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Calvez V, Puca P, Di Vincenzo F, Del Gaudio A, Bartocci B, Murgiano M, Iaccarino J, Parand E, Napolitano D, Pugliese D, Gasbarrini A, Scaldaferri F. Novel Insights into the Pathogenesis of Inflammatory Bowel Diseases. Biomedicines 2025; 13:305. [PMID: 40002718 PMCID: PMC11853239 DOI: 10.3390/biomedicines13020305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 01/17/2025] [Accepted: 01/21/2025] [Indexed: 02/27/2025] Open
Abstract
Inflammatory bowel diseases (IBDs), encompassing Crohn's disease and ulcerative colitis, are complex chronic disorders characterized by an intricate interplay between genetic predisposition, immune dysregulation, gut microbiota alterations, and environmental exposures. This review aims to synthesize recent advances in IBD pathogenesis, exploring key mechanisms and potential avenues for prevention and personalized therapy. A comprehensive literature search was conducted across major bibliographic databases, selecting the most recent and impactful studies on IBD pathogenesis. The review integrates findings from multi-omics analyses, single-cell transcriptomics, and longitudinal cohort studies, focusing on immune regulation, gut microbiota dynamics, and environmental factors influencing disease onset and progression. Immune dysregulation, including macrophage polarization (M1 vs. M2) and Th17 activation, emerges as a cornerstone of IBD pathogenesis. Dysbiosis, as a result of reduced alpha and beta diversity and overgrowth of harmful taxa, is one of the main contributing factors in causing inflammation in IBD. Environmental factors, including air and water pollutants, maternal smoking, and antibiotic exposure during pregnancy and infancy, significantly modulate IBD risk through epigenetic and microbiota-mediated mechanisms. While recent advances have supported the development of new therapeutic strategies, deeply understanding the complex dynamics of IBD pathogenesis remains challenging. Future efforts should aim to reduce the burden of disease with precise, personalized treatments and lower the incidence of IBD through early-life prevention and targeted interventions addressing modifiable risk factors.
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Affiliation(s)
- Valentin Calvez
- IBD Unit, UOC CEMAD Medicina Interna e Gastroenterologia, Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (V.C.); (P.P.); (D.N.); (D.P.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
| | - Pierluigi Puca
- IBD Unit, UOC CEMAD Medicina Interna e Gastroenterologia, Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (V.C.); (P.P.); (D.N.); (D.P.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
| | - Federica Di Vincenzo
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
| | - Angelo Del Gaudio
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
| | - Bianca Bartocci
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
| | - Marco Murgiano
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
| | - Jacopo Iaccarino
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
| | - Erfan Parand
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
| | - Daniele Napolitano
- IBD Unit, UOC CEMAD Medicina Interna e Gastroenterologia, Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (V.C.); (P.P.); (D.N.); (D.P.)
| | - Daniela Pugliese
- IBD Unit, UOC CEMAD Medicina Interna e Gastroenterologia, Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (V.C.); (P.P.); (D.N.); (D.P.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
| | - Antonio Gasbarrini
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
| | - Franco Scaldaferri
- IBD Unit, UOC CEMAD Medicina Interna e Gastroenterologia, Centro Malattie dell’Apparato Digerente, Dipartimento di Scienze Mediche e Chirurgiche Addominali ed Endocrino Metaboliche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (V.C.); (P.P.); (D.N.); (D.P.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (F.D.V.); (A.D.G.); (B.B.); (M.M.); (J.I.); (E.P.); (A.G.)
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Covello C, Becherucci G, Di Vincenzo F, Del Gaudio A, Pizzoferrato M, Cammarota G, Gasbarrini A, Scaldaferri F, Mentella MC. Parenteral Nutrition, Inflammatory Bowel Disease, and Gut Barrier: An Intricate Plot. Nutrients 2024; 16:2288. [PMID: 39064731 PMCID: PMC11279609 DOI: 10.3390/nu16142288] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Revised: 07/14/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Malnutrition poses a critical challenge in inflammatory bowel disease, with the potential to detrimentally impact medical treatment, surgical outcomes, and general well-being. Parenteral nutrition is crucial in certain clinical scenarios, such as with patients suffering from short bowel syndrome, intestinal insufficiency, high-yielding gastrointestinal fistula, or complete small bowel obstruction, to effectively manage malnutrition. Nevertheless, research over the years has attempted to define the potential effects of parenteral nutrition on the intestinal barrier and the composition of the gut microbiota. In this narrative review, we have gathered and analyzed findings from both preclinical and clinical studies on this topic. Based on existing evidence, there is a clear correlation between short- and long-term parenteral nutrition and negative effects on the intestinal system. These include mucosal atrophic damage and immunological and neuroendocrine dysregulation, as well as alterations in gut barrier permeability and microbiota composition. However, the mechanistic role of these changes in inflammatory bowel disease remains unclear. Therefore, further research is necessary to effectively address the numerous gaps and unanswered questions pertaining to these issues.
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Affiliation(s)
- Carlo Covello
- Gastroenterology Department, Centro di Malattie dell’Apparato Digerente (CEMAD), Center for Diagnosis and Treatment of Digestive Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (C.C.); (F.D.V.); (A.D.G.); (A.G.)
| | - Guia Becherucci
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (G.B.); (F.S.)
| | - Federica Di Vincenzo
- Gastroenterology Department, Centro di Malattie dell’Apparato Digerente (CEMAD), Center for Diagnosis and Treatment of Digestive Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (C.C.); (F.D.V.); (A.D.G.); (A.G.)
| | - Angelo Del Gaudio
- Gastroenterology Department, Centro di Malattie dell’Apparato Digerente (CEMAD), Center for Diagnosis and Treatment of Digestive Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (C.C.); (F.D.V.); (A.D.G.); (A.G.)
| | - Marco Pizzoferrato
- UOC Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (M.P.); (G.C.)
| | - Giovanni Cammarota
- UOC Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (M.P.); (G.C.)
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Gastroenterology Department, Centro di Malattie dell’Apparato Digerente (CEMAD), Center for Diagnosis and Treatment of Digestive Diseases, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (C.C.); (F.D.V.); (A.D.G.); (A.G.)
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Franco Scaldaferri
- UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell’Apparato Digerente (CEMAD), Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy; (G.B.); (F.S.)
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Maria Chiara Mentella
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- UOC di Nutrizione Clinica, Dipartimento Scienze Mediche e Chirurgiche Addominali ed Endocrino-Metaboliche, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
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Agrawal G, Borody TJ, Aitken JM. Mapping Crohn's Disease Pathogenesis with Mycobacterium paratuberculosis: A Hijacking by a Stealth Pathogen. Dig Dis Sci 2024; 69:2289-2303. [PMID: 38896362 DOI: 10.1007/s10620-024-08508-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 05/21/2024] [Indexed: 06/21/2024]
Abstract
Mycobacterium avium ssp. paratuberculosis (MAP) has been implicated in the development of Crohn's disease (CD) for over a century. Similarities have been noted between the (histo)pathological presentation of MAP in ruminants, termed Johne's disease (JD), and appearances in humans with CD. Analyses of disease presentation and pathology suggest a multi-step process occurs that consists of MAP infection, dysbiosis of the gut microbiome, and dietary influences. Each step has a role in the disease development and requires a better understanding to implementing combination therapies, such as antibiotics, vaccination, faecal microbiota transplants (FMT) and dietary plans. To optimise responses, each must be tailored directly to the activity of MAP, otherwise therapies are open to interpretation without microbiological evidence that the organism is present and has been influenced. Microscopy and histopathology enables studies of the mycobacterium in situ and how the associated disease processes manifest in the patient e.g., granulomas, fissuring, etc. The challenge for researchers has been to prove the relationship between MAP and CD with available laboratory tests and methodologies, such as polymerase chain reaction (PCR), MAP-associated DNA sequences and bacteriological culture investigations. These have, so far, been inconclusive in revealing the relationship of MAP in patients with CD. Improved and accurate methods of detection will add to evidence for an infectious aetiology of CD. Specifically, if the bacterial pathogen can be isolated, identified and cultivated, then causal relationships to disease can be confirmed, especially if it is present in human gut tissue. This review discusses how MAP may cause the inflammation seen in CD by relating its known pathogenesis in cattle, and from examples of other mycobacterial infections in humans, and how this would impact upon the difficulties with diagnostic tests for the organism.
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Affiliation(s)
- Gaurav Agrawal
- Division of Diabetes & Nutritional Sciences, King's College London, Franklin-Wilkins Building, London, SE1 9NH, UK.
- , Sydney, Australia.
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Mizzi R, Plain KM, Timms VJ, Marsh I, Whittington RJ. Characterisation of IS1311 in Mycobacterium avium subspecies paratuberculosis genomes: Typing, continental clustering, microbial evolution and host adaptation. PLoS One 2024; 19:e0294570. [PMID: 38349924 PMCID: PMC10863896 DOI: 10.1371/journal.pone.0294570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 11/04/2023] [Indexed: 02/15/2024] Open
Abstract
Johne's disease (JD), caused by Mycobacterium avium subspecies paratuberculosis (MAP) is a global burden for livestock producers and has an association with Crohn's disease in humans. Within MAP there are two major lineages, S/Type I/TypeIII and C/Type II, that vary in phenotype including culturability, host preference and virulence. These lineages have been identified using the IS1311 element, which contains a conserved, single nucleotide polymorphism. IS1311 and the closely related IS1245 element belong to the IS256 family of insertion sequences, are dispersed throughout M. avium taxa but remain poorly characterised. To investigate the distribution and diversity of IS1311 in MAP, 805 MAP genomes were collated from public databases. IS1245 was absent, while IS1311 sequence, copy number and insertion loci were conserved between MAP S lineages and varied within the MAP C lineage. One locus was specific to the S strains, which contained nine IS1311 copies. In contrast, C strains contained either seven or eight IS1311 loci. Most insertion loci were associated with the boundaries of homologous regions that had undergone genome rearrangement between the MAP lineages, suggesting that this sequence may be a driver of recombination. Phylogenomic geographic clustering of MAP subtypes was demonstrated for the first time, at continental scale, and indicated that there may have been recent MAP transmission between Europe and North America, in contrast to Australia where importation of live ruminants is generally prohibited. This investigation confirmed the utility of IS1311 typing in epidemiological studies and resolved anomalies in past studies. The results shed light on potential mechanisms of niche/host adaptation, virulence of MAP and global transmission dynamics.
