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1
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Ríos Colombo NS, Paul Ross R, Hill C. Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control. Gut Microbes 2025; 17:2451081. [PMID: 39817466 PMCID: PMC11740676 DOI: 10.1080/19490976.2025.2451081] [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: 06/28/2024] [Revised: 12/04/2024] [Accepted: 01/02/2025] [Indexed: 01/18/2025] Open
Abstract
Clostridioides difficile is a major cause of nosocomial diarrhea. As current antibiotic treatment failures and recurrence of infections are highly frequent, alternative strategies are needed for the treatment of this disease. This study explores the use of bacteriocins, specifically lacticin 3147 and pediocin PA-1, which have reported inhibitory activity against C. difficile. We engineered Lactococcus lactis strains to produce these bacteriocins individually or in combination, aiming to enhance their activity against C. difficile. Our results show that lacticin 3147 and pediocin PA-1 display synergy, resulting in higher anti-C. difficile activity. We then evaluated the effects of these L. lactis strains in a Simplified Human Intestinal Microbiome (SIHUMI-C) model, a bacterial consortium of eight diverse human gut species that includes C. difficile. After introducing the bacteriocin-producing L. lactis strains into SIHUMI-C, samples were collected over 24 hours, and the genome copies of each species were assessed using qPCR. Contrary to expectations, the combined bacteriocins increased C. difficile levels in the consortium despite showing synergy against C. difficile in agar-based screening. This can be rationally explained by antagonistic inter-species interactions within SIHUMI-C, providing new insights into how broad-spectrum antimicrobials might fail to control targeted species in complex gut microbial communities. These findings highlight the need to mitigate off-target effects in complex gut microbiomes when developing bacteriocin-based therapies with potential clinical implications for infectious disease treatment.
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Affiliation(s)
| | - R. Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Colin Hill
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
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2
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Tüsüz Önata E, Özdemir Ö. Fecal microbiota transplantation in allergic diseases. World J Methodol 2025; 15:101430. [DOI: 10.5662/wjm.v15.i2.101430] [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: 09/13/2024] [Revised: 10/17/2024] [Accepted: 11/01/2024] [Indexed: 11/27/2024] Open
Abstract
Microorganisms such as bacteria, fungi, viruses, parasites living in the human intestine constitute the human intestinal microbiota. Dysbiosis refers to compositional and quantitative changes that negatively affect healthy gut microbiota. In recent years, with the demonstration that many diseases are associated with dysbiosis, treatment strategies targeting the correction of dysbiosis in the treatment of these diseases have begun to be investigated. Faecal microbiota transplantation (FMT) is the process of transferring faeces from a healthy donor to another recipient in order to restore the gut microbiota and provide a therapeutic benefit. FMT studies have gained popularity after probiotic, prebiotic, symbiotic studies in the treatment of dysbiosis and related diseases. FMT has emerged as a potential new therapy in the treatment of allergic diseases as it is associated with the maintenance of intestinal microbiota and immunological balance (T helper 1/T helper 2 cells) and thus suppression of allergic responses. In this article, the definition, application, safety and use of FMT in allergic diseases will be discussed with current data.
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Affiliation(s)
- Ece Tüsüz Önata
- Division of Pediatric Allergy and Immunology, Medical Faculty, Sakarya University, Adapazarı 54100, Sakarya, Türkiye
| | - Öner Özdemir
- Division of Pediatric Allergy and Immunology, Medical Faculty, Sakarya University, Adapazarı 54100, Sakarya, Türkiye
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3
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Ressler AM, Rao K, Young VB. Current Approaches to Treat and Prevent Recurrence of Clostridioides difficile. Gastroenterol Clin North Am 2025; 54:259-275. [PMID: 40348487 DOI: 10.1016/j.gtc.2025.02.005] [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] [Indexed: 05/14/2025]
Abstract
Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) are significant causes of morbidity and mortality. The microbiome plays a significant role in the body's defense against CDI and rCDI. Antibiotics can cause significant injury to the microbiome which leads to an increased risk of CDI and rCDI. Ongoing perturbations of the microbiome perpetuate this risk. Antibiotic treatments for CDI can kill C difficile but also can impact the microbiome. Microbiome therapeutics are effective in restoring the function of the gut microbiota and re-establishing colonization resistance. The field of microbiome therapeutics is evolving with newer, more refined, modalities in development.
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Affiliation(s)
- Adam M Ressler
- Department of Internal Medicine, Infectious Disease Division, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Krishna Rao
- Department of Internal Medicine, Infectious Disease Division, University of Michigan Medicine, Ann Arbor, MI, USA
| | - Vincent B Young
- Department of Internal Medicine, Infectious Disease Division, University of Michigan Medicine, Ann Arbor, MI, USA; Department of Microbiology & Immunology.
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4
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Hou S, Yu J, Li Y, Zhao D, Zhang Z. Advances in Fecal Microbiota Transplantation for Gut Dysbiosis-Related Diseases. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2025; 12:e2413197. [PMID: 40013938 PMCID: PMC11967859 DOI: 10.1002/advs.202413197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/22/2025] [Indexed: 02/28/2025]
Abstract
This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.
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Affiliation(s)
- Shuna Hou
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Jiachen Yu
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Yongshuang Li
- Department of general surgeryThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Duoyi Zhao
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
| | - Zhiyu Zhang
- Department of OrthopedicsThe Fourth Affiliated Hospital of China Medical UniversityChina Medical UniversityLiao NingShen Yang110032P. R. China
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5
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Ullah H, Arbab S, Chang C, Bibi S, Muhammad N, Rehman SU, Suleman, Ullah I, Hassan IU, Tian Y, Li K. Gut microbiota therapy in gastrointestinal diseases. Front Cell Dev Biol 2025; 13:1514636. [PMID: 40078367 PMCID: PMC11897527 DOI: 10.3389/fcell.2025.1514636] [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: 10/21/2024] [Accepted: 02/03/2025] [Indexed: 03/14/2025] Open
Abstract
The human gut microbiota, consisting of trillions of microorganisms, plays a crucial role in gastrointestinal (GI) health and disease. Dysbiosis, an imbalance in microbial composition, has been linked to a range of GI disorders, including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, and colorectal cancer. These conditions are influenced by the interactions between the gut microbiota, the host immune system, and the gut-brain axis. Recent research has highlighted the potential for microbiome-based therapeutic strategies, such as probiotics, prebiotics, fecal microbiota transplantation (FMT), and dietary modifications, to restore microbial balance and alleviate disease symptoms. This review examines the role of gut microbiota in the pathogenesis of common gastrointestinal diseases and explores emerging therapeutic approaches aimed at modulating the microbiome. We discuss the scientific foundations of these interventions, their clinical effectiveness, and the challenges in their implementation. The review underscores the therapeutic potential of microbiome-targeted treatments as a novel approach to managing GI disorders, offering personalized and alternative options to conventional therapies. As research in this field continues to evolve, microbiome-based interventions hold promise for improving the treatment and prevention of gastrointestinal diseases.
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Affiliation(s)
- Hanif Ullah
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Safia Arbab
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China
| | - Chengting Chang
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Saira Bibi
- Department of Zoology Hazara University Manshera, Dhodial, Pakistan
| | - Nehaz Muhammad
- Hebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, Hebei Collaborative Innovation Center for Eco-Environment, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei, China
| | - Sajid Ur Rehman
- School of Public Health and Emergency Management, School of Medicine, Southern University of Science and Technology, Shenzhen, China
| | - Suleman
- Department of Zoology, Government Post Graduate Collage, Swabi, Pakistan
- Higher Education Department, Civil Secretariat Peshawar, Peshawar, Pakistan
| | - Irfan Ullah
- Department of Biotechnology and Genetics Engineering, Hazara University, Manshera, Pakistan
| | - Inam Ul Hassan
- Department of Microbiology, Hazara University Manshera, Manshera, Pakistan
| | - Yali Tian
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Ka Li
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials, Nursing Key Laboratory of Sichuan Province, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
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6
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Klinhom S, Kunasol C, Sriwichaiin S, Kerdphoo S, Chattipakorn N, Chattipakorn SC, Thitaram C. Characteristics of gut microbiota profiles in Asian elephants (Elephas maximus) with gastrointestinal disorders. Sci Rep 2025; 15:1327. [PMID: 39779898 PMCID: PMC11711614 DOI: 10.1038/s41598-025-85495-0] [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: 09/20/2024] [Accepted: 01/03/2025] [Indexed: 01/11/2025] Open
Abstract
Colic and diarrhea are common gastrointestinal (GI) disorders in captive Asian elephants, which can severely impact health and lead to mortality. Gut dysbiosis, indicated by alterations in gut microbiome composition, can be observed in individuals with GI disorders. However, changes in gut microbial profiles of elephants with GI disorders have never been investigated. Thus, this study aimed to elucidate the profiles of gut microbiota in captive elephants with different GI symptoms. Fecal samples were collected from eighteen elephants in Chiang Mai, Thailand, including seven healthy individuals, seven with impaction colic, and four with diarrhea. The samples were subjected to DNA extraction and amplification targeting the V3-V4 region of 16S rRNA gene for next-generation sequencing analysis. Elephants with GI symptoms exhibited a decreased microbial stability, as characterized by a significant reduction in microbiota diversity within individual guts and notable differences in microbial community composition when compared with healthy elephants. These changes included a decrease in the relative abundance of specific bacterial taxa, in elephants with GI symptoms such as a reduction in genera Rubrobacter, Rokubacteria, UBA1819, Nitrospira, and MND1. Conversely, an increase in genera Lysinibacillus, Bacteroidetes_BD2-2, and the family Marinifilaceae was observed when, compared with the healthy group. Variations in taxa of gut microbiota among elephants with GI disorders indicated diverse microbial characteristics associated with different GI symptoms. This study suggests that exploring gut microbiota dynamics in elephant health and GI disorders can lead to a better understanding of food and water management for maintaining a healthy gut and ensuring the longevity of the elephants.
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Affiliation(s)
- Sarisa Klinhom
- Center of Elephant and Wildlife Health, Animal Hospital, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand
| | - Chanon Kunasol
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Neurophysiology Unit, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Sirawit Sriwichaiin
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Neurophysiology Unit, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Sasiwan Kerdphoo
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Neurophysiology Unit, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Nipon Chattipakorn
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Neurophysiology Unit, Chiang Mai University, Chiang Mai, 50200, Thailand
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Siriporn C Chattipakorn
- Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Neurophysiology Unit, Chiang Mai University, Chiang Mai, 50200, Thailand.
- Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand.
| | - Chatchote Thitaram
- Center of Elephant and Wildlife Health, Animal Hospital, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand.
- Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, 50100, Thailand.
- Elephant, Wildlife and Companion Animals Research Group, Chiang Mai University, Chiang Mai, 50100, Thailand.
