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Iliev ID, Ananthakrishnan AN, Guo CJ. Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities. Nat Rev Microbiol 2025:10.1038/s41579-025-01163-0. [PMID: 40065181 DOI: 10.1038/s41579-025-01163-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2025] [Indexed: 03/26/2025]
Abstract
Perturbations in the intestinal microbiome are strongly linked to the pathogenesis of inflammatory bowel disease (IBD). Bacteria, fungi and viruses all make up part of a complex multi-kingdom community colonizing the gastrointestinal tract, often referred to as the gut microbiome. They can exert various effects on the host that can contribute to an inflammatory state. Advances in screening, multiomics and experimental approaches have revealed insights into host-microbiota interactions in IBD and have identified numerous mechanisms through which the microbiota and its metabolites can exert a major influence on the gastrointestinal tract. Looking into the future, the microbiome and microbiota-associated processes will be likely to provide unparalleled opportunities for novel diagnostic, therapeutic and diet-inspired solutions for the management of IBD through harnessing rationally designed microbial communities, powerful bacterial and fungal metabolites, individually or in combination, to foster intestinal health. In this Review, we examine the current understanding of the cross-kingdom gut microbiome in IBD, focusing on bacterial and fungal components and metabolites. We examine therapeutic and diagnostic opportunities, the microbial metabolism, immunity, neuroimmunology and microbiome-inspired interventions to link mechanisms of disease and identify novel research and therapeutic opportunities for IBD.
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Affiliation(s)
- Iliyan D Iliev
- Joan and Sanford I. Weill Department of Medicine, Gastroenterology and Hepatology Division, Weill Cornell Medicine, New York, NY, USA.
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA.
- Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Chun-Jun Guo
- Joan and Sanford I. Weill Department of Medicine, Gastroenterology and Hepatology Division, Weill Cornell Medicine, New York, NY, USA
- The Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, New York, NY, USA
- Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA
- Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA
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2
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Arroyo-Mendoza M, Proctor A, Correa-Medina A, DeWolf S, Brand M, Rosas V, Lorenzi H, Wannemuehler M, Phillips G, Hinton D. A single rare σ70 variant establishes a unique gene expression pattern in the E. coli pathobiont LF82. Nucleic Acids Res 2024; 52:11552-11570. [PMID: 39258538 PMCID: PMC11514462 DOI: 10.1093/nar/gkae773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/08/2024] [Accepted: 08/28/2024] [Indexed: 09/12/2024] Open
Abstract
LF82, an adherent-invasive Escherichia coli (AIEC) pathobiont, is associated with Crohn's disease, an inflammatory bowel disease of unknown etiology. Although AIEC phenotypes differ from those of 'commensal' or pathogenic E. coli, work has failed to identify genetic features accounting for these differences. We have investigated a natural, but rare, single nucleotide polymorphism (SNP) in LF82 present within the highly conserved rpoD gene, encoding σ70 [primary sigma factor, RNA polymerase (RNAP)]. We demonstrate that σ70 D445V results in transcriptomic and phenotypic changes consistent with LF82 phenotypes, including increased antibiotic resistance and biofilm formation and increased capacity for methionine biosynthesis. RNA-seq analyses comparing σ70 V445 versus σ70 D445 identified 24 genes upregulated by σ70 V445 in both LF82 and the laboratory E. coli K-12 strain MG1655. Using in vitro transcription, we demonstrate that σ70 D445V directly increases transcription from promoters for several of the up-regulated genes and that the presence of a 16 bp spacer and -14 G:C is associated with this increase. The position of D445V within RNAP suggests that it could affect RNAP/spacer interaction. Our work represents the first identification of a distinguishing SNP for this pathobiont and suggests an underrecognized mechanism by which pathobionts and strain variants can emerge.
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Affiliation(s)
- Melissa Arroyo-Mendoza
- Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Dr., Bethesda, MD, USA
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
| | - Alexandra Proctor
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
| | - Abraham Correa-Medina
- Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Dr., Bethesda, MD, USA
| | - Sarah DeWolf
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
| | - Meghan Wymore Brand
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
| | - Virginia Rosas
- Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Dr., Bethesda, MD, USA
| | - Hernan Lorenzi
- TriLab Bioinformatics Group, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Dr., Bethesda, MD, USA
| | - Michael J Wannemuehler
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
| | - Gregory J Phillips
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA
| | - Deborah M Hinton
- Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Dr., Bethesda, MD, USA
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Fujimoto K, Hayashi T, Yamamoto M, Sato N, Shimohigoshi M, Miyaoka D, Yokota C, Watanabe M, Hisaki Y, Kamei Y, Yokoyama Y, Yabuno T, Hirose A, Nakamae M, Nakamae H, Uematsu M, Sato S, Yamaguchi K, Furukawa Y, Akeda Y, Hino M, Imoto S, Uematsu S. An enterococcal phage-derived enzyme suppresses graft-versus-host disease. Nature 2024; 632:174-181. [PMID: 38987594 PMCID: PMC11291292 DOI: 10.1038/s41586-024-07667-8] [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: 05/21/2022] [Accepted: 06/04/2024] [Indexed: 07/12/2024]
Abstract
Changes in the gut microbiome have pivotal roles in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogenic haematopoietic cell transplantation (allo-HCT)1-6. However, effective methods for safely resolving gut dysbiosis have not yet been established. An expansion of the pathogen Enterococcus faecalis in the intestine, associated with dysbiosis, has been shown to be a risk factor for aGVHD7-10. Here we analyse the intestinal microbiome of patients with allo-HCT, and find that E. faecalis escapes elimination and proliferates in the intestine by forming biofilms, rather than by acquiring drug-resistance genes. We isolated cytolysin-positive highly pathogenic E. faecalis from faecal samples and identified an anti-E. faecalis enzyme derived from E. faecalis-specific bacteriophages by analysing bacterial whole-genome sequencing data. The antibacterial enzyme had lytic activity against the biofilm of E. faecalis in vitro and in vivo. Furthermore, in aGVHD-induced gnotobiotic mice that were colonized with E. faecalis or with patient faecal samples characterized by the domination of Enterococcus, levels of intestinal cytolysin-positive E. faecalis were decreased and survival was significantly increased in the group that was treated with the E. faecalis-specific enzyme, compared with controls. Thus, administration of a phage-derived antibacterial enzyme that is specific to biofilm-forming pathogenic E. faecalis-which is difficult to eliminate with existing antibiotics-might provide an approach to protect against aGVHD.
