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Rauer L, De Tomassi A, Müller CL, Hülpüsch C, Traidl-Hoffmann C, Reiger M, Neumann AU. De-biasing microbiome sequencing data: bacterial morphology-based correction of extraction bias and correlates of chimera formation. MICROBIOME 2025; 13:38. [PMID: 39905530 PMCID: PMC11792448 DOI: 10.1186/s40168-024-01998-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 12/04/2024] [Indexed: 02/06/2025]
Abstract
INTRODUCTION Microbiome amplicon sequencing data are distorted by multiple protocol-dependent biases from bacterial DNA extraction, contamination, sequence errors, and chimeras, hindering clinical microbiome applications. In particular, extraction bias is a major confounder in sequencing-based microbiome analyses, with no correction method available to date. Here, we suggest using mock community controls to computationally correct extraction bias based on bacterial morphological properties. METHODS We compared dilution series of 3 cell mock communities with an even or staggered composition. DNA of these mock, and additional skin microbiome samples, was extracted with 8 different extraction protocols (2 buffers, 2 extraction kits, 2 lysis conditions). Extracted DNA was sequenced (V1-V3 16S rRNA gene) together with corresponding DNA mocks. RESULTS Microbiome composition was significantly different between extraction kits and lysis conditions, but not between buffers. Independent of the extraction protocol, chimera formation increased with higher input cell numbers. Contaminants originated mostly from buffers, and considerable cross-contamination was observed in low-input samples. Comparing the microbiome composition of the cell mocks to corresponding DNA mocks revealed taxon-specific protocol-dependent extraction bias. Strikingly, this extraction bias per species was predictable by bacterial cell morphology. Morphology-based computational correction of extraction bias significantly improved resulting microbial compositions when applied to different mock samples, even with different taxa. Equivalent correction of the skin samples showed a substantial impact on microbiome compositions. CONCLUSIONS Our results indicate that higher DNA density increases chimera formation during PCR amplification. Furthermore, we show that computational correction of extraction bias based on bacterial cell morphology would be feasible using appropriate positive controls, thus constituting an important step toward overcoming protocol biases in microbiome analysis. Video Abstract.
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Affiliation(s)
- Luise Rauer
- Institute of Environmental Medicine and Integrative Health, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
- Chair of Environmental Medicine, Technical University of Munich, Munich, Germany.
- Institute of Environmental Medicine, Helmholtz Munich, Augsburg, Germany.
| | - Amedeo De Tomassi
- Institute of Environmental Medicine and Integrative Health, Faculty of Medicine, University of Augsburg, Augsburg, Germany
| | - Christian L Müller
- Institute of Computational Biology, Helmholtz Munich, Neuherberg, Germany
- Department of Statistics, Ludwig Maximilian University of Munich, Munich, Germany
- Center for Computational Mathematics, Flatiron Institute, New York, USA
| | - Claudia Hülpüsch
- Institute of Environmental Medicine and Integrative Health, Faculty of Medicine, University of Augsburg, Augsburg, Germany
- Chair of Environmental Medicine, Technical University of Munich, Munich, Germany
- CK CARE, Christine Kühne Center for Allergy Research and Education, Davos, Switzerland
| | - Claudia Traidl-Hoffmann
- Institute of Environmental Medicine and Integrative Health, Faculty of Medicine, University of Augsburg, Augsburg, Germany
- Chair of Environmental Medicine, Technical University of Munich, Munich, Germany
- Institute of Environmental Medicine, Helmholtz Munich, Augsburg, Germany
- CK CARE, Christine Kühne Center for Allergy Research and Education, Davos, Switzerland
- ZIEL - Institute for Food & Health, Technical University of Munich, Freising-Weihenstephan, Germany
| | - Matthias Reiger
- Institute of Environmental Medicine and Integrative Health, Faculty of Medicine, University of Augsburg, Augsburg, Germany
- Chair of Environmental Medicine, Technical University of Munich, Munich, Germany
- Institute of Environmental Medicine, Helmholtz Munich, Augsburg, Germany
| | - Avidan U Neumann
- Institute of Environmental Medicine and Integrative Health, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
- Institute of Environmental Medicine, Helmholtz Munich, Augsburg, Germany.
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Yilmaz B, Macpherson AJ. Delving the depths of 'terra incognita' in the human intestine - the small intestinal microbiota. Nat Rev Gastroenterol Hepatol 2025; 22:71-81. [PMID: 39443711 DOI: 10.1038/s41575-024-01000-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/25/2024] [Indexed: 10/25/2024]
Abstract
The small intestinal microbiota has a crucial role in gastrointestinal health, affecting digestion, immune function, bile acid homeostasis and nutrient metabolism. The challenges of accessibility at this site mean that our knowledge of the small intestinal microbiota is less developed than of the colonic or faecal microbiota. Here, we summarize the features and fluctuations of the microbiota along the small intestinal tract, focusing on humans, and discuss physicochemical factors and assessment methods, including the technical challenges of investigating the low microbial biomass of the proximal small bowel. We highlight the essential protective mechanisms of the small intestine, including motility, the paracellular barrier and mucus, and secretory immunity, to show their roles in limiting excessive exposure of host tissues to microbial metabolites. We address current knowledge gaps, particularly the variability among individuals, the effects of dysbiosis of the small intestinal microbiota on health and how different taxa in small intestinal microbiota could compensate for each other functionally.
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Affiliation(s)
- Bahtiyar Yilmaz
- Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
- Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland.
- Bern Center for Precision Medicine (BCPM), University of Bern, Bern, Switzerland.
| | - Andrew J Macpherson
- Department of Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland.
- Maurice Müller Laboratories, Department for Biomedical Research, University of Bern, Bern, Switzerland.
- Bern Center for Precision Medicine (BCPM), University of Bern, Bern, Switzerland.