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Affiliation(s)
- Rachel Mizzi
- School of Veterinary Science, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia
| | - Karren M. Plain
- School of Veterinary Science, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia
| | - Verlaine J. Timms
- Neilan Laboratory of Microbial and Molecular Diversity, College of Engineering, Science and Environment, The University of Newcastle, New South Wales, Australia
| | - Ian Marsh
- Microbiology and Parasitology Research, Elizabeth Macarthur Agricultural Institute, Menangle, New South Wales, Australia
| | - Richard J. Whittington
- School of Veterinary Science, Faculty of Science, The University of Sydney, Sydney, New South Wales, Australia
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Aitken JM, Aitken JE, Agrawal G. Mycobacterium avium ssp. paratuberculosis and Crohn's Disease-Diagnostic Microbiological Investigations Can Inform New Therapeutic Approaches. Antibiotics (Basel) 2024; 13:158. [PMID: 38391544 PMCID: PMC10886072 DOI: 10.3390/antibiotics13020158] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 01/24/2024] [Accepted: 02/03/2024] [Indexed: 02/24/2024] Open
Abstract
Mycobacterium avium ssp. paratuberculosis (MAP) is the cause of Johne's disease (JD), which is a chronic infectious gastrointestinal disease of ruminants and is often fatal. In humans, MAP has been associated with Crohn's disease (CD) for over a century, without conclusive evidence of pathogenicity. Numerous researchers have contributed to the subject, but there is still a need for evidence of the causation of CD by MAP. An infectious aetiology in CD that is attributable to MAP can only be proven by bacteriological investigations. There is an urgency in resolving this question due to the rising global incidence rates of CD. Recent papers have indicated the "therapeutic ceiling" may be close in the development of new biologics. Clinical trial outcomes have demonstrated mild or inconsistent improvements in therapeutic interventions over the last decades when compared with placebo. The necessity to revisit therapeutic options for CD is becoming more urgent and a renewed focus on causation is essential for progress in identifying new treatment options. This manuscript discusses newer interventions, such as vaccination, FMT, dietary remediation and gut microbiome regulation, that will become more relevant as existing therapeutic options expire. Revisiting the MAP theory as a potential infectious cause of CD, rather than the prevailing concept of an "aberrant immune response" will require expanding the current therapeutic programme to include potential new alternatives, and combinations of existing treatments. To advance research on MAP in humans, it is essential for microbiologists and medical scientists to microscopically detect CWDM and to biologically amplify the growth by directed culture.
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Affiliation(s)
- John M Aitken
- Otakaro Pathways Ltd., Innovation Park, Christchurch 7675, New Zealand
| | - Jack E Aitken
- Otakaro Pathways Ltd., Innovation Park, Christchurch 7675, New Zealand
| | - Gaurav Agrawal
- Division of Diabetes & Nutritional Sciences, Franklin-Wilkins Building, King's College London, London SE1 9NH, UK
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Ferreira AV, Alarcon-Barrera JC, Domínguez-Andrés J, Bulut Ö, Kilic G, Debisarun PA, Röring RJ, Özhan HN, Terschlüsen E, Ziogas A, Kostidis S, Mohammed Y, Matzaraki V, Renieris G, Giamarellos-Bourboulis EJ, Netea MG, Giera M. Fatty acid desaturation and lipoxygenase pathways support trained immunity. Nat Commun 2023; 14:7385. [PMID: 37968313 PMCID: PMC10651900 DOI: 10.1038/s41467-023-43315-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 11/06/2023] [Indexed: 11/17/2023] Open
Abstract
Infections and vaccines can induce enhanced long-term responses in innate immune cells, establishing an innate immunological memory termed trained immunity. Here, we show that monocytes with a trained immunity phenotype, due to exposure to the Bacillus Calmette-Guérin (BCG) vaccine, are characterized by an increased biosynthesis of different lipid mediators (LM) derived from long-chain polyunsaturated fatty acids (PUFA). Pharmacological and genetic approaches show that long-chain PUFA synthesis and lipoxygenase-derived LM are essential for the BCG-induced trained immunity responses of human monocytes. Furthermore, products of 12-lipoxygenase activity increase in monocytes of healthy individuals after BCG vaccination. Grasping the underscoring lipid metabolic pathways contributes to our understanding of trained immunity and may help to identify therapeutic tools and targets for the modulation of innate immune responses.
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Affiliation(s)
- Anaísa V Ferreira
- Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands.
- Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, 4050-313, Porto, Portugal.
| | | | - Jorge Domínguez-Andrés
- Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands
| | - Özlem Bulut
- Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands
| | - Gizem Kilic
- Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands
| | - Priya A Debisarun
- Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands
| | - Rutger J Röring
- Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands
| | - Hatice N Özhan
- Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands
| | - Eva Terschlüsen
- Department of Medical Microbiology, Radboud University Medical Centre, 6500HB, Nijmegen, The Netherlands
| | - Athanasios Ziogas
- Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands
| | - Sarantos Kostidis
- Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333ZA, Leiden, the Netherlands
| | - Yassene Mohammed
- Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333ZA, Leiden, the Netherlands
| | - Vasiliki Matzaraki
- Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands
| | - George Renieris
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece
| | | | - Mihai G Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Center, 6500HB, Nijmegen, The Netherlands
- Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115, Bonn, Germany
| | - Martin Giera
- Center for Proteomics and Metabolomics, Leiden University Medical Center, 2333ZA, Leiden, the Netherlands.
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Najafpour R, Zolfaghari MR, Mosavari N, Nazari R, Tadayon K. More insights about genomic population structure of Mycobacterium avium subspecies paratuberculosis (Map) from multiple hosts in west and central provinces of Iran using a boosted genotyping approach. Comp Immunol Microbiol Infect Dis 2023; 100:101912. [PMID: 37487314 DOI: 10.1016/j.cimid.2022.101912] [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: 08/11/2022] [Revised: 11/05/2022] [Accepted: 11/09/2022] [Indexed: 11/13/2022]
Abstract
To investigate the population genetic of Mycobacterium avium subsp. paratuberculosis (Map) in Iran, Mycobacterial Interspersed Repetitive Units (MIRUs) and Multi Locus Short Sequence Repeat (MLSSR) system were employed. Numerous genotypes by MIRU (N = 11) and MLSSR (N = 9) methods bearing discriminatory indices of 0.90 and 0.79 respectively, were obtained. Browsing the INRA-Nouzilly list (http://mac-inmv.tours.inra.fr/) detected 3 of the found patterns as new types. Some loci either MIRU-VNTR or SSR proved more polymorphic and therefore are recommended to be applied in priority for strain typing in the Iranian environment. While identical MIRU-VNTR or MLSSR patterns were detected among different conspecifics and geographical locations, dissimilar types were also observed at the same farms an indication of coexistence of Map strains within one herd. We suggest extension of the genotyping work described here to include more endogenous isolates in order to better analysis of transmission and virulence in epidemiology and control of paratuberculosis.
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Affiliation(s)
- Reza Najafpour
- Department of Microbiology, Faculty of Basic Science, Qom Branch, Islamic Azad University, Qom, Iran
| | - Mohammad Reza Zolfaghari
- Department of Microbiology, Faculty of Basic Science, Qom Branch, Islamic Azad University, Qom, Iran.
| | - Nader Mosavari
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Bovine Tuberculosis Laboratory, Tuberculin and Mallein Research & Production Department, Karaj, Iran
| | - Razieh Nazari
- Department of Microbiology, Faculty of Basic Science, Qom Branch, Islamic Azad University, Qom, Iran
| | - Keyvan Tadayon
- Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Veterinary, Aerobic Bacteria Vaccines Department, Karaj, Iran.
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Triantaphyllopoulos KA. Long Non-Coding RNAs and Their "Discrete" Contribution to IBD and Johne's Disease-What Stands out in the Current Picture? A Comprehensive Review. Int J Mol Sci 2023; 24:13566. [PMID: 37686376 PMCID: PMC10487966 DOI: 10.3390/ijms241713566] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/23/2023] [Accepted: 08/27/2023] [Indexed: 09/10/2023] Open
Abstract
Non-coding RNAs (ncRNA) have paved the way to new perspectives on the regulation of gene expression, not only in biology and medicine, but also in associated fields and technologies, ensuring advances in diagnostic means and therapeutic modalities. Critical in this multistep approach are the associations of long non-coding RNA (lncRNA) with diseases and their causal genes in their networks of interactions, gene enrichment and expression analysis, associated pathways, the monitoring of the involved genes and their functional roles during disease progression from one stage to another. Studies have shown that Johne's Disease (JD), caused by Mycobacterium avium subspecies partuberculosis (MAP), shares common lncRNAs, clinical findings, and other molecular entities with Crohn's Disease (CD). This has been a subject of vigorous investigation owing to the zoonotic nature of this condition, although results are still inconclusive. In this review, on one hand, the current knowledge of lncRNAs in cells is presented, focusing on the pathogenesis of gastrointestinal-related pathologies and MAP-related infections and, on the other hand, we attempt to dissect the associated genes and pathways involved. Furthermore, the recently characterized and novel lncRNAs share common pathologies with IBD and JD, including the expression, molecular networks, and dataset analysis results. These are also presented in an attempt to identify potential biomarkers pertinent to cattle and human disease phenotypes.
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Affiliation(s)
- Kostas A Triantaphyllopoulos
- Department of Biotechnology, School of Applied Biology and Biotechnology, Agricultural University of Athens, 75 Iera Odos St., 11855 Athens, Greece
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Wiredu Ocansey DK, Hang S, Yuan X, Qian H, Zhou M, Valerie Olovo C, Zhang X, Mao F. The diagnostic and prognostic potential of gut bacteria in inflammatory bowel disease. Gut Microbes 2023; 15:2176118. [PMID: 36794838 PMCID: PMC9980661 DOI: 10.1080/19490976.2023.2176118] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 01/26/2023] [Indexed: 02/17/2023] Open
Abstract
The gut microbiome serves as a signaling hub that integrates environmental inputs with genetic and immune signals to influence the host's metabolism and immunity. Gut bacteria are intricately connected with human health and disease state, with specific bacteria species driving the characteristic dysbiosis found in gastrointestinal conditions such as inflammatory bowel disease (IBD); thus, gut bacteria changes could be harnessed to improve IBD diagnosis, prognosis, and treatment. The advancement in next-generation sequencing techniques such as 16S rRNA and whole-genome shotgun sequencing has allowed the exploration of the complexity of the gut microbial ecosystem with high resolution. Current microbiome data is promising and appears to perform better in some studies than the currently used fecal inflammation biomarker, calprotectin, in predicting IBD from healthy controls and irritable bowel syndrome (IBS). This study reviews current data on the differential potential of gut bacteria within IBD cohorts, and between IBD and other gastrointestinal diseases.