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Affiliation(s)
- Kosuke Fujimoto
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
- Division of Metagenome Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Tetsuya Hayashi
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
- Department of Hematology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Mako Yamamoto
- Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Noriaki Sato
- Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Masaki Shimohigoshi
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Daichi Miyaoka
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Chieko Yokota
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Miki Watanabe
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Yuki Hisaki
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Yukari Kamei
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Yuki Yokoyama
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Takato Yabuno
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Asao Hirose
- Department of Hematology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Mika Nakamae
- Department of Hematology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
- Department of Laboratory Medicine and Medical Informatics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Hirohisa Nakamae
- Department of Hematology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Miho Uematsu
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Shintaro Sato
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
- Department of Microbiology and Immunology, School of Pharmaceutical Sciences, Wakayama Medical University, Wakayama, Japan
| | - Kiyoshi Yamaguchi
- Division of Clinical Genome Research, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Yoichi Furukawa
- Division of Clinical Genome Research, Institute of Medical Science, University of Tokyo, Tokyo, Japan
| | - Yukihiro Akeda
- Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan
| | - Masayuki Hino
- Department of Hematology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
- Department of Laboratory Medicine and Medical Informatics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Seiya Imoto
- Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
- Collaborative Research Institute for Innovative Microbiology, University of Tokyo, Tokyo, Japan.
| | - Satoshi Uematsu
- Department of Immunology and Genomics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan.
- Division of Metagenome Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
- Collaborative Research Institute for Innovative Microbiology, University of Tokyo, Tokyo, Japan.
- Reseach Institute for Drug Discovery Science, Osaka Metropolitan University, Osaka, Japan.
- Osaka International Research Center for Infectious Diseases, Osaka Metropolitan University, Osaka, Japan.
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Chevarin C, Xu Z, Martin L, Robin F, Beyrouthy R, Colombel JF, Sulakvelidze A, Ng SC, Bonnet R, Buisson A, Barnich N. Comparison of Crohn's disease-associated adherent-invasive Escherichia coli (AIEC) from France and Hong Kong: results from the Pacific study. Gut Microbes 2024; 16:2431645. [PMID: 39587720 PMCID: PMC11601055 DOI: 10.1080/19490976.2024.2431645] [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: 07/16/2024] [Revised: 09/27/2024] [Accepted: 11/14/2024] [Indexed: 11/27/2024] Open
Abstract
Association between ileal colonization by Adherent-Invasive Escherichia coli (AIEC) and Crohn's disease (CD) has been widely described in high-incidence Western countries but remains unexplored in Asian countries with a fast increase in CD incidence. In the PACIFIC study, we compared the characteristics of AIEC pathobionts retrieved from ileal biopsies of CD patients enrolled in France (FR) and Hong Kong (HK). The prevalence of AIEC was similar in France (24.5%, 25/102) and Hong Kong (30.0%, 18/60) (p = 0.44). No difference was observed between the two populations of AIEC regarding adhesion and invasion levels. When tested for antibiotic resistance, the proportion of AIEC strains resistant to ampicillin, piperacillin, tobramycin, and gentamicin was significantly higher in HK AIEC strains compared to French strains. AIEC strains from FR or HK population were both able to persist in the mice intestine (DSS-treated CEABAC10 mice model). Moreover, genomic analysis of 25 FR and 17 hK AIEC strains using next-generation sequencing revealed the co-existence of several virulence factors associated with enteric E. coli pathotypes, although no single virulence factor was significantly associated with either country of origin or AIEC status. In vitro, all AIEC strains (FR and HK) were sensitive to the EcoActive™ phage cocktail, suggesting that it could be a promising option to target AIEC in CD across the world.
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Affiliation(s)
- Caroline Chevarin
- Microbes, Intestin, Inflammation et Susceptibilité de l’Hôte (M2iSH), Université Clermont Auvergne/Inserm U1071, USC INRAE 1382, Clermont-Ferrand, France
| | - Zhilu Xu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
- Microbiota I-Center (MagIC), Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lucas Martin
- Microbes, Intestin, Inflammation et Susceptibilité de l’Hôte (M2iSH), Université Clermont Auvergne/Inserm U1071, USC INRAE 1382, Clermont-Ferrand, France
| | - Frederic Robin
- Microbes, Intestin, Inflammation et Susceptibilité de l’Hôte (M2iSH), Université Clermont Auvergne/Inserm U1071, USC INRAE 1382, Clermont-Ferrand, France
- Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire, Clermont-Ferrand, France
| | - Racha Beyrouthy
- Microbes, Intestin, Inflammation et Susceptibilité de l’Hôte (M2iSH), Université Clermont Auvergne/Inserm U1071, USC INRAE 1382, Clermont-Ferrand, France
- Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire, Clermont-Ferrand, France
| | | | | | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, China
- Microbiota I-Center (MagIC), Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Richard Bonnet
- Microbes, Intestin, Inflammation et Susceptibilité de l’Hôte (M2iSH), Université Clermont Auvergne/Inserm U1071, USC INRAE 1382, Clermont-Ferrand, France
- Centre National de Référence de la Résistance aux Antibiotiques, Centre Hospitalier Universitaire, Clermont-Ferrand, France
| | - Anthony Buisson
- Microbes, Intestin, Inflammation et Susceptibilité de l’Hôte (M2iSH), Université Clermont Auvergne/Inserm U1071, USC INRAE 1382, Clermont-Ferrand, France
- Service d’Hépato-Gastro Entérologie, Université Clermont Auvergne, Inserm, 3iHP, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Nicolas Barnich
- Microbes, Intestin, Inflammation et Susceptibilité de l’Hôte (M2iSH), Université Clermont Auvergne/Inserm U1071, USC INRAE 1382, Clermont-Ferrand, France
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5
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Bleich RM, Li C, Sun S, Ahn JH, Dogan B, Barlogio CJ, Broberg CA, Franks AR, Bulik-Sullivan E, Carroll IM, Simpson KW, Fodor AA, Arthur JC. A consortia of clinical E. coli strains with distinct in vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice. MICROBIOME 2023; 11:277. [PMID: 38124090 PMCID: PMC10731797 DOI: 10.1186/s40168-023-01710-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 10/26/2023] [Indexed: 12/23/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in vitro definition fully predicts mucosal colonization in vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis. RESULTS Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortium of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization. CONCLUSIONS Our findings establish the in vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in vivo colonization dynamics of patient-derived bacteria in murine models. Video Abstract.