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7
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Pagan-Rivera LH, Ocasio-Rivera SE, Godoy-Vitorino F, Miranda JD. Spinal cord injury: pathophysiology, possible treatments and the role of the gut microbiota. Front Microbiol 2024; 15:1490855. [PMID: 39744391 PMCID: PMC11688470 DOI: 10.3389/fmicb.2024.1490855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 12/05/2024] [Indexed: 01/11/2025] Open
Abstract
Spinal cord injury (SCI) is a devastating pathological state causing motor, sensory, and autonomic dysfunction. To date, SCI remains without viable treatment for its patients. After the injury, molecular events centered at the lesion epicenter create a non-permissive environment for cell survival and regeneration. This newly hostile setting is characterized by necrosis, inflammation, demyelination, axotomy, apoptosis, and gliosis, among other events that limit locomotor recovery. This review provides an overview of the pathophysiology of SCI, highlighting the potential role of the gut microbiota in modulating the inflammatory response and influencing neurological recovery following trauma to the spinal cord. Emphasis on the bidirectional communication between the gut and central nervous system, known as the gut-brain axis is given. After trauma, the gut-brain/spinal cord axis promotes the production of pro-inflammatory metabolites that provide a non-permissive environment for cell survival and locomotor recovery. Therefore, any possible pharmacological treatment, including antibiotics and painkillers, must consider their effects on microbiome dysbiosis to promote cell survival, regeneration, and behavioral improvement. Overall, this review provides valuable insights into the pathophysiology of SCI and the evolving understanding of the role of the gut microbiota in SCI, with implications for future research and clinical practice.
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Affiliation(s)
- Luis H. Pagan-Rivera
- Physiology Department, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Samuel E. Ocasio-Rivera
- Physiology Department, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Filipa Godoy-Vitorino
- Microbiology and Medical Zoology Department, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
| | - Jorge D. Miranda
- Physiology Department, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico
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8
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Tafader A, Bajaj JS. Present and future of fecal microbiome transplantation in cirrhosis. Liver Transpl 2024:01445473-990000000-00519. [PMID: 39591377 DOI: 10.1097/lvt.0000000000000542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 11/15/2024] [Indexed: 11/28/2024]
Abstract
Over the last few decades, there have been tremendous advances in our understanding of the role of the gut microbiome in cirrhosis and the clinical sequelae that follow. Progressive dysbiosis and immune dysregulation occur in patients with cirrhosis. In fact, alterations in the gut microbiome occur long before a diagnosis of cirrhosis is made. Understandably, our attention has recently been diverted toward potential modulators of the gut microbiome and the gut-liver axis as targets for treatment. The goal of this review is to highlight the utility of manipulating the gut microbiome with a focus on fecal microbiome transplantation (FMT) in patients with cirrhosis. In addition, we will provide an overview of disease-specific microbial alterations and the resultant impact this has on cirrhosis-related complications.
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Affiliation(s)
- Asiya Tafader
- Department of Medicine, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia, USA
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Meléndez-Vázquez NM, Gomez-Manzano C, Godoy-Vitorino F. Oncolytic Virotherapies and Adjuvant Gut Microbiome Therapeutics to Enhance Efficacy Against Malignant Gliomas. Viruses 2024; 16:1775. [PMID: 39599889 PMCID: PMC11599061 DOI: 10.3390/v16111775] [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: 10/11/2024] [Revised: 11/08/2024] [Accepted: 11/11/2024] [Indexed: 11/29/2024] Open
Abstract
Glioblastoma (GBM) is the most prevalent malignant brain tumor. Current standard-of-care treatments offer limited benefits for patient survival. Virotherapy is emerging as a novel strategy to use oncolytic viruses (OVs) for the treatment of GBM. These engineered and non-engineered viruses infect and lyse cancer cells, causing tumor destruction without harming healthy cells. Recent advances in genetic modifications to OVs have helped improve their targeting capabilities and introduce therapeutic genes, broadening the therapeutic window and minimizing potential side effects. The efficacy of oncolytic virotherapy can be enhanced by combining it with other treatments such as immunotherapy, chemotherapy, or radiation. Recent studies suggest that manipulating the gut microbiome to enhance immune responses helps improve the therapeutic efficacy of the OVs. This narrative review intends to explore OVs and their role against solid tumors, especially GBM while emphasizing the latest technologies used to enhance and improve its therapeutic and clinical responses.
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Affiliation(s)
- Natalie M. Meléndez-Vázquez
- Department of Microbiology and Medical Zoology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00918, USA;
| | - Candelaria Gomez-Manzano
- Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;
| | - Filipa Godoy-Vitorino
- Department of Microbiology and Medical Zoology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00918, USA;
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10
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Pavelescu LA, Profir M, Enache RM, Roşu OA, Creţoiu SM, Gaspar BS. A Proteogenomic Approach to Unveiling the Complex Biology of the Microbiome. Int J Mol Sci 2024; 25:10467. [PMID: 39408795 PMCID: PMC11476728 DOI: 10.3390/ijms251910467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 09/26/2024] [Accepted: 09/26/2024] [Indexed: 10/20/2024] Open
Abstract
The complex biology of the microbiome was elucidated once the genomics era began. The proteogenomic approach analyzes and integrates genetic makeup (genomics) and microbial communities' expressed proteins (proteomics). Therefore, researchers gained insights into gene expression, protein functions, and metabolic pathways, understanding microbial dynamics and behavior, interactions with host cells, and responses to environmental stimuli. In this context, our work aims to bring together data regarding the application of genomics, proteomics, and bioinformatics in microbiome research and to provide new perspectives for applying microbiota modulation in clinical practice with maximum efficiency. This review also synthesizes data from the literature, shedding light on the potential biomarkers and therapeutic targets for various diseases influenced by the microbiome.
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Affiliation(s)
- Luciana Alexandra Pavelescu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (L.A.P.); (M.P.); (O.A.R.)
| | - Monica Profir
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (L.A.P.); (M.P.); (O.A.R.)
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Robert Mihai Enache
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania;
| | - Oana Alexandra Roşu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (L.A.P.); (M.P.); (O.A.R.)
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Sanda Maria Creţoiu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (L.A.P.); (M.P.); (O.A.R.)
| | - Bogdan Severus Gaspar
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Surgery Clinic, Bucharest Emergency Clinical Hospital, 014461 Bucharest, Romania
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11
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Blair M, Garner E, Ji P, Pruden A. What is the Difference between Conventional Drinking Water, Potable Reuse Water, and Nonpotable Reuse Water? A Microbiome Perspective. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2024; 58. [PMID: 39258328 PMCID: PMC11428167 DOI: 10.1021/acs.est.4c04679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 08/27/2024] [Accepted: 08/27/2024] [Indexed: 09/12/2024]
Abstract
As water reuse applications expand, there is a need for more comprehensive means to assess water quality. Microbiome analysis could provide the ability to supplement fecal indicators and pathogen profiling toward defining a "healthy" drinking water microbiota while also providing insight into the impact of treatment and distribution. Here, we utilized 16S rRNA gene amplicon sequencing to identify signature features in the composition of microbiota across a wide spectrum of water types (potable conventional, potable reuse, and nonpotable reuse). A clear distinction was found in the composition of microbiota as a function of intended water use (e.g., potable vs nonpotable) across a very broad range of U.S. water systems at both the point of compliance (Betadisper p > 0.01; ANOSIM p < 0.01, r-stat = 0.71) and point of use (Betadisper p > 0.01; ANOSIM p < 0.01, r-stat = 0.41). Core and discriminatory analysis further served in identifying distinct differences between potable and nonpotable water microbiomes. Taxa were identified at both the phylum (Desulfobacterota, Patescibacteria, and Myxococcota) and genus (Aeromonas and NS11.12_marine_group) levels that effectively discriminated between potable and nonpotable waters, with the most discriminatory taxa being core/abundant in nonpotable waters (with few exceptions, such as Ralstonia being abundant in potable conventional waters). The approach and findings open the door to the possibility of microbial community signature profiling as a water quality monitoring approach for assessing efficacy of treatments and suitability of water for intended use/reuse application.
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Affiliation(s)
- Matthew
F. Blair
- Via
Department of Civil and Environmental Engineering, Virginia Tech, Blacksburg, Virginia 24061, United States
| | - Emily Garner
- Wadsworth
Department of Civil and Environmental Engineering, West Virginia University, Morgantown, West Virginia 26506, United States
| | - Pan Ji
- Via
Department of Civil and Environmental Engineering, Virginia Tech, Blacksburg, Virginia 24061, United States
| | - Amy Pruden
- Via
Department of Civil and Environmental Engineering, Virginia Tech, Blacksburg, Virginia 24061, United States
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12
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Acevedo-Román A, Pagán-Zayas N, Velázquez-Rivera LI, Torres-Ventura AC, Godoy-Vitorino F. Insights into Gut Dysbiosis: Inflammatory Diseases, Obesity, and Restoration Approaches. Int J Mol Sci 2024; 25:9715. [PMID: 39273662 PMCID: PMC11396321 DOI: 10.3390/ijms25179715] [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: 06/24/2024] [Revised: 08/30/2024] [Accepted: 09/07/2024] [Indexed: 09/15/2024] Open
Abstract
The gut microbiota is one of the most critical factors in human health. It involves numerous physiological processes impacting host health, mainly via immune system modulation. A balanced microbiome contributes to the gut's barrier function, preventing the invasion of pathogens and maintaining the integrity of the gut lining. Dysbiosis, or an imbalance in the gut microbiome's composition and function, disrupts essential processes and contributes to various diseases. This narrative review summarizes key findings related to the gut microbiota in modern multifactorial inflammatory conditions such as ulcerative colitis or Crohn's disease. It addresses the challenges posed by antibiotic-driven dysbiosis, particularly in the context of C. difficile infections, and the development of novel therapies like fecal microbiota transplantation and biotherapeutic drugs to combat these infections. An emphasis is given to restoration of the healthy gut microbiome through dietary interventions, probiotics, prebiotics, and novel approaches for managing gut-related diseases.
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Affiliation(s)
- Andy Acevedo-Román
- Microbiology Department, University of Puerto Rico Medical Sciences Campus, San Juan 00936, Puerto Rico
| | - Natalia Pagán-Zayas
- Microbiology Department, University of Puerto Rico Medical Sciences Campus, San Juan 00936, Puerto Rico
| | - Liz I Velázquez-Rivera
- Microbiology Department, University of Puerto Rico Medical Sciences Campus, San Juan 00936, Puerto Rico
| | - Aryanne C Torres-Ventura
- Microbiology Department, University of Puerto Rico Medical Sciences Campus, San Juan 00936, Puerto Rico
| | - Filipa Godoy-Vitorino
- Microbiology Department, University of Puerto Rico Medical Sciences Campus, San Juan 00936, Puerto Rico
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13
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Demirturk M, Cinar MS, Avci FY. The immune interactions of gut glycans and microbiota in health and disease. Mol Microbiol 2024; 122:313-330. [PMID: 38703041 DOI: 10.1111/mmi.15267] [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: 10/13/2023] [Revised: 04/11/2024] [Accepted: 04/12/2024] [Indexed: 05/06/2024]
Abstract
The human digestive system harbors a vast diversity of commensal bacteria and maintains a symbiotic relationship with them. However, imbalances in the gut microbiota accompany various diseases, such as inflammatory bowel diseases (IBDs) and colorectal cancers (CRCs), which significantly impact the well-being of populations globally. Glycosylation of the mucus layer is a crucial factor that plays a critical role in maintaining the homeostatic environment in the gut. This review delves into how the gut microbiota, immune cells, and gut mucus layer work together to establish a balanced gut environment. Specifically, the role of glycosylation in regulating immune cell responses and mucus metabolism in this process is examined.