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Kverka M, Stepan JJ. Associations Among Estrogens, the Gut Microbiome and Osteoporosis. Curr Osteoporos Rep 2024; 23:2. [PMID: 39585466 PMCID: PMC11588883 DOI: 10.1007/s11914-024-00896-w] [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] [Accepted: 10/25/2024] [Indexed: 11/26/2024]
Abstract
PURPOSE OF THE REVIEW The purpose of this Review was to summarize the evidence on the associations among estrogen status, cellular senescence, the gut microbiome and osteoporosis. RECENT FINDINGS Indicate that osteoporosis is a global public health problem that impacts individuals and society. In postmenopausal women, a decrease in estrogen levels is associated with a decrease in gut microbial diversity and richness, as well as increased permeability of the gut barrier, which allows for low-grade inflammation. The direct effects of estrogen status on the association between bone and the gut microbiome were observed in untreated and treated ovariectomized women. In addition to the direct effects of estrogens on bone remodeling, estrogen therapy could reduce the risk of postmenopausal osteoporosis by preventing increased gut epithelial permeability, bacterial translocation and inflammaging. However, in studies comparing the gut microbiota of older women, there were no changes at the phylum level, suggesting that age-related comorbidities may have a greater impact on changes in the gut microbiota than menopausal status does. Estrogens modify bone health not only by directly influencing bone remodeling, but also indirectly by influencing the gut microbiota, gut barrier function and the resulting changes in immune system reactivity.
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Affiliation(s)
- Miloslav Kverka
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czechia
| | - Jan J Stepan
- Institute of Rheumatology, Prague, Czechia.
- Department of Rheumatology, First Faculty of Medicine, Charles University, Kateřinská 32, Praha 2, 121 08, Czech Republic.
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Donadio JLS, Fabi JP. Comparative analysis of pectin and prebiotics on human microbiota modulation in early life stages and adults. Food Funct 2024; 15:6825-6846. [PMID: 38847603 DOI: 10.1039/d4fo01231c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
The gut microbiota is essential in human health, influencing various physiological processes ranging from digestion and metabolism to immune function and mental health. Dietary fiber pectins and prebiotics have emerged as key modulators of gut microbiota composition and function, offering potential therapeutic implications for promoting gut health and preventing intestinal inflammatory diseases. In this review, we explore the modulation of gut microbiota by dietary fiber pectins and prebiotics in infants and adults. We begin with an overview of the gut microbiota composition and function in different age groups, highlighting the factors in shaping microbial communities in both age groups, especially the effect of diet. We then delve into the impact of dietary fiber pectins and prebiotics on gut microbiota composition and function, examining their effects on digestive health, intestinal barrier integrity, immune function, metabolic health, and mental health across different life stages. We further compare how aging affects the gut function and immune system, and we discuss the main health outcomes associated with dietary fiber intake and prebiotics, including the impact on digestive health, improvement in immune function, improvement in cholesterol and glucose metabolism, weight management, mental health, and prevention of diseases. Finally, we highlight the challenges and future directions for research. By advancing the understanding of gut microbiota dynamics and translating scientific insights into clinical practice, it could harness the full potential of dietary fiber pectins and prebiotics to optimize gut health, improve overall well-being across the lifespan, and increase longevity.
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Affiliation(s)
- Janaina Lombello Santos Donadio
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
- Food Research Center (FoRC), CEPID-FAPESP (Research, Innovation and Dissemination Centers, São Paulo Research Foundation), São Paulo, Brazil
| | - João Paulo Fabi
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil.
- Food Research Center (FoRC), CEPID-FAPESP (Research, Innovation and Dissemination Centers, São Paulo Research Foundation), São Paulo, Brazil
- Food and Nutrition Research Center (NAPAN), University of São Paulo, São Paulo, Brazil
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Sun B, Tan B, Zhang P, Zhu L, Wei H, Huang T, Li C, Yang W. Iron deficiency anemia: a critical review on iron absorption, supplementation and its influence on gut microbiota. Food Funct 2024; 15:1144-1157. [PMID: 38235788 DOI: 10.1039/d3fo04644c] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2024]
Abstract
Iron deficiency anemia (IDA) caused by micronutrient iron deficiency has attracted global attention due to its adverse health effects. The regulation of iron uptake and metabolism is finely controlled by various transporters and hormones in the body. Dietary iron intake and regulation are essential in maintaining human health and iron requirements. The review aims to investigate literature concerning dietary iron intake and systemic regulation. Besides, recent IDA treatment and dietary iron supplementation are discussed. Considering the importance of the gut microbiome, the interaction between bacteria and micronutrient iron in the gut is also a focus of this review. The iron absorption efficiency varies considerably according to iron type and dietary factors. Iron fortification remains the cost-effective strategy, although challenges exist in developing suitable iron fortificants and food vehicles regarding bioavailability and acceptability. Iron deficiency may alter the microbiome structure and promote the growth of pathogenic bacteria in the gut, affecting immune balance and human health.
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Affiliation(s)
- Bolun Sun
- College of Food and Pharmaceutical Sciences, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, Ningbo University, Ningbo 315211, China.
- School of Nursing, Wenzhou Medical University, Wenzhou 325035, China
| | - Beibei Tan
- School of Agriculture and Food, Faculty of Science, University of Melbourne, Australia
| | - Panxue Zhang
- College of Food and Pharmaceutical Sciences, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, Ningbo University, Ningbo 315211, China.
| | - Lianlian Zhu
- School of Nursing, Wenzhou Medical University, Wenzhou 325035, China
| | - Huamao Wei
- College of Food and Pharmaceutical Sciences, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, Ningbo University, Ningbo 315211, China.
| | - Tao Huang
- College of Food and Pharmaceutical Sciences, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, Ningbo University, Ningbo 315211, China.
| | - Chao Li
- College of Food and Pharmaceutical Sciences, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, Ningbo University, Ningbo 315211, China.
| | - Wenge Yang
- College of Food and Pharmaceutical Sciences, Key Laboratory of Animal Protein Food Deep Processing Technology of Zhejiang Province, Ningbo University, Ningbo 315211, China.