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Affiliation(s)
- Dickson Kofi Wiredu Ocansey
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, P.R. China
- Directorate of University Health Services, University of Cape Coast, PMB, Cape Coast, Ghana
| | - Sanhua Hang
- The People’s Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Zhenjiang, P.R. China
| | - Xinyi Yuan
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, P.R. China
| | - Hua Qian
- Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, P.R. China
| | - Mengjiao Zhou
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, P.R. China
| | - Chinasa Valerie Olovo
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, P.R. China
- Department of Microbiology, University of Nigeria, Nsukka, Nigeria
| | - Xu Zhang
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, P.R. China
| | - Fei Mao
- Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, P.R. China
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10
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Phylogenetic and Multiple-Locus Variable number tandem repeat analysis of Mycobacterium avium subsp. paratuberculosis isolates from Argentina. Vet Res Commun 2022; 46:1121-1129. [PMID: 35948855 DOI: 10.1007/s11259-022-09983-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 08/03/2022] [Indexed: 10/15/2022]
Abstract
Paratuberculosis is a worldwide chronic enteric disease of ruminants, caused by Mycobacterium avium subsp. paratuberculosis (MAP). While MAP has been widely investigated all around the world, little is known about the different strains that circulate in each country. This study describes the genetic diversity of MAP isolates from different bovine and deer herds from Argentina, analyzed by Multiple-Locus Variable number tandem repeat Analysis (MLVA), as well as the phylogenetic relatedness between geographically distant isolates through Whole Genome Sequencing (WGS) and core-genome analysis. A total of 90 MAP isolates were analyzed. The results showed seven different MLVA genotypes, with almost 75% of them belonging to pattern INMV 1, described in all the herds studied. WGS results suggested the presence of a common INMV 1 strain circulating throughout the country. Our results allow confirming the coexistence of different strains in time and space and the mixed infections identified in some animals. These observations suggest the absence of animal monitoring prior to introduction to the herds and the need for a control program in the country. This study represents the first to report WGS of MAP strains in Argentina.
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11
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Vieujean S, Caron B, Haghnejad V, Jouzeau JY, Netter P, Heba AC, Ndiaye NC, Moulin D, Barreto G, Danese S, Peyrin-Biroulet L. Impact of the Exposome on the Epigenome in Inflammatory Bowel Disease Patients and Animal Models. Int J Mol Sci 2022; 23:7611. [PMID: 35886959 PMCID: PMC9321337 DOI: 10.3390/ijms23147611] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 07/05/2022] [Accepted: 07/06/2022] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn's disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits, vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated.
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Affiliation(s)
- Sophie Vieujean
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, 4000 Liege, Belgium;
| | - Bénédicte Caron
- Department of Gastroenterology NGERE (INSERM U1256), Nancy University Hospital, University of Lorraine, Vandœuvre-lès-Nancy, F-54052 Nancy, France; (B.C.); (V.H.)
| | - Vincent Haghnejad
- Department of Gastroenterology NGERE (INSERM U1256), Nancy University Hospital, University of Lorraine, Vandœuvre-lès-Nancy, F-54052 Nancy, France; (B.C.); (V.H.)
| | - Jean-Yves Jouzeau
- CNRS (French National Centre for Scientific Research), Laboratoire IMoPA, Université de Lorraine, UMR 7365, F-54000 Nancy, France; (J.-Y.J.); (P.N.); (D.M.); (G.B.)
| | - Patrick Netter
- CNRS (French National Centre for Scientific Research), Laboratoire IMoPA, Université de Lorraine, UMR 7365, F-54000 Nancy, France; (J.-Y.J.); (P.N.); (D.M.); (G.B.)
| | - Anne-Charlotte Heba
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), National Institute of Health and Medical Research, University of Lorraine, F-54000 Nancy, France; (A.-C.H.); (N.C.N.)
| | - Ndeye Coumba Ndiaye
- NGERE (Nutrition-Genetics and Exposure to Environmental Risks), National Institute of Health and Medical Research, University of Lorraine, F-54000 Nancy, France; (A.-C.H.); (N.C.N.)
| | - David Moulin
- CNRS (French National Centre for Scientific Research), Laboratoire IMoPA, Université de Lorraine, UMR 7365, F-54000 Nancy, France; (J.-Y.J.); (P.N.); (D.M.); (G.B.)
| | - Guillermo Barreto
- CNRS (French National Centre for Scientific Research), Laboratoire IMoPA, Université de Lorraine, UMR 7365, F-54000 Nancy, France; (J.-Y.J.); (P.N.); (D.M.); (G.B.)
- Lung Cancer Epigenetics, Max-Planck-Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany
- International Laboratory EPIGEN, Consejo de Ciencia y Tecnología del Estado de Puebla (CONCYTEP), Universidad de la Salud del Estado de Puebla, Puebla 72000, Mexico
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita-Salute San Raffaele, 20132 Milan, Italy;
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology NGERE (INSERM U1256), Nancy University Hospital, University of Lorraine, Vandœuvre-lès-Nancy, F-54052 Nancy, France; (B.C.); (V.H.)
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12
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Mizzi R, Plain KM, Whittington R, Timms VJ. Global Phylogeny of Mycobacterium avium and Identification of Mutation Hotspots During Niche Adaptation. Front Microbiol 2022; 13:892333. [PMID: 35602010 PMCID: PMC9121174 DOI: 10.3389/fmicb.2022.892333] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Accepted: 04/06/2022] [Indexed: 12/27/2022] Open
Abstract
Mycobacterium avium is separated into four subspecies: M. avium subspecies avium (MAA), M. avium subspecies silvaticum (MAS), M. avium subspecies hominissuis (MAH), and M. avium subspecies paratuberculosis (MAP). Understanding the mechanisms of host and tissue adaptation leading to their clinical significance is vital to reduce the economic, welfare, and public health concerns associated with diseases they may cause in humans and animals. Despite substantial phenotypic diversity, the subspecies nomenclature is controversial due to high genetic similarity. Consequently, a set of 1,230 M. avium genomes was used to generate a phylogeny, investigate SNP hotspots, and identify subspecies-specific genes. Phylogeny reiterated the findings from previous work and established that Mycobacterium avium is a species made up of one highly diverse subspecies, known as MAH, and at least two clonal pathogens, named MAA and MAP. Pan-genomes identified coding sequences unique to each subspecies, and in conjunction with a mapping approach, mutation hotspot regions were revealed compared to the reference genomes for MAA, MAH, and MAP. These subspecies-specific genes may serve as valuable biomarkers, providing a deeper understanding of genetic differences between M. avium subspecies and the virulence mechanisms of mycobacteria. Furthermore, SNP analysis demonstrated common regions between subspecies that have undergone extensive mutations during niche adaptation. The findings provide insights into host and tissue specificity of this genetically conserved but phenotypically diverse species, with the potential to provide new diagnostic targets and epidemiological and therapeutic advances.
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Affiliation(s)
- Rachel Mizzi
- Farm Animal Health, School of Veterinary Science, Faculty of Science, The University of Sydney, Camden, NSW, Australia
| | - Karren M Plain
- Farm Animal Health, School of Veterinary Science, Faculty of Science, The University of Sydney, Camden, NSW, Australia.,Microbiology and Parasitology Research, Elizabeth Macarthur Agricultural Institute, Menangle, NSW, Australia
| | - Richard Whittington
- Farm Animal Health, School of Veterinary Science, Faculty of Science, The University of Sydney, Camden, NSW, Australia
| | - Verlaine J Timms
- Neilan Laboratory of Microbial and Molecular Diversity, College of Engineering, Science and Environment, The University of Newcastle, Newcastle, NSW, Australia
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13
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Knific T, Ocepek M, Kirbiš A, Krt B, Prezelj J, Gethmann JM. Quantitative Risk Assessment of Exposure to Mycobacterium avium subsp. paratuberculosis (MAP) via Different Types of Milk for the Slovenian Consumer. Foods 2022; 11:foods11101472. [PMID: 35627042 PMCID: PMC9140596 DOI: 10.3390/foods11101472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/05/2022] [Accepted: 05/17/2022] [Indexed: 11/16/2022] Open
Abstract
This study aimed to assess the risk of exposure to Mycobacterium avium subsp. paratuberculosis (MAP) via milk for the Slovenian consumer. MAP is suspected to be associated with several diseases in humans, therefore the risk of exposure should be better understood. The primary source of MAP for humans is thought to be cattle, in which MAP causes paratuberculosis or Johne’s disease. We developed a stochastic quantitative risk assessment model using Monte Carlo simulations. Considering the assumptions and uncertainties, we estimated the overall risk of exposure to MAP via milk to be low. For people consuming raw milk from MAP positive farms, the risk was high. On-farm pasteurisation reduced the risk considerably, but not completely. The risk of exposure via pasteurised retail milk was most likely insignificant. However, with a higher paratuberculosis prevalence the risk would also increase. Given the popularity of raw milk vending machines and homemade dairy products, this risk should not be ignored. To reduce the risk, consumers should heat raw milk before consumption. To prevent a potential public health scare and safeguard farmers’ livelihoods, a reduction in paratuberculosis prevalence should be sought. Our results show that culling clinically infected cows was insufficient to reduce milk contamination with MAP.
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Affiliation(s)
- Tanja Knific
- Institute of Food Safety, Feed and Environment, Veterinary Faculty, University of Ljubljana, Gerbičeva ulica 60, 1000 Ljubljana, Slovenia;
- Correspondence:
| | - Matjaž Ocepek
- Institute of Microbiology and Parasitology, Veterinary Faculty, University of Ljubljana, Gerbičeva ulica 60, 1000 Ljubljana, Slovenia; (M.O.); (B.K.)
| | - Andrej Kirbiš
- Institute of Food Safety, Feed and Environment, Veterinary Faculty, University of Ljubljana, Gerbičeva ulica 60, 1000 Ljubljana, Slovenia;
| | - Branko Krt
- Institute of Microbiology and Parasitology, Veterinary Faculty, University of Ljubljana, Gerbičeva ulica 60, 1000 Ljubljana, Slovenia; (M.O.); (B.K.)
| | - Jasna Prezelj
- Department of Mathematics, Faculty of Mathematics and Physics, University of Ljubljana, Jadranska ulica 19, 1000 Ljubljana, Slovenia;
- Department of Mathematics, Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, Glagoljaška 8, 6000 Koper, Slovenia
- Institute of Mathematics, Physics and Mechanics, Jadranska ulica 19, 1000 Ljubljana, Slovenia
| | - Jörn M. Gethmann
- Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Institute of Epidemiology, Südufer 10, 17493 Greifswald-Insel Riems, Germany;
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14
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Kirkpatrick BW, Cooke ME, Frie M, Sporer KRB, Lett B, Wells SJ, Coussens PM. Genome-wide association analysis for susceptibility to infection by Mycobacterium avium ssp. paratuberculosis in US Holsteins. J Dairy Sci 2022; 105:4301-4313. [PMID: 35307176 DOI: 10.3168/jds.2021-21276] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 01/27/2022] [Indexed: 12/19/2022]
Abstract
Paratuberculosis, or Johne's disease, is a chronic, granulomatous, gastrointestinal tract disease of cattle and other ruminants caused by the bacterium Mycobacterium avium subspecies paratuberculosis (MAP). Control of Johne's disease is based on programs of testing and culling animals positive for infection with MAP and concurrently modifying management to reduce the likelihood of infection. The current study was motivated by the hypothesis that genetic variation in host susceptibility to MAP infection can be dissected and quantifiable associations with genetic markers identified. Two separate GWAS analyses were conducted, the first using 897 genotyped Holstein artificial insemination sires with phenotypes derived from incidence of MAP infection among daughters based on milk ELISA testing records. The second GWAS analysis was a case-control design using US Holstein cows phenotyped for MAP infection by serum ELISA or fecal culture tests. Cases included cows positive for either serum ELISA, fecal culture, or both. Controls consisted of animals negative for all tests conducted. A total of 376 samples (70 cases and 306 controls) from a University of Minnesota Johne's management demonstration project and 184 samples (76 cases and 108 controls) from a Michigan State University study were used. Medium-density (sires) and high-density (cows) genotype data were imputed to full genome sequence for the analyses. Marker-trait associations were analyzed using the single-step (ss)GWAS procedure implemented in the BLUPF90 suite of programs. Evidence of significant genomic contributions for susceptibility to MAP infection were observed on multiple chromosomes. Results were combined across studies in a meta-analysis, and increased support for genomic regions on BTA7 and BTA21 were observed. Gene set enrichment analysis suggested pathways for antigen processing and presentation, antimicrobial peptides and natural killer cell-mediated cytotoxicity are relevant to variation in host susceptibility to MAP infection, among others. Genomic prediction was evaluated using a 5-fold cross-validation, and moderate correlations were observed between genomic breeding value predictions and daughter averages (∼0.43 to 0.53) for MAP infection in testing data sets. These results suggest that genomic selection against susceptibility to MAP infection is feasible in Holstein cattle.