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Affiliation(s)
- Mahmut Demirturk
- Department of Biochemistry, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Mukaddes Sena Cinar
- Department of Biochemistry, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Fikri Y Avci
- Department of Biochemistry, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA
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14
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Xie W, Sharma A, Kaushik H, Sharma L, Nistha, Anwer MK, Sachdeva M, Elossaily GM, Zhang Y, Pillappan R, Kaur M, Behl T, Shen B, Singla RK. Shaping the future of gastrointestinal cancers through metabolic interactions with host gut microbiota. Heliyon 2024; 10:e35336. [PMID: 39170494 PMCID: PMC11336605 DOI: 10.1016/j.heliyon.2024.e35336] [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: 04/09/2024] [Revised: 07/19/2024] [Accepted: 07/26/2024] [Indexed: 08/23/2024] Open
Abstract
Gastrointestinal (GI) cancers represent a significant global health challenge, driving relentless efforts to identify innovative diagnostic and therapeutic approaches. Recent strides in microbiome research have unveiled a previously underestimated dimension of cancer progression that revolves around the intricate metabolic interplay between GI cancers and the host's gut microbiota. This review aims to provide a comprehensive overview of these emerging metabolic interactions and their potential to catalyze a paradigm shift in precision diagnosis and therapeutic breakthroughs in GI cancers. The article underscores the groundbreaking impact of microbiome research on oncology by delving into the symbiotic connection between host metabolism and the gut microbiota. It offers valuable insights into tailoring treatment strategies to individual patients, thus moving beyond the traditional one-size-fits-all approach. This review also sheds light on novel diagnostic methodologies that could transform the early detection of GI cancers, potentially leading to more favorable patient outcomes. In conclusion, exploring the metabolic interactions between host gut microbiota and GI cancers showcases a promising frontier in the ongoing battle against these formidable diseases. By comprehending and harnessing the microbiome's influence, the future of precision diagnosis and therapeutic innovation for GI cancers appears more optimistic, opening doors to tailored treatments and enhanced diagnostic precision.
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Affiliation(s)
- Wen Xie
- Department of Pharmacy and Institutes for Systems Genetics, Center for High Altitude Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Aditi Sharma
- School of Pharmaceutical Sciences, Shoolini University, Solan, H.P, 173229, India
| | - Hitesh Kaushik
- School of Pharmaceutical Sciences, Shoolini University, Solan, H.P, 173229, India
| | - Lalit Sharma
- School of Pharmaceutical Sciences, Shoolini University, Solan, H.P, 173229, India
| | - Nistha
- School of Pharmaceutical Sciences, Shoolini University, Solan, H.P, 173229, India
| | - Md Khalid Anwer
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia
| | - Monika Sachdeva
- Fatima College of Health Sciences, Al Ain, United Arab Emirates
| | - Gehan M. Elossaily
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh, 11597, Saudi Arabia
| | - Yingbo Zhang
- Institutes for Systems Genetics, West China Tianfu Hospital, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610218, China
| | - Ramkumar Pillappan
- Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences, Mangaluru, Karnataka, India
| | - Maninderjit Kaur
- Department of Pharmaceutical Sciences, lovely Professional University, Phagwara, India
| | - Tapan Behl
- Amity School of Pharmaceutical Sciences, Amity University, Sahibzada Ajit Singh Nagar, Punjab, India
| | - Bairong Shen
- Department of Pharmacy and Institutes for Systems Genetics, Center for High Altitude Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
| | - Rajeev K. Singla
- Department of Pharmacy and Institutes for Systems Genetics, Center for High Altitude Medicine, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 1444411, India
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15
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Ullah H, Arbab S, Tian Y, Chen Y, Liu CQ, Li Q, Li K. Crosstalk between gut microbiota and host immune system and its response to traumatic injury. Front Immunol 2024; 15:1413485. [PMID: 39144142 PMCID: PMC11321976 DOI: 10.3389/fimmu.2024.1413485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Accepted: 06/04/2024] [Indexed: 08/16/2024] Open
Abstract
Millions of microorganisms make up the complex microbial ecosystem found in the human gut. The immune system's interaction with the gut microbiota is essential for preventing inflammation and maintaining intestinal homeostasis. Numerous metabolic products that can cross-talk between immune cells and the gut epithelium are metabolized by the gut microbiota. Traumatic injury elicits a great and multifaceted immune response in the minutes after the initial offense, containing simultaneous pro- and anti-inflammatory responses. The development of innovative therapies that improve patient outcomes depends on the gut microbiota and immunological responses to trauma. The altered makeup of gut microbes, or gut dysbiosis, can also dysregulate immunological responses, resulting in inflammation. Major human diseases may become more common as a result of chronic dysbiosis and the translocation of bacteria and the products of their metabolism beyond the mucosal barrier. In this review, we briefly summarize the interactions between the gut microbiota and the immune system and human disease and their therapeutic probiotic formulations. We also discuss the immune response to traumatic injury.
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Affiliation(s)
- Hanif Ullah
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Safia Arbab
- Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, China
| | - Yali Tian
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Yuwen Chen
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Chang-qing Liu
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Qijie Li
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
| | - Ka Li
- Medicine and Engineering Interdisciplinary Research Laboratory of Nursing & Materials/Nursing Key Laboratory of Sichuan Province, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, Sichuan, China
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16
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Lambert A, Budinich M, Mahé M, Chaffron S, Eveillard D. Community metabolic modeling of host-microbiota interactions through multi-objective optimization. iScience 2024; 27:110092. [PMID: 38952683 PMCID: PMC11215293 DOI: 10.1016/j.isci.2024.110092] [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: 10/30/2023] [Revised: 03/12/2024] [Accepted: 05/21/2024] [Indexed: 07/03/2024] Open
Abstract
The human gut microbiota comprises various microorganisms engaged in intricate interactions among themselves and with the host, affecting its health. While advancements in omics technologies have led to the inference of clear associations between microbiome composition and health conditions, we usually lack a causal and mechanistic understanding of these associations. For modeling mechanisms driving the interactions, we simulated the organism's metabolism using in silico genome-scale metabolic models (GEMs). We used multi-objective optimization to predict and explain metabolic interactions among gut microbes and an intestinal epithelial cell. We developed a score integrating model simulation results to predict the type (competition, neutralism, mutualism) and quantify the interaction between several organisms. This framework uncovered a potential cross-feeding for choline, explaining the predicted mutualism between Lactobacillus rhamnosus GG and the epithelial cell. Finally, we analyzed a five-organism ecosystem, revealing that a minimal microbiota can favor the epithelial cell's maintenance.
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Affiliation(s)
- Anna Lambert
- Nantes Université, École Centrale Nantes, CNRS, LS2N, UMR 6004, 44000 Nantes, France
| | - Marko Budinich
- Nantes Université, École Centrale Nantes, CNRS, LS2N, UMR 6004, 44000 Nantes, France
| | - Maxime Mahé
- Nantes Université, Inserm, TENS UMR1235, The Enteric Nervous System in Gut and Brain Diseases, IMAD, Nantes, France
- Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
- Center for Stem Cell and Organoid Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
| | - Samuel Chaffron
- Nantes Université, École Centrale Nantes, CNRS, LS2N, UMR 6004, 44000 Nantes, France
| | - Damien Eveillard
- Nantes Université, École Centrale Nantes, CNRS, LS2N, UMR 6004, 44000 Nantes, France
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17
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Ma S, Wang Y, Ji X, Dong S, Wang S, Zhang S, Deng F, Chen J, Lin B, Khan BA, Liu W, Hou K. Relationship between gut microbiota and the pathogenesis of gestational diabetes mellitus: a systematic review. Front Cell Infect Microbiol 2024; 14:1364545. [PMID: 38868299 PMCID: PMC11168118 DOI: 10.3389/fcimb.2024.1364545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2024] [Accepted: 03/01/2024] [Indexed: 06/14/2024] Open
Abstract
Introduction Gestational diabetes mellitus (GDM) is a form of gestational diabetes mellitus characterized by insulin resistance and abnormal function of pancreatic beta cells. In recent years, genomic association studies have revealed risk and susceptibility genes associated with genetic susceptibility to GDM. However, genetic predisposition cannot explain the rising global incidence of GDM, which may be related to the increased influence of environmental factors, especially the gut microbiome. Studies have shown that gut microbiota is closely related to the occurrence and development of GDM. This paper reviews the relationship between gut microbiota and the pathological mechanism of GDM, in order to better understand the role of gut microbiota in GDM, and to provide a theoretical basis for clinical application of gut microbiota in the treatment of related diseases. Methods The current research results on the interaction between GDM and gut microbiota were collected and analyzed through literature review. Keywords such as "GDM", "gut microbiota" and "insulin resistance" were used for literature search, and the methodology, findings and potential impact on the pathophysiology of GDM were systematically evaluated. Results It was found that the composition and diversity of gut microbiota were significantly associated with the occurrence and development of GDM. Specifically, the abundance of certain gut bacteria is associated with an increased risk of GDM, while other changes in the microbiome may be associated with improved insulin sensitivity. In addition, alterations in the gut microbiota may affect blood glucose control through a variety of mechanisms, including the production of short-chain fatty acids, activation of inflammatory pathways, and metabolism of the B vitamin group. Discussion The results of this paper highlight the importance of gut microbiota in the pathogenesis of GDM. The regulation of the gut microbiota may provide new directions for the treatment of GDM, including improving insulin sensitivity and blood sugar control through the use of probiotics and prebiotics. However, more research is needed to confirm the generality and exact mechanisms of these findings and to explore potential clinical applications of the gut microbiota in the management of gestational diabetes. In addition, future studies should consider the interaction between environmental and genetic factors and how together they affect the risk of GDM.
