake of AndoSan™ or placebo. Blood samples taken before (visit 1) and after 21 days' (visit 3) consumption were analysed for cytokines IL-1ß, IL-2, IL-4-8, IL-10, IL-12-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, MIP-1ß and TNF-α. Baseline cytokine levels were similar in CD and UC. In CD, cytokine levels at visit 1 versus visit 3 were unaltered within the AndoSan™ and the placebo groups. Only IL-2 was significantly reduced at visit 3 in the Andosan™ compared with the placebo group. However, when combining IL-1ß, IL-6 and G-CSF in the patients with CD, the cytokine levels were significantly lower in the AndoSanTM - versus the placebo group, visit 3. In UC, levels of IL-2, IL-5 and MIP-1ß were reduced within the AndoSan™ group. IL-5 was also reduced at visit 3 compared with placebo. Generally, the effect on reduction in systemic cytokine levels by consumption of AndoSan™ was limited and supported only marginally anti-inflammatory effects in these patients. Therefore, other explanations behind the clinical anti-inflammatory effects than the contribution of cytokines seem more pertinent, including anti-allergic and antioxidant activities.
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Affiliation(s)
- S P Therkelsen
- Department of Gastrointestinal and Pediatric Surgery, Oslo University Hospital, Ullevål, Norway
| | - G Hetland
- Immunology and Transfusion Medicine, Oslo University Hospital, Ullevål, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway
| | - T Lyberg
- Medical Biochemistry, Oslo University Hospital, Ullevål, Norway
| | - I Lygren
- Medicine, Oslo University Hospital, Ullevål, Norway
| | - E Johnson
- Department of Gastrointestinal and Pediatric Surgery, Oslo University Hospital, Ullevål, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway
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Hetland G, Eide DM, Tangen JM, Haugen MH, Mirlashari MR, Paulsen JE. The Agaricus blazei-Based Mushroom Extract, Andosan™, Protects against Intestinal Tumorigenesis in the A/J Min/+ Mouse. PLoS One 2016; 11:e0167754. [PMID: 28002446 PMCID: PMC5176274 DOI: 10.1371/journal.pone.0167754] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 11/18/2016] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND The novel A/J Min/+ mouse, which is a model for human Familial Adenomatous Polyposis (FAP), develops spontaneously multiple adenocarcinomas in the colon as well as in the small intestine. Agaricus blazei Murill (AbM) is an edible Basidiomycetes mushroom that has been used in traditional medicine against cancer and other diseases. The mushroom contains immunomodulating β-glucans and is shown to have antitumor effects in murine cancer models. Andosan™ is a water extract based on AbM (82%), but it also contains the medicinal Basidiomycetes mushrooms Hericeum erinaceus and Grifola frondosa. METHODS AND FINDINGS Tap water with 10% Andosan™ was provided as the only drinking water for 15 or 22 weeks to A/J Min/+ mice and A/J wild-type mice (one single-nucleotide polymorphism (SNP) difference), which then were exsanguinated and their intestines preserved in formaldehyde and the serum frozen. The intestines were examined blindly by microscopy and also stained for the tumor-associated protease, legumain. Serum cytokines (pro- and anti-inflammatory, Th1-, Th2 -and Th17 type) were measured by Luminex multiplex analysis. Andosan™ treated A/J Min/+ mice had a significantly lower number of adenocarcinomas in the intestines, as well as a 60% significantly reduced intestinal tumor load (number of tumors x size) compared to control. There was also reduced legumain expression in intestines from Andosan™ treated animals. Moreover, Andosan™ had a significant cytotoxic effect correlating with apoptosis on the human cancer colon cell line, Caco-2, in vitro. When examining serum from both A/J Min/+ and wild type mice, there was a significant increase in anti-tumor Th1 type and pro-inflammatory cytokines in the Andosan™ treated mice. CONCLUSIONS The results from this mouse model for colorectal cancer shows significant protection of orally administered Andosan™ against development of intestinal cancer. This is supported by the finding of less legumain in intestines of Andosan™ treated mice and increased systemic Th1 cytokine response. The mechanism is probably both immuno-modulatory and growth inhibition of tumor cells by induction of apoptosis.
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Affiliation(s)
- Geir Hetland
- Department of Immunology, Oslo University Hospital, Oslo, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Dag M. Eide
- Department of Chemicals and Radiation, Norwegian Institute of Public Health, Oslo, Norway
| | - Jon M. Tangen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Acute Medicine & National CBRNE Medical and Advisory Centre–Norway, Oslo University Hospital, Oslo, Norway
| | - Mads H. Haugen
- Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital – The Norwegian Radium Hospital, Oslo, Norway
| | | | - Jan E. Paulsen
- Norwegian University of Life Sciences, Department of Food Safety and Infection Biology, Oslo, Norway
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Therkelsen SP, Hetland G, Lyberg T, Lygren I, Johnson E. Effect of the Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSanTM, on Symptoms, Fatigue and Quality of Life in Patients with Crohn's Disease in a Randomized Single-Blinded Placebo Controlled Study. PLoS One 2016; 11:e0159288. [PMID: 27415795 PMCID: PMC4944955 DOI: 10.1371/journal.pone.0159288] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 06/30/2016] [Indexed: 11/19/2022] Open
Abstract
Background Ingestion of AndoSanTM, based on the mushroom Agaricus blazei Murill, has previously shown an anti-inflammatory effect through reduction of pro-inflammatory cytokines in healthy individuals and patients with Crohn’s disease (CD). In this randomized single-blinded placebo-controlled study we examined whether intake of AndoSanTM also resulted in clinical effects. Methods and Findings 50 patients with symptomatic CD were randomized for oral daily consumption of AndoSanTM or placebo for a 21-day experimental period, in this per-protocol study. Patients reported validated scores for symptoms, fatigue and health related quality of life (HRQoL) at days 0, 14 and 21. Fecal calprotectin and general blood parameters were also analyzed. In the AndoSanTM group (n = 25) symptoms improved from baseline (day 0) to days 14 and 21, with respective mean scores (95% CI) of 5.52 (4.64–6.40), 4.48 (3.69–5.27) and 4.08 (3.22–4.94) (p<0,001). We found significant improvements in symptom score for both genders in the AndoSanTM group, and no significant changes in the placebo (n = 25) group. There were however no significant differences between the groups (p = 0.106), although a marginal effect in symptom score for men (p = 0.054). There were comparable improvements in physical, mental and total fatigue for both groups. HRQoL versus baseline were at day 21 improved for bodily pain and vitality in the AndoSanTM group and for vitality and social functioning in the placebo group. No crucial changes in general blood samples and fecal calprotectin were detected. Conclusions The results from this single-blinded randomized clinical trial shows significant improvement on symptoms, for both genders, in the AndoSanTM group, but no significant differences between the study groups. The results on fatigue, HRQoL, fecal calprotectin and blood samples were quite similar compared with placebo. The patients did not report any harms or unintended effects of AndoSanTM. CD patients with mild to moderate symptoms may have beneficiary effects of AndoSanTM as a safe supplement in addition to conventional medication. Trial Registration ClinicalTrials.gov NCT01496053
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Affiliation(s)
- Stig Palm Therkelsen
- Department of Gastrointestinal and Pediatric Surgery, Oslo University Hospital, Ullevål, Oslo, Norway
- * E-mail:
| | - Geir Hetland
- Immunology and Transfusion Medicine, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Torstein Lyberg
- Medical Biochemistry, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Idar Lygren
- Medicine, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Egil Johnson
- Department of Gastrointestinal and Pediatric Surgery, Oslo University Hospital, Ullevål, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
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