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Affiliation(s)
- Rachel M Bleich
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Biology, Appalachian State University, Boone, NC, USA
| | - Chuang Li
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Shan Sun
- College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, NC, USA
| | - Ju-Hyun Ahn
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Belgin Dogan
- Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY, USA
| | - Cassandra J Barlogio
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Christopher A Broberg
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Adrienne R Franks
- Center for Gastrointestinal Biology & Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Emily Bulik-Sullivan
- Center for Gastrointestinal Biology & Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Ian M Carroll
- Center for Gastrointestinal Biology & Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Kenneth W Simpson
- Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY, USA
| | - Anthony A Fodor
- College of Computing and Informatics, University of North Carolina at Charlotte, Charlotte, NC, USA
| | - Janelle C Arthur
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Center for Gastrointestinal Biology & Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
- Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
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Habib I, Elbediwi M, Mohteshamuddin K, Mohamed MYI, Lakshmi GB, Abdalla A, Anes F, Ghazawi A, Khan M, Khalifa H. Genomic profiling of extended-spectrum β-lactamase-producing Escherichia coli from Pets in the United Arab Emirates: Unveiling colistin resistance mediated by mcr-1.1 and its probable transmission from chicken meat - A One Health perspective. J Infect Public Health 2023; 16 Suppl 1:163-171. [PMID: 37957104 DOI: 10.1016/j.jiph.2023.10.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 10/27/2023] [Accepted: 10/30/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND The United Arab Emirates (UAE) has witnessed rapid urbanization and a surge in pet ownership, sparking concerns about the possible transfer of antimicrobial resistance (AMR) from pets to humans and the environment. This study delves into the whole-genome sequencing analysis of ESBL-producing E. coli strains from healthy cats and dogs in the UAE, which exhibit multidrug resistance (MDR). Additionally, it provides a genomic exploration of the mobile colistin resistance gene mcr-1.1, marking the first instance of its detection in Middle Eastern pets. METHODS We investigate 17 ESBL-producing E. coli strains from healthy UAE pets using WGS and bioinformatics analysis to identify genes encoding virulence factors, assign diverse typing schemes to the isolates, and scrutinize the presence of AMR genes. Furthermore, we characterized plasmid contigs housing the mcr-1.1 gene and conducted phylogenomic analysis to evaluate their relatedness to previously identified UAE isolates. RESULTS Our study unveiled a variety of virulence factor-encoding genes within the isolates, with fimH emerging as the most prevalent. Regarding β-lactamase resistance genes, the blaCTX group 1 gene family predominated, with CTX-M-15 found in 52.9% (9/17) of the isolates, followed by CTX-M-55 in 29.4% (5/17). These isolates were categorized into multiple sequence types (STs), with the epidemic ST131 being the most frequent. The presence of the mcr-1.1 gene, linked to colistin resistance, was confirmed in two isolates. These isolates belonged to ST1011 and displayed distinct profiles of β-lactamase resistance genes. Phylogenomic analysis revealed close connections between the isolates and those from chicken meat in the UAE. CONCLUSION Our study underscores the presence of MDR ESBL-producing E. coli in UAE pets. The identification of mcr-1.1-carrying isolates warrants the urgency of comprehensive AMR surveillance and highlights the role of companion animals in AMR epidemiology. These findings underscore the significance of adopting a One Health approach to mitigate AMR transmission risks effectively.
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Affiliation(s)
- Ihab Habib
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, United Arab Emirates University, P.O. Box 1555, Al Ain, United Arab Emirates; Department of Environmental Health, High Institute of Public Health, Alexandria University, Alexandria, Egypt.
| | - Mohammed Elbediwi
- Evolutionary Biology, Institute for Biology, Freie Universität Berlin, Berlin, Germany; Animal Health Research Institute, Agriculture Research Centre, Cairo, Egypt
| | - Khaja Mohteshamuddin
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, United Arab Emirates University, P.O. Box 1555, Al Ain, United Arab Emirates
| | - Mohamed-Yousif Ibrahim Mohamed
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, United Arab Emirates University, P.O. Box 1555, Al Ain, United Arab Emirates
| | - Glindya Bhagya Lakshmi
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, United Arab Emirates University, P.O. Box 1555, Al Ain, United Arab Emirates
| | - Afra Abdalla
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, United Arab Emirates University, P.O. Box 1555, Al Ain, United Arab Emirates
| | - Febin Anes
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, United Arab Emirates University, P.O. Box 1555, Al Ain, United Arab Emirates
| | - Akela Ghazawi
- Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 1555, Al Ain, United Arab Emirates
| | - Mushtaq Khan
- Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 1555, Al Ain, United Arab Emirates; Zayed Center for Health Sciences, United Arab Emirates University, P.O. Box 15551, Al Ain, United Arab Emirates
| | - Hazim Khalifa
- Department of Veterinary Medicine, College of Agriculture and Veterinary Medicine, United Arab Emirates University, P.O. Box 1555, Al Ain, United Arab Emirates; Department of Pharmacology, Faculty of Veterinary Medicine, Kafrelsheikh University, Egypt
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7
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Bleich RM, Li C, Sun S, Barlogio CJ, Broberg CA, Franks AR, Bulik-Sullivan E, Dogan B, Simpson KW, Carroll IM, Fodor AA, Arthur JC. A consortia of clinical E. coli strains with distinct in-vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice. RESEARCH SQUARE 2023:rs.3.rs-2899665. [PMID: 37214858 PMCID: PMC10197778 DOI: 10.21203/rs.3.rs-2899665/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Background Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in-vitro definition fully predicts mucosal colonization in-vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis. Results Germ-free inflammation-susceptible interleukin-10-deficient (Il10-/-) and inflammation-resistant WT mice were colonized with a consortia of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10-/- mice. These E. coli expand in Il10-/- mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization. Conclusions Our findings establish the in-vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in-vivo colonization dynamics of patient-derived bacteria in murine models.
