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Zhou SH, Du Y, Xue WQ, He MJ, Zhou T, Zhao ZY, Pei L, Chen YW, Xie JR, Huang CL, He YQ, Wang TM, Liao Y, Jia WH. Oral microbiota signature predicts the prognosis of colorectal carcinoma. NPJ Biofilms Microbiomes 2025; 11:71. [PMID: 40325090 PMCID: PMC12053567 DOI: 10.1038/s41522-025-00702-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Accepted: 04/12/2025] [Indexed: 05/07/2025] Open
Abstract
Emerging evidence links oral-derived gut microbes to colorectal cancer (CRC) development, but CRC prognosis-related microbial alterations in oral remain underexplored. In a retrospective study of 312 CRC patients, we examined the oral microbiota using 16S rRNA gene full-length amplicon sequencing to identify prognostic microbial biomarkers for CRC. Neisseria oralis and Campylobacter gracilis increased CRC progression risk (HR = 2.63 with P = 0.007, HR = 2.27 with P = 0.001, respectively), while Treponema medium showed protective effects (HR = 0.41, P = 0.0002). A microbial risk score (MRS) incorporating these species effectively predicted CRC progression risk (C-index = 0.68, 95% CI = 0.61-0.76). When compared to a model constructed solely from clinical factors, including tumor stage, lymphatic metastasis, and perineural invasion, the predictive accuracy significantly improved with the addition of the MRS, resulting in a C-index rising to 0.77 (P = 2.33 × 10-5). Our findings suggest that oral microbiota biomarkers may contribute to personalized CRC monitoring strategies, their implementation in clinical surveillance necessitates confirmatory studies.
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Affiliation(s)
- Shi-Hao Zhou
- School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Yan Du
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R, China
| | - Wen-Qiong Xue
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R, China
| | - Min-Jun He
- School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Ting Zhou
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R, China
| | - Zhi-Yang Zhao
- School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Lu Pei
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R, China
| | - Yi-Wei Chen
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R, China
| | - Jin-Ru Xie
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R, China
| | - Chang-Ling Huang
- School of Public Health, Sun Yat-sen University, Guangzhou, China
| | - Yong-Qiao He
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R, China
| | - Tong-Min Wang
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R, China
| | - Ying Liao
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R, China.
| | - Wei-Hua Jia
- School of Public Health, Sun Yat-sen University, Guangzhou, China.
- State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, P.R, China.
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Giraudon E, Miendje Deyi VY, Martiny D. Assessing the Prevalence and Dynamics of Emerging Campylobacterales in Human Stool Samples in Brussels by Filtration Culture. Pathogens 2024; 13:475. [PMID: 38921773 PMCID: PMC11206970 DOI: 10.3390/pathogens13060475] [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: 05/02/2024] [Revised: 05/24/2024] [Accepted: 05/28/2024] [Indexed: 06/27/2024] Open
Abstract
Thermophilic C. jejuni/coli is reported to be the first bacterial cause of gastroenteritis worldwide and the most common zoonosis in Europe. Although non-jejuni/coli Campylobacter sp. are increasingly suspected to be responsible for diarrhoea or to be involved in inflammatory bowel disease, they remain poorly isolated due to their fastidious and non-thermophilic nature. Additionally, they are not targeted by commercial syndromic PCR assays. In this study, we present routine diagnostic results over 6 years (2017-2019 and 2021-2023) of Campylobacter sp. and related species, obtained by optimised culture from 51,065 stools by both 0.65 µm pore filtration on antibiotic-free agar, incubated in an H2-enriched atmosphere at 37 °C (also known as the Cape Town protocol), and the use of selective inhibitory Butzler medium incubated at 42 °C. This allowed the isolation of 16 Campylobacter species, 2 Aliarcobacter species, and 2 Helicobacter species, providing a completely different view of the epidemiology of Campylobacterales, in which C. jejuni/coli represents only 30.0% of all isolates, while C. concisus represents 44.4%. C. ureolyticus, representing only 5.5% of all Campylobacterales pre-COVID-19, represented 20.6% of all strains post-COVID-19 (218% increase; p < 0.05). At the same time, the proportions of C. jejuni, C. coli, and C. concisus decreased by 37, 53, and 28%, respectively (p < 0.05).
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Affiliation(s)
- Emmanuelle Giraudon
- Department of Microbiology, Laboratoire Hospitalier Universitaire de Bruxelles-Brussel Universitair Laboratorium (LHUB-ULB), Université Libre de Bruxelles (ULB), 1000 Brussels, Belgium (D.M.)
- Belgium National Reference Center for Campylobacter (LHUB-ULB), 1000 Brussels, Belgium
| | - V. Y. Miendje Deyi
- Department of Microbiology, Laboratoire Hospitalier Universitaire de Bruxelles-Brussel Universitair Laboratorium (LHUB-ULB), Université Libre de Bruxelles (ULB), 1000 Brussels, Belgium (D.M.)
- Belgium National Reference Center for Campylobacter (LHUB-ULB), 1000 Brussels, Belgium
| | - Delphine Martiny
- Department of Microbiology, Laboratoire Hospitalier Universitaire de Bruxelles-Brussel Universitair Laboratorium (LHUB-ULB), Université Libre de Bruxelles (ULB), 1000 Brussels, Belgium (D.M.)
- Belgium National Reference Center for Campylobacter (LHUB-ULB), 1000 Brussels, Belgium
- Faculty of Medicine and Pharmacy, University of Mons (UMONS), 7000 Mons, Belgium
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3
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Eriksen C, Danneskiold-Samsøe NB, Moll JM, Myers PN, Bondegaard PW, Vejrum S, Hansen TB, Rosholm LB, Rausch P, Allin KH, Jess T, Kristiansen K, Penders J, Jonkers D, Brix S. Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn's disease. Gut 2024; 73:448-458. [PMID: 38123984 DOI: 10.1136/gutjnl-2023-330677] [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: 07/12/2023] [Accepted: 12/04/2023] [Indexed: 12/23/2023]
Abstract
OBJECTIVE Patients with Crohn's disease (CD) exhibit great heterogeneity in disease presentation and treatment responses, where distinct gut bacteria and immune interactions may play part in the yet unresolved disease aetiology. Given the role of antibodies in the barrier defence against microbes, we hypothesised that gut bacterial antibody-coating patterns may influence underlying disease-mediated processes. DESIGN Absolute and relative single and multicoating of gut bacteria with IgA, IgG1, IgG2, IgG3 and IgG4 in patients with CD and healthy controls were characterised and compared with disease activity. IgG2-coated and non-coated taxa from patients with severe CD were identified, profiled for pathogenic characteristics and monitored for enrichment during active disease across cohorts. RESULTS Patients with severe CD exhibited higher gut bacterial IgG2-coating. Supervised clustering identified 25 bacteria to be enriched in CD patients with high IgG2-coating. Sorting, sequencing and in silico-based assessments of the virulent potential of IgG2-coated and bulk stool bacteria were performed to evaluate the nature and pathogenicity of IgG2-coated and non-coated bacteria. The analyses demonstrated IgG2-coating of both known pathogenic and non-pathogenic bacteria that co-occurred with two non-coated pathobionts, Campylobacter and Mannheimia. The two non-coated pathobionts exhibited low prevalence, rarely coincided and were strongly enriched during disease flares in patients with CD across independent and geographically distant cohorts. CONCLUSION Distinct gut bacterial IgG2-coating was demonstrated in patients with severe CD and during disease flares. Co-occurrence of non-coated pathobionts with IgG2-coated bacteria points to an uncontrolled inflammatory condition in severe CD mediated via escape from antibody coating by two gut pathobionts.
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Affiliation(s)
- Carsten Eriksen
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | | | - Janne Marie Moll
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Pernille Neve Myers
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Pi W Bondegaard
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Simone Vejrum
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Tine Brodka Hansen
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Lisbeth Buus Rosholm
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
| | - Philipp Rausch
- Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
- Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany
| | - Kristine Højgaard Allin
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Tine Jess
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
| | - Karsten Kristiansen
- Center for Molecular Prediction of Inflammatory Bowel Disease, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark
- Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - John Penders
- Department of Medical Microbiology, Infectious Diseases and Infection Prevention, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Daisy Jonkers
- Division Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School for Nutrition and Translation Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Susanne Brix
- Department of Biotechnology and Biomedicine, Technical University of Denmark, Kgs. Lyngby, Denmark
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4
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Luk CYM, Lee SA, Naidovski N, Liu F, Tay ACY, Wang L, Riordan S, Zhang L. Investigation of Campylobacter concisus gastric epithelial pathogenicity using AGS cells. Front Microbiol 2024; 14:1289549. [PMID: 38274743 PMCID: PMC10808343 DOI: 10.3389/fmicb.2023.1289549] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 12/19/2023] [Indexed: 01/27/2024] Open
Abstract
Campylobacter concisus is an oral bacterium. Recent studies suggest that C. concisus may be involved in human gastric diseases. The mechanisms, however, by which C. concisus causes human gastric diseases have not been investigated. Here we examined the gastric epithelial pathogenicity of C. concisus using a cell culture model. Six C. concisus strains and the human gastric epithelial cell line AGS cells were used. IL-8 produced by AGS cells after incubation with C. concisus was measured using enzyme-linked immunosorbent assay (ELISA), and AGS cell apoptosis was determined by caspase 3/7 activities. The effects of C. concisus on actin arrangement in AGS cells was determined using fluorescence staining. The effects of C. concisus on global gene expression in AGS cells was determined by transcriptomic analysis and quantitative real-time PCR (qRT-PCR). The role of the upregulated CYP1A1 gene in gastric cancer survival was assessed using the Kaplan-Meier method. C. concisus induced production of IL-8 by AGS cells with strain variation. Significantly increased caspase 3/7 activities were observed in AGS cells incubated with C. concisus strains when compared to AGS cells without bacteria. C. concisus induced actin re-arrangement in AGS cells. C. concisus upregulated 30 genes in AGS cells and the upregulation of CYP1A1 gene was confirmed by qRT-PCR. The Kaplan-Meier analysis showed that upregulation of CYP1A1 gene is associated with worse survival in gastric cancer patients. Our findings suggest that C. concisus may play a role in gastric inflammation and the progression of gastric cancer. Further investigation in clinical studies is warranted.
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Affiliation(s)
- Christopher Yau Man Luk
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Seul A. Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Nicholas Naidovski
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Alfred Chin Yen Tay
- Helicobacter Research Laboratory, School of Pathology and Laboratory Medicine, Marshall Centre for Infectious Diseases Research and Training, University of Western Australia, Perth, WA, Australia
| | - Liang Wang
- Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
- The Center for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia
- Department of Medical Informatics, School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Stephen Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
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5
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Huq M, Wahid SUH, Istivan T. Biofilm Formation in Campylobacter concisus: The Role of the luxS Gene. Microorganisms 2023; 12:46. [PMID: 38257873 PMCID: PMC10820981 DOI: 10.3390/microorganisms12010046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 12/19/2023] [Accepted: 12/22/2023] [Indexed: 01/24/2024] Open
Abstract
Campylobacter concisus is a bacterium that inhabits human oral cavities and is an emerging intestinal tract pathogen known to be a biofilm producer and one of the bacterial species found in dental plaque. In this study, biofilms of oral and intestinal C. concisus isolates were phenotypically characterized. The role of the luxS gene, which is linked to the regulation of biofilm formation in other pathogens, was assessed in relation to the pathogenic potential of this bacterium. Biofilm formation capacity was assessed using phenotypic assays. Oral strains were shown to be the highest producers. A luxS mutant was created by inserting a kanamycin cassette within the luxS gene of the highest biofilm-forming isolate. The loss of the polar flagellum was observed with scanning and transmission electron microscopy (SEM and TEM). Furthermore, the luxS mutant exhibited a significant reduction (p < 0.05) in biofilm formation, motility, and its expression of flaB, in addition to the capability to invade intestinal epithelial cells, compared to the parental strain. The study concluded that C. concisus oral isolates are significantly higher biofilm producers than the intestinal isolates and that LuxS plays a role in biofilm formation, invasion, and motility in this bacterium.