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Benešová I, Křížová Ľ, Kverka M. Microbiota as the unifying factor behind the hallmarks of cancer. J Cancer Res Clin Oncol 2023; 149:14429-14450. [PMID: 37555952 PMCID: PMC10590318 DOI: 10.1007/s00432-023-05244-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 08/01/2023] [Indexed: 08/10/2023]
Abstract
The human microbiota is a complex ecosystem that colonizes body surfaces and interacts with host organ systems, especially the immune system. Since the composition of this ecosystem depends on a variety of internal and external factors, each individual harbors a unique set of microbes. These differences in microbiota composition make individuals either more or less susceptible to various diseases, including cancer. Specific microbes are associated with cancer etiology and pathogenesis and several mechanisms of how they drive the typical hallmarks of cancer were recently identified. Although most microbes reside in the distal gut, they can influence cancer initiation and progression in distant tissues, as well as modulate the outcomes of established cancer therapies. Here, we describe the mechanisms by which microbes influence carcinogenesis and discuss their current and potential future applications in cancer diagnostics and management.
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Affiliation(s)
- Iva Benešová
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology v.v.i., Czech Academy of Sciences, Vídeňská 1083, 142 00, Prague 4-Krč, Czech Republic
| | - Ľudmila Křížová
- Department of Oncology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
| | - Miloslav Kverka
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology v.v.i., Czech Academy of Sciences, Vídeňská 1083, 142 00, Prague 4-Krč, Czech Republic.
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Elwyn R, Mitchell J, Kohn MR, Driver C, Hay P, Lagopoulos J, Hermens DF. Novel ketamine and zinc treatment for anorexia nervosa and the potential beneficial interactions with the gut microbiome. Neurosci Biobehav Rev 2023; 148:105122. [PMID: 36907256 DOI: 10.1016/j.neubiorev.2023.105122] [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: 11/01/2022] [Revised: 03/04/2023] [Accepted: 03/07/2023] [Indexed: 03/13/2023]
Abstract
Anorexia nervosa (AN) is a severe illness with diverse aetiological and maintaining contributors including neurobiological, metabolic, psychological, and social determining factors. In addition to nutritional recovery, multiple psychological and pharmacological therapies and brain-based stimulations have been explored; however, existing treatments have limited efficacy. This paper outlines a neurobiological model of glutamatergic and γ-aminobutyric acid (GABA)-ergic dysfunction, exacerbated by chronic gut microbiome dysbiosis and zinc depletion at a brain and gut level. The gut microbiome is established early in development, and early exposure to stress and adversity contribute to gut microbial disturbance in AN, early dysregulation to glutamatergic and GABAergic networks, interoceptive impairment, and inhibited caloric harvest from food (e.g., zinc malabsorption, competition for zinc ions between gut bacteria and host). Zinc is a key part of glutamatergic and GABAergic networks, and also affects leptin and gut microbial function; systems dysregulated in AN. Low doses of ketamine in conjunction with zinc, could provide an efficacious combination to act on NMDA receptors and normalise glutamatergic, GABAergic and gut function in AN.
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Affiliation(s)
- Rosiel Elwyn
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia.
| | - Jules Mitchell
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Michael R Kohn
- AYA Medicine Westmead Hospital, CRASH (Centre for Research into Adolescent's Health) Western Sydney Local Health District, Sydney University, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Christina Driver
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Phillipa Hay
- Translational Health Research Institute (THRI) School of Medicine, Western Sydney University, Campbelltown, NSW, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Jim Lagopoulos
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Daniel F Hermens
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
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Cerdó T, García-Santos JA, Rodríguez-Pöhnlein A, García-Ricobaraza M, Nieto-Ruíz A, G. Bermúdez M, Campoy C. Impact of Total Parenteral Nutrition on Gut Microbiota in Pediatric Population Suffering Intestinal Disorders. Nutrients 2022; 14:4691. [PMID: 36364953 PMCID: PMC9658482 DOI: 10.3390/nu14214691] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/01/2022] [Accepted: 11/04/2022] [Indexed: 08/10/2023] Open
Abstract
Parenteral nutrition (PN) is a life-saving therapy providing nutritional support in patients with digestive tract complications, particularly in preterm neonates due to their gut immaturity during the first postnatal weeks. Despite this, PN can also result in several gastrointestinal complications that are the cause or consequence of gut mucosal atrophy and gut microbiota dysbiosis, which may further aggravate gastrointestinal disorders. Consequently, the use of PN presents many unique challenges, notably in terms of the potential role of the gut microbiota on the functional and clinical outcomes associated with the long-term use of PN. In this review, we synthesize the current evidence on the effects of PN on gut microbiome in infants and children suffering from diverse gastrointestinal diseases, including necrotizing enterocolitis (NEC), short bowel syndrome (SBS) and subsequent intestinal failure, liver disease and inflammatory bowel disease (IBD). Moreover, we discuss the potential use of pre-, pro- and/or synbiotics as promising therapeutic strategies to reduce the risk of severe gastrointestinal disorders and mortality. The findings discussed here highlight the need for more well-designed studies, and harmonize the methods and its interpretation, which are critical to better understand the role of the gut microbiota in PN-related diseases and the development of efficient and personalized approaches based on pro- and/or prebiotics.