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Affiliation(s)
| | - Chuang Li
- University of North Carolina at Chapel Hill
| | - Shan Sun
- University of North Carolina at Charlotte
| | | | | | | | | | - Belgin Dogan
- Cornell University College of Veterinary Medicine
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8
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Arroyo-Mendoza M, Proctor A, Correa-Medina A, Brand MW, Rosas V, Wannemuehler MJ, Phillips GJ, Hinton DM. The E. coli pathobiont LF82 encodes a unique variant of σ 70 that results in specific gene expression changes and altered phenotypes. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.02.08.523653. [PMID: 36798310 PMCID: PMC9934711 DOI: 10.1101/2023.02.08.523653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
LF82, an adherent invasive Escherichia coli pathobiont, is associated with ileal Crohn's disease, an inflammatory bowel disease of unknown etiology. Although LF82 contains no virulence genes, it carries several genetic differences, including single nucleotide polymorphisms (SNPs), that distinguish it from nonpathogenic E. coli. We have identified and investigated an extremely rare SNP that is within the highly conserved rpoD gene, encoding σ70, the primary sigma factor for RNA polymerase. We demonstrate that this single residue change (D445V) results in specific transcriptome and phenotypic changes that are consistent with multiple phenotypes observed in LF82, including increased antibiotic resistance and biofilm formation, modulation of motility, and increased capacity for methionine biosynthesis. Our work demonstrates that a single residue change within the bacterial primary sigma factor can lead to multiple alterations in gene expression and phenotypic changes, suggesting an underrecognized mechanism by which pathobionts and other strain variants with new phenotypes can emerge.
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Affiliation(s)
- Melissa Arroyo-Mendoza
- Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Dr., Bethesda, MD, United States, 20892
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States, 50011
| | - Alexandra Proctor
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States, 50011
| | - Abraham Correa-Medina
- Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Dr., Bethesda, MD, United States, 20892
| | - Meghan Wymore Brand
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States, 50011
| | - Virginia Rosas
- Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Dr., Bethesda, MD, United States, 20892
| | - Michael J Wannemuehler
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States, 50011
| | - Gregory J Phillips
- Department of Veterinary Microbiology and Preventative Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States, 50011
| | - Deborah M Hinton
- Gene Expression and Regulation Section, Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Dr., Bethesda, MD, United States, 20892
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9
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FUJIMOTO K. Metagenome data-based phage therapy for intestinal bacteria-mediated diseases. BIOSCIENCE OF MICROBIOTA, FOOD AND HEALTH 2023; 42:8-12. [PMID: 36660604 PMCID: PMC9816054 DOI: 10.12938/bmfh.2022-061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 09/14/2022] [Indexed: 11/07/2022]
Abstract
Improvements in genome analysis technology using next-generation sequencing have revealed that abnormalities in the composition of the intestinal microbiota are important in numerous diseases. Furthermore, intestinal commensal pathogens that are directly involved in the onset and exacerbation of disease have been identified. Specific control of them is strongly desired. However, antibiotics are not appropriate for the control of intestinal commensal pathogens because they may kill beneficial bacteria as well. The intestinal tract contains many viruses: most are bacteriophages (phages) that infect intestinal bacteria rather than viruses that infect human cells. Phages have very high specificity for their host bacteria. Therefore, phage therapy is considered potentially useful for controlling intestinal commensal pathogens. However, the intestinal tract is a specialized, anaerobic environment, and it is impossible to isolate phages that infect host intestinal bacteria if the bacteria cannot be cultured. Furthermore, genomic analysis methods for intestinal phages have not been well established, so until recently, a complete picture of the intestinal phage has not been clear. In this review, I summarize the importance of next-generation phage therapy based on metagenomic data and describe a novel therapy against Clostridioides difficile developed using such data.
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Affiliation(s)
- Kosuke FUJIMOTO
- Department of Immunology and Genomics, Osaka Metropolitan
University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka-shi, Osaka
545-8585, Japan,Division of Metagenome Medicine, Human Genome Center, The
Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku,
Tokyo 108-8639, Japan
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10
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Zheng L, Duan SL, Dai YC, Wu SC. Role of adherent invasive Escherichia coli in pathogenesis of inflammatory bowel disease. World J Clin Cases 2022; 10:11671-11689. [PMID: 36405271 PMCID: PMC9669839 DOI: 10.12998/wjcc.v10.i32.11671] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 09/04/2022] [Accepted: 10/11/2022] [Indexed: 02/05/2023] Open
Abstract
Gut microbiota imbalances play an important role in inflammatory bowel disease (IBD), but no single pathogenic microorganism critical to IBD that is specific to the IBD terminal ileum mucosa or can invade intestinal epithelial cells has been found. Invasive Escherichia coli (E. coli) adhesion to macrophages is considered to be closely related to the pathogenesis of inflammatory bowel disease. Further study of the specific biological characteristics of adherent invasive E. coli (AIEC) may contribute to a further understanding of IBD pathogenesis. This review explores the relationship between AIEC and the intestinal immune system, discusses the prevalence and relevance of AIEC in Crohn's disease and ulcerative colitis patients, and describes the relationship between AIEC and the disease site, activity, and postoperative recurrence. Finally, we highlight potential therapeutic strategies to attenuate AIEC colonization in the intestinal mucosa, including the use of phage therapy, antibiotics, and anti-adhesion molecules. These strategies may open up new avenues for the prevention and treatment of IBD in the future.