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Affiliation(s)
- B W Kirkpatrick
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison 53706.
| | - M E Cooke
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison 53706
| | - M Frie
- Department of Animal Science, Michigan State University, 474 S Shaw Ln, East Lansing 48824
| | - K R B Sporer
- Department of Animal Science, Michigan State University, 474 S Shaw Ln, East Lansing 48824
| | - B Lett
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison 53706
| | - S J Wells
- Department of Veterinary Population Medicine, University of Minnesota, 1365 Gortner Avenue, St. Paul 55108
| | - P M Coussens
- Department of Animal Science, Michigan State University, 474 S Shaw Ln, East Lansing 48824
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15
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Ibeagha-Awemu EM, Bissonnette N, Bhattarai S, Wang M, Dudemaine PL, McKay S, Zhao X. Whole Genome Methylation Analysis Reveals Role of DNA Methylation in Cow's Ileal and Ileal Lymph Node Responses to Mycobacterium avium subsp. paratuberculosis Infection. Front Genet 2021; 12:797490. [PMID: 34992636 PMCID: PMC8724574 DOI: 10.3389/fgene.2021.797490] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 11/22/2021] [Indexed: 12/27/2022] Open
Abstract
Johne's Disease (JD), caused by Mycobacterium avium subsp paratuberculosis (MAP), is an incurable disease of ruminants and other animal species and is characterized by an imbalance of gut immunity. The role of MAP infection on the epigenetic modeling of gut immunity during the progression of JD is still unknown. This study investigated the DNA methylation patterns in ileal (IL) and ileal lymph node (ILLN) tissues from cows diagnosed with persistent subclinical MAP infection over a one to 4 years period. DNA samples from IL and ILLN tissues from cows negative (MAPneg) (n = 3) or positive for MAP infection (MAPinf) (n = 4) were subjected to whole genome bisulfite sequencing. A total of 11,263 and 62,459 differentially methylated cytosines (DMCs), and 1259 and 8086 differentially methylated regions (DMRs) (FDR<0.1) were found between MAPinf and MAPneg IL and ILLN tissues, respectively. The DMRs were found on 394 genes (denoted DMR genes) in the IL and on 1305 genes in the ILLN. DMR genes with hypermethylated promoters/5'UTR [3 (IL) and 88 (ILLN)] or hypomethylated promoters/5'UTR [10 (IL) and 25 (ILLN)] and having multiple functions including response to stimulus/immune response (BLK, BTC, CCL21, AVPR1A, CHRNG, GABRA4, TDGF1), cellular processes (H2AC20, TEX101, GLA, NCKAP5L, RBM27, SLC18A1, H2AC20BARHL2, NLGN3, SUV39H1, GABRA4, PPA1, UBE2D2) and metabolic processes (GSTO2, H2AC20, SUV39H1, PPA1, UBE2D2) are potential DNA methylation candidate genes of MAP infection. The ILLN DMR genes were enriched for more biological process (BP) gene ontology (GO) terms (n = 374), most of which were related to cellular processes (27.6%), biological regulation (16.6%), metabolic processes (15.4%) and response to stimulus/immune response (8.2%) compared to 75 BP GO terms (related to cellular processes, metabolic processes and transport, and system development) enriched for IL DMR genes. ILLN DMR genes were enriched for more pathways (n = 47) including 13 disease pathways compared with 36 enriched pathways, including 7 disease/immune pathways for IL DMR genes. In conclusion, the results show tissue specific responses to MAP infection with more epigenetic changes (DMCs and DMRs) in the ILLN than in the IL tissue, suggesting that the ILLN and immune processes were more responsive to regulation by methylation of DNA relative to IL tissue. Our data is the first to demonstrate a potential role for DNA methylation in the pathogenesis of MAP infection in dairy cattle.
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Affiliation(s)
- Eveline M. Ibeagha-Awemu
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada
| | - Nathalie Bissonnette
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada
| | - Suraj Bhattarai
- Department of Animal and Veterinary Sciences, University of Vermont, Burlington, VT, United States
| | - Mengqi Wang
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada
| | - Pier-Luc Dudemaine
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada
| | - Stephanie McKay
- Department of Animal and Veterinary Sciences, University of Vermont, Burlington, VT, United States
| | - Xin Zhao
- Department of Animal Science, McGill University, Ste-Anne-Be-Bellevue, QC, Canada
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16
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Aitken JM, Phan K, Bodman SE, Sharma S, Watt A, George PM, Agrawal G, Tie ABM. A Mycobacterium species for Crohn's disease? Pathology 2021; 53:818-823. [PMID: 34158180 DOI: 10.1016/j.pathol.2021.03.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 02/18/2021] [Accepted: 03/03/2021] [Indexed: 12/13/2022]
Abstract
In ruminants Mycobacterium avium subspecies paratuberculosis (MAP) is the causative organism of a chronic granulomatous inflammatory bowel disease called Johne's disease (JD). Some researchers have hypothesised that MAP is also associated with Crohn's disease (CD), an inflammatory bowel disease in humans that shares some histological features of JD. Despite numerous attempts to demonstrate causality by researchers, direct microbiological evidence of MAP involvement in CD remains elusive. Importantly, it has not been possible to reliably and reproducibly demonstrate mycobacteria in the tissue of CD patients. Past attempts to visualise mycobacteria in tissue may have been hampered by the use of stains optimised for Mycobacterium tuberculosis complex (MTB) and the lack of reliable bacteriological culture media for both non-tuberculous mycobacteria (NTM) and cell-wall-deficient mycobacteria (CWDM). Here we describe a Ziehl-Neelsen (ZN) staining method for the demonstration of CWDM in resected tissue from patients with Crohn's disease, revealing the association of CWDM in situ with host tissue reactions, and posit this as a cause of the tissue inflammation. Using the ZN stain described we demonstrated the presence of CWDM in 18 out of 18 excised tissue samples from patients diagnosed as having Crohn's disease, and in zero samples out of 15 non-inflammatory bowel disease controls.
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Affiliation(s)
| | - Khoi Phan
- Southern Community Laboratories, Wellington Hospital, Wellington, New Zealand
| | | | | | | | | | - Gaurav Agrawal
- Guy's and St Thomas' Hospitals NHS Foundation Trust, Kings College, London, UK
| | - Andrew B M Tie
- Southern Community Laboratories, Wellington Hospital, Wellington, New Zealand
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17
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Axelrad JE, Cadwell KH, Colombel JF, Shah SC. The role of gastrointestinal pathogens in inflammatory bowel disease: a systematic review. Therap Adv Gastroenterol 2021; 14:17562848211004493. [PMID: 33868457 PMCID: PMC8020742 DOI: 10.1177/17562848211004493] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 03/04/2021] [Indexed: 02/04/2023] Open
Abstract
The inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), are chronic, progressive, inflammatory conditions of the gastrointestinal tract. Imbalance in the gut microbial community, or dysbiosis, and the subsequent immune response, represent the critical relationship between genetic susceptibility, microbes, and environment factors, that result in IBD. Gastrointestinal pathogens - a common cause of dysbiosis - have been implicated as an environmental trigger in new onset IBD, as well as flare of existing IBD. In this article, we systematically review clinical data regarding the association between specific gastrointestinal pathogens and IBD. Numerous bacteria, viruses, fungi, and parasites have been implicated in the pathogenesis of IBD, and exacerbations of existing disease. In this article, we will also specifically discuss the less recognized microbes that have an inverse association with IBD, including certain bacterial pathogens, such as Helicobacter pylori, and parasites, such as Trichuris species. Future prospective and experimental studies are required to establish causality and clarify potential mechanisms of enteric pathogens in modifying the risk and course of IBD.
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Affiliation(s)
| | - Ken H. Cadwell
- Division of Gastroenterology, Department of Medicine, NYU Grossman School of Medicine, New York, NY, USA,Kimmel Center for Biology and Medicine at the Skirball Institute, NYU Grossman School of Medicine, New York, NY, USA,Department of Microbiology, NYU Grossman School of Medicine, New York, NY, USA
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Shailja C. Shah
- Section of Gastroenterology, Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN,San Diego Health System, La Jolla, CA, USA,Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
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18
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Proietti E, Fuhler GM, Peppelenbosch MP. Mycobacterium Avium Subspecies Paratuberculosis Infection and Biological Treatment of IBD: Cause or Consequence? J Crohns Colitis 2021; 15:1247-1249. [PMID: 33735385 PMCID: PMC8328286 DOI: 10.1093/ecco-jcc/jjab027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- E Proietti
- Erasmus MC, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands
| | - G M Fuhler
- Erasmus MC, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands
| | - M P Peppelenbosch
- Erasmus MC, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands,Corresponding author: M. P. Peppelenbosch, Department of Gastroenterology and Hepatology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. Tel: 0031 10 703292;
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19
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Mizzi R, Timms VJ, Price-Carter ML, Gautam M, Whittington R, Heuer C, Biggs PJ, Plain KM. Comparative Genomics of Mycobacterium avium Subspecies Paratuberculosis Sheep Strains. Front Vet Sci 2021; 8:637637. [PMID: 33659287 PMCID: PMC7917049 DOI: 10.3389/fvets.2021.637637] [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: 12/04/2020] [Accepted: 01/25/2021] [Indexed: 12/15/2022] Open
Abstract
Mycobacterium avium subspecies paratuberculosis (MAP) is the aetiological agent of Johne's disease (JD), a chronic enteritis that causes major losses to the global livestock industry. Further, it has been associated with human Crohn's disease. Several strains of MAP have been identified, the two major groups being sheep strain MAP, which includes the Type I and Type III sub-lineages, and the cattle strain or Type II MAP lineage, of which bison strains are a sub-grouping. Major genotypic, phenotypic and pathogenic variations have been identified in prior comparisons, but the research has predominately focused on cattle strains of MAP. In countries where the sheep industries are more prevalent, however, such as Australia and New Zealand, ovine JD is a substantial burden. An information gap exists regarding the genomic differences between sheep strain sub-lineages and the relevance of Type I and Type III MAP in terms of epidemiology and/or pathogenicity. We therefore investigated sheep MAP isolates from Australia and New Zealand using whole genome sequencing. For additional context, sheep MAP genome datasets were downloaded from the Sequence Read Archive and GenBank. The final dataset contained 18 Type III and 16 Type I isolates and the K10 cattle strain MAP reference genome. Using a pan-genome approach, an updated global phylogeny for sheep MAP from de novo assemblies was produced. When rooted with the K10 cattle reference strain, two distinct clades representing the lineages were apparent. The Australian and New Zealand isolates formed a distinct sub-clade within the type I lineage, while the European type I isolates formed another less closely related group. Within the type III lineage, isolates appeared more genetically diverse and were from a greater number of continents. Querying of the pan-genome and verification using BLAST analysis revealed lineage-specific variations (n = 13) including genes responsible for metabolism and stress responses. The genetic differences identified may represent important epidemiological and virulence traits specific to sheep MAP. This knowledge will potentially contribute to improved vaccine development and control measures for these strains.