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Affiliation(s)
- Sheng Ma
- Anhui Province Maternity & Child Health Hospital, Hefei, Anhui, China
| | - Yuping Wang
- School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Xiaoxia Ji
- Nursing Department, Shantou Central Hospital, Shantou, Guangdong, China
| | - Sunjuan Dong
- School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Shengnan Wang
- School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Shuo Zhang
- Shantou University Medical College, Shantou, Guangdong, China
| | - Feiying Deng
- Shantou University Medical College, Shantou, Guangdong, China
| | - Jingxian Chen
- Shantou University Medical College, Shantou, Guangdong, China
| | - Benwei Lin
- School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, United Kingdom
| | - Barkat Ali Khan
- Drug Delivery and Cosmetic Lab (DDCL), Gomal Center of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan, Pakistan
| | - Weiting Liu
- School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Kaijian Hou
- School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
- School of Public Health, Shantou University, Shantou, Guangdong, China
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18
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Ishaq HM, Yasin R, Mohammad IS, Fan Y, Li H, Shahzad M, Xu J. The gut-brain-axis: A positive relationship between gut microbial dysbiosis and glioblastoma brain tumour. Heliyon 2024; 10:e30494. [PMID: 38756585 PMCID: PMC11096965 DOI: 10.1016/j.heliyon.2024.e30494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 04/28/2024] [Accepted: 04/28/2024] [Indexed: 05/18/2024] Open
Abstract
The glioblastoma brain tumour (GBM) stands out as the most aggressive and resistant-to-treatment malignancy. Nevertheless, the gut-brain connection plays a pivotal role in influencing the growth and activation of the central nervous system. In this particular investigation, we aimed to assess and characterize the gut microbial ecosystem in GBM patients, both quantitatively and qualitatively. We collected faecal samples from 15 healthy volunteers and 25 GBM patients. To delve into the microbial content, we employed PCR-DGGE, targeting the V3 region of the 16S rRNA gene, and conducted qPCR to measure the levels of crucial intestinal bacteria. For a more in-depth analysis, high-throughput sequencing was performed on a selection of 20 random faecal samples (10 from healthy individuals and 10 from GBM patients), targeting the V3+V4 region of the 16S rRNA gene. Our findings from examining the richness and diversity of the gut microbiota unveiled that GBM patients exhibited significantly higher microbial diversity compared to healthy individuals. At the phylum level, Proteobacteria saw a significant increase, while Firmicutes experienced a noteworthy decrease in the GBM group. Moving down to the family level, we observed significantly elevated levels of Enterobacteriaceae, Bacteroidaceae, and Lachnospiraceae in GBM patients, while levels of Veillonellaceae, Rikenellaceae, and Prevotellaceae were notably lower. Delving into genera statistics, we noted a substantial increase in the abundance of Parasutterella, Escherichia-Shigella, and Bacteroides, alongside significantly lower levels of Ruminococcus 2, Faecalibacterium, and Prevotella_9 in the GBM group compared to the control group. Furthermore, when examining specific species, we found a significant increase in Bacteroides vulgatus and Escherichia coli in the GBM group. These observations collectively indicate a marked dysbiosis in the gut microbial composition of GBM patients. Additionally, the GBM group exhibited notably higher levels of alpha diversity when compared to the control group. This increase in diversity suggests a significant bacterial overgrowth in the gut of GBM patients in contrast to the controls. As a result, this research opens up potential avenues to gain a better understanding of the underlying mechanisms, pathways, and potential treatments for GBM, stemming from the significant implications of gut microbial dysbiosis in these patients.
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Affiliation(s)
- Hafiz Muhammad Ishaq
- Department of Microbiology and Immunology, Key Laboratory of Environment and Genes Related to Diseases of Chinese Ministry of Education, School of Medicine, Xi'an Jiaotong University, Xi'an, China
- Department of Pathobiology and Biomedical Sciences, Faculty of Veterinary and Animal Sciences, Muhammad Nawaz Shareef University of Agriculture Multan, Pakistan
| | - Riffat Yasin
- Department of Zoology University of Education Lahore, D.G. Khan Campus, Pakistan
| | - Imran Shair Mohammad
- Department of Radiology, City of Hope National Medical Center, 1500 East Duarte Rd., Duarte, CA, 91010, USA
| | - Yang Fan
- Department of Microbiology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China
| | - Huan Li
- Xi'an Mental Health Centre, Xi'an, China
| | - Muhammad Shahzad
- Department of Pharmacology, University of Health Sciences, Khyaban-e-Jamia Punjab, Lahore, Pakistan
| | - Jiru Xu
- Department of Microbiology and Immunology, Key Laboratory of Environment and Genes Related to Diseases of Chinese Ministry of Education, School of Medicine, Xi'an Jiaotong University, Xi'an, China
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19
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Wang Y, Hunt A, Danziger L, Drwiega EN. A Comparison of Currently Available and Investigational Fecal Microbiota Transplant Products for Recurrent Clostridioides difficile Infection. Antibiotics (Basel) 2024; 13:436. [PMID: 38786164 PMCID: PMC11117328 DOI: 10.3390/antibiotics13050436] [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: 04/17/2024] [Revised: 05/09/2024] [Accepted: 05/10/2024] [Indexed: 05/25/2024] Open
Abstract
Clostridioides difficile infection (CDI) is an intestinal infection that causes morbidity and mortality and places significant burden and cost on the healthcare system, especially in recurrent cases. Antibiotic overuse is well recognized as the leading cause of CDI in high-risk patients, and studies have demonstrated that even short-term antibiotic exposure can cause a large and persistent disturbance to human colonic microbiota. The recovery and sustainability of the gut microbiome after dysbiosis have been associated with fewer CDI recurrences. Fecal microbiota transplantation (FMT) refers to the procedure in which human donor stool is processed and transplanted to a patient with CDI. It has been historically used in patients with pseudomembranous colitis even before the discovery of Clostridioides difficile. More recent research supports the use of FMT as part of the standard therapy of recurrent CDI. This article will be an in-depth review of five microbiome therapeutic products that are either under investigation or currently commercially available: Rebyota (fecal microbiota, live-jslm, formerly RBX2660), Vowst (fecal microbiota spores, live-brpk, formerly SER109), VE303, CP101, and RBX7455. Included in this review is a comparison of the products' composition and dosage forms, available safety and efficacy data, and investigational status.
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Affiliation(s)
- Yifan Wang
- Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, IL 60612, USA
| | - Aaron Hunt
- Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, IL 60612, USA
| | - Larry Danziger
- Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, IL 60612, USA
- Division of Infectious Diseases, University of Illinois at Chicago College of Medicine, Chicago, IL 60612, USA
| | - Emily N. Drwiega
- Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, Chicago, IL 60612, USA
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20
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Wongkuna S, Ambat A, Ghimire S, Mattiello SP, Maji A, Kumar R, Antony L, Chankhamhaengdecha S, Janvilisri T, Nelson E, Doerner KC, More S, Behr M, Scaria J. Identification of a microbial sub-community from the feral chicken gut that reduces Salmonella colonization and improves gut health in a gnotobiotic chicken model. Microbiol Spectr 2024; 12:e0162123. [PMID: 38315031 PMCID: PMC10913435 DOI: 10.1128/spectrum.01621-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 12/16/2023] [Indexed: 02/07/2024] Open
Abstract
A complex microbial community in the gut may prevent the colonization of enteric pathogens such as Salmonella. Some individual or a combination of species in the gut may confer colonization resistance against Salmonella. To gain a better understanding of the colonization resistance against Salmonella enterica, we isolated a library of 1,300 bacterial strains from feral chicken gut microbiota which represented a total of 51 species. Using a co-culture assay, we screened the representative species from this library and identified 30 species that inhibited Salmonella enterica subspecies enterica serovar Typhimurium in vitro. To improve the Salmonella inhibition capacity, from a pool of fast-growing species, we formulated 66 bacterial blends, each of which composed of 10 species. Bacterial blends were more efficient in inhibiting Salmonella as compared to individual species. The blend that showed maximum inhibition (Mix10) also inhibited other serotypes of Salmonella frequently found in poultry. The in vivo effect of Mix10 was examined in a gnotobiotic and conventional chicken model. The Mix10 consortium significantly reduced Salmonella load at day 2 post-infection in gnotobiotic chicken model and decreased intestinal tissue damage and inflammation in both models. Cell-free supernatant of Mix10 did not show Salmonella inhibition, indicating that Mix10 inhibits Salmonella through either nutritional competition, competitive exclusion, or through reinforcement of host immunity. Out of 10 species, 3 species in Mix10 did not colonize, while 3 species constituted more than 70% of the community. Two of these species were previously uncultured bacteria. Our approach could be used as a high-throughput screening system to identify additional bacterial sub-communities that confer colonization resistance against enteric pathogens and its effect on the host.IMPORTANCESalmonella colonization in chicken and human infections originating from Salmonella-contaminated poultry is a significant problem. Poultry has been identified as the most common food linked to enteric pathogen outbreaks in the United States. Since multi-drug-resistant Salmonella often colonize chicken and cause human infections, methods to control Salmonella colonization in poultry are needed. The method we describe here could form the basis of developing gut microbiota-derived bacterial blends as a microbial ecosystem therapeutic against Salmonella.
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Affiliation(s)
- Supapit Wongkuna
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand
- Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA
| | - Achuthan Ambat
- Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA
- Department of Veterinary Pathobiology, Oklahoma State University, Stillwater, Oklahoma, USA
| | - Sudeep Ghimire
- Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA
| | - Samara Paula Mattiello
- Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA
| | - Abhijit Maji
- Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA
| | - Roshan Kumar
- Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA
| | - Linto Antony
- Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA
| | | | - Tavan Janvilisri
- Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand
| | - Eric Nelson
- Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA
| | - Kinchel C. Doerner
- Department of Biology and Microbiology, South Dakota State University, Brookings, South Dakota, USA
| | - Sunil More
- Department of Veterinary Pathobiology, Oklahoma State University, Stillwater, Oklahoma, USA
| | - Melissa Behr
- Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA
| | - Joy Scaria
- Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, USA
- Department of Veterinary Pathobiology, Oklahoma State University, Stillwater, Oklahoma, USA
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21
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Bahitham W, Alghamdi S, Omer I, Alsudais A, Hakeem I, Alghamdi A, Abualnaja R, Sanai FM, Rosado AS, Sergi CM. Double Trouble: How Microbiome Dysbiosis and Mitochondrial Dysfunction Drive Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis. Biomedicines 2024; 12:550. [PMID: 38540163 PMCID: PMC10967987 DOI: 10.3390/biomedicines12030550] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 02/12/2024] [Accepted: 02/18/2024] [Indexed: 11/22/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are closely related liver conditions that have become more prevalent globally. This review examines the intricate interplay between microbiome dysbiosis and mitochondrial dysfunction in the development of NAFLD and NASH. The combination of these two factors creates a synergistic situation referred to as "double trouble", which promotes the accumulation of lipids in the liver and the subsequent progression from simple steatosis (NAFLD) to inflammation (NASH). Microbiome dysbiosis, characterized by changes in the composition of gut microbes and increased intestinal permeability, contributes to the movement of bacterial products into the liver. It triggers metabolic disturbances and has anti-inflammatory effects. Understanding the complex relationship between microbiome dysbiosis and mitochondrial dysfunction in the development of NAFLD and NASH is crucial for advancing innovative therapeutic approaches that target these underlying mechanisms.
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Affiliation(s)
- Wesam Bahitham
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
- Bioscience, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia;
| | - Siraj Alghamdi
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Ibrahim Omer
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Ali Alsudais
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Ilana Hakeem
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Arwa Alghamdi
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Reema Abualnaja
- King Abdullah International Medical Research Center-WR, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard for Health Affairs, Riyadh 11426, Saudi Arabia; (W.B.); (S.A.); (I.O.); (A.A.); (I.H.); (A.A.); (R.A.)
| | - Faisal M. Sanai
- Gastroenterology Unit, Department of Medicine, King Abdulaziz Medical City, Jeddah 21423, Saudi Arabia;
| | - Alexandre S. Rosado
- Bioscience, Biological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia;
| | - Consolato M. Sergi
- Anatomic Pathology, Children’s Hospital of Eastern Ontario (CHEO), University of Ottawa, Ottawa, ON K1N 6N5, Canada
- Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2B7, Canada
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22
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Kelly CR, Allegretti JR. Review Article: Gastroenterology and Clostridium difficile Infection: Past, Present, and Future. Clin Infect Dis 2023; 77:S463-S470. [PMID: 38051967 DOI: 10.1093/cid/ciad644] [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] [Indexed: 12/07/2023] Open
Abstract
Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms.