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Affiliation(s)
- Lie Zheng
- Department of Gastroenterology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an 322000, Shaanxi Province, China
| | - Sheng-Lei Duan
- Department of Gastroenterology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an 322000, Shaanxi Province, China
| | - Yan-Cheng Dai
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Shi-Cheng Wu
- Department of Proctology, Gansu Academy of Traditional Chinese Medicine, Gansu Hospital of Traditional Chinese Medicine, Lanzhou 730050, Gansu Province, China
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11
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Geurtsen J, de Been M, Weerdenburg E, Zomer A, McNally A, Poolman J. Genomics and pathotypes of the many faces of Escherichia coli. FEMS Microbiol Rev 2022; 46:fuac031. [PMID: 35749579 PMCID: PMC9629502 DOI: 10.1093/femsre/fuac031] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2021] [Accepted: 06/22/2022] [Indexed: 01/09/2023] Open
Abstract
Escherichia coli is the most researched microbial organism in the world. Its varied impact on human health, consisting of commensalism, gastrointestinal disease, or extraintestinal pathologies, has generated a separation of the species into at least eleven pathotypes (also known as pathovars). These are broadly split into two groups, intestinal pathogenic E. coli (InPEC) and extraintestinal pathogenic E. coli (ExPEC). However, components of E. coli's infinite open accessory genome are horizontally transferred with substantial frequency, creating pathogenic hybrid strains that defy a clear pathotype designation. Here, we take a birds-eye view of the E. coli species, characterizing it from historical, clinical, and genetic perspectives. We examine the wide spectrum of human disease caused by E. coli, the genome content of the bacterium, and its propensity to acquire, exchange, and maintain antibiotic resistance genes and virulence traits. Our portrayal of the species also discusses elements that have shaped its overall population structure and summarizes the current state of vaccine development targeted at the most frequent E. coli pathovars. In our conclusions, we advocate streamlining efforts for clinical reporting of ExPEC, and emphasize the pathogenic potential that exists throughout the entire species.
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Affiliation(s)
- Jeroen Geurtsen
- Janssen Vaccines and Prevention B.V., 2333 Leiden, the Netherlands
| | - Mark de Been
- Janssen Vaccines and Prevention B.V., 2333 Leiden, the Netherlands
| | | | - Aldert Zomer
- Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 Utrecht, the Netherlands
| | - Alan McNally
- Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, B15 2TT Birmingham, United Kingdom
| | - Jan Poolman
- Janssen Vaccines and Prevention B.V., 2333 Leiden, the Netherlands
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12
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Fu Q, Song T, Ma X, Cui J. Research progress on the relationship between intestinal microecology and intestinal bowel disease. Animal Model Exp Med 2022; 5:297-310. [PMID: 35962562 PMCID: PMC9434592 DOI: 10.1002/ame2.12262] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 06/21/2022] [Indexed: 12/02/2022] Open
Abstract
Intestinal microecology is the main component of human microecology. Intestinal microecology consists of intestinal microbiota, intestinal epithelial cells, and intestinal mucosal immune system. These components are interdependent and establish a complex interaction network that restricts each other. According to the impact on the human body, there are three categories of symbiotic bacteria, opportunistic pathogens, and pathogenic bacteria. The intestinal microecology participates in digestion and absorption, and material metabolism, and inhibits the growth of pathogenic microorganisms. It also acts as the body's natural immune barrier, regulates the innate immunity of the intestine, controls the mucosal barrier function, and also participates in the intestinal epithelial cells' physiological activities such as hyperplasia or apoptosis. When the steady‐state balance of the intestinal microecology is disturbed, the existing core intestinal microbiota network changes and leads to obesity, diabetes, and many other diseases, especially irritable bowel syndrome, inflammatory bowel disease (IBD), and colorectal malignancy. Intestinal diseases, including tumors, are particularly closely related to intestinal microecology. This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis, treatment methods of IBD, and the changes in intestinal microbiota.
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Affiliation(s)
- Qianhui Fu
- School of Pharmacy, Minzu University of China, Beijing, China.,Ministry of Education, Key Laboratory of Ethnomedicine, Minzu University of China, Beijing, China
| | - Tianyuan Song
- School of Pharmacy, Minzu University of China, Beijing, China.,Ministry of Education, Key Laboratory of Ethnomedicine, Minzu University of China, Beijing, China
| | - Xiaoqin Ma
- School of Pharmacy, Minzu University of China, Beijing, China.,Ministry of Education, Key Laboratory of Ethnomedicine, Minzu University of China, Beijing, China
| | - Jian Cui
- School of Pharmacy, Minzu University of China, Beijing, China.,Ministry of Education, Key Laboratory of Ethnomedicine, Minzu University of China, Beijing, China
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13
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Enciso-Martínez Y, González-Aguilar GA, Martínez-Téllez MA, González-Pérez CJ, Valencia-Rivera DE, Barrios-Villa E, Ayala-Zavala JF. Relevance of tracking the diversity of Escherichia coli pathotypes to reinforce food safety. Int J Food Microbiol 2022; 374:109736. [DOI: 10.1016/j.ijfoodmicro.2022.109736] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 05/13/2022] [Accepted: 05/16/2022] [Indexed: 12/21/2022]
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14
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Xu Z, Dong X, Yang K, Chevarin C, Zhang J, Lin Y, Zuo T, Chu LC, Sun Y, Zhang F, Chan FK, Sung JJ, Yu J, Buisson A, Barnich N, Colombel JF, Wong SH, Miao Y, Ng SC. Association of Adherent-invasive Escherichia coli with severe Gut Mucosal dysbiosis in Hong Kong Chinese population with Crohn's disease. Gut Microbes 2022; 13:1994833. [PMID: 34812117 PMCID: PMC8632309 DOI: 10.1080/19490976.2021.1994833] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Adherent invasive Escherichia Coli (AIEC) has been implicated in the pathogenesis of Crohn's disease (CD) in Western populations. Whether the presence of AIEC is also seen in CD populations of different genetic susceptibility and has negative impact on host microbiota ecology and therapeutics are unclear. AIEC presence was assessed in ileal tissues of 60 Hong Kong Chinese patients with CD and 56 healthy subjects. Mucosa microbiota was analyzed by 16s rRNA sequencing. Impact of AIEC on the gut microbiota was determined in a mouse model. AIEC was significantly more prevalent in ileal tissues of patients with CD than controls (30% vs 7.1%). Presence of AIEC in ileal tissues was associated with more severe mucosa microbiota dysbiosis in CD with decreased diversity and lower abundance of Firmicutes including butyrate producing Roseburia and probiotic Bacillus. A random forest model predicted the presence of AIEC with area under the curve of 0.89. AIEC exacerbated dysbiosis in dextran sodium sulfate (DSS)-induced colitis mice and led to resistance to restoration of normal gut microbiota by fecal microbiota transplantation (FMT). Proportion of donor-derived bacteria in AIEC-colonized mice was significantly lower than that in uninfected mice. AIEC was prevalent and associated with severe mucosa microbiota dysbiosis in CD in Hong Kong Chinese population. The presence of AIEC impeded restoration of normal gut microbiota. AIEC may serve as a keystone bacterium in CD and impact the efficacy of FMT.