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Affiliation(s)
- Mohsina Huq
- School of Science, STEM College, RMIT University, Bundoora, Melbourne, VIC 3083, Australia
- Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
| | | | - Taghrid Istivan
- School of Science, STEM College, RMIT University, Bundoora, Melbourne, VIC 3083, Australia
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6
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Kato I, Minkevitch J, Sun J. Oncogenic potential of Campylobacter infection in the gastrointestinal tract: narrative review. Scand J Gastroenterol 2023; 58:1453-1465. [PMID: 37366241 DOI: 10.1080/00365521.2023.2228954] [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: 03/13/2023] [Revised: 05/26/2023] [Accepted: 06/16/2023] [Indexed: 06/28/2023]
Abstract
BACKGROUND Campylobacter jejuni is the leading cause of zoonotic gastroenteritis. The other emerging group of Campylobacters spp. are part of human oral commensal, represented by C. concisus (CC), which has been recently linked to non-oral conditions. Although long-term gastrointestinal (GI) complications from these two groups of Campylobacters have been previously reviewed individually, overall impact of Campylobacter infection on GI carcinogenesis and their inflammatory precursor lesions has not been assessed collectively. AIMS To evaluate the available evidence concerning the association between Campylobacter infection/colonization and inflammatory bowel disease (IBD), reflux esophagitis/metaplasia colorectal cancer (CRC) and esophageal cancer (EC). METHODS We performed a comprehensive literature search of PubMed for relevant original publications and systematic reviews/meta-analyses of epidemiological and clinical studies. In addition, we gathered additional information concerning microbiological data, animal models and mechanistic data from in vitro studies. RESULTS Both retrospective and prospective studies on IBD showed relatively consistent increased risk associated with Campylobacter infection. Despite lack of supporting prospective studies, retrospective studies based on tissue/fecal microbiome revealed consistent enrichment of Campylobacter in CRC samples. Studies on EC precursor lesions (esophagitis and metaplasia) were generally supportive for the association with Campylobacter, while inconsistent observations on EC. Studies on both IBD and EC precursors suggested the predominant role of CC, but studies on CRC were not informative of species. CONCLUSIONS There is sufficient evidence calling for concerted effort in unveiling direct and indirect connection of this organism to colorectal and esophageal cancer in humans.
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Affiliation(s)
- Ikuko Kato
- Department of Oncology and Pathology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Julia Minkevitch
- Rosalind Franklin University of Medicine and Science, Chicago, IL, USA
| | - Jun Sun
- Department of Microbiology/Immunology, University of Illinois at Chicago (UIC), Chicago, IL, USA
- UIC Cancer Center, Chicago, IL, USA
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7
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Soto-Beltrá N M, Lee BG, Amézquita-López BA, Quiñones B. Overview of methodologies for the culturing, recovery and detection of Campylobacter. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2023; 33:307-323. [PMID: 35168460 DOI: 10.1080/09603123.2022.2029366] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 01/11/2022] [Indexed: 06/14/2023]
Abstract
Campylobacter species are responsible for human gastroenteritis with diverse clinical spectra, ranging from acute watery or bloody diarrhea to life-threatening autoimmune disorders. Given the importance of Campylobacter in causing human illness, this article has reviewed the transmission and attribution sources as well as methodologies for the detection and virulence characterization of campylobacteria. The recovery and detection of Campylobacter from clinical, food and environmental samples has been achieved by the combinatorial use of selective enrichment and culturing methods. Biochemical, immunological, and nucleic acid-based methodologies have enabled the detection and differentiation of closely related Campylobacter isolates in foodborne outbreak investigations and have assessed the diversity and phylogenetic relationships of these bacterial pathogens. Analyses of motility, adherence, and invasiveness in host cells have assessed the pathogenic potential of campylobacteria. Further examination of determinants conferring antimicrobial resistance in Campylobacter have supported the growing need to closely monitor antimicrobials use in clinical and agricultural sectors.
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Affiliation(s)
- Marcela Soto-Beltrá N
- Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, Culiacán, México
| | - Bertram G Lee
- Produce Safety and Microbiology Research Unit, United States Department of Agriculture/Agricultural Research Service,Western Regional Research Center, Albany, CA, USA
| | | | - Beatriz Quiñones
- Produce Safety and Microbiology Research Unit, United States Department of Agriculture/Agricultural Research Service,Western Regional Research Center, Albany, CA, USA
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8
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Lynch C, Peeters C, Walsh N, McCarthy C, Coffey A, Lucey B, Vandamme P. Campylobacter majalis sp. nov. and Campylobacter suis sp. nov., novel Campylobacter species isolated from porcine gastrointestinal mucosa. Int J Syst Evol Microbiol 2022; 72. [PMID: 36748456 DOI: 10.1099/ijsem.0.005510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Strains LMG 7974T and LMG 8286T represent single, novel Campylobacter lineages with Campylobacter pinnipediorum and Campylobacter mucosalis as nearest phylogenomic neighbours, respectively. The results of average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) analyses of LMG 7974T, LMG 8286T and type strains of species of the genus Campylobacter confirmed that these strains represent novel species of the genus Campylobacter. The 16S rRNA gene sequences of both strains showed highest identity towards C. mucosalis (97.84 and 98.74 %, respectively). Strains LMG 7974T and LMG 8286T shared 72.5 and 73.7% ANI, respectively, with their nearest phylogenomic neighbours and less than 21 % dDDH. The draft genome sizes of LMG 7974T and LMG 8286T are 1 945429 bp and 1 708214 bp in length with percentage DNA G+C contents of 33.8 and 37.2 %, respectively. Anomalous biochemical characteristics and low MALDI-TOF mass spectrometry log scores supported their designation as representing novel species of the genus Campylobacte. We therefore propose to classify strain LMG 7974T (=CCUG 20705T) as the type strain of the novel species Campylobacter majalis sp. nov. and strain LMG 8286T (=CCUG 24193T, NCTC 11879T) as the type strain of the novel species Campylobacter suis sp. nov.
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Affiliation(s)
- Caoimhe Lynch
- Department of Biological Sciences, Munster Technological University, Rossa Ave, Bishopstown Cork T12 P928, Ireland
| | - Charlotte Peeters
- Laboratory of Microbiology, Department of Biochemistry and Microbiology, Faculty of Sciences, Ghent University, K. L. Ledeganckstraat 35, 9000 Ghent, Belgium
| | - Niamh Walsh
- Department of Biological Sciences, Munster Technological University, Rossa Ave, Bishopstown Cork T12 P928, Ireland
| | - Conor McCarthy
- Department of Biological Sciences, Munster Technological University, Rossa Ave, Bishopstown Cork T12 P928, Ireland
| | - Aidan Coffey
- Department of Biological Sciences, Munster Technological University, Rossa Ave, Bishopstown Cork T12 P928, Ireland.,APC Microbiome Institute, Cork, Ireland
| | - Brigid Lucey
- Department of Biological Sciences, Munster Technological University, Rossa Ave, Bishopstown Cork T12 P928, Ireland
| | - Peter Vandamme
- Laboratory of Microbiology, Department of Biochemistry and Microbiology, Faculty of Sciences, Ghent University, K. L. Ledeganckstraat 35, 9000 Ghent, Belgium
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9
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Liu F, Lee SA, Xue J, Riordan SM, Zhang L. Global epidemiology of campylobacteriosis and the impact of COVID-19. Front Cell Infect Microbiol 2022; 12:979055. [PMID: 36519137 PMCID: PMC9742372 DOI: 10.3389/fcimb.2022.979055] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 10/21/2022] [Indexed: 11/29/2022] Open
Abstract
Campylobacteriosis is a gastroenteritis caused by pathogenic Campylobacter species and an important topic in public health. Here we review the global epidemiology of campylobacteriosis in the last eight years between 2014-2021, providing comprehensive and updated information on the reported incidence and outbreaks of Campylobacter infections. The government public health website of each of the 195 countries and publications from 2014 to September 2022 in public databases were searched. The reported incidence of campylobacteriosis in pre-COVID-19 years was compared to that during the COVID-19 pandemic in countries where data were available. Czech Republic had the highest reported incidence of campylobacteriosis worldwide (215 per 100,000 in 2019), followed by Australia (146.8 per 100,000 in 2016) and New Zealand (126.1 per 100,000 in 2019). Campylobacter was one of the most common human enteric pathogens in both developed and developing countries. About 90% of cases of campylobacteriosis were caused by Campylobacter jejuni, whereas less than 10% of cases were caused by Campylobacter coli. Other Campylobacter species were also isolated. The reported incidence and case numbers of campylobacteriosis in developed nations have remained steadily high prior to the COVID-19 pandemic, whilst some countries reported an increasing trend such as France and Japan. While outbreaks were more frequently reported in some countries, Campylobacter infections were mainly sporadic cases in most of the developed countries. Campylobacter infection was more common in summer in some but not all countries. Campylobacter infection was more common in males than females. The COVID-19 pandemic has reduced the reported incidence of campylobacteriosis in most countries where 2020 epidemiology data were available. In conclusion, Campylobacter infection remains a global health concern. Increased research and improved strategies are needed for prevention and reduction of Campylobacter infection.
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Affiliation(s)
- Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Seul A. Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Jessica Xue
- Faculty of Medicine, Monash University, Melbourne, VIC, Australia
| | - Stephen M. Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
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10
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Insight into the Relationship between Oral Microbiota and the Inflammatory Bowel Disease. Microorganisms 2022; 10:microorganisms10091868. [PMID: 36144470 PMCID: PMC9505529 DOI: 10.3390/microorganisms10091868] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 09/03/2022] [Accepted: 09/09/2022] [Indexed: 11/17/2022] Open
Abstract
Inflammatory bowel disease has been a growing concern of lots of people globally, including both adults and children. As a chronic inflammatory disease of the intestine, even though the etiology of inflammatory bowel disease is still unclear, the available evidence from clinic observations has suggested a close association with microorganisms. The oral microbiota possesses the characteristics of a large number and abundant species, second only to the intestinal microbiota in the human body; as a result, it successfully attracts the attention of researchers. The highly diverse commensal oral microbiota is not only a normal part of the oral cavity but also has a pronounced impact on the pathophysiology of general health. Numerous studies have shown the potential associations between the oral microbiota and inflammatory bowel disease. Inflammatory bowel disease can affect the composition of the oral microbiota and lead to a range of oral pathologies. In turn, there are a variety of oral microorganisms involved in the development and progression of inflammatory bowel disease, including Streptococcus spp., Fusobacterium nucleatum, Porphyromonas gingivalis, Campylobacter concisus, Klebsiella pneumoniae, Saccharibacteria (TM7), and Candida albicans. Based on the above analysis, the purpose of this review is to summarize this relationship of mutual influence and give further insight into the detection of flora as a target for the diagnosis and treatment of inflammatory bowel disease to open up a novel approach in future clinical practice.
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11
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Piazzesi A, Putignani L. Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention. Front Microbiol 2022; 13:958346. [PMID: 36071979 PMCID: PMC9441770 DOI: 10.3389/fmicb.2022.958346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 07/25/2022] [Indexed: 11/15/2022] Open
Abstract
Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.
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Affiliation(s)
- Antonia Piazzesi
- Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Lorenza Putignani
- Department of Diagnostic and Laboratory Medicine, Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
- *Correspondence: Lorenza Putignani,
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12
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Kitamoto S, Kamada N. Periodontal connection with intestinal inflammation: Microbiological and immunological mechanisms. Periodontol 2000 2022; 89:142-153. [PMID: 35244953 PMCID: PMC9018512 DOI: 10.1111/prd.12424] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Humans have coevolved with the trillions of resident microbes that populate every nook and cranny of the body. At each site, the resident microbiota creates a unique ecosystem specialized to its environment, benefiting the development and maintenance of human physiology through harmonious symbiotic relationships with the host. However, when the resident microbiota is perturbed, significant complications may arise with disastrous consequences that affect the local and distant ecosystems. In this context, periodontal disease results in inflammation beyond the oral cavity, such as in the gastrointestinal tract. Accumulating evidence indicates that potentially harmful oral resident bacteria (referred to as pathobionts) and pathogenic immune cells in the oral mucosa can migrate to the lower gastrointestinal tract and contribute to intestinal inflammation. We will review the most recent advances concerning the periodontal connection with intestinal inflammation from microbiological and immunological perspectives. Potential therapeutic approaches that target the connection between the mouth and the gut to treat gastrointestinal diseases, such as inflammatory bowel disease, will be examined. Deciphering the complex interplay between microbes and immunity along the mouth-gut axis will provide a better understanding of the pathogenesis of both oral and gut pathologies and present therapeutic opportunities.