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Affiliation(s)
- Colleen R Kelly
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
| | - Jessica R Allegretti
- Harvard Medical School, Boston, Massachusetts, USA
- Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA
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23
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D T, Venkatesh MP. Fecal microbiota transplantation: History, procedure and regulatory considerations. Presse Med 2023; 52:104204. [PMID: 37944641 DOI: 10.1016/j.lpm.2023.104204] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 08/07/2023] [Accepted: 10/25/2023] [Indexed: 11/12/2023] Open
Abstract
Fecal microbiota transplantation (FMT) is a medical treatment which involves the transfer of feces from a healthy donor to a recipient to restore the balance of gut microbiota and improve clinical outcomes. FMT has gained recognition in recent years due to its effectiveness in treating recurrent Clostridioides difficile infections (rCDI) and other gastrointestinal disorders. Additionally, it has been studied as an intervention for some other conditions, like inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This review covers regulatory considerations related to FMT, including the current state of FMT regulation and the need for further research to fully understand the safety and efficacy of this treatment. For transplantation of fecal microbiota, the Food and Drug Administration (FDA) classifies the treatment as an investigational new drug (IND), which typically requires physicians and scientists to submit an IND application. Ethical issues surrounding FMT, including the necessity of informed consent from donors and recipients and the potential transmission of infectious agents, are also discussed. Overall, FMT has the potential to offer significant therapeutic benefits, but it also raises regulatory and ethical considerations that require careful consideration. Further research is necessary to fully comprehend risks and benefits of FMT and to develop guidelines for its use in clinical practice.
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Affiliation(s)
- Thanush D
- Research Student - Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education Research, Mysuru, Karnataka, India
| | - M P Venkatesh
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education Research, S.S. Nagar, Mysuru, 570015 Karnataka, India; Faculty of Pharmaceutical Sciences, UCSI University, Malaysia.
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24
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Gu X, Chen ZH, Zhang SC. Fecal microbiota transplantation in childhood: past, present, and future. World J Pediatr 2023; 19:813-822. [PMID: 36484871 PMCID: PMC9734408 DOI: 10.1007/s12519-022-00655-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 11/13/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) has been well described in the treatment of pediatric diseases; however, the latest updates regarding its use in children are unclear and the concepts involved need to be revisited. DATA SOURCES We performed advanced searches in the MEDLINE, EMBASE, and Cochrane databases using the keywords "Fecal microbiota transplantation OR Fecal microbiota transfer" in the [Title/Abstract] to identify relevant articles published in English within the last five years. To identify additional studies, reference lists of review articles and included studies were manually searched. Retrieved manuscripts (case reports, reviews, and abstracts) were assessed by the authors. RESULTS Among the articles, studies were based on the mechanism (n = 28), sample preparation (n = 9), delivery approaches (n = 23), safety (n = 26), and indications (n = 67), including Clostridium difficile infection (CDI) and recurrent C. difficile infection (rCDI; n = 21), non-alcoholic fatty liver disease (NAFLD; n = 10), irritable bowel syndrome (IBS; n = 5), inflammatory bowel disease (IBD; n = 15), diabetes (n = 5), functional constipation (FC; n = 4), and autism spectrum disorder (ASD; n = 7). CONCLUSIONS Concepts of FMT in pediatric diseases have been updated with respect to underlying mechanisms, methodology, indications, and safety. Evidence-based clinical trials for the use of FMT in pediatric diseases should be introduced to resolve the challenges of dosage, duration, initiation, and the end point of treatment.
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Affiliation(s)
- Xu Gu
- Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street Heping District, Shenyang, 110004, China
| | - Zhao-Hong Chen
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Shu-Cheng Zhang
- Department of Pediatrics, Shengjing Hospital of China Medical University, 36 Sanhao Street Heping District, Shenyang, 110004, China.
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25
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Li S, Zheng J, He J, Liu H, Huang Y, Huang L, Wang K, Zhao X, Feng B, Che L, Fang Z, Li J, Xu S, Lin Y, Jiang X, Hua L, Zhuo Y, Wu D. Dietary fiber during gestation improves lactational feed intake of sows by modulating gut microbiota. J Anim Sci Biotechnol 2023; 14:65. [PMID: 37143119 PMCID: PMC10161572 DOI: 10.1186/s40104-023-00870-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 03/14/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND The feed intake of sows during lactation is often lower than their needs. High-fiber feed is usually used during gestation to increase the voluntary feed intake of sows during lactation. However, the mechanism underlying the effect of bulky diets on the appetites of sows during lactation have not been fully clarified. The current study was conducted to determine whether a high-fiber diet during gestation improves lactational feed intake (LFI) of sows by modulating gut microbiota. METHODS We selected an appropriate high-fiber diet during gestation and utilized the fecal microbial transplantation (FMT) method to conduct research on the role of the gut microbiota in feed intake regulation of sows during lactation, as follows: high-fiber (HF) diet during gestation (n = 23), low-fiber (LF) diet during gestation (n = 23), and low-fiber diet + HF-FMT (LFM) during gestation (n = 23). RESULTS Compared with the LF, sows in the HF and LFM groups had a higher LFI, while the sows also had higher peptide tyrosine tyrosine and glucagon-like peptide 1 on d 110 of gestation (G110 d). The litter weight gain of piglets during lactation and weaning weight of piglets from LFM group were higher than LF group. Sows given a HF diet had lower Proteobacteria, especially Escherichia-Shigella, on G110 d and higher Lactobacillus, especially Lactobacillus_mucosae_LM1 and Lactobacillus_amylovorus, on d 7 of lactation (L7 d). The abundance of Escherichia-Shigella was reduced by HF-FMT in numerically compared with the LF. In addition, HF and HF-FMT both decreased the perinatal concentrations of proinflammatory factors, such as endotoxin (ET), lipocalin-2 (LCN-2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). The concentration of ET and LCN-2 and the abundance of Proteobacteria and Escherichia-Shigella were negatively correlated with the LFI of sows. CONCLUSION The high abundance of Proteobacteria, especially Escherichia-Shigella of LF sows in late gestation, led to increased endotoxin levels, which result in inflammatory responses and adverse effects on the LFI of sows. Adding HF during gestation reverses this process by increasing the abundance of Lactobacillus, especially Lactobacillus_mucosae_LM1 and Lactobacillus_amylovorus.
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Affiliation(s)
- Shuang Li
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Jie Zheng
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Jiaqi He
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Hao Liu
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Yingyan Huang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Liansu Huang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Ke Wang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Xilun Zhao
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Bin Feng
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Lianqiang Che
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Zhengfeng Fang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Jian Li
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Shengyu Xu
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Yan Lin
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Xuemei Jiang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Lun Hua
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China
| | - Yong Zhuo
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China.
| | - De Wu
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, No. 211, Huimin Road, Wenjiang District, Chengdu, 611130, Sichuan, People's Republic of China.
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Dahiya M, Jovel J, Monaghan T, Wong K, Elhenawy W, Chui L, McAlister F, Kao D. In Silico Analysis of Changes in Predicted Metabolic Capabilities of Intestinal Microbiota after Fecal Microbial Transplantation for Treatment of Recurrent Clostridioides difficile Infection. Microorganisms 2023; 11:microorganisms11041078. [PMID: 37110500 PMCID: PMC10143790 DOI: 10.3390/microorganisms11041078] [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: 02/15/2023] [Revised: 04/11/2023] [Accepted: 04/14/2023] [Indexed: 04/29/2023] Open
Abstract
IMPORTANCE Although highly effective in treating recurrent Clostridioides difficile infection (RCDI), the mechanisms of action of fecal microbial transplantation (FMT) are not fully understood. AIM The aim of this study was to explore microbially derived products or pathways that could contribute to the therapeutic efficacy of FMT. METHODS Stool shotgun metagenomic sequencing data from 18 FMT-treated RCDI patients at 4 points in time were used for the taxonomic and functional profiling of their gut microbiome. The abundance of the KEGG orthology (KO) groups was subjected to univariate linear mixed models to assess the significance of the observed differences between 0 (pre-FMT), 1, 4, and 12 weeks after FMT. RESULTS Of the 59,987 KO groups identified by shotgun metagenomic sequencing, 27 demonstrated a statistically significant change after FMT. These KO groups are involved in many cellular processes, including iron homeostasis, glycerol metabolism, and arginine regulation, all of which have been implicated to play important roles in bacterial growth and virulence in addition to modulating the intestinal microbial composition. CONCLUSION Our findings suggest potential changes in key KO groups post-FMT, which may contribute to FMT efficacy beyond the restored microbial composition/diversity and metabolism of bile acids and short-chain fatty acids. Future larger studies that include a fecal metabolomics analysis combined with animal model validation work are required to further elucidate the molecular mechanisms.
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Affiliation(s)
- Monica Dahiya
- Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Juan Jovel
- Faculty of Veterinary Medicine, University of Calgary, Calgary, AB T2N 4Z6, Canada
| | - Tanya Monaghan
- National Institute for Health Research, Nottingham Biomedical Research Centre, Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham NG7 2UH, UK
| | - Karen Wong
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Wael Elhenawy
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Linda Chui
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada
- Public Health Laboratory, Alberta Precision Laboratories, Edmonton, AB T6G 2R3, Canada
| | - Finlay McAlister
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada
| | - Dina Kao
- Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada
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27
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Watson AR, Füssel J, Veseli I, DeLongchamp JZ, Silva M, Trigodet F, Lolans K, Shaiber A, Fogarty E, Runde JM, Quince C, Yu MK, Söylev A, Morrison HG, Lee STM, Kao D, Rubin DT, Jabri B, Louie T, Eren AM. Metabolic independence drives gut microbial colonization and resilience in health and disease. Genome Biol 2023; 24:78. [PMID: 37069665 PMCID: PMC10108530 DOI: 10.1186/s13059-023-02924-x] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 04/07/2023] [Indexed: 04/19/2023] Open
Abstract
BACKGROUND Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge. RESULTS Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients. CONCLUSIONS These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.
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Affiliation(s)
- Andrea R Watson
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
- Committee On Microbiology, The University of Chicago, Chicago, IL, 60637, USA
| | - Jessika Füssel
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
- Institute for Chemistry and Biology of the Marine Environment, University of Oldenburg, 26129, Oldenburg, Germany
| | - Iva Veseli
- Biophysical Sciences Program, The University of Chicago, Chicago, IL, 60637, USA
| | | | - Marisela Silva
- Department of Medicine, The University of Calgary, Calgary, AB, T2N 1N4, Canada
| | - Florian Trigodet
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Karen Lolans
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Alon Shaiber
- Biophysical Sciences Program, The University of Chicago, Chicago, IL, 60637, USA
| | - Emily Fogarty
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
- Committee On Microbiology, The University of Chicago, Chicago, IL, 60637, USA
| | - Joseph M Runde
- Department of Pediatrics, Lurie Children's Hospital of Chicago, Chicago, IL, 60611, USA
| | - Christopher Quince
- Organisms and Ecosystems, Earlham Institute, Norwich, Norwich, NR4 7UZ, UK
- Gut Microbes and Health, Quadram Institute, Norwich, NR4 7UQ, UK
| | - Michael K Yu
- Toyota Technological Institute at Chicago, Chicago, IL, 60637, USA
| | - Arda Söylev
- Department of Computer Engineering, Konya Food and Agriculture University, Konya, Turkey
| | - Hilary G Morrison
- Marine Biological Laboratory, Josephine Bay Paul Center, Woods Hole, Falmouth, MA, 02543, USA
| | - Sonny T M Lee
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Dina Kao
- Department of Medicine, University of Alberta, Edmonton, AB, T6G 2G3, Canada
| | - David T Rubin
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Bana Jabri
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA
| | - Thomas Louie
- Department of Medicine, The University of Calgary, Calgary, AB, T2N 1N4, Canada
| | - A Murat Eren
- Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
- Committee On Microbiology, The University of Chicago, Chicago, IL, 60637, USA.