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Affiliation(s)
- Rachel Mizzi
- Farm Animal Health Group, Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, Camden, NSW, Australia
| | - Verlaine J Timms
- Centre for Infectious Diseases and Microbiology, Public Health, Westmead Hospital, Westmead, NSW, Australia
| | | | - Milan Gautam
- School of Veterinary Science, Massey University, Palmerston North, New Zealand
| | - Richard Whittington
- Farm Animal Health Group, Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, Camden, NSW, Australia
| | - Cord Heuer
- School of Veterinary Science, Massey University, Palmerston North, New Zealand
| | - Patrick J Biggs
- School of Veterinary Science, Massey University, Palmerston North, New Zealand.,School of Fundamental Sciences, Massey University, Palmerston North, New Zealand
| | - Karren M Plain
- Farm Animal Health Group, Sydney School of Veterinary Science, Faculty of Science, The University of Sydney, Camden, NSW, Australia
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20
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Abdissa K, Ruangkiattikul N, Ahrend W, Nerlich A, Beineke A, Laarmann K, Janze N, Lobermeyer U, Suwandi A, Falk C, Schleicher U, Weiss S, Bogdan C, Goethe R. Relevance of inducible nitric oxide synthase for immune control of Mycobacterium avium subspecies paratuberculosis infection in mice. Virulence 2021; 11:465-481. [PMID: 32408806 PMCID: PMC7239028 DOI: 10.1080/21505594.2020.1763055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne’s disease (JD), an incurable chronic intestinal bowel disease in ruminants. JD occurs worldwide and causes enormous economic burden in dairy industry. Research on JD pathobiology is hampered by its complexity which cannot completely be mimicked by small animal models. As a model the mouse allows dissecting some pathogenicity features of MAP. However, for unknown reasons MAP exhibits reduced growth in granulomas of infected mice compared to other Mycobacterium avium subspecies. Here, we characterized immune reactions of MAP-infected C57BL/6 mice. After infection, mice appeared fully immunocompetent. A strong antigen-specific T cell response was elicited indicated by IFNγ production of splenic T cells re-stimulated with MAP antigens. Function of splenic dendritic cells and proliferation of adoptively transferred antigen-specific CD4+ T cells was unaltered. Isolated splenic myeloid cells from infected mice revealed that MAP resides in CD11b+ macrophages. Importantly, sorted CD11b+CD11c− cells expressed high level of type 2 nitric oxide synthase (NOS2) but only low levels of pro- and anti-inflammatory cytokines. Correspondingly, MAP-infected MAC2 expressing myeloid cells in spleen and liver granuloma displayed strong expression of NOS2. In livers of infected Nos2−/−mice higher bacterial loads, more granuloma and larger areas of tissue damage were observed 5 weeks post infection compared to wild type mice. In vitro, MAP was sensitive to NO released by a NO-donor. Thus, a strong T cell response and concomitant NOS2/NO activity appears to control MAP infection, but allows development of chronicity and pathogen persistence. A similar mechanism might explain persistence of MAP in ruminants.
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Affiliation(s)
- Ketema Abdissa
- Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany.,Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | | | - Wiebke Ahrend
- Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Andreas Nerlich
- Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Andreas Beineke
- Institute for Pathology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Kristin Laarmann
- Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Nina Janze
- Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany
| | - Ulrike Lobermeyer
- Mouse Pathology, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Abdulhadi Suwandi
- Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
| | - Christine Falk
- Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany
| | - Ulrike Schleicher
- Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie Und Hygiene, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Siegfried Weiss
- Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.,Institute of Immunology, Hannover Medical School, Hannover, Germany
| | - Christian Bogdan
- Mikrobiologisches Institut, Klinische Mikrobiologie, Immunologie Und Hygiene, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany
| | - Ralph Goethe
- Institute for Microbiology, University of Veterinary Medicine Hannover, Hannover, Germany
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21
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A Protective Vaccine against Johne's Disease in Cattle. Microorganisms 2020; 8:microorganisms8091427. [PMID: 32957508 PMCID: PMC7564561 DOI: 10.3390/microorganisms8091427] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 09/12/2020] [Accepted: 09/15/2020] [Indexed: 01/16/2023] Open
Abstract
Johne’s disease (JD) caused by Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) is a chronic infection characterized by the development of granulomatous enteritis in wild and domesticated ruminants. It is one of the most significant livestock diseases not only in the USA but also globally, accounting for USD 200–500 million losses annually for the USA alone with potential link to cases of Crohn’s disease in humans. Developing safe and protective vaccines is of a paramount importance for JD control in dairy cows. The current study evaluated the safety, immunity and protective efficacy of a novel live attenuated vaccine (LAV) candidate with and without an adjuvant in comparison to an inactivated vaccine. Results indicated that the LAV, irrespective of the adjuvant presence, induced robust T cell immune responses indicated by proinflammatory cytokine production such as IFN-γ, IFN-α, TNF-α and IL-17 as well as strong response to intradermal skin test against M. paratuberculosis antigens. Furthermore, the LAV was safe with minimal tissue pathology. Finally, calves vaccinated with adjuvanted LAV did not shed M. paratuberculosis post-challenge, a much-desired characteristic of an effective vaccine against JD. Together, this data suggests a strong potential of testing LAV in field trials to curb JD in dairy herds.
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22
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Çınar MU, Akyüz B, Arslan K, White SN, Neibergs HL, Gümüşsoy KS. The EDN2 rs110287192 gene polymorphism is associated with paratuberculosis susceptibility in multibreed cattle population. PLoS One 2020; 15:e0238631. [PMID: 32881967 PMCID: PMC7470282 DOI: 10.1371/journal.pone.0238631] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 08/20/2020] [Indexed: 12/12/2022] Open
Abstract
Paratuberculosis (pTB), also known as Johne's disease (JD), is a contagious, chronic, and granulomatous inflammatory disease of the intestines of ruminants which is caused by Mycobacterium avium subsp. paratuberculosis (MAP) infection, resulting in billions of dollars in economic losses worldwide. Since, currently, no effective cure is available for MAP infection, it is important to explore the genetic variants that affect the host MAP susceptibility. The aim of this study was to analyze a potential association between EDN2 synonymous gene mutations (rs110287192, rs109651404 and rs136707411), that modifies susceptibility to pTB. EDN2 rs110287192, rs109651404 and rs136707411 mutations were genotyped in 68 infected and 753 healthy animals from East Anatolian Red crossbred, Anatolian Black crossbred and Holstein breed cattle by using Custom TaqMan SNP Genotyping Assays. For pTB status, serum antibody levels S/P ≥ 1.0 were assessed in carriers of the different EDN2 genotypes. EDN2 rs110287192 mutation showed a significant association with bovine pTB (adj. p < 0.05). For rs110287192 locus, the odd ratios for GG and TG genotypes versus TT genotypes were 1.73; (95% CI = 0.34–8.59) and 0.53 (95% CI = 0.12–2.37) respectively, which indicated that proportion of TG heterozygotes were significantly higher in control animals as compared to pTB animals. On the other hand, while rs136707411 mutation showed a suggestive association with pTB status in the examined cattle population (nominal p < 0.05); no association was detected between rs109651404 genotypes and pTB status. Selecting animals against rs110287192-GG genotype may decrease the risk of pTB in cattle of the Bos taurus taurus subspecies.
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Affiliation(s)
- Mehmet Ulaş Çınar
- Department of Animal Science, Faculty of Agriculture, Erciyes University, Kayseri, Turkey
- Department of Veterinary Microbiology & Pathology, Washington State University, Pullman, WA, United States of America
- * E-mail:
| | - Bilal Akyüz
- Department of Genetics, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Turkey
| | - Korhan Arslan
- Department of Genetics, Faculty of Veterinary Medicine, Erciyes University, Kayseri, Turkey
| | - Stephen N. White
- Department of Veterinary Microbiology & Pathology, Washington State University, Pullman, WA, United States of America
- Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Pullman, WA, United States of America
- Center for Reproductive Biology, Washington State University, Pullman, WA, United States of America
| | - Holly L. Neibergs
- Center for Reproductive Biology, Washington State University, Pullman, WA, United States of America
- Department of Animal Science, Washington State University, Pullman, WA, United States of America
| | - Kadir Semih Gümüşsoy
- Department of Microbiology, Erciyes University, Faculty of Veterinary Medicine, Kayseri, Turkey
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23
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Rullo J, Far PM, Quinn M, Sharma N, Bae S, Irrcher I, Sharma S. Local oral and nasal microbiome diversity in age-related macular degeneration. Sci Rep 2020; 10:3862. [PMID: 32123200 PMCID: PMC7052252 DOI: 10.1038/s41598-020-60674-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Accepted: 02/11/2020] [Indexed: 11/15/2022] Open
Abstract
Age-related macular degeneration (AMD) is a chronic degenerative disease of the retina. Recent reports have highlighted the potential role of mucosal surface microbes in the pathogenesis of AMD. In this case-control study, the composition of the nasal and oral microbiota in newly diagnosed neovascular age-related macular degeneration cases (6 male, 7 female) was compared to controls without retinal diseases (2 male, 3 female). PCR amplification of 16S rRNA genes was performed with universal primers amplifying the V4 variable region (515F-806R). Distinct microbial community characterization was achieved using Principal Coordinates Analysis (PCoA) of the Bray-Curtis index with comparative analysis between cases and controls performed within QIIME 2. Sequencing of all cases and controls revealed clear separation with strong beta diversity between oral and nasal microbial communities (p < 0.001). Microbial composition differed between cases and controls in both oral and nasal samples. The top three oral microbes identified as different compared to controls included Burkholderiales (7.41 log2fold change, p = 3.29E-05), Actinomyceataceae (6.22 log2fold change, p = 3.73E-06) and Gemella (5.28 log2fold change, p = 0.0002). The top three nasal microbes identified as different compared to controls included Rothia (13.6 log2fold change, p = 3.63E-18), Actinobacteria (10.29 log2fold change, p = 9.81E-10) and Propionibacteriales (8.73 log2fold change, p = 6.74E-09). These relative shifts in communities of bacteria detected in newly diagnosed neovascular AMD patients may suggest additional mechanistic links in disease pathogenesis.