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Affiliation(s)
- Tomás Cerdó
- Maimonides Institute for Research in Biomedicine of Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain
| | - José Antonio García-Santos
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Anna Rodríguez-Pöhnlein
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - María García-Ricobaraza
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Ana Nieto-Ruíz
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Mercedes G. Bermúdez
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Cristina Campoy
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
- Spanish Network of Biomedical Research in Epidemiology and Public Health (CIBERESP), Granada’s Node, Carlos III Health Institute, Avda. Monforte de Lemos 5, 28028 Madrid, Spain
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Brichová M, Svozílková P, Klímová A, Dušek O, Kverka M, Heissigerová J. MICROBIOME AND UVEITIDES. A REVIEW. CESKA A SLOVENSKA OFTALMOLOGIE : CASOPIS CESKE OFTALMOLOGICKE SPOLECNOSTI A SLOVENSKE OFTALMOLOGICKE SPOLECNOSTI 2022; 78:47-52. [PMID: 35105146 DOI: 10.31348/2021/30] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Microorganisms inhabiting all surfaces of mucous membranes and skin and forming a complex ecosystem with the host is called microbiota. The term microbiome is used for the aggregate genome of microbiota. The microbiota plays important role in the mechanisms of number of physiological and pathological processes, especially of the hosts immune system. The origin and course of autoimmune diseases not only of the digestive tract, but also of the distant organs, including the eye, are significantly influenced by intestinal microbiota. The role of microbiota and its changes (dysbiosis) in the etiopathogenesis of uveitis has so far been studied mainly in experimental models. Reduction of severity of non-infectious intraocular inflammation in germ-free mice or in conventional mice treated with broad-spectrum antibiotics was observed in both the induced experimental autoimmune uveitis model (EAU) and the spontaneous R161H model. Studies have confirmed that autoreactive T cell activation occurs in the intestinal wall in the absence of retinal antigen. Recent experiments focused on the effect of probiotic administration on the composition of intestinal microbiota and on the course of autoimmune uveitis. Our study group demonstrated significant prophylactic effect of the administration of the probiotic Escherichia coli Nissle 1917 on the intensity of inflammation in EAU. To date, only a few studies have been published investigating intestinal dysbiosis in patients with uveitis (e.g., in Behcets disease or Vogt-Koyanagi-Harada syndrome). The results of preclinical studies will be presumably used in clinical practice, mainly in the sense of prophylaxis and therapy, such as change in the lifestyle, diet and especially the therapeutic use of probiotics or the transfer of faecal microbiota.
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Ceccarelli I, Bioletti L, Peparini S, Solomita E, Ricci C, Casini I, Miceli E, Aloisi AM. Estrogens and phytoestrogens in body functions. Neurosci Biobehav Rev 2021; 132:648-663. [PMID: 34890602 DOI: 10.1016/j.neubiorev.2021.12.007] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 12/03/2021] [Accepted: 12/04/2021] [Indexed: 12/23/2022]
Abstract
Estrogens are the hormones of reproduction in women as well as of many other important functions in the male and female body. They undergo significant changes in the different phases of life, e.g. during puberty, pregnancy or at menopause/andropause. Phytoestrogens are natural non-steroidal phenolic plant compounds that can mimic the activity of estrogens and their beneficial effects in women and in men. This narrative review summarizes the literature on the physiological role of estrogens and the several potential health benefits of phytoestrogens, with particular attention given to the possible role of phytoestrogens in aging.
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Affiliation(s)
- Ilaria Ceccarelli
- Department Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Lucia Bioletti
- Department Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Sofia Peparini
- Department Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Erminia Solomita
- Department Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Comasia Ricci
- Department Life Sciences, University of Siena, Siena, Italy
| | - Ilenia Casini
- Department Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Elisangela Miceli
- Department Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
| | - Anna Maria Aloisi
- Department Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
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Contribution of Infectious Agents to the Development of Celiac Disease. Microorganisms 2021; 9:microorganisms9030547. [PMID: 33800833 PMCID: PMC8001938 DOI: 10.3390/microorganisms9030547] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Revised: 02/28/2021] [Accepted: 03/02/2021] [Indexed: 02/07/2023] Open
Abstract
The ingestion of wheat gliadin (alcohol-soluble proteins, an integral part of wheat gluten) and related proteins induce, in genetically predisposed individuals, celiac disease (CD), which is characterized by immune-mediated impairment of the small intestinal mucosa. The lifelong omission of gluten and related grain proteins, i.e., a gluten-free diet (GFD), is at present the only therapy for CD. Although a GFD usually reduces CD symptoms, it does not entirely restore the small intestinal mucosa to a fully healthy state. Recently, the participation of microbial components in pathogenetic mechanisms of celiac disease was suggested. The present review provides information on infectious diseases associated with CD and the putative role of infections in CD development. Moreover, the involvement of the microbiota as a factor contributing to pathological changes in the intestine is discussed. Attention is paid to the mechanisms by which microbes and their components affect mucosal immunity, including tolerance to food antigens. Modulation of microbiota composition and function and the potential beneficial effects of probiotics in celiac disease are discussed.
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Splichalova A, Donovan SM, Tlaskalova-Hogenova H, Stranak Z, Splichalova Z, Splichal I. Monoassociation of Preterm Germ-Free Piglets with Bifidobacterium animalis Subsp. lactis BB-12 and Its Impact on Infection with Salmonella Typhimurium. Biomedicines 2021; 9:biomedicines9020183. [PMID: 33670419 PMCID: PMC7917597 DOI: 10.3390/biomedicines9020183] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 02/05/2021] [Accepted: 02/06/2021] [Indexed: 02/06/2023] Open
Abstract
Preterm germ-free piglets were monoassociated with probiotic Bifidobacterium animalis subsp. lactis BB-12 (BB12) to verify its safety and to investigate possible protection against subsequent infection with Salmonella Typhimurium strain LT2 (LT2). Clinical signs of salmonellosis, bacterial colonization in the intestine, bacterial translocation to mesenteric lymph nodes (MLN), blood, liver, spleen, and lungs, histopathological changes in the ileum, claudin-1 and occludin mRNA expression in the ileum and colon, intestinal and plasma concentrations of IL-8, TNF-α, and IL-10 were evaluated. Both BB12 and LT2 colonized the intestine of the monoassociated piglets. BB12 did not translocate in the BB12-monoassociated piglets. BB12 was detected in some cases in the MLN of piglets, consequently infected with LT2, but reduced LT2 counts in the ileum and liver of these piglets. LT2 damaged the luminal structure of the ileum, but a previous association with BB12 mildly alleviated these changes. LT2 infection upregulated claudin-1 mRNA in the ileum and colon and downregulated occludin mRNA in the colon. Infection with LT2 increased levels of IL-8, TNF-α, and IL-10 in the intestine and plasma, and BB12 mildly downregulated them compared to LT2 alone. Despite reductions in bacterial translocation and inflammatory cytokines, clinical signs of LT2 infection were not significantly affected by the probiotic BB12. Thus, we hypothesize that multistrain bacterial colonization of preterm gnotobiotic piglets may be needed to enhance the protective effect against the infection with S. Typhimurium LT2.