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Affiliation(s)
- Sho Kitamoto
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineUniversity of MichiganAnn ArborMichiganUSA
| | - Nobuhiko Kamada
- Division of Gastroenterology and HepatologyDepartment of Internal MedicineUniversity of MichiganAnn ArborMichiganUSA
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13
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Zhang L, Liu F, Xue J, Lee SA, Liu L, Riordan SM. Bacterial Species Associated With Human Inflammatory Bowel Disease and Their Pathogenic Mechanisms. Front Microbiol 2022; 13:801892. [PMID: 35283816 PMCID: PMC8908260 DOI: 10.3389/fmicb.2022.801892] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 01/25/2022] [Indexed: 12/17/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with unknown etiology. The pathogenesis of IBD results from immune responses to microbes in the gastrointestinal tract. Various bacterial species that are associated with human IBD have been identified. However, the microbes that trigger the development of human IBD are still not clear. Here we review bacterial species that are associated with human IBD and their pathogenic mechanisms to provide an updated broad understanding of this research field. IBD is an inflammatory syndrome rather than a single disease. We propose a three-stage pathogenesis model to illustrate the roles of different IBD-associated bacterial species and gut commensal bacteria in the development of human IBD. Finally, we recommend microbe-targeted therapeutic strategies based on the three-stage pathogenesis model.
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Affiliation(s)
- Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Jessica Xue
- Faculty of Medicine, Monash University, Melbourne, VIC, Australia
| | - Seul A. Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Lu Liu
- School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Stephen M. Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia
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14
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Qi Y, Wu HM, Yang Z, Zhou YF, Jin L, Yang MF, Wang FY. New Insights into the Role of Oral Microbiota Dysbiosis in the Pathogenesis of Inflammatory Bowel Disease. Dig Dis Sci 2022; 67:42-55. [PMID: 33527328 DOI: 10.1007/s10620-021-06837-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 01/09/2021] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory disorders with a prolonged duration characterized by recurrent relapse and remission. The exact etiology of IBD remains poorly understood despite the identification of relevant risk factors, including individual genetic susceptibility, environmental triggers, and disruption of immune homeostasis. Dysbiosis of the gut microbiota is believed to exacerbate the progression of IBD. Recently, increasing evidence has also linked oral microbiota dysbiosis with the development of IBD. On the one hand, IBD patients show significantly unbalanced composition and function of the oral microbiota known as dysbiosis. On the other, overabundances of oral commensal bacteria with opportunistic pathogenicity have been found in the gut microbiota of IBD patients. Herein, we review the current information on the causative factors of IBD, especially recent evidence of IBD-associated oral microbiota dysbiosis, which has seldom been covered in the previous literature review, highlighting the pathogenic mechanisms of specific oral bacteria in the development of IBD. Ectopic colonization of several oral bacteria, including a subset of Porphyromonas gingivalis, Streptococcus mutans, Fusobacterium nucleatum, Campylobacter concisus, and Klebsiella pneumoniae, may lead to destruction of the intestinal epithelial barrier, excessive secretion of inflammatory cytokines, disruption of the host immune system, and dysbiosis of gut microbiota, consequently aggravating chronic intestinal inflammation. Studying oral microbiota dysbiosis may open future horizons for understanding IBD pathogenesis and provide novel biomarkers for IBD. This review also presents the current treatment and new perspectives for IBD treatment.
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Affiliation(s)
- Ying Qi
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China
| | - Hui-Min Wu
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China
| | - Zhao Yang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China
| | - Yi-Fei Zhou
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China
| | - Lei Jin
- Department of Stomatology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Miao-Fang Yang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China
| | - Fang-Yu Wang
- Department of Gastroenterology and Hepatology, Jinling Hospital, Medical School of Nanjing University, Zhongshan East Road 305, Nanjing, 210002, China.
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15
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Yang K, Wang Y, Zhang S, Zhang D, Hu L, Zhao T, Zheng H. Oral Microbiota Analysis of Tissue Pairs and Saliva Samples From Patients With Oral Squamous Cell Carcinoma - A Pilot Study. Front Microbiol 2021; 12:719601. [PMID: 34712209 PMCID: PMC8546327 DOI: 10.3389/fmicb.2021.719601] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Accepted: 09/23/2021] [Indexed: 12/24/2022] Open
Abstract
Oral microbiota dysbiosis is associated with the occurrence and progression of oral cancer. To investigate the association between the microbiota and risk of oral squamous cell carcinoma (OSCC), we identified the microbial composition of paired tumor (TT)/normal paracancerous tissues (NPT) and saliva (TS) samples in OSCC patients through 16S rRNA gene sequencing. A total of 22 phyla, 321 genera, and 869 species were identified in the oral samples. Paired comparisons revealed significant differences between TT, NPT, and TS groups, with the genus Filifactor significantly enriched in TT. The phylum Actinobacteria; genus Veillonella; and species Granulicatella adiacens, Streptococcus sanguinis, and Veillonella rogosae were significantly enriched in NPT, while the phylum Bacteroidetes; genera Capnocytophaga, Haemophilus, and Prevotella; and seven species, including Capnocytophaga sp., Haemophilus sp., and Neisseria sp., were significantly enriched in TS. In TTs, the abundance of Prevotella intermedia was profoundly higher in the gingiva, while Capnocytophaga gingivalis and Rothia mucilaginosa were enriched in the lining mucosa and tongue. Increasing in abundance from the early tumor stage to the late stage, Solobacterium moorei in TT and Campylobacter sp. strain HMT 044 in TS were positively correlated with OSCC development, suggesting that bacteria were selected by different microenvironments. The correlation between 11 microbial species and 17 pathway abundances was revealed, indicating the potential function of low-abundance bacteria. Overall, our analysis revealed that multiple oral bacterial taxa are associated with a subsequent risk of OSCC and may be used as biomarkers for risk prediction and intervention in oral cancers.
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Affiliation(s)
- Ke Yang
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.,Department of Health Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Yuezhu Wang
- NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai, China.,Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai and Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China
| | - Shizhou Zhang
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Dongsheng Zhang
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Lihua Hu
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Tengda Zhao
- Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Huajun Zheng
- NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai, China
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16
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Lee SA, Liu F, Yun DY, Riordan SM, Tay ACY, Liu L, Lee CS, Zhang L. Campylobacter concisus upregulates PD-L1 mRNA expression in IFN-γ sensitized intestinal epithelial cells and induces cell death in esophageal epithelial cells. J Oral Microbiol 2021; 13:1978732. [PMID: 34552702 PMCID: PMC8451702 DOI: 10.1080/20002297.2021.1978732] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/20/2021] [Accepted: 09/06/2021] [Indexed: 12/23/2022] Open
Abstract
Introduction: Campylobacter concisus is an oral bacterium that is associated with inflammatory bowel disease (IBD) and Barrett's esophagus (BE). Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that is used by tumor cells for immune evasion and has increased expression in patients with IBD and BE. We examined whether C. concisus upregulates PD-L1 expression in intestinal and esophageal epithelial cells. Methods: Human intestinal epithelial HT-29 cells and esophageal epithelial FLO-1 cells with and without interferon (IFN)-γ sensitization were incubated with C. concisus strains. The level of PD-L1 mRNA was quantified using quantitative real-time PCR. Cytokines were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Apoptosis of HT-29 and FLO-1 cells were measured using caspase 3/7 assay. Results: We found that intestinal epithelial cells with IFN-γ sensitization incubated with C. concisus significantly upregulated PD-L1 expression and significantly increased the production of interleukin (IL)-8. Whereas, PD-L1 expression was significantly inhibited in IFN-γ sensitized FLO-1 cells incubated with C. concisus strains. Furthermore, FLO-1 cells with and without IFN-γ sensitization incubated with C. concisus strains both had significantly higher levels of cell death. Conclusion: C. concisushas the potential to cause damage to both intestinal and esophageal epithelial cells, however, with different pathogenic effects.
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Affiliation(s)
- Seul A Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Doo Young Yun
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Stephen M Riordan
- Gastrointestinal and Liver Unit,Prince of Wales Hospital, University of New South Wales, Sydney, Australia
| | - Alfred Chin Yen Tay
- Helicobacter Research Laboratory, Marshall Centre for Infectious Diseases Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia
| | - Lu Liu
- School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Cheok Soon Lee
- School of Medicine, Western Sydney University, Sydney, Australia
- South Western Sydney Clinical School, University of New South Wales, Sydney, Australia
- Central Clinical School, University of Sydney, Sydney, Australia
- Department of Anatomical Pathology, Liverpool Hospital, Sydney, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
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17
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Association of Fungi and Archaea of the Gut Microbiota with Crohn's Disease in Pediatric Patients-Pilot Study. Pathogens 2021; 10:pathogens10091119. [PMID: 34578152 PMCID: PMC8468012 DOI: 10.3390/pathogens10091119] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 08/29/2021] [Accepted: 08/29/2021] [Indexed: 01/10/2023] Open
Abstract
The composition of bacteria is often altered in Crohn’s disease (CD), but its connection to the disease is not fully understood. Gut archaea and fungi have recently been suggested to play a role as well. In our study, the presence and number of selected species of fungi and archaea in pediatric patients with CD and healthy controls were evaluated. Stool samples were collected from children with active CD (n = 54), non-active CD (n = 37) and control subjects (n = 33). The prevalence and the number of selected microorganisms were assessed by real-time PCR. The prevalence of Candida tropicalis was significantly increased in active CD compared to non-active CD and the control group (p = 0.011 and p = 0.036, respectively). The number of Malassezia spp. cells was significantly lower in patients with active CD compared to the control group, but in non-active CD, a significant increase was observed (p = 0.005 and p = 0.020, respectively). There were no statistically significant differences in the colonization by archaea. The obtained results indicate possible correlations with the course of the CD; however, further studies of the entire archeobiome and the mycobiome are necessary in order to receive a complete picture.
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18
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Khan IA, Nayak B, Markandey M, Bajaj A, Verma M, Kumar S, Singh MK, Kedia S, Ahuja V. Differential prevalence of pathobionts and host gene polymorphisms in chronic inflammatory intestinal diseases: Crohn's disease and intestinal tuberculosis. PLoS One 2021; 16:e0256098. [PMID: 34407136 PMCID: PMC8372915 DOI: 10.1371/journal.pone.0256098] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 07/31/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Crohn's disease (CD) and Intestinal tuberculosis (ITB) are chronic inflammatory ulcero-constrictive intestinal diseases with similar phenotype. Although both are disease models of chronic inflammation and their clinical presentations, imaging, histological and endoscopic findings are very similar, yet their etiologies are diverse. Hence, we aimed to look at differences in the prevalence of pathobionts like adherent-invasive Escherichia coli (AIEC), Listeria monocytogenes, Campylobacter jejuni and Yersinia enterocolitica in CD and ITB as well as their associations with host-associated genetic polymorphisms in genes majorly involved in pathways of microbial handling and immune responses. METHODS The study cohort included 142 subjects (69 patients with CD, 32 with ITB and 41 controls). RT- PCR amplification was used to detect the presence of AIEC, L. monocytogenes, C. jejuni, and Y. enterocolitica DNA in colonic mucosal biopsies. Additionally, we tested three SNPs in IRGM (rs13361189, rs10065172, and rs4958847), one SNP in ATG16L1 (rs2241880) and one SNP in TNFRSF1A (rs4149570) by real-time PCR with SYBR green from peripheral blood samples in this cohort. RESULTS In patients with CD, AIEC was most frequently present (16/ 69, 23.19%) followed by L. monocytogenes (14/69, 20.29%), C. jejuni (9/69, 13.04%), and Y. enterocolitica (7/69, 10.14%). Among them, L. monocytogenes and Y. enterocolitica were significantly associated with CD (p = 0.02). In addition, we identified all the three SNPs in IRGM (rs13361189, rs10065172, and rs4958847), one SNP in ATG16L1 (rs2241880) and TNFRSF1A (rs4149570) with a significant difference in frequency in patients with CD compared with ITB and controls (p<0.05). CONCLUSION Higher prevalence of host gene polymorphisms, as well as the presence of pathobionts, was seen in the colonic mucosa of patients with CD as compared to ITB, although both are disease models of chronic inflammation.