- Institute for Chemistry and Biology of the Marine Environment, University of Oldenburg, 26129, Oldenburg, Germany.
- Marine Biological Laboratory, Josephine Bay Paul Center, Woods Hole, Falmouth, MA, 02543, USA.
- Helmholtz Institute for Functional Marine Biodiversity, 26129, Oldenburg, Germany.
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28
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Gholam-Mostafaei FS, Azimirad M, Naseri K, Nabavi-Rad A, Asadzadeh Aghdaei H, Shahrokh S, Ebrahimi Daryani N, Yadegar A, Zali MR. Intestinal microbiota changes pre- and post-fecal microbiota transplantation for treatment of recurrent Clostridioides difficile infection among Iranian patients with concurrent inflammatory bowel disease. Front Microbiol 2023; 14:1147945. [PMID: 36910213 PMCID: PMC9998922 DOI: 10.3389/fmicb.2023.1147945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 02/08/2023] [Indexed: 02/26/2023] Open
Abstract
INTRODUCTION Patients with inflammatory bowel disease (IBD) are at a greater risk for the recurrence of Clostridioides difficile infection (rCDI) that is triggered by intestinal microbiota dysbiosis. Fecal microbiota transplantation (FMT) has emerged as a highly effective therapeutic option for this complication. However, little is known about the impact of FMT on intestinal microbiota alterations in rCDI patients suffering from IBD. In this study, we aimed to investigate post-FMT intestinal microbiota alterations in Iranian rCDI patients with underlying IBD. METHODS A total of 21 fecal samples were collected including 14 samples pre- and post-FMT and 7 samples from healthy donors. Microbial analysis was performed by quantitative real-time PCR (RT-qPCR) assay targeting the 16S rRNA gene. The pre-FMT profile and composition of the fecal microbiota were compared to the microbial changes of samples collected 28 days after FMT. RESULTS AND DISCUSSION Overall, the fecal microbiota profile of recipients was more similar to donor samples after the transplantation. We observed a significant increase in the relative abundance of Bacteroidetes post-FMT, compared to the pre-FMT microbial profile. Furthermore, there were remarkable differences between the microbial profile of pre-FMT, post-FMT, and healthy donor samples by PCoA analysis based on the ordination distance. This study demonstrates FMT as a safe and effective approach to restore the indigenous composition of the intestinal microbiota in rCDI patients and ultimately results in the treatment of concurrent IBD.
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Affiliation(s)
- Fahimeh Sadat Gholam-Mostafaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kaveh Naseri
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasser Ebrahimi Daryani
- Department of Gastroenterology and Hepatology, Tehran University of Medical Sciences, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Liu J, Lin H, Cao M, Lin T, Lin A, Xu W, Wang H, He J, Li Y, Tang H, Zhang B. Shifts and importance of viable bacteria in treatment of DSS-induced ulcerative colitis mice with FMT. Front Cell Infect Microbiol 2023; 13:1124256. [PMID: 36814445 PMCID: PMC9939747 DOI: 10.3389/fcimb.2023.1124256] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 01/16/2023] [Indexed: 02/09/2023] Open
Abstract
Background and Aims Ulcerative colitis (UC) has become a global public health concern, and is in urgent need of novel therapies. Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of UC. Despite its recent successes, it is still largely unknown how FMT functionally modulates the gut microbiota and improves the disease. Methods We prospectively collected fecal samples from the 40 mice (30 mice for dextran sulfate sodium (DSS)-induced, 10 for controls), followed by Propidium monoazide treatment for 16S rRNA gene sequencing. These 30 mice were divided equally into 3 groups, which were transplanted with original donor microbiota (DO), inactivated donor microbiota (DI) and saline, respectively. Subsequently, we used 16S rRNA gene sequencing to analyze the viable gut bacteria of ulcerative colitis (UC) mice and histological analysis to evaluate the effects of fecal microbiota transplantation (FMT) with viable microbiota. Results We demonstrated that the community structure of viable bacteria was significantly different from fecal bacteria based on total DNA. Furthermore, the intestinal viable microbiota and colonic mucosal structure of mice were significantly changed by DSS induction. The histological analysis showed that only the mice treated with original donor microbiota group (HF) achieved a significant improvement. Compared with inactivated donor microbiota group (IF) and saline (NF), Lactobacillus and Halomonas were significantly enriched in the HF group. Conclusion We inferred that only live bacteria from human donor reversed the histopathology and symptoms of UC in mice and altered the gut microbiota. The activity of gut microbiota in donor samples should be considered in FMT and that detailed analysis of viable microbiota is essential to understand the mechanisms by which FMT produces therapeutic effects in the future.
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Affiliation(s)
- Jinglong Liu
- Department of Gastroenterology, Shanxi Provincial People’s Hospital, Taiyuan, China
| | - Hao Lin
- Center for Microecological Medical Technology, Xiamen Institute of Union Respiratory Health, Xiamen, China
| | - Man Cao
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
| | - Tan Lin
- Center for Microecological Medical Technology, Xiamen Institute of Union Respiratory Health, Xiamen, China
| | - Aiqiang Lin
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Wei Xu
- Center for Microecological Medical Technology, Xiamen Institute of Union Respiratory Health, Xiamen, China
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Han Wang
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Jianquan He
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
| | - Yuantao Li
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
- *Correspondence: Yuantao Li, ; Hailing Tang, ; Bangzhou Zhang,
| | - Hailing Tang
- Division of Gastroenterology, Xi’an Central Hospital, Xi’an, China
- *Correspondence: Yuantao Li, ; Hailing Tang, ; Bangzhou Zhang,
| | - Bangzhou Zhang
- Center for Research and Development, Xiamen Treatgut Biotechnology Co., Ltd., Xiamen, China
- Department of Gastroenterology, The Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, China
- School of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China
- *Correspondence: Yuantao Li, ; Hailing Tang, ; Bangzhou Zhang,
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Raufaste-Cazavieille V, Santiago R, Droit A. Multi-omics analysis: Paving the path toward achieving precision medicine in cancer treatment and immuno-oncology. Front Mol Biosci 2022; 9:962743. [PMID: 36304921 PMCID: PMC9595279 DOI: 10.3389/fmolb.2022.962743] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 09/21/2022] [Indexed: 11/13/2022] Open
Abstract
The acceleration of large-scale sequencing and the progress in high-throughput computational analyses, defined as omics, was a hallmark for the comprehension of the biological processes in human health and diseases. In cancerology, the omics approach, initiated by genomics and transcriptomics studies, has revealed an incredible complexity with unsuspected molecular diversity within a same tumor type as well as spatial and temporal heterogeneity of tumors. The integration of multiple biological layers of omics studies brought oncology to a new paradigm, from tumor site classification to pan-cancer molecular classification, offering new therapeutic opportunities for precision medicine. In this review, we will provide a comprehensive overview of the latest innovations for multi-omics integration in oncology and summarize the largest multi-omics dataset available for adult and pediatric cancers. We will present multi-omics techniques for characterizing cancer biology and show how multi-omics data can be combined with clinical data for the identification of prognostic and treatment-specific biomarkers, opening the way to personalized therapy. To conclude, we will detail the newest strategies for dissecting the tumor immune environment and host–tumor interaction. We will explore the advances in immunomics and microbiomics for biomarker identification to guide therapeutic decision in immuno-oncology.
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Affiliation(s)
| | - Raoul Santiago
- CHU de Québec Research Center, Université Laval, Québec, QC, Canada
- Division of Pediatric Hematology-Oncology, Centre Hospitalier Universitaire de L’Université Laval, Charles Bruneau Cancer Center, Québec, QC, Canada
- *Correspondence: Raoul Santiago, ; Arnaud Droit,
| | - Arnaud Droit
- CHU de Québec Research Center, Université Laval, Québec, QC, Canada
- *Correspondence: Raoul Santiago, ; Arnaud Droit,
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31
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Ahmed E, Hens K. Microbiome in Precision Psychiatry: An Overview of the Ethical Challenges Regarding Microbiome Big Data and Microbiome-Based Interventions. AJOB Neurosci 2022; 13:270-286. [PMID: 34379050 DOI: 10.1080/21507740.2021.1958096] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/09/2023]
Abstract
There has been a spurt in both fundamental and translational research that examines the underlying mechanisms of the human microbiome in psychiatric disorders. The personalized and dynamic features of the human microbiome suggest the potential of its manipulation for precision psychiatry in ways to improve mental health and avoid disease. However, findings in the field of microbiome also raise philosophical and ethical questions. From a philosophical point of view, they may yet be another attempt at providing a biological cause for phenomena that ultimately cannot be so easily localized. From an ethical point of view, it is relevant that the human gut microbiome comprises data on the individual's lifestyle, disease history, previous medications, and mental health. Massive datasets of microbiome sequences are collected to facilitate comparative studies to identify specific links between the microbiome and mental health. Although this emerging research domain may show promise for psychiatric patients, it is surrounded by ethical challenges regarding patient privacy, health risks, effects on personal identity, and concerns about responsibility. This narrative overview displays the roles and advances of microbiome research in psychiatry and discusses the philosophical and ethical implications of microbiome big data and microbiome-based interventions for psychiatric patients. We also investigate whether these issues are really "new," or "old wine in new bottles."
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Affiliation(s)
- Eman Ahmed
- University of Antwerp.,Suez Canal University
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32
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Madhogaria B, Bhowmik P, Kundu A. Correlation between human gut microbiome and diseases. INFECTIOUS MEDICINE 2022; 1:180-191. [PMID: 38077626 PMCID: PMC10699709 DOI: 10.1016/j.imj.2022.08.004] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/07/2022] [Accepted: 08/16/2022] [Indexed: 03/21/2024]
Abstract
Human gut microbiome is a major source of human bacterial population and a significant contribution to both positive and harmful effects. Due to its involvement in a variety of interactions, gut microorganisms have a great impact on our health throughout our lives. The impact of gut microbial population is been studied intensively in last two decades. Extensive literature survey focusing developments in the field were searched in English language Electronic Databases like PubMed, Google Scholar, Pubag, Google books, and Research Gate were mostly used to understand the role of human gut mirobiome and its role in different human diseases. Gut microbiome in healthy subjects differs from those who suffer from diseases. Type 2 diabetes, obesity, non-alcoholic liver disease, and cardiometabolic diseases have all been linked to dysbiosis of the gut microbiota. Pathogenesis of many disorders is also linked to changes in gut microbiota. Other diseases like cancer, arithritis, autism, depression, anxiety, sleep disorder, HIV, hypertension, and gout are also related to gut microbiota dysbiosis. We focus in this review on recent studies looking into the link between gut microbiome dysbiosis and disease etiology. Research on how gut microbiota affects host metabolism has been changed in past decades from descriptive analyses to high throughput integrative omics data analysis such as metagenomics and metabolomics. Identification of molecular mechanisms behind reported associations is been carried out in human, animals, and cells for measure of host physiology and mechanics. Still many the mechanisms are not completely understood.