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Affiliation(s)
- Alla Splichalova
- Laboratory of Gnotobiology, Institute of Microbiology, Czech Academy of Sciences, 549 22 Novy Hradek, Czech Republic; (A.S.); (Z.S.)
| | - Sharon M. Donovan
- Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801, USA;
| | - Helena Tlaskalova-Hogenova
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, 142 20 Prague, Czech Republic;
| | - Zbynek Stranak
- Department of Neonatology, Institute for the Care of Mother and Child, 147 00 Prague, Czech Republic;
| | - Zdislava Splichalova
- Laboratory of Gnotobiology, Institute of Microbiology, Czech Academy of Sciences, 549 22 Novy Hradek, Czech Republic; (A.S.); (Z.S.)
| | - Igor Splichal
- Laboratory of Gnotobiology, Institute of Microbiology, Czech Academy of Sciences, 549 22 Novy Hradek, Czech Republic; (A.S.); (Z.S.)
- Correspondence: ; Tel.: +420-491-418-539
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13
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Gorlé N, Bauwens E, Haesebrouck F, Smet A, Vandenbroucke RE. Helicobacter and the Potential Role in Neurological Disorders: There Is More Than Helicobacter pylori. Front Immunol 2021; 11:584165. [PMID: 33633723 PMCID: PMC7901999 DOI: 10.3389/fimmu.2020.584165] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 12/04/2020] [Indexed: 12/17/2022] Open
Abstract
Trillions of symbiotic microbial cells colonize our body, of which the larger part is present in the human gut. These microbes play an essential role in our health and a shift in the microbiome is linked to several diseases. Recent studies also suggest a link between changes in gut microbiota and neurological disorders. Gut microbiota can communicate with the brain via several routes, together called the microbiome–gut–brain axis: the neuronal route, the endocrine route, the metabolic route and the immunological route. Helicobacter is a genus of Gram-negative bacteria colonizing the stomach, intestine and liver. Several papers show the role of H. pylori in the development and progression of neurological disorders, while hardly anything is known about other Helicobacter species and the brain. We recently reported a high prevalence of H. suis in patients with Parkinson’s disease and showed an effect of a gastric H. suis infection on the mouse brain homeostasis. Here, we discuss the potential role of H. suis in neurological disorders and how it may affect the brain via the microbiome–gut–brain axis.
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Affiliation(s)
- Nina Gorlé
- VIB Center for Inflammation Research, Ghent, Belgium.,Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, Ghent, Belgium
| | - Eva Bauwens
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Freddy Haesebrouck
- Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Annemieke Smet
- Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
| | - Roosmarijn E Vandenbroucke
- VIB Center for Inflammation Research, Ghent, Belgium.,Department of Biomedical Molecular Biology, Faculty of Sciences, Ghent University, Ghent, Belgium
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Severity of Experimental Autoimmune Uveitis Is Reduced by Pretreatment with Live Probiotic Escherichia coli Nissle 1917. Cells 2020; 10:cells10010023. [PMID: 33375578 PMCID: PMC7823395 DOI: 10.3390/cells10010023] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 12/16/2020] [Accepted: 12/22/2020] [Indexed: 02/07/2023] Open
Abstract
Non-infectious uveitis is considered an autoimmune disease responsible for a significant burden of blindness in developed countries and recent studies have linked its pathogenesis to dysregulation of the gut microbiota. We tested the immunomodulatory properties of two probiotics, Escherichia coli Nissle 1917 (EcN) and E. coli O83:K24:H31 (EcO), in a model of experimental autoimmune uveitis (EAU). To determine the importance of bacterial viability and treatment timing, mice were orally treated with live or autoclaved bacteria in both preventive and therapeutic schedules. Disease severity was assessed by ophthalmoscopy and histology, immune phenotypes in mesenteric and cervical lymph nodes were analyzed by flow cytometry and the gut immune environment was analyzed by RT-PCR and/or gut tissue culture. EcN, but not EcO, protected against EAU but only as a live organism and only when administered before or at the time of disease induction. Successful prevention of EAU was accompanied by a decrease in IRBP-specific T cell response in the lymph nodes draining the site of immunization as early as 7 days after the immunization and eye-draining cervical lymph nodes when the eye inflammation became apparent. Furthermore, EcN promoted an anti-inflammatory response in Peyer’s patches, increased gut antimicrobial peptide expression and decreased production of inducible nitric oxide synthase in macrophages. In summary, we show here that EcN controls inflammation in EAU and suggest that probiotics may have a role in regulating the gut–eye axis.
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15
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Lin B, Liu Y, Zhang W, Zou W. Role of diet on intestinal metabolites and appetite control factors in SD rats. Exp Ther Med 2020; 20:2665-2674. [PMID: 32765760 PMCID: PMC7401913 DOI: 10.3892/etm.2020.8993] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Accepted: 05/31/2019] [Indexed: 12/17/2022] Open
Abstract
The present study aimed to investigate changes in the levels of metabolites and appetite control factors caused by different dietary interventions in Sprague Dawley (SD) rats. A total of 35 male SD rats were weaned and immediately randomly assigned to five groups. The control group was given ad libitum access to a normal chow diet, and the other groups received a high-fat diet (FAT group), high-sugar diet, high-fibre or high-protein diet (PRO group) for 4 weeks. The high-fat diet contributed to weight gain and adipose tissue formation, and affected lipid indexed. The FAT group had a higher body weight, Lee's index, adipose mass and glucose tolerance than all of the other groups. The opposite effect was observed in the PRO group. High-performance liquid chromatography revealed that short-chain fatty acid and amino acid formation were affected by the various diets. In addition, differences in the mRNA expression levels of leptin, ghrelin and associated receptors were determined in the gastrointestinal, adipose and hypothalamus tissues. The present study provides further evidence of the role of diet in obesity development and prevention. It also highlights the role of intestinal metabolites and appetite control factor expression in the pathogenesis of obesity in SD rats.