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Affiliation(s)
- Imteyaz Ahmad Khan
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Baibaswata Nayak
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Manasvini Markandey
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Aditya Bajaj
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Mahak Verma
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Sambudhha Kumar
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Mukesh Kumar Singh
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India
- * E-mail:
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19
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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: 36] [Impact Index Per Article: 9.0] [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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20
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Cornelius AJ, Huq M, On SLW, French NP, Vandenberg O, Miller WG, Lastovica AJ, Istivan T, Biggs PJ. Genetic characterisation of Campylobacter concisus: Strategies for improved genomospecies discrimination. Syst Appl Microbiol 2021; 44:126187. [PMID: 33677170 DOI: 10.1016/j.syapm.2021.126187] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 02/03/2021] [Accepted: 02/08/2021] [Indexed: 02/08/2023]
Abstract
Although at least two genetically distinct groups, or genomospecies, have been well documented for Campylobacter concisus, no phenotype has yet been identified for their differentiation and thus formal description as separate species. C. concisus has been isolated from a variety of sites in the human body, including saliva and stool samples from both healthy and diarrhoeic individuals. We evaluated the ability of a range of whole genome-based tools to distinguish between the two C. concisus genomospecies (GS) using a collection of 190 C. concisus genomes. Nine genomes from related Campylobacter species were included in some analyses to provide context. Analyses incorporating sequence analysis of multiple ribosomal genes generated similar levels of C. concisus GS discrimination as genome-wide comparisons. The C. concisus genomes formed two groups; GS1 represented by ATCC 33237T and GS2 by CCUG 19995. The two C. concisus GS were separated from the nine genomes of related species. GS1 and GS2 also differed in G+C content with medians of 37.56% and 39.51%, respectively. The groups are consistent with previously established GS and are supported by DNA reassociation results. Average Nucleotide Identity using MUMmer (ANIm) and Genome BLAST Distance Phylogeny generated in silico DNA-DNA hybridisation (isDDH) (against ATCC 33237T and CCUG 19995), plus G+C content provides cluster-independent GS discrimination suitable for routine use. Pan-genomic analysis identified genes specific to GS1 and GS2. WGS data and genomic species identification methods support the existence of two GS within C. concisus. These data provide genome-level metrics for strain identification to genomospecies level.
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Affiliation(s)
- Angela J Cornelius
- Institute of Environmental Science and Research Ltd, P.O. Box 29181, Christchurch 8540, New Zealand.
| | - Mohsina Huq
- School of Science, RMIT University, G.P.O. Box 2476, Bundoora, Victoria 3001, Australia
| | - Stephen L W On
- Lincoln University, P.O. Box 85084, Lincoln 7647, New Zealand
| | - Nigel P French
- Massey University, Private Bag 11 222, Palmerston North 4442, New Zealand
| | - Olivier Vandenberg
- National Reference Centre for Campylobacter, Laboratoire Hospitalier Universitaire de Bruxelles, 322 rue Haute, 1000 Brussels, Belgium; School of Public Health, Campus Erasme - Bâtiment A, Route de Lennik 808 - CP591, Université Libre de Bruxelles, 1070 Bruxelles, Belgium
| | - William G Miller
- Produce Safety and Microbiology Research Unit, Agricultural Research Service, United States Department of Agriculture, 800 Buchanan Street, Albany, CA 94710, USA
| | - Albert J Lastovica
- University of Western Cape, Private Bag X17, Bellville 7535, South Africa
| | - Taghrid Istivan
- School of Science, RMIT University, G.P.O. Box 2476, Bundoora, Victoria 3001, Australia
| | - Patrick J Biggs
- Massey University, Private Bag 11 222, Palmerston North 4442, New Zealand
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21
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Kim SH, Chelliah R, Ramakrishnan SR, Perumal AS, Bang WS, Rubab M, Daliri EBM, Barathikannan K, Elahi F, Park E, Jo HY, Hwang SB, Oh DH. Review on Stress Tolerance in Campylobacter jejuni. Front Cell Infect Microbiol 2021; 10:596570. [PMID: 33614524 PMCID: PMC7890702 DOI: 10.3389/fcimb.2020.596570] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/03/2020] [Indexed: 01/17/2023] Open
Abstract
Campylobacter spp. are the leading global cause of bacterial colon infections in humans. Enteropathogens are subjected to several stress conditions in the host colon, food complexes, and the environment. Species of the genus Campylobacter, in collective interactions with certain enteropathogens, can manage and survive such stress conditions. The stress-adaptation mechanisms of Campylobacter spp. diverge from other enteropathogenic bacteria, such as Escherichia coli, Salmonella enterica serovar Typhi, S. enterica ser. Paratyphi, S. enterica ser. Typhimurium, and species of the genera Klebsiella and Shigella. This review summarizes the different mechanisms of various stress-adaptive factors on the basis of species diversity in Campylobacter, including their response to various stress conditions that enhance their ability to survive on different types of food and in adverse environmental conditions. Understanding how these stress adaptation mechanisms in Campylobacter, and other enteric bacteria, are used to overcome various challenging environments facilitates the fight against resistance mechanisms in Campylobacter spp., and aids the development of novel therapeutics to control Campylobacter in both veterinary and human populations.
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Affiliation(s)
- Se-Hun Kim
- Food Microbiology Division, Food Safety Evaluation Department, National Institute of Food and Drug Safety Evaluation, Cheongju, South Korea.,College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Ramachandran Chelliah
- College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Sudha Rani Ramakrishnan
- School of Food Science, Department of Food Science and Biotechnology, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, South Korea
| | | | - Woo-Suk Bang
- Department of Food and Nutrition, College of Human Ecology and Kinesiology, Yeungnam University, Gyeongsan, South Korea
| | - Momna Rubab
- College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Eric Banan-Mwine Daliri
- College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Kaliyan Barathikannan
- College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Fazle Elahi
- College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Eunji Park
- College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Hyeon Yeong Jo
- College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Su-Bin Hwang
- College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
| | - Deog Hwan Oh
- College of Agriculture and Life Sciences, Kangwon National University, Chuncheon, South Korea
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22
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Liu F, Chen S, Luu LDW, Lee SA, Tay ACY, Wu R, Riordan SM, Lan R, Liu L, Zhang L. Analysis of complete Campylobacter concisus genomes identifies genomospecies features, secretion systems and novel plasmids and their association with severe ulcerative colitis. Microb Genom 2020; 6:mgen000457. [PMID: 33111662 PMCID: PMC7725323 DOI: 10.1099/mgen.0.000457] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 10/01/2020] [Indexed: 12/12/2022] Open
Abstract
Campylobacter concisus is an emerging enteric pathogen that is associated with several gastrointestinal diseases, such as inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). Currently, only three complete C. concisus genomes are available and more complete C. concisus genomes are needed in order to better understand the genomic features and pathogenicity of this emerging pathogen. DNA extracted from 22 C. concisus strains were subjected to Oxford Nanopore genome sequencing. Complete genome assembly was performed using Nanopore genome data in combination with previously reported short-read Illumina data. Genome features of complete C. concisus genomes were analysed using bioinformatic tools. The enteric disease associations of C. concisus plasmids were examined using 239 C. concisus strains and confirmed using PCRs. Proteomic analysis was used to examine T6SS secreted proteins. We successfully obtained 13 complete C. concisus genomes in this study. Analysis of 16 complete C. concisus genomes (3 from public databases) identified multiple novel plasmids. pSma1 plasmid was found to be associated with severe UC. Sec-SRP, Tat and T6SS were found to be the main secretion systems in C. concisus and proteomic data showed a functional T6SS despite the lack of ClpV. T4SS was found in 25% of complete C. concisus genomes. This study also found that GS2 strains had larger genomes and higher GC content than GS1 strains and more often had plasmids. In conclusion, this study provides fundamental genomic data for understanding C. concisus plasmids, genomospecies features, evolution, secretion systems and pathogenicity.
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Affiliation(s)
- Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Siying Chen
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Laurence Don Wai Luu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Seul A. Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Alfred Chin Yen Tay
- Helicobacter Research Laboratory, Marshall Centre for Infectious Diseases Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia
| | - Ruochen Wu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Stephen M. Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, Australia
| | - Ruiting Lan
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Lu Liu
- School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
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23
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The microbiome in inflammatory bowel diseases: from pathogenesis to therapy. Protein Cell 2020; 12:331-345. [PMID: 32601832 PMCID: PMC8106558 DOI: 10.1007/s13238-020-00745-3] [Citation(s) in RCA: 154] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 05/30/2020] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease (IBD) has become a global disease with accelerating incidence worldwide in the 21st century while its accurate etiology remains unclear. In the past decade, gut microbiota dysbiosis has consistently been associated with IBD. Although many IBD-associated dysbiosis have not been proven to be a cause or an effect of IBD, it is often hypothesized that at least some of alteration in microbiome is protective or causative. In this article, we selectively reviewed the hypothesis supported by both association studies in human and pathogenesis studies in biological models. Specifically, we reviewed the potential protective bacterial pathways and species against IBD, as well as the potential causative bacterial pathways and species of IBD. We also reviewed the potential roles of some members of mycobiome and virome in IBD. Lastly, we covered the current status of therapeutic approaches targeting microbiome, which is a promising strategy to alleviate and cure this inflammatory disease.
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24
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Chen J, Liu F, Lee SA, Chen S, Zhou X, Ye P, Riordan SM, Liu L, Zhang L. Detection of IL-18 and IL-1β protein and mRNA in human oral epithelial cells induced by Campylobacter concisus strains. Biochem Biophys Res Commun 2019; 518:44-49. [PMID: 31400853 DOI: 10.1016/j.bbrc.2019.08.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Accepted: 08/02/2019] [Indexed: 01/20/2023]
Abstract
Campylobacter concisus is an emerging bacterial pathogen that may play a role in the development of inflammatory bowel disease and oral inflammatory conditions such as periodontal disease. To elucidate the role and pathogenic mechanisms of C. concisus in contributing to oral inflammation, this study examined the production of IL-1 family proinflammatory cytokines IL-18 and IL-1β in oral epithelial cells induced by C. concisus strains using enzyme-linked immunosorbent assay (ELISA), Western-blot and quantitative real-time PCR. C. concisus increased the mRNA levels of IL-18 and IL-1β in oral epithelial cells. Furthermore, a large amount of IL-18 in the supernatants of oral epithelial cells infected with C. concisus strains was detected by ELISA, and various experiments demonstrated that this positive signal was derived from C. concisus bacterium. The findings that C. concisus upregulated IL-18 and IL-1β in oral epithelial cells from this study support a role of C. concisus in oral inflammatory diseases. Furthermore, the finding that C. concisus released a molecule that was strongly cross-reactive to anti-human IL-18 monoclonal antibodies suggests that in future studies examining cytokines induced by bacterial microbes, a bacterium control should be included.
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Affiliation(s)
- Jieqiong Chen
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Seul A Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Siying Chen
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Xiaoyan Zhou
- Institute of Dental Research, Centre for Oral Health, University of Sydney, Sydney, Australia
| | - Ping Ye
- Institute of Dental Research, Centre for Oral Health, University of Sydney, Sydney, Australia
| | - Stephen M Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, Australia
| | - Lu Liu
- School of Medical Sciences, University of New South Wales, Sydney, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
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25
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Abstract
Campylobacter is among the four main causes of gastroenteritis worldwide and has increased in both developed and developing countries over the last 10 years. The vast majority of reported Campylobacter infections are caused by Campylobacter jejuni and, to a lesser extent, C. coli; however, the increasing recognition of other emerging Campylobacter pathogens is urgently demanding a better understanding of how these underestimated species cause disease, transmit, and evolve. In parallel to the enhanced clinical awareness of campylobacteriosis due to improved diagnostic protocols, the application of high-throughput sequencing has increased the number of whole-genome sequences available to dozens of strains of many emerging campylobacters. This has allowed for comprehensive comparative pathogenomic analyses for several species, such as C. fetus and C. concisus These studies have started to reveal the evolutionary forces shaping their genomes and have brought to light many genomic features related to pathogenicity in these neglected species, promoting the development of new tools and approaches relevant for clinical microbiology. Despite the need for additional characterization of genomic diversity in emerging campylobacters, the increasing body of literature describing pathogenomic studies on these species deserves to be discussed from an integrative perspective. This review compiles the current knowledge and highlights future work toward deepening our understanding about genome dynamics and the mechanisms governing the evolution of pathogenicity in emerging Campylobacter species, which is urgently needed to develop strategies to prevent or control the spread of these pathogens.