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Affiliation(s)
- Zhilu Xu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China,Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Xiangqian Dong
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan, China,Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Keli Yang
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China,Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Caroline Chevarin
- Centre De Recherche En Nutrition Humaine Auvergne, Université Clermont Auvergne, Inserm U1071, Usc-inrae 2018, Microbes, Intestin, Inflammation Et Susceptibilité De l’Hôte (M2ish), Clermont-Ferrand, France
| | - Jingwan Zhang
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China,Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Yu Lin
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China,Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Tao Zuo
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China,Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Lok Cheung Chu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China
| | - Yang Sun
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan, China,Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Fengrui Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan, China,Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China
| | - Francis Kl Chan
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China,Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Joseph Jy Sung
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China
| | - Jun Yu
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China
| | - Anthony Buisson
- Centre De Recherche En Nutrition Humaine Auvergne, Université Clermont Auvergne, Inserm U1071, Usc-inrae 2018, Microbes, Intestin, Inflammation Et Susceptibilité De l’Hôte (M2ish), Clermont-Ferrand, France,3iHP, Chu Clermont-Ferrand, Service d’Hépato-Gastro Entérologie, Clermont-Ferrand, France
| | - Nicolas Barnich
- Centre De Recherche En Nutrition Humaine Auvergne, Université Clermont Auvergne, Inserm U1071, Usc-inrae 2018, Microbes, Intestin, Inflammation Et Susceptibilité De l’Hôte (M2ish), Clermont-Ferrand, France
| | | | - Sunny Hei Wong
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China
| | - Yinglei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan, China,Yunnan Province Clinical Research Center for Digestive Diseases, Kunming, Yunnan, China,Yinglei Miao, Professor, Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University
| | - Siew C Ng
- Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, Lks Institute of Health Science, the Chinese University of Hong Kong, Hong Kong, China,Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China,CONTACT Siew C NG
Professor,Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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15
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Kamali Dolatabadi R, Feizi A, Halaji M, Fazeli H, Adibi P. The Prevalence of Adherent-Invasive Escherichia coli and Its Association With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Front Med (Lausanne) 2021; 8:730243. [PMID: 34926490 PMCID: PMC8678049 DOI: 10.3389/fmed.2021.730243] [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: 06/28/2021] [Accepted: 10/22/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are known as chronic gastrointestinal inflammatory disorders. The present systematic review and meta analysis was conducted to estimate the prevalence of adherent-invasive Escherichia coli (AIEC) isolates and their phylogenetic grouping among IBD patients compared with the controls. A systematic literature search was conducted among published papers by international authors until April 30, 2020 in Web of Science, Scopus, EMBASE, and PubMed databases. The pooled prevalence of AIEC isolates and their phylogenetic grouping among IBD patients as well as in controls was estimated using fixed or random effects models. Furthermore, for estimating the association of colonization by AIEC with IBD, odds ratio along with 95% confidence interval was reported. A total of 205 articles retrieved by the initial search of databases, 13 case–control studies met the eligibility criteria for inclusion in the meta analysis. There were 465 IBD cases (348 CD and 117 UC) and 307 controls. The pooled prevalence of AIEC isolates were 28% (95% CI: 18–39%), 29% (95% CI: 20–40%), 13% (95% CI: 1–30%), and 9% (95% CI: 3–19%), respectively among IBD, CD, UC, and control group, respectively. Our results revealed that the most frequent AIEC phylogroup in the IBD, CD, and control groups was B2. Fixed-effects meta analysis showed that colonization of AIEC is significantly associated with IBD (OR: 2.93; 95% CI: 1.90–4.52; P < 0.001) and CD (OR: 3.07; 95% CI: 1.99–4.74; P < 0.001), but not with UC (OR: 2.29; 95% CI: 0.81–6.51; P = 0.11). In summary, this meta analysis revealed that colonization by AIEC is more frequent in IBD and is associated with IBD (CD and UC). Our results suggested that the affects of IBD in patients colonized with the AIEC pathovar is not random, it is in fact a specific disease-related pathovar.
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Affiliation(s)
- Razie Kamali Dolatabadi
- Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Awat Feizi
- Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehrdad Halaji
- Infectious Diseases and Tropical Medicine Research Center, Babol University of Medical Sciences, Babol, Iran.,Department of Microbiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Hossein Fazeli
- Department of Microbiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Peyman Adibi
- Gastroenterology and Hepatology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
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16
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Pakbin B, Brück WM, Rossen JWA. Virulence Factors of Enteric Pathogenic Escherichia coli: A Review. Int J Mol Sci 2021; 22:9922. [PMID: 34576083 PMCID: PMC8468683 DOI: 10.3390/ijms22189922] [Citation(s) in RCA: 80] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 09/09/2021] [Accepted: 09/12/2021] [Indexed: 12/18/2022] Open
Abstract
Escherichia coli are remarkably versatile microorganisms and important members of the normal intestinal microbiota of humans and animals. This harmless commensal organism can acquire a mixture of comprehensive mobile genetic elements that contain genes encoding virulence factors, becoming an emerging human pathogen capable of causing a broad spectrum of intestinal and extraintestinal diseases. Nine definite enteric E. coli pathotypes have been well characterized, causing diseases ranging from various gastrointestinal disorders to urinary tract infections. These pathotypes employ many virulence factors and effectors subverting the functions of host cells to mediate their virulence and pathogenesis. This review summarizes new developments in our understanding of diverse virulence factors associated with encoding genes used by different pathotypes of enteric pathogenic E. coli to cause intestinal and extraintestinal diseases in humans.