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Affiliation(s)
- Bo Lin
- Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, P.R. China
| | - Yueming Liu
- Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, P.R. China
| | - Wei Zhang
- Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, P.R. China
| | - Wenli Zou
- Department of Nephrology, Zhejiang Provincial People's Hospital, Hangzhou, 310014, P.R. China.,Department of Nephrology, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China
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16
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Skrypnik K, Bogdański P, Schmidt M, Suliburska J. The Effect of Multispecies Probiotic Supplementation on Iron Status in Rats. Biol Trace Elem Res 2019; 192:234-243. [PMID: 30746586 PMCID: PMC6820595 DOI: 10.1007/s12011-019-1658-1] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 01/29/2019] [Indexed: 12/16/2022]
Abstract
A range of interactions between gut microbiota and iron (Fe) metabolism is described. Oral probiotics ameliorate host's iron status. However, this has been proven for single-strain probiotic supplements. Dose-dependence of beneficial probiotic supplementation effect on iron turnover remains unexplored. Our study aimed to investigate the effects of oral multispecies probiotic supplementation in two doses on iron status in rats. Thirty rats were randomized into three groups receiving multispecies probiotic supplement at a daily dose of 2.5 × 109 CFU (PA group, n = 10) and 1 × 1010 CFU (PB group, n = 10) or placebo (KK group, n = 10). After 6 weeks, rats were sacrificed for analysis, blood samples, and organs (the liver, heart, kidneys, spleen, pancreas, femur, testicles, duodenum, and hair) were collected. The total fecal bacteria content was higher in the PB group vs. PA group. Unsaturated iron-binding capacity was higher in the PB group vs. KK group. Serum Fe was lower in both PA and PB vs. KK group. Iron content in the liver was higher in the PB group vs. KK group; in the pancreas, this was higher in the PB group vs. the KK and PA group, and in the duodenum, it was higher in both supplemented groups vs. the KK group. A range of alterations in zinc and copper status and correlations between analyzed parameters were found. Oral multispecies probiotic supplementation exerts dose-independent and beneficial effect on iron bioavailability and duodenal iron absorption in the rat model, induces a dose-independent iron shift from serum and intensifies dose-dependent pancreatic and liver iron uptake.
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Affiliation(s)
- Katarzyna Skrypnik
- Institute of Human Nutrition and Dietetics, Poznan University of Life Sciences, Wojska Polskiego St. 31, 60-624, Poznan, Poland.
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, Szamarzewskiego St. 82/84, 60-569, Poznan, Poland
| | - Marcin Schmidt
- Department of Food Biotechnology and Microbiology, Poznan University of Life Sciences, Wojska Polskiego St. 48, Poznan, 60-627, Poland
| | - Joanna Suliburska
- Institute of Human Nutrition and Dietetics, Poznan University of Life Sciences, Wojska Polskiego St. 31, 60-624, Poznan, Poland
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Abstract
PURPOSE OF REVIEW The goal of the review is to assess the appropriateness of menopausal hormone therapy (MHT) for the primary prevention of bone loss in women at elevated risk in the early years after menopause. RECENT FINDINGS Estrogen alone or combined with progestin to protect the uterus from cancer significantly reduces the risk of osteoporosis-related fractures. MHT increases type 1 collagen production and osteoblast survival and maintains the equilibrium between bone resorption and bone formation by modulating osteoblast/osteocyte and T cell regulation of osteoclasts. Estrogens have positive effects on muscle and cartilage. Estrogen, but not antiresorptive therapies, can attenuate the inflammatory bone-microenvironment associated with estrogen deficiency. However, already on second year of administration, MHT is associated with excess breast cancer risk, increasing steadily with duration of use. MHT should be considered in women with premature estrogen deficiency and increased risk of bone loss and osteoporotic fractures. However, MHT use for the prevention of bone loss is hindered by increase in breast cancer risk even in women younger than 60 years old or who are within 10 years of menopause onset.
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Affiliation(s)
- Jan J Stepan
- Institute of Rheumatology, Prague, Czech Republic.
| | - Hana Hruskova
- Department of Obstetrics and Gynecology, First Faculty of Medicine, Prague, Czech Republic
- Charles University, Prague, Czech Republic
- General University Hospital in Prague, Prague, Czech Republic
| | - Miloslav Kverka
- Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague, Czech Republic
- Institute of Experimental Medicine of the Czech Academy of Sciences, v.v.i., Prague, Czech Republic
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18
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Ben Othman M, Sakamoto K. Effect of inactivated Bifidobacterium longum intake on obese diabetes model mice (TSOD). Food Res Int 2019; 129:108792. [PMID: 32036897 DOI: 10.1016/j.foodres.2019.108792] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 10/28/2019] [Accepted: 10/30/2019] [Indexed: 02/06/2023]
Abstract
Obesity and diabetes have been increasing at an alarming rate worldwide. Studies have shown the futility of chemical drugs in the treatment of obesity and diabetes. Bifidobacterium longum (BL), a common member of the gut microbiota throughout the human lifespan, has been widely reported to play a role in host health and disease. Here, we evaluated the effects of inactivated cells of BL (IBL) on obesity and blood glucose levels in TSOD mice by administering IBL orally for 5 weeks. The treated mice showed a significant decrease of body weight gain, adipose tissue mass and blood glucose levels, as well as a significant reduction in blood glucose during an oral glucose tolerance test. The treatment also resulted in reduced levels of cholesterol, triglycerides, and NEFA. Moreover, serum and urine analysis showed low creatinine levels in IBL-treated mice. These data demonstrate that IBL may have the potential to prevent obesity and diabetes.