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Affiliation(s)
- Daniela Costa
- Microbial Genomics Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Sección Genética Evolutiva, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay
| | - Gregorio Iraola
- Microbial Genomics Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay
- Center for Integrative Biology, Universidad Mayor, Santiago de Chile, Chile
- Wellcome Sanger Institute, Hinxton, United Kingdom
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26
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Hsu T, Gemmell MR, Franzosa EA, Berry S, Mukhopadhya I, Hansen R, Michaud M, Nielsen H, Miller WG, Nielsen H, Bajaj-Elliott M, Huttenhower C, Garrett WS, Hold GL. Comparative genomics and genome biology of Campylobacter showae. Emerg Microbes Infect 2019; 8:827-840. [PMID: 31169073 PMCID: PMC6567213 DOI: 10.1080/22221751.2019.1622455] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Campylobacter showae a bacterium historically linked to gingivitis and periodontitis, has recently been associated with inflammatory bowel disease and colorectal cancer. Our aim was to generate genome sequences for new clinical C. showae strains and identify functional properties explaining their pathogenic potential. Eight C. showae genomes were assessed, four strains isolated from inflamed gut tissues from paediatric Crohn’s disease patients, three strains from colonic adenomas, and one from a gastroenteritis patient stool. Genome assemblies were analyzed alongside the only 3 deposited C. showae genomes. The pangenome from these 11 strains consisted of 4686 unique protein families, and the core genome size was estimated at 1050 ± 15 genes with each new genome contributing an additional 206 ± 16 genes. Functional assays indicated that colonic strains segregated into 2 groups: adherent/invasive vs. non-adherent/non-invasive strains. The former possessed Type IV secretion machinery and S-layer proteins, while the latter contained Cas genes and other CRISPR associated proteins. Comparison of gene profiles with strains in Human Microbiome Project metagenomes showed that gut-derived isolates share genes specific to tongue dorsum and supragingival plaque counterparts. Our findings indicate that C. showae strains are phenotypically and genetically diverse and suggest that secretion systems may play an important role in virulence potential.
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Affiliation(s)
- Tiffany Hsu
- a Department of Biostatistics , Harvard T. H. Chan School of Public Health , Boston , USA
| | - Matthew R Gemmell
- b School of Medicine, Medical Sciences and Nutrition , Centre for Genome Enabled Biology and Medicine, University of Aberdeen , Aberdeen , UK
| | - Eric A Franzosa
- a Department of Biostatistics , Harvard T. H. Chan School of Public Health , Boston , USA
| | - Susan Berry
- c School of Medicine, Medical Sciences and Nutrition , GI Research Group, University of Aberdeen , Aberdeen , UK
| | - Indrani Mukhopadhya
- c School of Medicine, Medical Sciences and Nutrition , GI Research Group, University of Aberdeen , Aberdeen , UK
| | - Richard Hansen
- d Department of Paediatric Gastroenterology , Royal Hospital for Children , Glasgow , UK
| | - Monia Michaud
- e Departments of Genetics and Complex Diseases and Immunology and Infectious Diseases , Harvard T. H. Chan School of Public Health , Boston , USA
| | - Hans Nielsen
- f Department of Clinical Microbiology , Aalborg University Hospital , Aalborg , Denmark
| | - William G Miller
- g Produce Safety and Microbiology Research Unit, U.S. Department of Agriculture , Agricultural Research Service , Albany , USA
| | - Henrik Nielsen
- h Department of Infectious Diseases , Aalborg University Hospital Aalborg , Denmark
| | - Mona Bajaj-Elliott
- i Infection, Immunity, Inflammation Programme , UCL Great Ormond Street Institute of Child Health , London , UK
| | - Curtis Huttenhower
- a Department of Biostatistics , Harvard T. H. Chan School of Public Health , Boston , USA
| | - Wendy S Garrett
- e Departments of Genetics and Complex Diseases and Immunology and Infectious Diseases , Harvard T. H. Chan School of Public Health , Boston , USA
| | - Georgina L Hold
- a Department of Biostatistics , Harvard T. H. Chan School of Public Health , Boston , USA.,c School of Medicine, Medical Sciences and Nutrition , GI Research Group, University of Aberdeen , Aberdeen , UK.,e Departments of Genetics and Complex Diseases and Immunology and Infectious Diseases , Harvard T. H. Chan School of Public Health , Boston , USA.,j St George and Sutherland Clinical School , Microbiome Research Centre, University of New South Wales , Sydney , Australia
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27
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King SJ, McCole DF. Epithelial-microbial diplomacy: escalating border tensions drive inflammation in inflammatory bowel disease. Intest Res 2019; 17:177-191. [PMID: 30836737 PMCID: PMC6505084 DOI: 10.5217/ir.2018.00170] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Accepted: 02/01/2019] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic conditions of the gastrointestinal tract-the main site of host-microbial interaction in the body. Development of IBD is not due to a single event but rather is a multifactorial process where a patient’s genetic background, behavioral habits, and environmental exposures contribute to disease pathogenesis. IBD patients exhibit alterations to gut bacterial populations “dysbiosis” due to the inflammatory microenvironment, however whether this alteration of the gut microbiota precedes inflammation has not been confirmed. Emerging evidence has highlighted the important role of gut microbes in developing measured immune responses and modulating other host responses such as metabolism. Much of the work on the gut microbiota has been correlative and there is an increasing need to understand the intimate relationship between host and microbe. In this review, we highlight how commensal and pathogenic bacteria interact with host intestinal epithelial cells and explore how altered microenvironments impact these connections.
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Affiliation(s)
- Stephanie J King
- Division of Biomedical Sciences, University of California, Riverside, CA, USA
| | - Declan F McCole
- Division of Biomedical Sciences, University of California, Riverside, CA, USA
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28
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Brunner K, John CM, Phillips NJ, Alber DG, Gemmell MR, Hansen R, Nielsen HL, Hold GL, Bajaj-Elliott M, Jarvis GA. Novel Campylobacter concisus lipooligosaccharide is a determinant of inflammatory potential and virulence. J Lipid Res 2018; 59:1893-1905. [PMID: 30049709 DOI: 10.1194/jlr.m085860] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Revised: 06/29/2018] [Indexed: 12/15/2022] Open
Abstract
The pathogenicity of Campylobacter concisus, increasingly found in the human gastrointestinal (GI) tract, is unclear. Some studies indicate that its role in GI conditions has been underestimated, whereas others suggest that the organism has a commensal-like phenotype. For the enteropathogen C. jejuni, the lipooligosaccharide (LOS) is a main driver of virulence. We investigated the LOS structure of four C. concisus clinical isolates and correlated the inflammatory potential of each isolate with bacterial virulence. Mass spectrometric analyses of lipid A revealed a novel hexa-acylated diglucosamine moiety with two or three phosphoryl substituents. Molecular and fragment ion analysis indicated that the oligosaccharide portion of the LOS had only a single phosphate and lacked phosphoethanolamine and sialic acid substitution, which are hallmarks of the C. jejuni LOS. Consistent with our structural findings, C. concisus LOS and live bacteria induced less TNF-α secretion in human monocytes than did C. jejuni Furthermore, the C. concisus bacteria were less virulent than C. jejuni in a Galleria mellonella infection model. The correlation of the novel lipid A structure, decreased phosphorylation, and lack of sialylation along with reduced inflammatory potential and virulence support the significance of the LOS as a determinant in the relative pathogenicity of C. concisus.
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Affiliation(s)
- Katja Brunner
- Infection, Immunity and Inflammation Programme, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Constance M John
- Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, CA.,Department of Laboratory Medicine University of California, San Francisco, CA
| | - Nancy J Phillips
- Department of Pharmaceutical Chemistry, University of California, San Francisco, CA
| | - Dagmar G Alber
- Infection, Immunity and Inflammation Programme, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Matthew R Gemmell
- Center for Genome-Enabled Biology and Medicine, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom
| | - Richard Hansen
- Department of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, United Kingdom
| | - Hans L Nielsen
- Department of Infectious Diseases Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
| | - Georgina L Hold
- St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia
| | - Mona Bajaj-Elliott
- Infection, Immunity and Inflammation Programme, University College London Great Ormond Street Institute of Child Health, London, United Kingdom
| | - Gary A Jarvis
- Center for Immunochemistry, Veterans Affairs Medical Center, San Francisco, CA .,Department of Laboratory Medicine University of California, San Francisco, CA
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29
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Liu F, Ma R, Wang Y, Zhang L. The Clinical Importance of Campylobacter concisus and Other Human Hosted Campylobacter Species. Front Cell Infect Microbiol 2018; 8:243. [PMID: 30087857 PMCID: PMC6066527 DOI: 10.3389/fcimb.2018.00243] [Citation(s) in RCA: 78] [Impact Index Per Article: 11.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2018] [Accepted: 06/25/2018] [Indexed: 12/14/2022] Open
Abstract
Historically, Campylobacteriosis has been considered to be zoonotic; the Campylobacter species that cause human acute intestinal disease such as Campylobacter jejuni and Campylobacter coli originate from animals. Over the past decade, studies on human hosted Campylobacter species strongly suggest that Campylobacter concisus plays a role in the development of inflammatory bowel disease (IBD). C. concisus primarily colonizes the human oral cavity and some strains can be translocated to the intestinal tract. Genome analysis of C. concisus strains isolated from saliva samples has identified a bacterial marker that is associated with active Crohn's disease (one major form of IBD). In addition to C. concisus, humans are also colonized by a number of other Campylobacter species, most of which are in the oral cavity. Here we review the most recent advancements on C. concisus and other human hosted Campylobacter species including their clinical relevance, transmission, virulence factors, disease associated genes, interactions with the human immune system and pathogenic mechanisms.
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Affiliation(s)
| | | | | | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
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30
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García-Sánchez L, Melero B, Rovira J. Campylobacter in the Food Chain. ADVANCES IN FOOD AND NUTRITION RESEARCH 2018; 86:215-252. [PMID: 30077223 DOI: 10.1016/bs.afnr.2018.04.005] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Currently Campylobacter is the most commonly reported zoonosis in developed and developing countries. In the European Union, the number of reported confirmed cases of human campylobacteriosis was 246,307 in 2016, which represents 66.3 cases per 100,000 population. The genus Campylobacter includes 31 species with 10 subspecies. Within the genus Campylobacter, C. jejuni subsp. jejuni and C. coli are most frequently associated with human illness. Mainly, the infection is sporadic and self-limiting, although some cases of outbreaks have been also reported and some complications such as Guillain-Barré syndrome might appear sporadically. Although campylobacters are fastidious microaerophilic, unable to multiply outside the host and generally very sensitive, they can adapt and survive in the environment, exhibiting aerotolerance and resistance to starvation. Many mechanisms are involved in this, including pathogenicity, biofilm formation, and antibiotic resistant pathways. This chapter reviews the sources, transmission routes, the mechanisms, and strategies used by Campylobacter to persist in the whole food chain, from farm to fork. Additionally, different strategies are recommended for application along the poultry food chain to avoid the public health risk associated with this pathogen.
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Affiliation(s)
| | - Beatriz Melero
- Biotechnology and Food Science Department, University of Burgos, Burgos, Spain
| | - Jordi Rovira
- Biotechnology and Food Science Department, University of Burgos, Burgos, Spain.
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31
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Marlicz W, Skonieczna-Żydecka K, Dabos KJ, Łoniewski I, Koulaouzidis A. Emerging concepts in non-invasive monitoring of Crohn's disease. Therap Adv Gastroenterol 2018; 11:1756284818769076. [PMID: 29707039 PMCID: PMC5912292 DOI: 10.1177/1756284818769076] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an umbrella term for Crohn's disease (CD) and ulcerative colitis (UC). In light of evolving epidemiology of CD, its clinical management is still complex and remains a challenge for contemporary physicians. With the advent of new diagnostic and treatment paradigms, there is a growing need for new biomarkers to guide decision-making, differential diagnosis, disease activity monitoring, as well as prognosis. However, both clinical and endoscopic scoring systems, widely utilized for disease monitoring and prognosis, have drawbacks and limitations. In recent years, biochemical peptides have become available for IBD monitoring and more frequently used as surrogate markers of gut inflammation. Emerging concepts that revolve around molecular, stem cell, epigenetic, microbial or metabolomic pathways associated with vascular and epithelial gut barrier could lead to development of new CD biomarkers. Measurement of cell-derived microvesicles (MVs) in the blood of IBD patients is another emerging concept helpful in future disease management. In this review, we discuss novel concepts of non-invasive biomarkers, which may become useful in monitoring of CD activity and prognosis. We discuss metabolomics as a new powerful tool for clinicians to guide differential IBD diagnosis. In the coming years, new developments of prognostic tools are expected, aiming for breakthroughs in the management of patients with CD.