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Affiliation(s)
- Babak Pakbin
- Institute for Life Technologies, University of Applied Sciences Western Switzerland Valais-Wallis, 1950 Sion 2, Switzerland;
- Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands;
- Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin 15315-3419, Iran
| | - Wolfram M. Brück
- Institute for Life Technologies, University of Applied Sciences Western Switzerland Valais-Wallis, 1950 Sion 2, Switzerland;
| | - John W. A. Rossen
- Department of Medical Microbiology and Infection Prevention, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands;
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17
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Sodagari HR, Sahibzada S, Robertson I, Habib I, Wang P. Whole-Genome Comparative Analysis Reveals Association Between Salmonella Genomic Variation and Egg Production Systems. Front Vet Sci 2021; 8:666767. [PMID: 34322531 PMCID: PMC8311177 DOI: 10.3389/fvets.2021.666767] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 06/08/2021] [Indexed: 11/13/2022] Open
Abstract
Non-typhoidal Salmonella, particularly Salmonella enterica serovar Typhimurium (S. Typhimurium), is the predominant endemic serovar in the Australian egg production industry and is one of the most frequently reported serovars in foodborne infections in Australia. This study was conducted to investigate the genomic characteristics of Salmonella isolated from retail table eggs in Western Australia and to identify the impact of production systems on genomic characteristics of Salmonella such as virulence and antimicrobial resistance. A total of 40 non-typhoidal Salmonella isolates [S. Typhimurium isolates (n = 28) and Salmonella Infantis isolates (n = 12)] sourced from retail eggs produced by different production systems (barn-laid, cage, and free-range) in Western Australia were sequenced by whole-genome sequencing. The isolates were de novo assembled, annotated, and analyzed. The results indicated an association between Salmonella genomic variation and the system used to raise poultry for egg production (p-value < 0.05). All but one of the S. Infantis isolates were recovered from eggs collected from poultry raised under barn and cage production systems. A higher proportion (83.3%) of S. Typhimurium isolates were recovered from the eggs produced by free-range production system as compared with those produced under barn (76.9%) and cage production systems (53.3%). Our analysis indicated that Salmonella isolated from the eggs produced by barn and cage production systems had more virulence genes than the isolates of the free-range produced eggs. A low carriage of antimicrobial-resistant gene was detected in the isolates of this study. We have built a Salmonella genomics database and characteristics-linked gene pools to facilitate future study, characterization, and tracing of Salmonella outbreaks.
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Affiliation(s)
- Hamid Reza Sodagari
- School of Veterinary Medicine, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, Australia
| | - Shafi Sahibzada
- School of Veterinary Medicine, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, Australia
| | - Ian Robertson
- School of Veterinary Medicine, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, Australia
| | - Ihab Habib
- School of Veterinary Medicine, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, Australia
- Department of Veterinary Medicine, College of Food and Agriculture, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Penghao Wang
- Medical, Molecular and Forensic Sciences, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, WA, Australia
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18
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Puvača N, de Llanos Frutos R. Antimicrobial Resistance in Escherichia coli Strains Isolated from Humans and Pet Animals. Antibiotics (Basel) 2021; 10:69. [PMID: 33450827 PMCID: PMC7828219 DOI: 10.3390/antibiotics10010069] [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] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/06/2021] [Accepted: 01/12/2021] [Indexed: 12/12/2022] Open
Abstract
Throughout scientific literature, we can find evidence that antimicrobial resistance has become a big problem in the recent years on a global scale. Public healthcare systems all over the world are faced with a great challenge in this respect. Obviously, there are many bacteria that can cause infections in humans and animals alike, but somehow it seems that the greatest threat nowadays comes from the Enterobacteriaceae members, especially Escherichia coli. Namely, we are witnesses to the fact that the systems that these bacteria developed to fight off antibiotics are the strongest and most diverse in Enterobacteriaceae. Our great advantage is in understanding the systems that bacteria developed to fight off antibiotics, so these can help us understand the connection between these microorganisms and the occurrence of antibiotic-resistance both in humans and their pets. Furthermore, unfavorable conditions related to the ease of E. coli transmission via the fecal-oral route among humans, environmental sources, and animals only add to the problem. For all the above stated reasons, it is evident that the epidemiology of E. coli strains and resistance mechanisms they have developed over time are extremely significant topics and all scientific findings in this area will be of vital importance in the fight against infections caused by these bacteria.
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Affiliation(s)
- Nikola Puvača
- Faculty of Biomedical and Health Sciences, Jaume I University, Avinguda de Vicent Sos Baynat, s/n, 12071 Castelló de la Plana, Spain;
- Department of Engineering Management in Biotechnology, Faculty of Economics and Engineering Management in Novi Sad, University Business Academy in Novi Sad, Cvećarska 2, 21000 Novi Sad, Serbia
| | - Rosa de Llanos Frutos
- Faculty of Biomedical and Health Sciences, Jaume I University, Avinguda de Vicent Sos Baynat, s/n, 12071 Castelló de la Plana, Spain;
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19
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Fujimoto K, Kimura Y, Shimohigoshi M, Satoh T, Sato S, Tremmel G, Uematsu M, Kawaguchi Y, Usui Y, Nakano Y, Hayashi T, Kashima K, Yuki Y, Yamaguchi K, Furukawa Y, Kakuta M, Akiyama Y, Yamaguchi R, Crowe SE, Ernst PB, Miyano S, Kiyono H, Imoto S, Uematsu S. Metagenome Data on Intestinal Phage-Bacteria Associations Aids the Development of Phage Therapy against Pathobionts. Cell Host Microbe 2020; 28:380-389.e9. [PMID: 32652061 DOI: 10.1016/j.chom.2020.06.005] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 05/12/2020] [Accepted: 06/10/2020] [Indexed: 02/08/2023]
Abstract
The application of bacteriophages (phages) is proposed as a highly specific therapy for intestinal pathobiont elimination. However, the infectious associations between phages and bacteria in the human intestine, which is essential information for the development of phage therapies, have yet to be fully elucidated. Here, we report the intestinal viral microbiomes (viromes), together with bacterial microbiomes (bacteriomes), in 101 healthy Japanese individuals. Based on the genomic sequences of bacteriomes and viromes from the same fecal samples, the host bacteria-phage associations are illustrated for both temperate and virulent phages. To verify the usefulness of the comprehensive host bacteria-phage information, we screened Clostridioides difficile-specific phages and identified antibacterial enzymes whose activity is confirmed both in vitro and in vivo. These comprehensive metagenome analyses reveal not only host bacteria-phage associations in the human intestine but also provide vital information for the development of phage therapies against intestinal pathobionts.
