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Hetta HF, Ahmed R, Ramadan YN, Fathy H, Khorshid M, Mabrouk MM, Hashem M. Gut virome: New key players in the pathogenesis of inflammatory bowel disease. World J Methodol 2025; 15:92592. [DOI: 10.5662/wjm.v15.i2.92592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 05/28/2024] [Accepted: 07/23/2024] [Indexed: 11/27/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the intestine. While the mechanism underlying the pathogenesis of IBD is not fully understood, it is believed that a complex combination of host immunological response, environmental exposure, particularly the gut microbiota, and genetic susceptibility represents the major determinants. The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans. The gut virome varies greatly among individuals and is influenced by factors including lifestyle, diet, health and disease conditions, geography, and urbanization. The majority of research has focused on the significance of gut bacteria in the progression of IBD, although viral populations represent an important component of the microbiome. We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.
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Affiliation(s)
- Helal F Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
- Division of Microbiology, Immunology and Biotechnology, Faculty of pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Rehab Ahmed
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Yasmin N Ramadan
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Hayam Fathy
- Department of Internal Medicine, Division Hepatogastroenterology, Assiut University, Assiut 71515, Egypt
| | - Mohammed Khorshid
- Department of Clinical Research, Egyptian Developers of Gastroenterology and Endoscopy Foundation, Cairo 11936, Egypt
| | - Mohamed M Mabrouk
- Department of Internal Medicine, Faculty of Medicine. Tanta University, Tanta 31527, Egypt
| | - Mai Hashem
- Department of Tropical Medicine, Gastroenterology and Hepatology, Assiut University Hospital, Assiut 71515, Egypt
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Smith L, Goldobina E, Govi B, Shkoporov AN. Bacteriophages of the Order Crassvirales: What Do We Currently Know about This Keystone Component of the Human Gut Virome? Biomolecules 2023; 13:584. [PMID: 37189332 PMCID: PMC10136315 DOI: 10.3390/biom13040584] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/16/2023] [Accepted: 03/17/2023] [Indexed: 05/17/2023] Open
Abstract
The order Crassvirales comprises dsDNA bacteriophages infecting bacteria in the phylum Bacteroidetes that are found in a variety of environments but are especially prevalent in the mammalian gut. This review summarises available information on the genomics, diversity, taxonomy, and ecology of this largely uncultured viral taxon. With experimental data available from a handful of cultured representatives, the review highlights key properties of virion morphology, infection, gene expression and replication processes, and phage-host dynamics.
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Sinha A, Li Y, Mirzaei MK, Shamash M, Samadfam R, King IL, Maurice CF. Transplantation of bacteriophages from ulcerative colitis patients shifts the gut bacteriome and exacerbates the severity of DSS colitis. MICROBIOME 2022; 10:105. [PMID: 35799219 PMCID: PMC9264660 DOI: 10.1186/s40168-022-01275-2] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 04/13/2022] [Indexed: 05/03/2023]
Abstract
BACKGROUND Inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC) are characterized by chronic and debilitating gut inflammation. Altered bacterial communities of the intestine are strongly associated with IBD initiation and progression. The gut virome, which is primarily composed of bacterial viruses (bacteriophages, phages), is thought to be an important factor regulating and shaping microbial communities in the gut. While alterations in the gut virome have been observed in IBD patients, the contribution of these viruses to alterations in the bacterial community and heightened inflammatory responses associated with IBD patients remains largely unknown. RESULTS Here, we performed in vivo microbial cross-infection experiments to follow the effects of fecal virus-like particles (VLPs) isolated from UC patients and healthy controls on bacterial diversity and severity of experimental colitis in human microbiota-associated (HMA) mice. Shotgun metagenomics confirmed that several phages were transferred to HMA mice, resulting in treatment-specific alterations in the gut virome. VLPs from healthy and UC patients also shifted gut bacterial diversity of these mice, an effect that was amplified during experimental colitis. VLPs isolated from UC patients specifically altered the relative abundance of several bacterial taxa previously implicated in IBD progression. Additionally, UC VLP administration heightened colitis severity in HMA mice, as indicated by shortened colon length and increased pro-inflammatory cytokine production. Importantly, this effect was dependent on intact VLPs. CONCLUSIONS Our findings build on recent literature indicating that phages are dynamic regulators of bacterial communities in the gut and implicate the intestinal virome in modulating intestinal inflammation and disease. Video Abstract.