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Affiliation(s)
- Wojciech Marlicz
- Department of Gastroenterology, Pomeranian Medical University, Unii Lubelskiej 1, 71-252 Szczecin, Poland
| | | | | | - Igor Łoniewski
- Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Szczecin, Poland
- Sanprobi Sp. z o.o. Sp. K., Szczecin, Poland
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32
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Liu F, Ma R, Tay CYA, Octavia S, Lan R, Chung HKL, Riordan SM, Grimm MC, Leong RW, Tanaka MM, Connor S, Zhang L. Genomic analysis of oral Campylobacter concisus strains identified a potential bacterial molecular marker associated with active Crohn's disease. Emerg Microbes Infect 2018; 7:64. [PMID: 29636463 PMCID: PMC5893538 DOI: 10.1038/s41426-018-0065-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2018] [Revised: 03/14/2018] [Accepted: 03/20/2018] [Indexed: 02/08/2023]
Abstract
Campylobacter concisus is an oral bacterium that is associated with inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC). C. concisus consists of two genomospecies (GS) and diverse strains. This study aimed to identify molecular markers to differentiate commensal and IBD-associated C. concisus strains. The genomes of 63 oral C. concisus strains isolated from patients with IBD and healthy controls were examined, of which 38 genomes were sequenced in this study. We identified a novel secreted enterotoxin B homologue, Csep1. The csep1 gene was found in 56% of GS2 C. concisus strains, presented in the plasmid pICON or the chromosome. A six-nucleotide insertion at the position 654-659 bp in csep1 (csep1-6bpi) was found. The presence of csep1-6bpi in oral C. concisus strains isolated from patients with active CD (47%, 7/15) was significantly higher than that in strains from healthy controls (0/29, P = 0.0002), and the prevalence of csep1-6bpi positive C. concisus strains was significantly higher in patients with active CD (67%, 4/6) as compared to healthy controls (0/23, P = 0.0006). Proteomics analysis detected the Csep1 protein. A csep1 gene hot spot in the chromosome of different C. concisus strains was found. The pICON plasmid was only found in GS2 strains isolated from the two relapsed CD patients with small bowel complications. This study reports a C. concisus molecular marker (csep1-6bpi) that is associated with active CD.
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Affiliation(s)
- Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Rena Ma
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Chin Yen Alfred Tay
- Helicobacter Research Laboratory, Marshall Centre for Infectious Diseases Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, WA, Australia
| | - Sophie Octavia
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Ruiting Lan
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Heung Kit Leslie Chung
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Stephen M Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia
| | - Michael C Grimm
- St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Rupert W Leong
- Concord Hospital, University of New South Wales, Sydney, NSW, Australia
| | - Mark M Tanaka
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Susan Connor
- Liverpool Hospital, University of New South Wales, Sydney, NSW, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
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33
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Updating the genomic taxonomy and epidemiology of Campylobacter hyointestinalis. Sci Rep 2018; 8:2393. [PMID: 29403020 PMCID: PMC5799301 DOI: 10.1038/s41598-018-20889-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 01/25/2018] [Indexed: 12/24/2022] Open
Abstract
Campylobacter hyointestinalis is a member of an emerging group of zoonotic Campylobacter spp. that are increasingly identified in both gastric and non-gastric disease in humans. Here, we discovered C. hyointestinalis in three separate classes of New Zealand ruminant livestock; cattle, sheep and deer. To investigate the relevance of these findings we performed a systematic literature review on global C. hyointestinalis epidemiology and used comparative genomics to better understand and classify members of the species. We found that C. hyointestinalis subspecies hyointestinalis has an open pangenome, with accessory gene contents involved in many essential processes such as metabolism, virulence and defence. We observed that horizontal gene transfer is likely to have played an overwhelming role in species diversification, favouring a public-goods-like mechanism of gene ‘acquisition and resampling’ over a tree-of-life-like vertical inheritance model of evolution. As a result, simplistic gene-based inferences of taxonomy by similarity are likely to be misleading. Such genomic plasticity will also mean that local evolutionary histories likely influence key species characteristics, such as host-association and virulence. This may help explain geographical differences in reported C. hyointestinalis epidemiology and limits what characteristics may be generalised, requiring further genomic studies of C. hyointestinalis in areas where it causes disease.
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34
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Molecular epidemiology and comparative genomics of Campylobacter concisus strains from saliva, faeces and gut mucosal biopsies in inflammatory bowel disease. Sci Rep 2018; 8:1902. [PMID: 29382867 PMCID: PMC5790007 DOI: 10.1038/s41598-018-20135-4] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 01/12/2018] [Indexed: 12/17/2022] Open
Abstract
Campylobacter concisus is an emerging pathogen associated with inflammatory bowel disease (IBD), yet little is known about the genetic diversity of C. concisus in relation to host niches and disease. We isolated 104 C. concisus isolates from saliva, mucosal biopsies and faecal samples from 41 individuals (26 IBD, 3 Gastroenteritis (GE), 12 Healthy controls (HC)). Whole genomes were sequenced and the dataset pan-genome examined, and genomic information was used for typing using multi-locus-sequence typing (MLST). C. concisus isolates clustered into two main groups/genomospecies (GS) with 71 distinct sequence types (STs) represented. Sampling site (p < 0.001), rather than disease phenotype (p = 1.00) was associated with particular GS. We identified 97 candidate genes associated with increase or decrease in prevalence during the anatomical descent from the oral cavity to mucosal biopsies to faeces. Genes related to cell wall/membrane biogenesis were more common in oral isolates, whereas genes involved in cell transport, metabolism and secretory pathways were more prevalent in enteric isolates. Furthermore, there was no correlation between individual genetic diversity and clinical phenotype. This study confirms the genetic heterogeneity of C. concisus and provides evidence that genomic variation is related to the source of isolation, but not clinical phenotype.
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Zhang M, Sun K, Wu Y, Yang Y, Tso P, Wu Z. Interactions between Intestinal Microbiota and Host Immune Response in Inflammatory Bowel Disease. Front Immunol 2017; 8:942. [PMID: 28855901 PMCID: PMC5558048 DOI: 10.3389/fimmu.2017.00942] [Citation(s) in RCA: 236] [Impact Index Per Article: 29.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 07/24/2017] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Although the etiology and pathogenesis of IBD remain unclear, both genetic susceptibility and environmental factors are implicated in the initiation and progression of IBD. Recent studies with experimental animal models and clinical patients indicated that the intestinal microbiota is one of the critical environmental factors that influence nutrient metabolism, immune responses, and the health of the host in various intestinal diseases, including ulcerative colitis and Crohn’s disease. The objective of this review is to highlight the crosstalk between gut microbiota and host immune response and the contribution of this interaction to the pathogenesis of IBD. In addition, potential therapeutic strategies targeting the intestinal micro-ecosystem in IBD are discussed.
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Affiliation(s)
- Ming Zhang
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China
| | - Kaiji Sun
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China
| | - Yujun Wu
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China
| | - Ying Yang
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China
| | - Patrick Tso
- Department of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH, United States
| | - Zhenlong Wu
- State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China.,Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, China
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Wang Y, Liu F, Zhang X, Chung HKL, Riordan SM, Grimm MC, Zhang S, Ma R, Lee SA, Zhang L. Campylobacter concisus Genomospecies 2 Is Better Adapted to the Human Gastrointestinal Tract as Compared with Campylobacter concisus Genomospecies 1. Front Physiol 2017; 8:543. [PMID: 28824443 PMCID: PMC5541300 DOI: 10.3389/fphys.2017.00543] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 07/12/2017] [Indexed: 01/26/2023] Open
Abstract
Campylobacter concisus was previously shown to be associated with inflammatory bowel disease including Crohn's disease (CD) and ulcerative colitis (UC). C. concisus has two genomospecies (GS). This study systematically examined the colonization of GS1 and GS2 C. concisus in the human gastrointestinal tract. GS1 and GS2 specific polymorphisms in 23S rRNA gene were identified by comparison of the 23S rRNA genes of 49 C. concisus strains. Two newly designed PCR methods, based on the polymorphisms of 23S rRNA gene, were developed and validated. These PCR methods were used to detect and quantify GS1 and GS2 C. concisus in 56 oral and enteric samples collected from the gastrointestinal tract of patients with IBD and healthy controls. Meta-analysis of the composition of the isolated GS1 and GS2 C. concisus strains in previous studies was also conducted. The quantitative PCR methods revealed that there was more GS2 than GS1 C. concisus in samples collected from the upper and lower gastrointestinal tract of both patients with IBD and healthy controls, showing that GS2 C. concisus is better adapted to the human gastrointestinal tract. Analysis of GS1 and GS2 composition of isolated C. concisus strains in previous studies showed similar findings except that in healthy individuals a significantly lower GS2 than GS1 C. concisus strains were isolated from fecal samples, suggesting a potential difference in the C. concisus strains or the enteric environment between patients with gastrointestinal diseases and healthy controls. This study provides novel information regarding the adaptation of different genomospecies of C. concisus in the human gastrointestinal tract.
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Affiliation(s)
- Yiming Wang
- School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia
| | - Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia
| | - Xiang Zhang
- Clinical Research Center, The First Affiliated Hospital of Nanjing Medical UniversityNanjing, China
| | - Heung Kit Leslie Chung
- School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia
| | - Stephen M. Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South WalesSydney, NSW, Australia
| | - Michael C. Grimm
- St George and Sutherland Clinical School, University of New South WalesSydney, NSW, Australia
| | - Shu Zhang
- Clinical Research Center, The First Affiliated Hospital of Nanjing Medical UniversityNanjing, China
| | - Rena Ma
- School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia
| | - Seul A. Lee
- School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia
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Magana M, Chatzipanagiotou S, Burriel AR, Ioannidis A. Inquiring into the Gaps of Campylobacter Surveillance Methods. Vet Sci 2017; 4:E36. [PMID: 29056694 PMCID: PMC5644652 DOI: 10.3390/vetsci4030036] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Revised: 07/07/2017] [Accepted: 07/17/2017] [Indexed: 01/20/2023] Open
Abstract
Campylobacter is one of the most common pathogen-related causes of diarrheal illnesses globally and has been recognized as a significant factor of human disease for more than three decades. Molecular typing techniques and their combinations have allowed for species identification among members of the Campylobacter genus with good resolution, but the same tools usually fail to proceed to subtyping of closely related species due to high sequence similarity. This problem is exacerbated by the demanding conditions for isolation and detection from the human, animal or water samples as well as due to the difficulties during laboratory maintenance and long-term storage of the isolates. In an effort to define the ideal typing tool, we underline the strengths and limitations of the typing methodologies currently used to map the broad epidemiologic profile of campylobacteriosis in public health and outbreak investigations. The application of both the old and the new molecular typing tools is discussed and an indirect comparison is presented among the preferred techniques used in current research methodology.
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Affiliation(s)
- Maria Magana
- Department of Biopathology and Clinical Microbiology, Aeginition Hospital, Athens Medical School, Athens 15772, Greece.
| | - Stylianos Chatzipanagiotou
- Department of Biopathology and Clinical Microbiology, Aeginition Hospital, Athens Medical School, Athens 15772, Greece.
| | - Angeliki R Burriel
- Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta 23100, Greece.
| | - Anastasios Ioannidis
- Department of Biopathology and Clinical Microbiology, Aeginition Hospital, Athens Medical School, Athens 15772, Greece.
- Department of Nursing, Faculty of Human Movement and Quality of Life Sciences, University of Peloponnese, Sparta 23100, Greece.
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Liu F, Ma R, Riordan SM, Grimm MC, Liu L, Wang Y, Zhang L. Azathioprine, Mercaptopurine, and 5-Aminosalicylic Acid Affect the Growth of IBD-Associated Campylobacter Species and Other Enteric Microbes. Front Microbiol 2017; 8:527. [PMID: 28424670 PMCID: PMC5372805 DOI: 10.3389/fmicb.2017.00527] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 03/14/2017] [Indexed: 12/28/2022] Open
Abstract
Campylobacter concisus is a bacterium that is associated with inflammatory bowel disease (IBD). Immunosuppressive drugs including azathioprine (AZA) and mercaptopurine (MP), and anti-inflammatory drug such as 5-aminosalicylic acid (5-ASA) are commonly used to treat patients with IBD. This study aimed to examine the effects of AZA, MP, and 5-ASA on the growth of IBD-associated bacterial species and to identify bacterial enzymes involved in immunosuppressive drug metabolism. A total of 15 bacterial strains of five species including 11 C. concisus strains, Bacteroides fragilis, Bacteroides vulgatus, Enterococcus faecalis, and Escherichia coli were examined. The impact of AZA, MP, and 5-ASA on the growth of these bacterial species was examined quantitatively using a plate counting method. The presence of enzymes involved in AZA and MP metabolism in these bacterial species was identified using bioinformatics tools. AZA and MP significantly inhibited the growth of all 11 C. concisus strains. C. concisus strains were more sensitive to AZA than MP. 5-ASA showed inhibitory effects to some C. concisus strains, while it promoted the growth of other C. concisus strains. AZA and MP also significantly inhibited the growth of B. fragilis and B. vulgatus. The growth of E. coli was significantly inhibited by 200 μg/ml of AZA as well as 100 and 200 μg/ml of 5-ASA. Bacterial enzymes related to AZA and MP metabolism were found, which varied in different bacterial species. In conclusion, AZA and MP have inhibitory effects to IBD-associated C. concisus and other enteric microbes, suggesting an additional therapeutic mechanism of these drugs in the treatment of IBD. The strain dependent differential impact of 5-ASA on the growth of C. concisus may also have clinical implication given that in some cases 5-ASA medications were found to cause exacerbations of colitis.