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Affiliation(s)
- Mahmoud Ben Othman
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan
| | - Kazuichi Sakamoto
- Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
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Coufal S, Galanova N, Bajer L, Gajdarova Z, Schierova D, Jiraskova Zakostelska Z, Kostovcikova K, Jackova Z, Stehlikova Z, Drastich P, Tlaskalova-Hogenova H, Kverka M. Inflammatory Bowel Disease Types Differ in Markers of Inflammation, Gut Barrier and in Specific Anti-Bacterial Response. Cells 2019; 8:cells8070719. [PMID: 31337064 PMCID: PMC6678638 DOI: 10.3390/cells8070719] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 07/06/2019] [Accepted: 07/11/2019] [Indexed: 12/12/2022] Open
Abstract
Crohn’s disease (CD), ulcerative colitis (UC) and inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC-IBD), share three major pathogenetic mechanisms of inflammatory bowel disease (IBD)-gut dysbiosis, gut barrier failure and immune system dysregulation. While clinical differences among them are well known, the underlying mechanisms are less explored. To gain an insight into the IBD pathogenesis and to find a specific biomarker pattern for each of them, we used protein array, ELISA and flow cytometry to analyze serum biomarkers and specific anti-microbial B and T cell responses to the gut commensals. We found that decrease in matrix metalloproteinase (MMP)-9 and increase in MMP-14 are the strongest factors discriminating IBD patients from healthy subjects and that PSC-IBD patients have higher levels of Mannan-binding lectin, tissue inhibitor of metalloproteinases 1 (TIMP-1), CD14 and osteoprotegerin than patients with UC. Moreover, we found that low transforming growth factor-β1 (TGF-β1) is associated with disease relapse and low osteoprotegerin with anti-tumor necrosis factor-alpha (TNF-α) therapy. Patients with CD have significantly decreased antibody and increased T cell response mainly to genera Eubacterium, Faecalibacterium and Bacteroides. These results stress the importance of the gut barrier function and immune response to commensal bacteria and point at the specific differences in pathogenesis of PSC-IBD, UC and CD.
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Affiliation(s)
- Stepan Coufal
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
| | - Natalie Galanova
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
| | - Lukas Bajer
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
- Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Prague, Czech Republic
| | - Zuzana Gajdarova
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
| | - Dagmar Schierova
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
- Institute of Animal Physiology and Genetics of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
| | | | - Klara Kostovcikova
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
| | - Zuzana Jackova
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
| | - Zuzana Stehlikova
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
| | - Pavel Drastich
- Institute for Clinical and Experimental Medicine, Videnska 1958/9, 140 21 Prague, Czech Republic
| | - Helena Tlaskalova-Hogenova
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic
| | - Miloslav Kverka
- Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
- Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
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Roubalová R, Procházková P, Papežová H, Smitka K, Bilej M, Tlaskalová-Hogenová H. Anorexia nervosa: Gut microbiota-immune-brain interactions. Clin Nutr 2019; 39:676-684. [PMID: 30952533 DOI: 10.1016/j.clnu.2019.03.023] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 03/14/2019] [Accepted: 03/18/2019] [Indexed: 12/14/2022]
Abstract
Anorexia nervosa is a psychiatric disorder defined by an extremely low body weight, a devastating fear of weight gain, and body image disturbance, however the etiopathogenesis remains unclear. The objective of the article is to provide a comprehensive review on the potential role of gut microbiota in pathogenesis of anorexia nervosa. Recent advances in sequencing techniques used for microbial detection revealed that this disease is associated with disruption of the composition of normal gut microbiota (dysbiosis), manifested by low microbial diversity and taxonomic differences as compared to healthy individuals. Microorganisms present in the gut represent a part of the so called "microbiota-gut-brain" axis that affect the central nervous system and thus human behavior via the production of various neuroactive compounds. In addition, cells of the immune system are equipped with receptors for these neuroactive substances. Microbiota of the intestinal system also represent a very important antigenic source. These antigens can mimic some host neuropeptides and neurohormones and thus trigger the production of autoantibodies which cross-react with these compounds. The levels and affinities of these antibodies are thought to be associated with neuropsychiatric conditions including anxiety, depression, and eating and sleep disorders. The study of microbiota function in diseases could bring new insights to the pathogenetic mechanisms.
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Affiliation(s)
- Radka Roubalová
- Institute of Microbiology, Czech Academy of Sciences, Videnska 1083, Prague 4, Czech Republic.
| | - Petra Procházková
- Institute of Microbiology, Czech Academy of Sciences, Videnska 1083, Prague 4, Czech Republic
| | - Hana Papežová
- Department of Psychiatry, First Faculty of Medicine, Charles University and General University Hospital in Prague, Ke Karlovu 11, Prague 2, Czech Republic
| | - Kvido Smitka
- The Institute of Physiology, First Faculty of Medicine, Charles University, Albertov 5, Prague 2, Czech Republic
| | - Martin Bilej
- Institute of Microbiology, Czech Academy of Sciences, Videnska 1083, Prague 4, Czech Republic
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The role of microbiota in the pathogenesis of lupus: Dose it impact lupus nephritis? Pharmacol Res 2019; 139:191-198. [DOI: 10.1016/j.phrs.2018.11.023] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Revised: 11/14/2018] [Accepted: 11/15/2018] [Indexed: 02/06/2023]
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Roselli M, Finamore A, Brasili E, Rami R, Nobili F, Orsi C, Zambrini AV, Mengheri E. Beneficial effects of a selected probiotic mixture administered to high fat-fed mice before and after the development of obesity. J Funct Foods 2018. [DOI: 10.1016/j.jff.2018.03.039] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Skrypnik K, Suliburska J. Association between the gut microbiota and mineral metabolism. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2018; 98:2449-2460. [PMID: 28991359 DOI: 10.1002/jsfa.8724] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Revised: 08/23/2017] [Accepted: 09/27/2017] [Indexed: 06/07/2023]
Abstract
The aim of this review is to present the most recent scientific evidence of interactions between the intestinal microbiota and minerals, and the effect of this interaction on the health of the host. The Web of Science database from the years 2013-2017 on this topic was reviewed. Numerous in vitro studies have shown that iron significantly affects the intestinal microbiota. However, Bifidobacteriaceae are capable of binding iron in the large intestine, thereby limiting the formation of free radicals synthesized in the presence of iron, and thus reducing the risk of colorectal cancer. Animal studies have revealed that supplementation with probiotics, prebiotics and synbiotics has a significant effect on bone calcium, phosphate and bone metabolism. The dynamic interaction between microbiota and zinc was shown. Human studies have provided evidence of the influence of probiotic bacteria on parathormone, calcium and phosphate levels and thus on bone resorption. Recent studies have produced new information mainly on the impact of the intestinal bacteria on the metabolism of calcium and iron. From a scientific perspective, the most urgent fields that remain to be investigated are the identification of all human gut microbes and new therapies targeting the interaction between intestinal bacteria and minerals. © 2017 Society of Chemical Industry.