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Affiliation(s)
- Barkha Madhogaria
- Department of Microbiology, Techno India University, West Bengal EM-4 Sector-V, Salt Lake City, Kolkata 700091, West Bengal, India
| | - Priyanka Bhowmik
- Department of Biological Sciences, Adamas University, Barrackpore-Barasat Road, 24 Paragnas North, Jagannathpur, Kolkata, West Bengal, India
| | - Atreyee Kundu
- Department of Microbiology, Techno India University, West Bengal EM-4 Sector-V, Salt Lake City, Kolkata 700091, West Bengal, India
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33
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Li K, Liu J, Qin X. Research progress of gut microbiota in hepatocellular carcinoma. J Clin Lab Anal 2022; 36:e24512. [PMID: 35719048 PMCID: PMC9279976 DOI: 10.1002/jcla.24512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 04/27/2022] [Accepted: 04/28/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth leading cause of cancer-related death in the world. A number of challenges remain for the early detection and effective treatment of HCC. In recent years, microbiota have been proven to be associated with the development of HCC. Many studies have explored the pathogenesis, diagnostic marker, and therapeutic target potential of microbiota in hepatocellular carcinoma. Therefore, we aimed to introduce the research methods and achievements of gut microbiota in hepatocellular carcinoma and discuss the value of gut microbiota in the pathogenesis, diagnosis, and treatment of hepatocellular carcinoma. METHODS Keywords are used to search relevant articles which were mainly published from 2010 to 2021, and we further selected targeted articles and read the full text. RESULTS Gut microbiota involved in promoting the formation and development of hepatocellular carcinoma, and differential gut microbiota and microbial metabolites have the potential to be the biomarkers of hepatocellular carcinoma. Purposefully regulated gut microbiota can improve the prognosis of patients, which is expected to be used in hepatocellular carcinoma. CONCLUSION The study of gut microbiota in hepatocellular carcinoma is definitely worthy of study. In-depth and elaborate research design is crucial for the study of the mechanism of gut microbiota involved in hepatocellular carcinoma, which can provide new directions and targets for the diagnosis, treatment, and prognosis of hepatocellular carcinoma.
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Affiliation(s)
- Keliu Li
- Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China.,Liaoning Clinical Research Center for Laboratory Medicine, Shenyang, China
| | - Jianhua Liu
- Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China.,Liaoning Clinical Research Center for Laboratory Medicine, Shenyang, China
| | - Xiaosong Qin
- Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China.,Liaoning Clinical Research Center for Laboratory Medicine, Shenyang, China
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34
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Interaction of Gut Microbiota with Endocrine Homeostasis and Thyroid Cancer. Cancers (Basel) 2022; 14:cancers14112656. [PMID: 35681636 PMCID: PMC9179244 DOI: 10.3390/cancers14112656] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 05/22/2022] [Accepted: 05/24/2022] [Indexed: 01/27/2023] Open
Abstract
The gut microbiota plays a crucial role in healthy individuals as well as in patients with thyroid diseases, including thyroid cancer. Although the prognosis of differentiated thyroid cancer is predictable, that of some poorly differentiated, medullary, and anaplastic thyroid cancers remains unpromising. As the interaction between the gut microbiota and thyroid cancer has been gradually revealed in recent years, the thyroid gland, a crucial endocrine organ, is shown to have a complex connection with the body's metabolism and is involved in inflammation, autoimmunity, or cancer progression. Dysbiosis of the gut microbiota and its metabolites can influence changes in hormone levels and susceptibility to thyroid cancer through multiple pathways. In this review, we focus on the interactions of the gut microbiota with thyroid function diseases and thyroid cancer. In addition, we also discuss some potential new strategies for the prevention and treatment of thyroid disease and thyroid cancer. Our aim is to provide some possible clinical applications of gut microbiota markers for early diagnosis, treatment, and postoperative management of thyroid cancer. These findings were used to establish a better multi-disciplinary treatment and prevention management strategy and to individualize the treatment of patients in relation to their gut microbiota composition and pathological characteristics.
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Garey KW, McPherson J, Dinh AQ, Hu C, Jo J, Wang W, Lancaster CK, Gonzales-Luna AJ, Loveall C, Begum K, Alam MJ, Silverman MH, Hanson B. Efficacy, Safety, Pharmacokinetics, and Microbiome Changes of Ibezapolstat in Adults with Clostridioides difficile Infection: A Phase 2a Multicenter Clinical Trial. Clin Infect Dis 2022; 75:1164-1170. [PMID: 35134880 PMCID: PMC9525077 DOI: 10.1093/cid/ciac096] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Indexed: 12/17/2022] Open
Abstract
Background This study was the first human validation of the gram-positive bacterial DNA polymerase IIIC target in patients with Clostridioides difficile infection. The primary objectives were to assess clinical cure rates and adverse events (AEs). Secondary objectives were to evaluate plasma/fecal pharmacokinetics, microbiologic eradication, microbiome and bile acid effects, and sustained clinical cure (SCC) with ibezapolstat. Methods This single-arm, open-label, phase 2a study enrolled adults with C. difficile infection at 4 US centers. Patients received ibezapolstat 450 mg orally every 12 hours for 10 days and followed for an additional 28 days to assess study objectives. Results Ten patients with a mean (standard deviation [SD]) age of 49 [15] years were enrolled. Seven AEs were reported classified as mild-moderate. Plasma levels of ibezapolstat ranged from 233 to 578 ng/mL while mean (SD) fecal levels were 416 (494) µg/g stool by treatment day 3 and >1000 µg/g stool by days 8–10. A rapid increase in alpha diversity in the fecal microbiome was noted after starting ibezapolstat therapy, which was maintained after completion of therapy. A proportional decrease in Bacteroidetes phylum was observed (mean change [SD], −10.0% [4.8%]; P = .04) with a concomitantly increased proportion of Firmicutes phylum (+14.7% [5.4%]; P = .009). Compared with baseline, total primary bile acids decreased by a mean (SD) of 40.1 (9.6) ng/mg stool during therapy (P < .001) and 40.5 (14.1) ng/mg stool after completion of therapy (P = .007). Rates of both initial clinical cure and SCC at 28 days were 100% (10 of 10 patients). Conclusions In this phase 2a study, 10 of 10 patients achieved SCC, demonstrated favorable pharmacokinetics, minimal AEs, and beneficial microbiome and bile acids results. These results support continued clinical development.
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Affiliation(s)
- Kevin W Garey
- University of Houston College of Pharmacy, Houston, TX USA.,University of Texas School of Public Health, Houston, TX USA
| | | | - An Q Dinh
- University of Texas School of Public Health, Houston, TX USA
| | - Chenlin Hu
- University of Houston College of Pharmacy, Houston, TX USA
| | - Jinhee Jo
- University of Houston College of Pharmacy, Houston, TX USA
| | - Weiqun Wang
- University of Houston College of Pharmacy, Houston, TX USA
| | | | | | | | | | | | | | - Blake Hanson
- University of Texas School of Public Health, Houston, TX USA
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36
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Vasilescu IM, Chifiriuc MC, Pircalabioru GG, Filip R, Bolocan A, Lazăr V, Diţu LM, Bleotu C. Gut Dysbiosis and Clostridioides difficile Infection in Neonates and Adults. Front Microbiol 2022; 12:651081. [PMID: 35126320 PMCID: PMC8810811 DOI: 10.3389/fmicb.2021.651081] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 12/15/2021] [Indexed: 12/11/2022] Open
Abstract
In this review, we focus on gut microbiota profiles in infants and adults colonized (CDC) or infected (CDI) with Clostridioides difficile. After a short update on CDI epidemiology and pathology, we present the gut dysbiosis profiles associated with CDI in adults and infants, as well as the role of dysbiosis in C. difficile spores germination and multiplication. Both molecular and culturomic studies agree on a significant decrease of gut microbiota diversity and resilience in CDI, depletion of Firmicutes, Bacteroidetes, and Actinobacteria phyla and a high abundance of Proteobacteria, associated with low butyrogenic and high lactic acid-bacteria levels. In symptomatic cases, microbiota deviations are associated with high levels of inflammatory markers, such as calprotectin. In infants, colonization with Bifidobacteria that trigger a local anti-inflammatory response and abundance of Ruminococcus, together with lack of receptors for clostridial toxins and immunological factors (e.g., C. difficile toxins neutralizing antibodies) might explain the lack of clinical symptoms. Gut dysbiosis amelioration through administration of “biotics” or non-toxigenic C. difficile preparations and fecal microbiota transplantation proved to be very useful for the management of CDI.
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Affiliation(s)
- Iulia-Magdalena Vasilescu
- Department of Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania
- INBI “Prof. Dr. Matei Balş” – National Institute for Infectious Diseases, Bucharest, Romania
| | - Mariana-Carmen Chifiriuc
- Department of Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania
- Research Institute of the University of Bucharest, Bucharest, Romania
- Academy of Romanian Scientists, Bucharest, Romania
- The Romanian Academy, Bucharest, Romania
- *Correspondence: Mariana-Carmen Chifiriuc,
| | | | - Roxana Filip
- Faculty of Medicine and Biological Sciences, Stefan cel Mare University of Suceava, Suceava, Romania
- Regional County Emergency Hospital, Suceava, Romania
| | - Alexandra Bolocan
- Department of General Surgery, University Emergency Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Veronica Lazăr
- Department of Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania
| | - Lia-Mara Diţu
- Department of Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania
| | - Coralia Bleotu
- Department of Microbiology, Faculty of Biology, University of Bucharest, Bucharest, Romania
- Research Institute of the University of Bucharest, Bucharest, Romania
- Ştefan S. Nicolau Institute of Virology, Romanian Academy, Bucharest, Romania
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Azimirad M, Jo Y, Kim MS, Jeong M, Shahrokh S, Asadzadeh Aghdaei H, Zali MR, Lee S, Yadegar A, Shin JH. Alterations and Prediction of Functional Profiles of Gut Microbiota After Fecal Microbiota Transplantation for Iranian Recurrent Clostridioides difficile Infection with Underlying Inflammatory Bowel Disease: A Pilot Study. J Inflamm Res 2022; 15:105-116. [PMID: 35023946 PMCID: PMC8747792 DOI: 10.2147/jir.s338212] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 12/28/2021] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND AND PURPOSE Fecal microbiota transplantation (FMT) has emerged for the therapeutic treatment of recurrent Clostridioides difficile infection (rCDI) with concurrent inflammatory bowel disease (IBD). As the first Iranian population cohort, we examined how gut microbiota and their functional profiles change in Iranian rCDI patients with underlying IBD before and after FMT. PATIENTS AND METHODS FMT was performed to eight IBD patients via colonoscopy. Profiles of gut microbiota from donors and recipients were investigated using 16S rRNA gene sequence analysis. RESULTS Patients experienced no IBD flare-ups or other adverse effects, and all recovered to full health. Moreover, all rCDI patients lacked the Bacteroidetes present in donor samples. After FMT, the proportion of Bacteroidetes increased until a normal range was achieved. More specifically, the relative abundance of Prevotella was found to increase significantly following FMT. Prevotella was also found to correlate negatively with inflammation metrics, suggesting that Prevotella may be a key factor for resolving CDI and IBD. Gut microbiota diversity was found to increase following FMT, while dysbiosis decreased. However, the similarity of microbial communities of host and recipients did not increase, and wide variation in the extent of donor stool engraftment indicated that the gut bacterial communities of recipients do not shift towards those of donors. CONCLUSION FMT leads to significant alterations of the community structure of gut bacteria in rCDI patients with IBD. The change in relative abundance of Proteobacteria and bacterial diversity indicated that FMT promotes recovery from intestinal permeability and inflammation in rCDI patients. Moreover, strong negative correlation between Prevotella and inflammation index, and decreased dysbiosis index advocate that the improvement of CDI is possibly due to gut microbiome alteration. Collectively, our findings show that FMT would be a promising therapy to help reprogram the gut microbiome of Iranian rCDI patients with IBD.