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Affiliation(s)
- Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia
| | - Rena Ma
- School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia
| | - Stephen M. Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South WalesSydney, NSW, Australia
| | - Michael C. Grimm
- St George and Sutherland Clinical School, University of New South WalesSydney, NSW, Australia
| | - Lu Liu
- School of Medical Sciences, University of New South WalesSydney, NSW, Australia
| | - Yiming Wang
- School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South WalesSydney, NSW, Australia
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Huq M, Van TTH, Gurtler V, Elshagmani E, Allemailem KS, Smooker PM, Istivan T. The ribosomal RNA operon ( rrn ) of Campylobacter concisus supports molecular typing to genomospecies level. GENE REPORTS 2017; 6:8-14. [DOI: 10.1016/j.genrep.2016.10.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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Casey E, Fitzgerald E, Lucey B. Towards understanding clinical campylobacter infection and its transmission: time for a different approach? Br J Biomed Sci 2017; 74:53-64. [PMID: 28367739 DOI: 10.1080/09674845.2017.1291205] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Campylobacter spp. are among the most commonly diagnosed causes of human infection. Methods for detection of the 29 campylobacter species have mainly focused on cultivation of the thermophilic species. More than 99% of clinical campylobacter isolates notified in the UK in the recent past have been from faecal samples and associated with gastroenteritis. Campylobacter enteritis notifications in temperate zones show a seasonal increase during the summer months with a sharp decrease in the winter months, a pattern which remains incompletely understood. The striking seasonality in the expression of many human genes, some concerned with inflammation and immunity, suggests a need for further study of the host regarding the temporal distribution of many human infections, including campylobacteriosis. A tendency for campylobacter to enter a non-cultivable state under adverse conditions effects a reduction in the number of isolations. A Polymerase Chain Reaction (PCR)-based screening approach for the presence of the Campylobacter genus and followed by speciation has provided some insight into the limitations of cultivation for campylobacter, also allowing the discovery of new species. The increased sensitivity of the PCR-based approach over culture-based methods may make it difficult for the laboratory to differentiate asymptomatic campylobacter carriage from clinical campylobacter infection in non-sterile body sites. Campylobacter infection depends on a combination of host factors, and on acquisition of a suitably virulent strain with a tropism for human epithelium. The possibility of persistence of campylobacter in a viable but non-culturable latent form in the human body may also require further investigation. The scope of this review includes a discussion of current methods for diagnosing acute campylobacter infection and for detecting campylobacter in water and foodstuffs. The review also questions the prevailing view that poultry is the most common source of campylobacteriosis.
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Affiliation(s)
- E Casey
- a Department of Biological Sciences , Cork Institute of Technology , Bishopstown , Ireland
| | - E Fitzgerald
- a Department of Biological Sciences , Cork Institute of Technology , Bishopstown , Ireland
| | - B Lucey
- a Department of Biological Sciences , Cork Institute of Technology , Bishopstown , Ireland
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Castaño-Rodríguez N, Kaakoush NO, Lee WS, Mitchell HM. Dual role of Helicobacter and Campylobacter species in IBD: a systematic review and meta-analysis. Gut 2017; 66:235-249. [PMID: 26508508 DOI: 10.1136/gutjnl-2015-310545] [Citation(s) in RCA: 158] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2015] [Revised: 10/03/2015] [Accepted: 10/05/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To conduct a comprehensive global systematic review and meta-analysis on the association between Helicobacter pylori infection and IBD. As bacterial antigen cross-reactivity has been postulated to be involved in this association, published data on enterohepatic Helicobacter spp (EHS) and Campylobacter spp and IBD was also analysed. DESIGN Electronic databases were searched up to July 2015 for all case-control studies on H. pylori infection/EHS/Campylobacter spp and IBD. Pooled ORs (P-OR) and 95% CIs were obtained using the random effects model. Heterogeneity, sensitivity and stratified analyses were performed. RESULTS Analyses comprising patients with Crohn's disease (CD), UC and IBD unclassified (IBDU), showed a consistent negative association between gastric H. pylori infection and IBD (P-OR: 0.43, p value <1e-10). This association appears to be stronger in patients with CD (P-OR: 0.38, p value <1e-10) and IBDU (P-OR: 0.43, p value=0.008) than UC (P-OR: 0.53, p value <1e-10). Stratification by age, ethnicity and medications showed significant results. In contrast to gastric H. pylori, non H. pylori-EHS (P-OR: 2.62, p value=0.001) and Campylobacter spp, in particular C. concisus (P-OR: 3.76, p value=0.006) and C. showae (P-OR: 2.39, p value=0.027), increase IBD risk. CONCLUSIONS H. pylori infection is negatively associated with IBD regardless of ethnicity, age, H. pylori detection methods and previous use of aminosalicylates and corticosteroids. Antibiotics influenced the magnitude of this association. Closely related bacteria including EHS and Campylobacter spp increase the risk of IBD. These results infer that H. pylori might exert an immunomodulatory effect in IBD.
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Affiliation(s)
- Natalia Castaño-Rodríguez
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia
| | - Nadeem O Kaakoush
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia
| | - Way Seah Lee
- Department of Paediatrics, University Malaya Medical Centre, Kuala Lumpur, Malaysia.,University Malaya Pediatrics and Child Health Research Group, University Malaya, Kuala Lumpur, Malaysia
| | - Hazel M Mitchell
- School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia
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42
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Ovesen S, Kirk KF, Nielsen HL, Nielsen H. Motility of Campylobacter concisus isolated from saliva, feces, and gut mucosal biopsies. APMIS 2017; 125:230-235. [PMID: 28116789 DOI: 10.1111/apm.12655] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2016] [Accepted: 11/29/2016] [Indexed: 11/30/2022]
Abstract
Campylobacter concisus is an emerging pathogen associated with gastrointestinal disorders such as gastroenteritis and inflammatory bowel diseases (IBD), but the species is also found in healthy subjects. The heterogeneous genome of C. concisus increases the likelihood of varying virulence between strains. Flagella motility is a crucial virulence factor for the well-recognized Campylobacter jejuni; therefore, this study aimed to analyze the motility of C. concisus isolated from saliva, gut biopsies, and feces of patients with IBD, gastroenteritis, and healthy subjects. The motility zones of 63 isolates from 52 patients were measured after microaerobic growth in soft-agar plates for 72 hours. The motility of C. concisus was significantly lower than that of Campylobacter jejuni and Campylobacter fetus subsp. fetus. The motility of C. concisus varied between isolates (4-22 mm), but there was no statistical significant difference between isolates from IBD patients and healthy subjects (p = 0.14). A tendency of a larger motility zones was observed for IBD gut mucosa isolates, although it did not reach statistical significance (p = 0.13), and no difference was found between oral or fecal isolates between groups. In conclusion, the varying motility of C. concisus could not be related to disease outcome or colonization sites.
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Affiliation(s)
- Sandra Ovesen
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Karina Frahm Kirk
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Hans Linde Nielsen
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
| | - Henrik Nielsen
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark.,Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Chung HKL, Tay A, Octavia S, Chen J, Liu F, Ma R, Lan R, Riordan SM, Grimm MC, Zhang L. Genome analysis of Campylobacter concisus strains from patients with inflammatory bowel disease and gastroenteritis provides new insights into pathogenicity. Sci Rep 2016; 6:38442. [PMID: 27910936 PMCID: PMC5133609 DOI: 10.1038/srep38442] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Accepted: 11/09/2016] [Indexed: 12/14/2022] Open
Abstract
Campylobacter concisus is an oral bacterium that is associated with inflammatory bowel disease. C. concisus has two major genomospecies, which appear to have different enteric pathogenic potential. Currently, no studies have compared the genomes of C. concisus strains from different genomospecies. In this study, a comparative genome analysis of 36 C. concisus strains was conducted including 27 C. concisus strains sequenced in this study and nine publically available C. concisus genomes. The C. concisus core-genome was defined and genomospecies-specific genes were identified. The C. concisus core-genome, housekeeping genes and 23S rRNA gene consistently divided the 36 strains into two genomospecies. Two novel genomic islands, CON_PiiA and CON_PiiB, were identified. CON_PiiA and CON_PiiB islands contained proteins homologous to the type IV secretion system, LepB-like and CagA-like effector proteins. CON_PiiA islands were found in 37.5% of enteric C. concisus strains (3/8) isolated from patients with enteric diseases and none of the oral strains (0/27), which was statistically significant. This study reports the findings of C. concisus genomospecies-specific genes, novel genomic islands that contain type IV secretion system and putative effector proteins, and other new genomic features. These data provide novel insights into understanding of the pathogenicity of this emerging opportunistic pathogen.
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Affiliation(s)
- Heung Kit Leslie Chung
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Alfred Tay
- Helicobacter Research Laboratory, Marshall Centre for Infectious Diseases Research and Training, School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia
| | - Sophie Octavia
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Jieqiong Chen
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Rena Ma
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Ruiting Lan
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
| | - Stephen M Riordan
- Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, Australia
| | - Michael C. Grimm
- St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia
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Nielsen HL, Kirk KF, Bodilsen J, Ejlertsen T, Nielsen H. Azithromycin vs. Placebo for the Clinical Outcome in Campylobacter concisus Diarrhoea in Adults: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. PLoS One 2016; 11:e0166395. [PMID: 27893820 PMCID: PMC5125586 DOI: 10.1371/journal.pone.0166395] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 10/25/2016] [Indexed: 12/23/2022] Open
Abstract
Campylobacter concisus has been associated with prolonged mild diarrhoea, but investigations regarding the efficacy of antimicrobial treatment have not been reported previously. We initiated a phase 3, single-centre, randomized, double-blinded, placebo-controlled study comparing the efficacy of 500 mg once-daily dose of azithromycin with a 500 mg once-daily dose of placebo for three days, for the treatment of C. concisus diarrhoea in adult patients with a follow-up period of ten days. If symptoms persisted at day ten, the patient was offered cross-over study treatment of three days and another ten-day follow-up period. The primary efficacy endpoint was the clinical response, defined as time to cessation of diarrhoea (<3 stools/day or reversal of accompanying symptoms). Our estimated sample size was 100 patients. We investigated a total of 10,036 diarrheic stool samples from 7,089 adult patients. Five-hundred and eighty-eight C. concisus positive patients were assessed for eligibility, of which 559 were excluded prior to randomization. The three main reasons for exclusion were duration of diarrhoea longer than 21 days (n = 124), previous antibiotic treatment (n = 113), and co-pathogens in stools (n = 87). Therefore, 24 patients completed the trial with either azithromycin (n = 12) or placebo (n = 12). Both groups presented symptoms of mild, prolonged diarrhoea with a mean duration of 18 days (95% CI: 16-19). One person in the azithromycin group and four from the placebo group chose to continue with crossover medication after the initial ten-day period. In the azithromycin group, there was a mean of seven days (95% CI: 5-9) to clinical cure and for the placebo group it was ten days (95% CI: 6-14) (OR-3 (95% CI: -7-1). We observed no differences in all examined outcomes between azithromycin treatment and placebo. However, due to unforeseen recruitment difficulties we did not reach our estimated sample size of 100 patients and statistical power to conclude on an effect of azithromycin treatment was not obtained. TRIAL REGISTRATION Clinicaltrials.gov identifier: NCT01531218.
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Affiliation(s)
- Hans Linde Nielsen
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
- * E-mail:
| | - Karina Frahm Kirk
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Jacob Bodilsen
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Tove Ejlertsen
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
| | - Henrik Nielsen
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Nielsen HL, Nielsen H, Torpdahl M. Multilocus sequence typing of Campylobacter concisus from Danish diarrheic patients. Gut Pathog 2016; 8:44. [PMID: 27688814 PMCID: PMC5034547 DOI: 10.1186/s13099-016-0126-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2016] [Accepted: 09/13/2016] [Indexed: 12/11/2022] Open
Abstract
The emerging enteric pathogen Campylobacter concisus is associated with prolonged diarrhea and inflammatory bowel disease. Previous studies have shown that C. concisus strains are very genetically diverse. Nevertheless, C. concisus strains have been divided into two genomospecies, where GS1 strains have been isolated predominantly from healthy individuals, while the GS2 cluster consists of isolates primarily from diarrheic individuals. The aim of the present study was to determine the genetic diversity of C. concisus isolates from Danish diarrheic patients. Multilocus sequence typing using the loci aspA, atpA, glnA, gltA, glyA, ilvD and pgm, as well as genomospecies based on specific differences in the 23S rRNA, was used to characterize 67 isolates (63 fecal and 4 oral), from 49 patients with different clinical presentations (29 with diarrhea, eight with bloody diarrhea, seven with collagenous colitis and five with Crohn’s disease). MLST revealed a high diversity of C. concisus with 53 sequence types (STs), of which 52 were identified as ‘new’ STs. Allele sequences showed more than 90 % similarity between isolates, with only four outliers. Dendrogram profiles of each allele showed a division into two groups, which more or less correlated with genomospecies A and genomospecies B. However, in contrary to previous results, this subgrouping had no association to the clinical severity of disease.