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Affiliation(s)
- Jacob Rullo
- Queen's University, Kingston Health Sciences Center, Department of Ophthalmology, 166 Brock Street, Kingston, Ontario, K7L 5G2, Canada.
| | - Parsa Mehraban Far
- Queen's University, Kingston Health Sciences Center, Department of Ophthalmology, 166 Brock Street, Kingston, Ontario, K7L 5G2, Canada
| | - Matthew Quinn
- Queen's University, Kingston Health Sciences Center, Department of Ophthalmology, 166 Brock Street, Kingston, Ontario, K7L 5G2, Canada
| | - Neel Sharma
- Queen's University, Kingston Health Sciences Center, Department of Ophthalmology, 166 Brock Street, Kingston, Ontario, K7L 5G2, Canada
| | - Steven Bae
- Queen's University, Kingston Health Sciences Center, Department of Ophthalmology, 166 Brock Street, Kingston, Ontario, K7L 5G2, Canada
| | - Isabella Irrcher
- Queen's University, Kingston Health Sciences Center, Department of Ophthalmology, 166 Brock Street, Kingston, Ontario, K7L 5G2, Canada
| | - Sanjay Sharma
- Queen's University, Kingston Health Sciences Center, Department of Ophthalmology, 166 Brock Street, Kingston, Ontario, K7L 5G2, Canada
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24
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Ariel O, Gendron D, Dudemaine PL, Gévry N, Ibeagha-Awemu EM, Bissonnette N. Transcriptome Profiling of Bovine Macrophages Infected by Mycobacterium avium spp. paratuberculosis Depicts Foam Cell and Innate Immune Tolerance Phenotypes. Front Immunol 2020; 10:2874. [PMID: 31969876 PMCID: PMC6960179 DOI: 10.3389/fimmu.2019.02874] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 11/22/2019] [Indexed: 12/18/2022] Open
Abstract
Mycobacterium avium spp. paratuberculosis (MAP) is the causative agent of Johne's disease (JD), also known as paratuberculosis, in ruminants. The mechanisms of JD pathogenesis are not fully understood, but it is known that MAP subverts the host immune system by using macrophages as its primary reservoir. MAP infection in macrophages is often studied in healthy cows or experimentally infected calves, but reports on macrophages from naturally infected cows are lacking. In our study, primary monocyte-derived macrophages (MDMs) from cows diagnosed as positive (+) or negative (–) for JD were challenged in vitro with live MAP. Analysis using next-generation RNA sequencing revealed that macrophages from JD(+) cows did not present a definite pattern of response to MAP infection. Interestingly, a considerable number of genes, up to 1436, were differentially expressed in JD(–) macrophages. The signatures of the infection time course of 1, 4, 8, and 24 h revealed differential expression of ARG2, COL1A1, CCL2, CSF3, IL1A, IL6, IL10, PTGS2, PTX3, SOCS3, TNF, and TNFAIP6 among other genes, with major effects on host signaling pathways. While several immune pathways were affected by MAP, other pathways related to hepatic fibrosis/hepatic stellate cell activation, lipid homeostasis, such as LXR/RXR (liver X receptor/retinoid X receptor) activation pathways, and autoimmune diseases (rheumatoid arthritis or atherosclerosis) also responded to the presence of live MAP. Comparison of the profiles of the unchallenged MDMs from JD(+) vs. JD(–) cows showed that 868 genes were differentially expressed, suggesting that these genes were already affected before monocytes differentiated into macrophages. The downregulated genes predominantly modified the general cell metabolism by downregulating amino acid synthesis and affecting cholesterol biosynthesis and other energy production pathways while introducing a pro-fibrotic pattern associated with foam cells. The upregulated genes indicated that lipid homeostasis was already supporting fat storage in uninfected JD(+) MDMs. For JD(+) MDMs, differential gene expression expounds long-term mechanisms established during disease progression of paratuberculosis. Therefore, MAP could further promote disease persistence by influencing long-term macrophage behavior by using both tolerance and fat-storage states. This report contributes to a better understanding of MAP's controls over the immune cell response and mechanisms of MAP survival.
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Affiliation(s)
- Olivier Ariel
- Sherbrooke Research and Development Center, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada.,Department of Biology, Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Daniel Gendron
- Sherbrooke Research and Development Center, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada
| | - Pier-Luc Dudemaine
- Sherbrooke Research and Development Center, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada.,Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Nicolas Gévry
- Department of Biology, Université de Sherbrooke, Sherbrooke, QC, Canada
| | - Eveline M Ibeagha-Awemu
- Sherbrooke Research and Development Center, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada
| | - Nathalie Bissonnette
- Sherbrooke Research and Development Center, Agriculture and Agri-Food Canada, Sherbrooke, QC, Canada.,Department of Biology, Université de Sherbrooke, Sherbrooke, QC, Canada
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25
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Richardson H, Rhodes G, Henrys P, Sedda L, Weightman AJ, Pickup RW. Presence of Mycobacterium avium Subspecies paratuberculosis Monitored Over Varying Temporal and Spatial Scales in River Catchments: Persistent Routes for Human Exposure. Microorganisms 2019; 7:microorganisms7050136. [PMID: 31096696 PMCID: PMC6560452 DOI: 10.3390/microorganisms7050136] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 05/02/2019] [Accepted: 05/09/2019] [Indexed: 12/13/2022] Open
Abstract
Mycobacterium avium subspecies paratuberculosis (Map) was monitored by quantitative PCR over a range of temporal and spatial scales in the River Tywi catchment. This study shows the persistence of Map over a 10-year period with little change, which correlates with the recognised levels of Johne’s disease in British herds over that period (aim 1). Map was quantified within the river at up to 108 cell equivalents L−1 and was shown to be consistently present when monitored over finer timescales (aim 4). Small wastewater treatment plants where the ingress of human-associated Map might be expected had no significant effect (aim 2). Map was found for the first time to be located in natural river foams providing another route for spread via aerosols (aim 5). This study provides evidence for the environmental continuum of Map from the grazing infected animal via rain driven runoff through field drains and streams into main rivers; with detection at a high frequency throughout the year. Should Map need to be monitored in the future, we recommend that weekly or monthly sampling from a fixed location on a river will capture an adequate representation of the flow dynamics of Map in a catchment (aim 3). The human exposure to Map during this process and its impact on human health remains unquantified.
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Affiliation(s)
- Hollian Richardson
- Biomedical and Life Sciences Division, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK.
- Division of Molecular and Clinical Medicine, University of Dundee, Mailbox 12, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
| | - Glenn Rhodes
- Lake Ecosystems Group, Centre for Ecology and Hydrology, Lancaster Environment Centre, Lancaster LA1 4AP, UK.
| | - Peter Henrys
- Lake Ecosystems Group, Centre for Ecology and Hydrology, Lancaster Environment Centre, Lancaster LA1 4AP, UK.
| | - Luigi Sedda
- Centre for Health Informatics, Computing and Statistics (CHICAS), Lancaster Medical School, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK.
| | - Andrew J Weightman
- School of Biosciences, Cardiff University, Sir Martin Evans Building, Museum Avenue, Cardiff CF10 3AX, Wales.
| | - Roger W Pickup
- Biomedical and Life Sciences Division, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, UK.
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26
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Hobmaier BF, Lutterberg K, Kleinwort KJH, Mayer R, Hirmer S, Amann B, Hölzel C, Märtlbauer EP, Deeg CA. Characterization of plant lectins for their ability to isolate Mycobacterium avium subsp. paratuberculosis from milk. Food Microbiol 2019; 82:231-239. [PMID: 31027778 DOI: 10.1016/j.fm.2019.02.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 02/13/2019] [Accepted: 02/13/2019] [Indexed: 01/05/2023]
Affiliation(s)
- Bernhard F Hobmaier
- Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Veterinärstraße 13, D-80539, Munich, Germany
| | - Karina Lutterberg
- Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Veterinärstraße 13, D-80539, Munich, Germany
| | - Kristina J H Kleinwort
- Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Veterinärstraße 13, D-80539, Munich, Germany
| | - Ricarda Mayer
- Chair of Hygiene and Technology of Milk, Department of Veterinary Sciences, LMU Munich, Schönleutnerstr 8, D-85764, Oberschleißheim, Germany
| | - Sieglinde Hirmer
- Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Veterinärstraße 13, D-80539, Munich, Germany
| | - Barbara Amann
- Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Veterinärstraße 13, D-80539, Munich, Germany
| | - Christina Hölzel
- Chair of Hygiene and Technology of Milk, Department of Veterinary Sciences, LMU Munich, Schönleutnerstr 8, D-85764, Oberschleißheim, Germany; Institute of Animal Breeding and Husbandry, Faculty of Agricultural and Nutritional Sciences, CAU Kiel, Hermann-Rodewald-Str. 6, 24098 Kiel, Germany
| | - Erwin P Märtlbauer
- Chair of Hygiene and Technology of Milk, Department of Veterinary Sciences, LMU Munich, Schönleutnerstr 8, D-85764, Oberschleißheim, Germany
| | - Cornelia A Deeg
- Chair of Animal Physiology, Department of Veterinary Sciences, LMU Munich, Veterinärstraße 13, D-80539, Munich, Germany.
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27
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Balseiro A, Perez V, Juste RA. Chronic regional intestinal inflammatory disease: A trans-species slow infection? Comp Immunol Microbiol Infect Dis 2018; 62:88-100. [PMID: 30711052 DOI: 10.1016/j.cimid.2018.12.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 11/27/2018] [Accepted: 12/07/2018] [Indexed: 01/08/2023]
Abstract
Crohn's disease and ulcerative colitis in humans and paratuberculosis in domestic and wild ruminants can be defined as chronic regional intestinal inflammatory diseases (CRIID). This review is a literature overview on these diseases in humans, non-human primates, dogs, cats, rabbits, equids and ruminants with a focus on pathological and microbiological features aimed identifying common characteristics that could lead to a unified pathological classification for a better understanding of their mechanisms and causes. The result is a framework of inflammatory forms throughout the different species indicative of common mechanisms of the slow infection type characterized by a time course varying from weeks to months or even years, and where the inflammatory component would be more prominent in the intestinal interphase between host and environment and be morphologically characterized by an infiltrate ranging from lymphoplasmacytic to histiocytic. This should provide new insights for causation demonstration and therapeutic approaches in human IBD.