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Affiliation(s)
- Katarzyna Skrypnik
- Institute of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań, Poland
| | - Joanna Suliburska
- Institute of Human Nutrition and Dietetics, Poznań University of Life Sciences, Poznań, Poland
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24
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The role of gut microbiota in the pathogenesis of rheumatic diseases. Clin Rheumatol 2017; 37:25-34. [PMID: 28914372 DOI: 10.1007/s10067-017-3821-4] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Revised: 08/31/2017] [Accepted: 09/04/2017] [Indexed: 01/08/2023]
Abstract
Rheumatic diseases refer to many diseases with a loss of immune self-tolerance, leading to a chronic inflammation, degeneration, or metabolic derangement in multiple organs or tissues. The cause of rheumatic diseases remains to be elucidated, though both environmental and genetic factors are required for the development of rheumatic diseases. Over the past decades, emerging studies suggested that alteration of intestinal microbiota, known as gut dysbiosis, contributed to the occurrence or development of a range of rheumatic diseases, including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, systemic sclerosis, and Sjogren's syndrome, through profoundly affecting the balance between pro- and anti-inflammatory immune responses. In this article, we discussed the role of gut microbiota in the pathogenesis of rheumatic diseases based on a large number of experimental and clinical materials, thereby providing a new insight for microbiota-targeted therapies to prevent or cure rheumatic diseases.
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25
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Parenteral Nutrition-Associated Liver Disease: The Role of the Gut Microbiota. Nutrients 2017; 9:nu9090987. [PMID: 28880224 PMCID: PMC5622747 DOI: 10.3390/nu9090987] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 08/28/2017] [Accepted: 08/30/2017] [Indexed: 02/07/2023] Open
Abstract
Parenteral nutrition (PN) provides life-saving nutritional support in situations where caloric supply via the enteral route cannot cover the necessary needs of the organism. However, it does have serious adverse effects, including parenteral nutrition-associated liver disease (PNALD). The development of liver injury associated with PN is multifactorial, including non-specific intestine inflammation, compromised intestinal permeability, and barrier function associated with increased bacterial translocation, primary and secondary cholangitis, cholelithiasis, short bowel syndrome, disturbance of hepatobiliary circulation, lack of enteral nutrition, shortage of some nutrients (proteins, essential fatty acids, choline, glycine, taurine, carnitine, etc.), and toxicity of components within the nutrition mixture itself (glucose, phytosterols, manganese, aluminium, etc.). Recently, an increasing number of studies have provided evidence that some of these factors are directly or indirectly associated with microbial dysbiosis in the intestine. In this review, we focus on PN-induced changes in the taxonomic and functional composition of the microbiome. We also discuss immune cell and microbial crosstalk during parenteral nutrition, and the implications for the onset and progression of PNALD. Finally, we provide an overview of recent advances in the therapeutic utilisation of pro- and prebiotics for the mitigation of PN-associated liver complications.
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Park AM, Omura S, Fujita M, Sato F, Tsunoda I. Helicobacter pylori and gut microbiota in multiple sclerosis versus Alzheimer's disease: 10 pitfalls of microbiome studies. CLINICAL & EXPERIMENTAL NEUROIMMUNOLOGY 2017; 8:215-232. [PMID: 29158778 PMCID: PMC5693366 DOI: 10.1111/cen3.12401] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Alteration of microbiota has been associated with intestinal, inflammatory, and neurological diseases. Abundance of "good bacteria" such as Bifidobacterium, or their products have been generally believed to be beneficial for any diseases, while "bad bacteria" such as pathogenic Helicobacter pylori are assumed to be always detrimental for hosts. However, this is not the case when we compare and contrast the association of the gut microbiota with two neurological diseases, multiple sclerosis (MS) and Alzheimer's disease (AD). Following H. pylori infection, pro-inflammatory T helper (Th)1 and Th17 immune response are initially induced to eradicate bacteria. However, H. pylori evades the host immune response by inducing Th2 cells and regulatory T cells (Tregs) that produce anti-inflammatory interleukin (IL)-10. Suppression of anti-bacterial Th1/Th17 cells by Tregs may enhance gastric H. pylori propagation, followed by a cascade reaction involving vitamin B12 and folic acid malabsorption, plasma homocysteine elevation, and reactive oxygen species induction. This can damage the blood-brain barrier (BBB), leading to accumulation of amyloid-β in the brain, a hallmark of AD. On the other hand, this suppression of pro-inflammatory Th1/Th17 responses to H. pylori has protective effects on the hosts, since it prevents uncontrolled gastritis as well as suppresses the induction of encephalitogenic Th1/Th17 cells, which can mediate neuroinflammation in MS. The above scenario may explain why chronic H. pylori infection is positively associated with AD, while it is negatively associated with MS. Lastly, we list "10 pitfalls of microbiota studies", which will be useful for evaluating and designing clinical and experimental microbiota studies.
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Affiliation(s)
- Ah-Mee Park
- Corresponding author: Ah-Mee Park, Ph.D. and Ikuo Tsunoda, M.D., Ph.D., Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan, Tel: +81-72-366-0221, , ,
| | | | - Mitsugu Fujita
- Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan
| | - Fumitaka Sato
- Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan
| | - Ikuo Tsunoda
- Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan
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Bajer L, Kverka M, Kostovcik M, Macinga P, Dvorak J, Stehlikova Z, Brezina J, Wohl P, Spicak J, Drastich P. Distinct gut microbiota profiles in patients with primary sclerosing cholangitis and ulcerative colitis. World J Gastroenterol 2017; 23:4548-4558. [PMID: 28740343 PMCID: PMC5504370 DOI: 10.3748/wjg.v23.i25.4548] [Citation(s) in RCA: 258] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 04/10/2017] [Accepted: 06/01/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC).
METHODS Stool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with (n = 32) or without (n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low taxonomic levels. Data were further processed in QIIME employing MaAsLin and LEfSe tools for analysis of the output data.
RESULTS Microbial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease (IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales.
CONCLUSION PSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes (PSC-IBD and UC).
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