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Affiliation(s)
- Hans Linde Nielsen
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
| | - Henrik Nielsen
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark ; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Mia Torpdahl
- Department of Microbiology and Infection Control, Statens Serum Institut (SSI), Copenhagen, Denmark
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46
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Liu F, Lee H, Lan R, Zhang L. Zonula occludens toxins and their prophages in Campylobacter species. Gut Pathog 2016; 8:43. [PMID: 27651834 PMCID: PMC5025632 DOI: 10.1186/s13099-016-0125-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2016] [Accepted: 09/08/2016] [Indexed: 01/29/2023] Open
Abstract
BACKGROUND We previously showed that zonula occludens toxin (Zot) encoded by Campylobacter concisus zot (808T) gene has the potential to initiate inflammatory bowel disease. This Zot protein caused prolonged intestinal epithelial barrier damage, induced intestinal epithelial and macrophage production of tumor necrosis factor-α and enhanced the responses of macrophages to other microbes. In order to understand the potential virulence of Zot proteins in other Campylobacter species, in this study we examined their presence, similarities, motifs and prophages. METHODS The presence of Zot proteins in Campylobacter species was examined by searching for the Zot family domain in multiple protein databases. Walker A and Walker B motifs in Zot proteins were identified using protein sequence alignment. A phylogenetic tree based on Campylobacter zot genes was constructed using maximum-likelihood method. Campylobacter Zot proteins were compared using protein sequence alignment. The zot-containing prophages in Campylobacter species were identified and compared with known prophage proteins and other viral proteins using protein sequence alignment and protein BLAST. RESULTS Twelve Zot proteins were found in nine Campylobacter species/subspecies. Among these Campylobacter species, three species had two Zot proteins and the remaining six species/subspecies had one Zot protein. Walker A and Walker B motifs and a transmembrane domain were found in all identified Campylobacter Zot proteins. The twelve Campylobacter zot genes from the nine Campylobacter species/subspecies formed two clusters. The ZotCampyType_1 proteins encoded by Cluster 1 Campylobacter zot genes showed high similarities to each other. However, ZotCampyType_2 proteins encoded by Cluster 2 Campylobacter zot genes were more diverse. Furthermore, the zot-containing Campylobacter prophages were identified. CONCLUSION This study reports the identification of two types of Campylobacter Zot proteins. The high similarities of ZotCampyType_1 proteins suggest that they are likely to have similar virulence. ZotCampyType_2 proteins are less similar to each other and their virulent properties, if any, remain to be examined individually.
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Affiliation(s)
- Fang Liu
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Sydney, 2052 Australia
| | - Hoyul Lee
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Sydney, 2052 Australia
| | - Ruiting Lan
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Sydney, 2052 Australia
| | - Li Zhang
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Sydney, 2052 Australia
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Lee S, Lee J, Ha J, Choi Y, Kim S, Lee H, Yoon Y, Choi KH. Clinical relevance of infections with zoonotic and human oral species of Campylobacter. J Microbiol 2016; 54:459-67. [PMID: 27350611 DOI: 10.1007/s12275-016-6254-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2016] [Revised: 06/07/2016] [Accepted: 06/07/2016] [Indexed: 12/18/2022]
Abstract
Genus Campylobacter has been recognized as a causative bacterial agent of animal and human diseases. Human Campylobacter infections have caused more concern. Campylobacters can be classified into two groups in terms of their original host: zoonotic and human oral species. The major zoonotic species are Campylobacter jejuni and Campylobacter coli, which mostly reside in the intestines of avian species and are transmitted to humans via consumption of contaminated poultry products, thus causing human gastroenteritis and other diseases as sequelae. The other campylobacters, human oral species, include C. concisus, C. showae, C. gracilis, C. ureolyticus, C. curvus, and C. rectus. These species are isolated from the oral cavity, natural colonization site, but have potential clinical relevance in the periodontal region to varying extent. Two species, C. jejuni and C. coli, are believed to be mainly associated with intestinal diseases, but recent studies suggested that oral Campylobacter species also play a significant role in intestinal diseases. This review offers an outline of the two Campylobacter groups (zoonotic and human oral), their virulence traits, and the associated illnesses including gastroenteritis.
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Affiliation(s)
- Soomin Lee
- Department of Food and Nutrition, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - Jeeyeon Lee
- Department of Food and Nutrition, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - Jimyeong Ha
- Department of Food and Nutrition, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - Yukyung Choi
- Department of Food and Nutrition, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - Sejeong Kim
- Department of Food and Nutrition, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - Heeyoung Lee
- Department of Food and Nutrition, Sookmyung Women's University, Seoul, 04310, Republic of Korea
| | - Yohan Yoon
- Department of Food and Nutrition, Sookmyung Women's University, Seoul, 04310, Republic of Korea.
| | - Kyoung-Hee Choi
- Department of Oral Microbiology, College of Dentistry, Wonkwang University, Iksan, Chonbuk, 54538, Republic of Korea.
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Ahmed I, Roy BC, Khan SA, Septer S, Umar S. Microbiome, Metabolome and Inflammatory Bowel Disease. Microorganisms 2016; 4:microorganisms4020020. [PMID: 27681914 PMCID: PMC5029486 DOI: 10.3390/microorganisms4020020] [Citation(s) in RCA: 137] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 05/25/2016] [Accepted: 06/06/2016] [Indexed: 12/17/2022] Open
Abstract
Inflammatory Bowel Disease (IBD) is a multifactorial disorder that conceptually occurs as a result of altered immune responses to commensal and/or pathogenic gut microbes in individuals most susceptible to the disease. During Crohn’s Disease (CD) or Ulcerative Colitis (UC), two components of the human IBD, distinct stages define the disease onset, severity, progression and remission. Epigenetic, environmental (microbiome, metabolome) and nutritional factors are important in IBD pathogenesis. While the dysbiotic microbiota has been proposed to play a role in disease pathogenesis, the data on IBD and diet are still less convincing. Nonetheless, studies are ongoing to examine the effect of pre/probiotics and/or FODMAP reduced diets on both the gut microbiome and its metabolome in an effort to define the healthy diet in patients with IBD. Knowledge of a unique metabolomic fingerprint in IBD could be useful for diagnosis, treatment and detection of disease pathogenesis.
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Affiliation(s)
- Ishfaq Ahmed
- Department of Surgery, University of Kansas Medical Center, 3901 Rainbow Blvd, 4028 Wahl Hall East, Kansas City, KS 66160, USA.
| | - Badal C Roy
- Department of Surgery, University of Kansas Medical Center, 3901 Rainbow Blvd, 4028 Wahl Hall East, Kansas City, KS 66160, USA.
| | - Salman A Khan
- Department of Internal Medicine and Department of Pediatrics, University of Missouri, Kansas City, MO 64110, USA.
| | - Seth Septer
- Department of Internal Medicine and Department of Pediatrics, University of Missouri, Kansas City, MO 64110, USA.
| | - Shahid Umar
- Department of Surgery, University of Kansas Medical Center, 3901 Rainbow Blvd, 4028 Wahl Hall East, Kansas City, KS 66160, USA.
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Kirk KF, Nielsen HL, Thorlacius-Ussing O, Nielsen H. Optimized cultivation of Campylobacter concisus from gut mucosal biopsies in inflammatory bowel disease. Gut Pathog 2016; 8:27. [PMID: 27252786 PMCID: PMC4888738 DOI: 10.1186/s13099-016-0111-7] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Accepted: 05/19/2016] [Indexed: 12/19/2022] Open
Abstract
Background Campylobacter concisus is a commensal of the human oral flora that has been linked to prolonged diarrhea and inflammatory bowel disease (IBD). It has been detected more often from intestinal biopsies in patients with IBD compared to healthy controls using PCR-based techniques, whereas the number of C. concisus culture-positive biopsies in previous studies has been very limited. Determining the rate of viable isolates present in the gut mucosa is of great importance when evaluating the role in different disease presentations. We therefore investigated a novel two-step cultivation procedure combining anaerobic and microaerobic incubation from several gut mucosal sites to improve isolate yield, and compared this to PCR results, from IBD patients and healthy controls. Results Cultivation with the novel two-step procedure yielded a higher rate of C. concisus isolates from mucosal biopsies than previously reported by other methods. From 52 IBD patients, 52/245 (21 %) biopsies were culture positive for C. concisus, while 121/245 (49 %) of biopsies were PCR positive. For 26 healthy controls, the numbers were 23/182 (13 %) and 66/182 (36 %), respectively (p < 0.001). The rate of cultivation and PCR detection was higher for IBD patients compared to healthy controls (p = 0.021, p = 0.008, respectively). Conclusions Patients with IBD had a higher prevalence of C. concisus than healthy controls, by both cultivation and PCR detection. We found a higher rate of C. concisus isolates from gut mucosal biopsies in both IBD patients and healthy controls than in preceding studies, indicating that colonization of C. concisus in the gastrointestinal tract is more extensive than previously assumed.
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Affiliation(s)
- Karina Frahm Kirk
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark ; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Hans Linde Nielsen
- Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark
| | - Ole Thorlacius-Ussing
- Department of Clinical Medicine, Aalborg University, Aalborg, Denmark ; Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark
| | - Henrik Nielsen
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark ; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
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Mahendran V, Liu F, Riordan SM, Grimm MC, Tanaka MM, Zhang L. Examination of the effects of Campylobacter concisus zonula occludens toxin on intestinal epithelial cells and macrophages. Gut Pathog 2016; 8:18. [PMID: 27195022 PMCID: PMC4870807 DOI: 10.1186/s13099-016-0101-9] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 04/20/2016] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Campylobacter concisus is a Gram-negative bacterium that is associated with inflammatory bowel disease (IBD). Some C. concisus strains carry zonula occludens toxin (zot) gene which has polymorphisms. This study investigated the effects of C. concisus Zot on intestinal epithelial cells and macrophages using cell line models. METHODS Campylobacter concisus zot (808T) gene, a polymorphism that is associated with active IBD, was cloned and expressed in Escherichia coli. The effects of C. concisus Zot on intestinal epithelial barrier were examined using Caco-2 cell model. Apoptosis induced by C. concisus Zot in Caco-2 cells was assessed by measuring the levels of caspase 3/7. The production of pro-inflammatory cytokines induced by C. concisus Zot in HT-29 cells and in THP-1 macrophage-like cells was measured using ELISA kits. Whether exposure to C. concisus Zot can affect the responses of macrophages to E. coli K12 was also investigated. RESULTS Campylobacter concisus Zot caused prolonged intestinal epithelial barrier damage, induced intestinal epithelial cell apoptosis, induced epithelial production of TNF-α and IL-8 and upregulated TNF-α in THP-1 macrophage-like cells. Pre-exposure to C. concisus Zot significantly enhanced the production of TNF-α and IL-8 as well as phagocytosis by THP-1 macrophage-like cells in response to E. coli K12. CONCLUSION This study suggests that C. concisus Zot may have enteric pathogenic potential by damaging intestinal epithelial barrier, inducing intestinal epithelial and macrophage production of proinflammatory cytokines in particular TNF-α and enhancing the responses of macrophages to other enteric bacterial species.
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Affiliation(s)
- Vikneswari Mahendran
- />School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Sydney, NSW 2052 Australia
| | - Fang Liu
- />School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Sydney, NSW 2052 Australia
| | - Stephen M. Riordan
- />Gastrointestinal and Liver Unit, The Prince of Wales Hospital, Sydney, Australia
- />Prince of Wales Clinical School, University of New South Wales, Sydney, NSW 2052 Australia
| | - Michael C. Grimm
- />St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW 2052 Australia
| | - Mark M. Tanaka
- />School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Sydney, NSW 2052 Australia
| | - Li Zhang
- />School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, Sydney, NSW 2052 Australia
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