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Affiliation(s)
- Ana Balseiro
- Centro de Biotecnología Animal, Servicio Regional de Investigación y Desarrollo Agroalimentario (SERIDA), 33394 Gijón, Asturias, Spain
| | - Valentin Perez
- Departamento de Sanidad Animal, Instituto de Ganadería de Montaña (CSIC-ULE), Facultad de Veterinaria, Universidad de León, 24071 León, Spain
| | - Ramon A Juste
- Direccion. Servicio Regional de Investigación y Desarrollo Agroalimentario (SERIDA), 33300 Villaviciosa, Asturias, Spain.
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28
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Kiely CJ, Pavli P, O'Brien CL. The microbiome of translocated bacterial populations in patients with and without inflammatory bowel disease. Intern Med J 2018; 48:1346-1354. [DOI: 10.1111/imj.13998] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Revised: 04/20/2018] [Accepted: 06/07/2018] [Indexed: 12/17/2022]
Affiliation(s)
- Christopher J. Kiely
- IBD Research Laboratory, Medical School, College of Medicine, Biology and EnvironmentAustralian National University Canberra Capital of Australia Australia
| | - Paul Pavli
- IBD Research Laboratory, Medical School, College of Medicine, Biology and EnvironmentAustralian National University Canberra Capital of Australia Australia
- Gastroenterology and Hepatology UnitCanberra Hospital Canberra Australian Capital Territory Australia
| | - Claire L. O'Brien
- IBD Research Laboratory, Medical School, College of Medicine, Biology and EnvironmentAustralian National University Canberra Capital of Australia Australia
- Gastroenterology and Hepatology UnitCanberra Hospital Canberra Australian Capital Territory Australia
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29
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Chaubey KK, Singh SV, Gupta S, Singh M, Sohal JS, Kumar N, Singh MK, Bhatia AK, Dhama K. Mycobacterium avium subspecies paratuberculosis - an important food borne pathogen of high public health significance with special reference to India: an update. Vet Q 2018; 37:282-299. [PMID: 29090657 DOI: 10.1080/01652176.2017.1397301] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
This review underlines the public health significance of 'Indian Bison Type' of Mycobacterium avium subspecies paratuberculosis (MAP) and also its potential as 'zoonotic infection'. In the absence of control programs, bio-load of MAP is increasing and if we take total population of animals (500 million plus) and human beings (1.23 billion plus) into account, the number of infected animals and human beings will run into millions in India. Our research on screening of over 26,000 domestic livestock for MAP infection using 4 different diagnostic tests (microscopy, culture, ELISA and PCR), during last 31 years has shown that the average bio-load of MAP in the livestock population of India is very high (cattle 43%, buffaloes 36%, goats 23% and sheep 41%). 'Mass screening' of 28,291 human samples between 2008-2016 revealed also high bio-load of MAP. It has been proved that MAP is not in-activated during pasteurization and therefore live bacilli are continuously reaching human population by consumption of even pasteurized milk and other milk products. Live bacilli have also been recovered from meat products and the environment thus illustrating the potential of MAP as pathogen of public health concern. However, at present, there is inadequate scientific evidence to confirm a conclusive link between MAP infection and Johne's disease in ruminants and some cases of Crohn's disease in human beings.
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Affiliation(s)
- Kundan Kumar Chaubey
- a Animal Health Division, Central Institute for Research on Goats (CIRG) , Mathura , UP , India.,b Department of Microbiology and Immunology , GLA University , Mathura , UP , India
| | - Shoor Vir Singh
- a Animal Health Division, Central Institute for Research on Goats (CIRG) , Mathura , UP , India
| | - Saurabh Gupta
- a Animal Health Division, Central Institute for Research on Goats (CIRG) , Mathura , UP , India.,b Department of Microbiology and Immunology , GLA University , Mathura , UP , India
| | - Manju Singh
- a Animal Health Division, Central Institute for Research on Goats (CIRG) , Mathura , UP , India
| | - Jagdip Singh Sohal
- c Amity Institutes of Microbial Technology, Amity University , Jaipur , India
| | - Naveen Kumar
- d Veterinary Type Culture Collection, NRC On Equines , Indian Council of Agricultural Research , Hisar , India
| | - Manoj Kumar Singh
- a Animal Health Division, Central Institute for Research on Goats (CIRG) , Mathura , UP , India
| | - Ashok Kumar Bhatia
- b Department of Microbiology and Immunology , GLA University , Mathura , UP , India
| | - Kuldeep Dhama
- e Pathology Division , Indian Veterinary Research Institute (IVRI) , Bareilly , UP , India
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Pierce ES. Could Mycobacterium avium subspecies paratuberculosis cause Crohn's disease, ulcerative colitis…and colorectal cancer? Infect Agent Cancer 2018; 13:1. [PMID: 29308085 PMCID: PMC5753485 DOI: 10.1186/s13027-017-0172-3] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Accepted: 12/12/2017] [Indexed: 01/07/2023] Open
Abstract
Infectious agents are known causes of human cancers. Schistosoma japonicum and Schistosoma mansoni cause a percentage of colorectal cancers in countries where the respective Schistosoma species are prevalent. Colorectal cancer is a complication of ulcerative colitis and colonic Crohn’s disease, the two main forms of idiopathic inflammatory bowel disease (IIBD). Mycobacterium avium subspecies paratuberculosis (MAP), the cause of a chronic intestinal disease in domestic and wild ruminants, is one suspected cause of IIBD. MAP may therefore be involved in the pathogenesis of IIBD-associated colorectal cancer as well as colorectal cancer in individuals without IIBD (sporadic colorectal cancer) in countries where MAP infection of domestic livestock is prevalent and MAP’s presence in soil and water is extensive. MAP organisms have been identified in the intestines of patients with sporadic colorectal cancer and IIBD when high magnification, oil immersion light microscopy (×1000 total magnification rather than the usual ×400 total magnification) is used. Research has demonstrated MAP’s ability to invade intestinal goblet cells and cause acute and chronic goblet cell hyperplasia. Goblet cell hyperplasia is the little-recognized initial pathologic lesion of sporadic colorectal cancer, referred to as transitional mucosa, aberrant crypt foci, goblet cell hyperplastic polyps or transitional polyps. It is the even lesser-recognized initial pathologic feature of IIBD, referred to as hypermucinous mucosa, hyperplastic-like mucosal change, serrated epithelial changes, flat serrated changes, goblet cell rich mucosa or epithelial hyperplasia. Goblet cell hyperplasia is the precursor lesion of adenomas and dysplasia in the classical colorectal cancer pathway, of sessile serrated adenomas and serrated dysplasia in the serrated colorectal cancer pathway, and of flat and elevated dysplasia and dysplasia-associated lesions or masses in IIBD-associated intestinal cancers. MAP’s invasion of intestinal goblet cells may result in the initial pathologic lesion of IIBD and sporadic colorectal cancer. MAP’s persistence in infected intestines may result in the eventual development of both IIBD-associated and sporadic colorectal cancer.
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Abstract
A general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal microbiota (dysbiosis). However, a direct causal relationship between dysbiosis and IBD has not been definitively established in humans. Findings from animal models have revealed diverse and context-specific roles of the gut microbiota in health and disease, ranging from protective to pro-inflammatory actions. Moreover, evidence from these experimental models suggest that although gut bacteria often drive immune activation, chronic inflammation in turn shapes the gut microbiota and contributes to dysbiosis. The purpose of this Review is to summarize current associations between IBD and dysbiosis, describe the role of the gut microbiota in the context of specific animal models of colitis, and discuss the potential role of microbiota-focused interventions in the treatment of human IBD. Ultimately, more studies will be needed to define host-microbial relationships relevant to human disease and amenable to therapeutic interventions.
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Affiliation(s)
- Josephine Ni
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, 421 Curie Boulevard, 914 BRB II/III, Philadeplhia, Pennsylvania 19104, USA
| | - Gary D Wu
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, 421 Curie Boulevard, 914 BRB II/III, Philadeplhia, Pennsylvania 19104, USA
| | - Lindsey Albenberg
- Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
| | - Vesselin T Tomov
- Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, 421 Curie Boulevard, 914 BRB II/III, Philadeplhia, Pennsylvania 19104, USA
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Schwarz D, Lima M, Barros M, Valente F, Scatamburlo T, Rosado N, Oliveira C, Oliveira L, Moreira M. Short communication: Passive shedding of Mycobacterium avium ssp. paratuberculosis in commercial dairy goats in Brazil. J Dairy Sci 2017; 100:8426-8429. [DOI: 10.3168/jds.2017-12918] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2017] [Accepted: 06/06/2017] [Indexed: 11/19/2022]
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Kuenstner JT, Naser S, Chamberlin W, Borody T, Graham DY, McNees A, Hermon-Taylor J, Hermon-Taylor A, Dow CT, Thayer W, Biesecker J, Collins MT, Sechi LA, Singh SV, Zhang P, Shafran I, Weg S, Telega G, Rothstein R, Oken H, Schimpff S, Bach H, Bull T, Grant I, Ellingson J, Dahmen H, Lipton J, Gupta S, Chaubey K, Singh M, Agarwal P, Kumar A, Misri J, Sohal J, Dhama K, Hemati Z, Davis W, Hier M, Aitken J, Pierce E, Parrish N, Goldberg N, Kali M, Bendre S, Agrawal G, Baldassano R, Linn P, Sweeney RW, Fecteau M, Hofstaedter C, Potula R, Timofeeva O, Geier S, John K, Zayanni N, Malaty HM, Kahlenborn C, Kravitz A, Bulfon A, Daskalopoulos G, Mitchell H, Neilan B, Timms V, Cossu D, Mameli G, Angermeier P, Jelic T, Goethe R, Juste RA, Kuenstner L. The Consensus from the Mycobacterium avium ssp. paratuberculosis (MAP) Conference 2017. Front Public Health 2017; 5:208. [PMID: 29021977 PMCID: PMC5623710 DOI: 10.3389/fpubh.2017.00208] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Accepted: 07/28/2017] [Indexed: 01/29/2023] Open
Abstract
On March 24 and 25, 2017 researchers and clinicians from around the world met at Temple University in Philadelphia to discuss the current knowledge of Mycobacterium avium ssp. paratuberculosis (MAP) and its relationship to human disease. The conference was held because of shared concern that MAP is a zoonotic bacterium that poses a threat not only to animal health but also human health. In order to further study this problem, the conferees discussed ways to improve MAP diagnostic tests and discussed potential future anti-MAP clinical trials. The conference proceedings may be viewed on the www.Humanpara.org website. A summary of the salient work in this field is followed by recommendations from a majority of the conferees.