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Affiliation(s)
- Kosuke Fujimoto
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; Division of Metagenome Medicine, Human Genome Center, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Yasumasa Kimura
- Division of Systems Immunology, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Masaki Shimohigoshi
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Takeshi Satoh
- Division of Systems Immunology, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Shintaro Sato
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; Mucosal Vaccine Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan
| | - Georg Tremmel
- Laboratory of DNA Information Analysis, Human Genome Center, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Miho Uematsu
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Yunosuke Kawaguchi
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Yuki Usui
- Division of Systems Immunology, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Yoshiko Nakano
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Tetsuya Hayashi
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Koji Kashima
- Division of Mucosal Immunology, Department of Microbiology and Immunology, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Yoshikazu Yuki
- Division of Mucosal Immunology, Department of Microbiology and Immunology, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Kiyoshi Yamaguchi
- Division of Clinical Genome Research, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Yoichi Furukawa
- Division of Clinical Genome Research, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Masanori Kakuta
- Laboratory of DNA Information Analysis, Human Genome Center, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Yutaka Akiyama
- Department of Computer Science, Tokyo Institute of Technology, Tokyo 152-8550, Japan
| | - Rui Yamaguchi
- Laboratory of DNA Information Analysis, Human Genome Center, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Sheila E Crowe
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
| | - Peter B Ernst
- Division of Gastroenterology, Department of Medicine, CU-UCSD Center for Mucosal Immunology, Allergy and Vaccines, University of California, San Diego, La Jolla, CA 92093, USA; Division of Comparative Pathology and Medicine, Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA; Center for Veterinary Sciences and Comparative Medicine, University of California, San Diego, La Jolla, CA 92093, USA
| | - Satoru Miyano
- Laboratory of DNA Information Analysis, Human Genome Center, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Hiroshi Kiyono
- Division of Gastroenterology, Department of Medicine, CU-UCSD Center for Mucosal Immunology, Allergy and Vaccines, University of California, San Diego, La Jolla, CA 92093, USA; Division of Comparative Pathology and Medicine, Department of Pathology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Mucosal Immunology, IMSUT Distinguished Professor Unit, The Institute of Medical Sciences, The University of Tokyo, Tokyo 108-8639, Japan; International Research and Development Center for Mucosal Vaccines, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan
| | - Seiya Imoto
- Division of Health Medical Intelligence, Human Genome Center, The Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan; Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo 113-8657, Japan.
| | - Satoshi Uematsu
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; Division of Metagenome Medicine, Human Genome Center, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, the Institute of Medical Sciences, the University of Tokyo, Tokyo 108-8639, Japan; Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo 113-8657, Japan.
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20
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Fujimoto K, Uematsu S. Vaccine therapy for dysbiosis-related diseases. World J Gastroenterol 2020; 26:2758-2767. [PMID: 32550752 PMCID: PMC7284185 DOI: 10.3748/wjg.v26.i21.2758] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2019] [Revised: 03/27/2020] [Accepted: 05/23/2020] [Indexed: 02/06/2023] Open
Abstract
Progress in genomic analysis has resulted in the proposal that the intestinal microbiota is a crucial environmental factor in the development of multifactorial diseases, such as obesity, diabetes, rheumatoid arthritis, and inflammatory bowel diseases represented by Crohn’s disease and ulcerative colitis. Dysregulated gut microbiome contributes to the pathogenesis of such disorders; however, there are few effective treatments for controlling only disease-mediating bacteria. Here, we review current knowledge about the intestinal microbiome in health and disease, and discuss a regulatory strategy using a parenteral vaccine with emulsified curdlan and CpG oligodeoxynucleotides, which we have recently developed. Unlike other conventional injectable immunizations, our vaccine contributes to the induction of antigen-specific systemic and mucosal immunity. This vaccine strategy can prevent infectious diseases such as Streptococcus pneumoniae infection, and control metabolic symptoms mediated by intestinal bacteria (e.g. Clostridium ramosum) by induction of high titers of antigen-specific IgA at target mucosal sites. In the future, our vaccination approach could be an effective therapy for common infectious diseases and dysbiosis-related disorders that have been difficult to control so far.
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MESH Headings
- Administration, Mucosal
- Arthritis, Rheumatoid/immunology
- Arthritis, Rheumatoid/microbiology
- Arthritis, Rheumatoid/therapy
- Bacterial Vaccines/administration & dosage
- Bacterial Vaccines/immunology
- Diabetes Mellitus, Type 2/immunology
- Diabetes Mellitus, Type 2/microbiology
- Diabetes Mellitus, Type 2/therapy
- Dysbiosis/complications
- Dysbiosis/immunology
- Dysbiosis/microbiology
- Dysbiosis/therapy
- Gastrointestinal Microbiome/immunology
- Humans
- Immunity, Mucosal
- Immunization Schedule
- Immunization, Secondary
- Immunoglobulin A/immunology
- Immunoglobulin A/metabolism
- Inflammatory Bowel Diseases/immunology
- Inflammatory Bowel Diseases/microbiology
- Inflammatory Bowel Diseases/therapy
- Injections, Intramuscular
- Intestinal Mucosa/immunology
- Intestinal Mucosa/metabolism
- Intestinal Mucosa/microbiology
- Obesity/immunology
- Obesity/microbiology
- Obesity/therapy
- Oligodeoxyribonucleotides/administration & dosage
- Oligodeoxyribonucleotides/immunology
- Polysaccharides, Bacterial/administration & dosage
- Polysaccharides, Bacterial/immunology
- Vaccines, Synthetic/administration & dosage
- Vaccines, Synthetic/immunology
- beta-Glucans/administration & dosage
- beta-Glucans/immunology
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Affiliation(s)
- Kosuke Fujimoto
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
- Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 113-8654, Japan
- Division of Metagenome Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 113-8654, Japan
| | - Satoshi Uematsu
- Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
- Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 113-8654, Japan
- Division of Metagenome Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 113-8654, Japan
- Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo 113-8654, Japan
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