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Affiliation(s)
- Anshul Sinha
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada
| | - Yue Li
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, Guangdong, China
| | - Mohammadali Khan Mirzaei
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada
- Institute of Virology, Helmholtz Center Munich and Technical University of Munich, 85764, Neuherberg, Bavaria, Germany
| | - Michael Shamash
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada
| | - Rana Samadfam
- Charles River Laboratories, 22022 Transcanadienne, Senneville, QC, H9X 3R3, Canada
| | - Irah L King
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada.
- McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, QC, Canada.
| | - Corinne F Maurice
- Department of Microbiology & Immunology, McGill University, Montreal, QC, Canada.
- McGill Interdisciplinary Initiative in Infection and Immunity, Montreal, QC, Canada.
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Lin DM, Koskella B, Ritz NL, Lin D, Carroll-Portillo A, Lin HC. Transplanting Fecal Virus-Like Particles Reduces High-Fat Diet-Induced Small Intestinal Bacterial Overgrowth in Mice. Front Cell Infect Microbiol 2019; 9:348. [PMID: 31750259 PMCID: PMC6843071 DOI: 10.3389/fcimb.2019.00348] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Accepted: 09/30/2019] [Indexed: 12/30/2022] Open
Abstract
Fecal microbiota transplantation (FMT) is an effective tool for treating Clostridium difficile infection in the setting of dysbiosis of the intestinal microbiome. FMT for other forms of human disorders linked to dysbiosis have been less effective. The fecal microbiota contains a high density of virus-like particles (VLP), up to 90% of which are bacteriophages, thought to have a role in regulating gut bacterial populations. We hypothesized that transplantation of the phage-containing fecal VLP fraction may reduce bacterial density in the dysbiotic setting of small intestinal bacterial overgrowth (SIBO). In an experiment using fecal transplantation, we compared the effect of the fecal VLP fraction (bacteria removed) against “Whole” FMT (bacteria intact) on the ileal microbiome. Recipients were either treated with a 30-day high-fat diet (HFD) as a model of dysbiosis to induce SIBO or were on a standard diet (SD). We observed that transplantation of fecal VLPs from donors on a HFD was sufficient to alter the ileal microbiota, but the effect was dependent on diet of the recipient. In recipients on a HFD, ileal bacterial density was reduced. In recipients on a SD, the ileal microbiome transitioned toward the composition associated with a HFD. In both recipient groups, transplantation of fecal VLP fraction alone produced the same outcome as whole FMT. Neither treatment altered expression of antimicrobial peptides. These findings demonstrated a potential role of VLPs, likely phages, for modifying the gut microbiome during dysbiosis.
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Affiliation(s)
- Derek M Lin
- Medicine Service, New Mexico VA Health Care System, Albuquerque, NM, United States
| | - Britt Koskella
- Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, United States
| | - Nathaniel L Ritz
- Medicine Service, New Mexico VA Health Care System, Albuquerque, NM, United States
| | - Dongdong Lin
- Mind Research Network, University of New Mexico, Albuquerque, NM, United States
| | | | - Henry C Lin
- Medicine Service, New Mexico VA Health Care System, Albuquerque, NM, United States.,Division of Gastroenterology and Hepatology, The University of New Mexico, Albuquerque, NM, United States
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Abstract
Bacteriophages are the most prominent members of the gut microbiome, outnumbering their bacterial hosts by a factor of 10. Phages are bacteria-specific viruses that are gaining attention as highly influential regulators of the gut bacterial community. Dysregulation of the gut bacterial community contributes to dysbiosis, a microbiome disorder characterized by compositional and functional changes that contribute to disease. A role for phages in gut microbiome dysbiosis is emerging with evidence that the gut phage community is altered in dysbiosis-associated disorders such as colorectal cancer and inflammatory bowel disease. Several recent studies have linked successful fecal microbiota transplantation to uptake of the donor’s gut phage community, offering some insight into why some recipients respond to treatment whereas others do not. Here, we review the literature supporting a role for phages in mediating the gut bacterial community, giving special attention to Western diet dysbiosis as a case study to demonstrate a theoretical phage-based mechanism for the establishment and maintenance of dysbiosis.
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Affiliation(s)
- Derek M Lin
- Medicine Service, New Mexico VA Health Care System, Albuquerque, New Mexico, USA
| | - Henry C Lin
- Medicine Service, New Mexico VA Health Care System, Albuquerque, New Mexico, USA.,Department of Gastroenterology and Hepatology, University of New Mexico, Albuquerque, New Mexico, USA
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