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Affiliation(s)
- J Todd Kuenstner
- Temple University Health System, Philadelphia, PA, United States
| | - Saleh Naser
- Temple University Health System, Philadelphia, PA, United States
| | | | - Thomas Borody
- Temple University Health System, Philadelphia, PA, United States
| | - David Y Graham
- Temple University Health System, Philadelphia, PA, United States
| | - Adrienne McNees
- Temple University Health System, Philadelphia, PA, United States
| | | | | | - C Thomas Dow
- Temple University Health System, Philadelphia, PA, United States
| | - Walter Thayer
- Temple University Health System, Philadelphia, PA, United States
| | - James Biesecker
- Temple University Health System, Philadelphia, PA, United States
| | | | - Leonardo A Sechi
- Temple University Health System, Philadelphia, PA, United States
| | - Shoor Vir Singh
- Temple University Health System, Philadelphia, PA, United States
| | - Peilin Zhang
- Temple University Health System, Philadelphia, PA, United States
| | - Ira Shafran
- Temple University Health System, Philadelphia, PA, United States
| | - Stuart Weg
- Temple University Health System, Philadelphia, PA, United States
| | - Grzegorz Telega
- Temple University Health System, Philadelphia, PA, United States
| | - Robert Rothstein
- Temple University Health System, Philadelphia, PA, United States
| | - Harry Oken
- Temple University Health System, Philadelphia, PA, United States
| | - Stephen Schimpff
- Temple University Health System, Philadelphia, PA, United States
| | - Horacio Bach
- Temple University Health System, Philadelphia, PA, United States
| | - Tim Bull
- Temple University Health System, Philadelphia, PA, United States
| | - Irene Grant
- Temple University Health System, Philadelphia, PA, United States
| | - Jay Ellingson
- Temple University Health System, Philadelphia, PA, United States
| | - Heinrich Dahmen
- Temple University Health System, Philadelphia, PA, United States
| | - Judith Lipton
- Temple University Health System, Philadelphia, PA, United States
| | - Saurabh Gupta
- Temple University Health System, Philadelphia, PA, United States
| | - Kundan Chaubey
- Temple University Health System, Philadelphia, PA, United States
| | - Manju Singh
- Temple University Health System, Philadelphia, PA, United States
| | - Prabhat Agarwal
- Temple University Health System, Philadelphia, PA, United States
| | - Ashok Kumar
- Temple University Health System, Philadelphia, PA, United States
| | - Jyoti Misri
- Temple University Health System, Philadelphia, PA, United States
| | - Jagdip Sohal
- Temple University Health System, Philadelphia, PA, United States
| | - Kuldeep Dhama
- Temple University Health System, Philadelphia, PA, United States
| | - Zahra Hemati
- Temple University Health System, Philadelphia, PA, United States
| | - William Davis
- Temple University Health System, Philadelphia, PA, United States
| | - Michael Hier
- Temple University Health System, Philadelphia, PA, United States
| | - John Aitken
- Temple University Health System, Philadelphia, PA, United States
| | - Ellen Pierce
- Temple University Health System, Philadelphia, PA, United States
| | - Nicole Parrish
- Temple University Health System, Philadelphia, PA, United States
| | - Neil Goldberg
- Temple University Health System, Philadelphia, PA, United States
| | - Maher Kali
- Temple University Health System, Philadelphia, PA, United States
| | - Sachin Bendre
- Temple University Health System, Philadelphia, PA, United States
| | - Gaurav Agrawal
- Temple University Health System, Philadelphia, PA, United States
| | | | - Preston Linn
- Temple University Health System, Philadelphia, PA, United States
| | | | - Marie Fecteau
- Temple University Health System, Philadelphia, PA, United States
| | | | - Raghava Potula
- Temple University Health System, Philadelphia, PA, United States
| | - Olga Timofeeva
- Temple University Health System, Philadelphia, PA, United States
| | - Steven Geier
- Temple University Health System, Philadelphia, PA, United States
| | - Kuruvilla John
- Temple University Health System, Philadelphia, PA, United States
| | - Najah Zayanni
- Temple University Health System, Philadelphia, PA, United States
| | - Hoda M Malaty
- Temple University Health System, Philadelphia, PA, United States
| | | | - Amanda Kravitz
- Temple University Health System, Philadelphia, PA, United States
| | - Adriano Bulfon
- Temple University Health System, Philadelphia, PA, United States
| | | | - Hazel Mitchell
- Temple University Health System, Philadelphia, PA, United States
| | - Brett Neilan
- Temple University Health System, Philadelphia, PA, United States
| | - Verlaine Timms
- Temple University Health System, Philadelphia, PA, United States
| | - Davide Cossu
- Temple University Health System, Philadelphia, PA, United States
| | - Giuseppe Mameli
- Temple University Health System, Philadelphia, PA, United States
| | - Paul Angermeier
- Temple University Health System, Philadelphia, PA, United States
| | - Tomislav Jelic
- Temple University Health System, Philadelphia, PA, United States
| | - Ralph Goethe
- Temple University Health System, Philadelphia, PA, United States
| | - Ramon A Juste
- Temple University Health System, Philadelphia, PA, United States
| | - Lauren Kuenstner
- Temple University Health System, Philadelphia, PA, United States
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Foddai A, Grant I. Sensitive and specific detection of viableMycobacterium aviumsubsp.paratuberculosisin raw milk by the peptide-mediated magnetic separation-phage assay. J Appl Microbiol 2017; 122:1357-1367. [DOI: 10.1111/jam.13425] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 01/27/2017] [Accepted: 02/17/2017] [Indexed: 01/25/2023]
Affiliation(s)
- A.C.G. Foddai
- Institute for Global Food Security; School of Biological Sciences; Medical Biology Centre; Queen's University Belfast; Belfast UK
| | - I.R. Grant
- Institute for Global Food Security; School of Biological Sciences; Medical Biology Centre; Queen's University Belfast; Belfast UK
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Bull TJ, Munshi T, Mikkelsen H, Hartmann SB, Sørensen MR, Garcia JS, Lopez-Perez PM, Hofmann S, Hilpert K, Jungersen G. Improved Culture Medium (TiKa) for Mycobacterium avium Subspecies Paratuberculosis (MAP) Matches qPCR Sensitivity and Reveals Significant Proportions of Non-viable MAP in Lymphoid Tissue of Vaccinated MAP Challenged Animals. Front Microbiol 2017; 7:2112. [PMID: 28101082 PMCID: PMC5209360 DOI: 10.3389/fmicb.2016.02112] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Accepted: 12/14/2016] [Indexed: 11/13/2022] Open
Abstract
The quantitative detection of viable pathogen load is an important tool in determining the degree of infection in animals and contamination of foodstuffs. Current conventional culture methods are limited in their ability to determine these levels in Mycobacterium avium subspecies paratuberculosis (MAP) due to slow growth, clumping and low recoverability issues. The principle goal of this study was to evaluate a novel culturing process (TiKa) with unique ability to stimulate MAP growth from low sample loads and dilutions. We demonstrate it was able to stimulate a mean 29-fold increase in recoverability and an improved sensitivity of up to three logs when compared with conventional culture. Using TiKa culture, MAP clumping was minimal and produced visible colonies in half the time required by standard culture methods. Parallel quantitative evaluation of the TiKa culture approach and qPCR on MAP loads in tissue and gut mucosal samples from a MAP vaccine-challenge study, showed good correlations between colony counts (cfu) and qPCR derived genome equivalents (Geq) over a large range of loads with a 30% greater sensitivity for TiKa culture approach at low loads (two logs). Furthermore, the relative fold changes in Geq and cfu from the TiKa culture approach suggests that non-mucosal tissue loads from MAP infected animals contained a reduced proportion of non-viable MAP (mean 19-fold) which was reduced significantly further (mean 190-fold) in vaccinated “reactor” calves. This study shows TiKa culture equates well with qPCR and provides important evidence that accuracy in estimating viable MAP load using DNA tests alone may vary significantly between samples of mucosal and lymphatic origin.
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Affiliation(s)
- Tim J Bull
- Institute of Infection and Immunity, St George's University of London London, UK
| | - Tulika Munshi
- Institute of Infection and Immunity, St George's University of London London, UK
| | - Heidi Mikkelsen
- National Veterinary Institute, Technical University of Denmark (DTU) Kongens Lyngby, Denmark
| | - Sofie B Hartmann
- National Veterinary Institute, Technical University of Denmark (DTU) Kongens Lyngby, Denmark
| | - Maria R Sørensen
- National Veterinary Institute, Technical University of Denmark (DTU) Kongens Lyngby, Denmark
| | - Joanna S Garcia
- Institute of Infection and Immunity, St George's University of London London, UK
| | - Paula M Lopez-Perez
- Institute of Infection and Immunity, St George's University of London London, UK
| | - Sven Hofmann
- Institute of Infection and Immunity, St George's University of London London, UK
| | - Kai Hilpert
- Institute of Infection and Immunity, St George's University of London London, UK
| | - Gregers Jungersen
- National Veterinary Institute, Technical University of Denmark (DTU) Kongens Lyngby, Denmark
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Loganes C, Pin A, Naviglio S, Girardelli M, Bianco AM, Martelossi S, Tommasini A, Piscianz E. Altered pattern of tumor necrosis factor-alpha production in peripheral blood monocytes from Crohn's disease. World J Gastroenterol 2016; 22:9117-9126. [PMID: 27895399 PMCID: PMC5107593 DOI: 10.3748/wjg.v22.i41.9117] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/25/2016] [Accepted: 09/14/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the inflammatory state in Crohn's disease (CD) patients and correlate it with genetic background and microbial spreading. METHODS By means of flow cytometry, production of tumor necrosis factor-alpha (TNF-α) was measured in peripheral blood monocytes from patients suffering from CD, ulcerative colitis (UC) and in healthy subjects after stimulation of the NOD2 and TLR pathways. CD patients were genotyped for the three most common NOD2 variants (R702W, G908R and L1007Pfs*2) and basal production of TNF-α was correlated to NOD2 genotype. Also, production of TNF-α was correlated to plasmatic levels of LPS Binding Protein (LBP), soluble (s) CD14 and to the activity state of the disease. RESULTS The patients with CD were characterized by a significantly higher monocyte basal expression of TNF-α compared with healthy subjects and UC patients, and after stimulation with Pam3CSK4 (ligand of TLR2/1) and MDP-L18 (ligand of NOD2) this difference was maintained, while other microbial stimuli (LPS, ligand of TLR4 and PolyI:C, ligand of TLR3) induced massive activation in CD monocytes as well as in UC and in healthy control cells. There was no significant difference in the production of TNF-α between patients who carried CD-associated heterozygous or homozygous variants in NOD2 and patients with wild type NOD2 genotype. Although serum LBP levels have been shown to correlate positively with the state of activity of the disease, TNF-α production did not show a clear correlation with either LBP or sCD14 levels in plasma. Moreover, no clear correlation was seen between TNF-α production and activity indices in either CD or UC. CONCLUSION Peripheral monocytes from CD express higher basal and stimulated TNF-α than controls, regardless of NOD2 genotype and without a clear correlation with disease activity.
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