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Affiliation(s)
- Masoumeh Azimirad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - YoungJae Jo
- Department of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Min-Sueng Kim
- Department of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Minsoo Jeong
- Department of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Shabnam Shahrokh
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seungjun Lee
- Department of Food Science and Nutrition, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jae-Ho Shin
- Department of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea
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Wallenborn JT, Vonaesch P. OUP accepted manuscript. Gastroenterol Rep (Oxf) 2022; 10:goac010. [PMID: 35419206 PMCID: PMC8996373 DOI: 10.1093/gastro/goac010] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 12/10/2021] [Accepted: 02/16/2022] [Indexed: 11/15/2022] Open
Abstract
The intestinal microbiota plays a crucial role in health and changes in its composition are linked with major global human diseases. Fully understanding what shapes the human intestinal microbiota composition and knowing ways of modulating the composition are critical for promotion of life-course health, combating diseases, and reducing global health disparities. We aim to provide a foundation for understanding what shapes the human intestinal microbiota on an individual and global scale, and how interventions could utilize this information to promote life-course health and reduce global health disparities. We briefly review experiences within the first 1,000 days of life and how long-term exposures to environmental elements or geographic specific cultures have lasting impacts on the intestinal microbiota. We also discuss major public health threats linked to the intestinal microbiota, including antimicrobial resistance and disappearing microbial diversity due to globalization. In order to promote global health, we argue that the interplay of the larger ecosystem with intestinal microbiota research should be utilized for future research and urge for global efforts to conserve microbial diversity.
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Affiliation(s)
- Jordyn T Wallenborn
- Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Pascale Vonaesch
- Department of Fundamental Microbiology, University of Lausanne, Bâtiment Biophore Campus UNIL-Sorge, Lausanne, Switzerland
- Corresponding author. Department of Fundamental Microbiology, University of Lausanne, 1015 Lausanne, Switzerland. Tel: +41-21-692-5600;
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El-Sahhar S, Varga-Weisz P. The gut microbiome in health and disease: Inflammatory bowel diseases. ADV ECOL RES 2022. [DOI: 10.1016/bs.aecr.2022.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Sędzikowska A, Szablewski L. Human Gut Microbiota in Health and Selected Cancers. Int J Mol Sci 2021; 22:13440. [PMID: 34948234 PMCID: PMC8708499 DOI: 10.3390/ijms222413440] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Revised: 12/08/2021] [Accepted: 12/10/2021] [Indexed: 12/24/2022] Open
Abstract
The majority of the epithelial surfaces of our body, and the digestive tract, respiratory and urogenital systems, are colonized by a vast number of bacteria, archaea, fungi, protozoans, and viruses. These microbiota, particularly those of the intestines, play an important, beneficial role in digestion, metabolism, and the synthesis of vitamins. Their metabolites stimulate cytokine production by the human host, which are used against potential pathogens. The composition of the microbiota is influenced by several internal and external factors, including diet, age, disease, and lifestyle. Such changes, called dysbiosis, may be involved in the development of various conditions, such as metabolic diseases, including metabolic syndrome, type 2 diabetes mellitus, Hashimoto's thyroidis and Graves' disease; they can also play a role in nervous system disturbances, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and depression. An association has also been found between gut microbiota dysbiosis and cancer. Our health is closely associated with the state of our microbiota, and their homeostasis. The aim of this review is to describe the associations between human gut microbiota and cancer, and examine the potential role of gut microbiota in anticancer therapy.
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Affiliation(s)
| | - Leszek Szablewski
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, ul. Chalubinskiego 5, 02-004 Warsaw, Poland;
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41
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Parnell JM, Nicholson MR, Kellermayer R, Kahn SA. Pediatric Fecal Microbiota Transplantation in Recurrent Clostridioides Difficile. Pediatr Ann 2021; 50:e515-e521. [PMID: 34889135 DOI: 10.3928/19382359-20211111-01] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
With the rising rates of Clostridioides (Clostridium) difficile infection (CDI) in children, recognizing the limitations of CDI-directed antibiotic therapy, especially in recurrent CDI (rCDI), is important. Fecal microbiota transplantation (FMT), which directly targets the underlying gut dysbiosis present in rCDI, is an important treatment option to consider in rCDI. This article will summarize indications, procedures, effectiveness, and the safety of FMT for rCDI in pediatric patients. [Pediatr Ann. 2021;50(12):e515-e521.].
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Lee PC, Chang TE, Wang YP, Lee KC, Lin YT, Chiou JJ, Huang CW, Yang UC, Li FY, Huang HC, Wu CY, Huang YH, Hou MC. Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection. J Formos Med Assoc 2021; 121:1636-1646. [PMID: 34836663 DOI: 10.1016/j.jfma.2021.11.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 09/27/2021] [Accepted: 11/01/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND/PURPOSE Clostridium difficile infection (CDI) leads to a significant cause of hospital-acquired morbidity and mortality. Fecal microbiota transplantation (FMT) is effective to treat recurrent or refractory CDI (rCDI). However, the change of microbial composition contributed by FMT and its association with treatment outcomes is not well determined in Taiwan. We aimed to investigate the efficacy of FMT and the association with microbial alteration endemically. METHODS Twelve patients who received FMT for rCDI in Taipei Veterans General Hospital were prospectively enrolled from April 2019 to July 2020. The clinical assessments and fecal microbial analyses in comparison with fecal materials of unrelated donors were conducted before and after FMT. RESULTS The overall success rate of FMT for rCDI was 91.7%. A prominence of Proteobacteria, Gammaproteobacteria and Enterobacteriales were observed in the feces of patients with rCDI. Increased fecal phylogenetic diversities and a significant microbial dissimilarity were provided by successful FMT compared to patients before treatment. However, the distinctness was not obvious between patients' feces at baseline and after unsuccessful FMT. Moreover, dynamic change of fecal microbial composition after FMT was observed during follow-up but did not interrupt the treatment effects of FMT. CONCLUSION Gut dysbiosis commonly co-exists in patients with rCDI. Restoration of gut microbial communities by FMT provides a promising strategy to treat antibiotic-failed CDI, and the extent of microbial change would be related to the treatment outcomes of FMT. Besides, the effectiveness of FMT for CDI could be maintained even the gut microbiota has diverged over time.
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Affiliation(s)
- Pei-Chang Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Tien-En Chang
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yen-Po Wang
- Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Kuei-Chuan Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Tsung Lin
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jen-Jie Chiou
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chi-Wei Huang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ueng-Cheng Yang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Fen-Yau Li
- Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Hui-Chun Huang
- Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Ying Wu
- Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Gunardi TH, Susantono DP, Victor AA, Sitompul R. Atopobiosis and Dysbiosis in Ocular Diseases: Is Fecal Microbiota Transplant and Probiotics a Promising Solution? J Ophthalmic Vis Res 2021; 16:631-643. [PMID: 34840686 PMCID: PMC8593547 DOI: 10.18502/jovr.v16i4.9754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Accepted: 06/30/2021] [Indexed: 11/24/2022] Open
Abstract
PURPOSE To highlight the role of atopobiosis and dysbiosis in the pathomechanism of autoimmune uveitis, therefore supporting fecal microbiota transplant (FMT) and probiotics as potential targeted-treatment for uveitis. METHODS This review synthesized literatures upon the relation between gut microbiota, autoimmune uveitis, FMT, and probiotics, published from January 2001 to March 2021 and indexed in PubMed, Google Scholar, CrossRef. RESULTS The basis of the gut-eye axis revolves around occurrences of molecular mimicry, increase in pro-inflammatory cytokines, gut epithelial barrier disruption, and translocation of microbes to distant sites. In patients with autoimmune uveitis, an increase of gut Fusobacterium and Enterobacterium were found. With current knowledge of aforementioned mechanisms, studies modifying the gut microbiome and restoring the physiologic gut barrier has been the main focus for pathomechanism-based therapy. In mice models, FMT and probiotics targeting repopulation of gut microbiota has shown significant improvement in clinical manifestations of uveitis. Consequently, a better understanding in the homeostasis of gut microbiome along with their role in the gut-eye axis is needed to develop practical targeted treatment. CONCLUSION Current preliminary studies are promising in establishing a causative gut-eye axis relationship and the possibility of conducting FMT and probiotics as targeted treatment to mitigate autoimmune uveitis, to shorten disease duration, and to prevent further complications.
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Affiliation(s)
| | | | - Andi Arus Victor
- Department of Ophthalmology, Dr. Cipto Mangunkusumo National General
Hospital – Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Ratna Sitompul
- Department of Ophthalmology, Dr. Cipto Mangunkusumo National General
Hospital – Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
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Cui M, Sun T, Li S, Pan H, Liu J, Zhang X, Li L, Li S, Wei C, Yu C, Yang C, Ma N, Ma B, Lu S, Chang J, Zhang W, Wang H. NIR light-responsive bacteria with live bio-glue coatings for precise colonization in the gut. Cell Rep 2021; 36:109690. [PMID: 34525358 DOI: 10.1016/j.celrep.2021.109690] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 04/09/2021] [Accepted: 08/19/2021] [Indexed: 01/08/2023] Open
Abstract
Recombinant bacterial colonization plays an indispensable role in disease prevention, alleviation, and treatment. Successful application mainly depends on whether bacteria can efficiently spatiotemporally colonize the host gut. However, a primary limitation of existing methods is the lack of precise spatiotemporal regulation, resulting in uncontrolled methods that are less effective. Herein, we design upconversion microgels (UCMs) to convert near-infrared light (NIR) into blue light to activate recombinant light-responsive bacteria (Lresb) in vivo, where autocrine "functional cellular glues" made of adhesive proteins assist Lresb inefficiently colonizing the gut. The programmable engineering platform is further developed for the controlled and effective colonization of Escherichia coli Nissle 1917 (EcN) in the gut. The colonizing bacteria effectively alleviate DSS-induced colitis in mice. We anticipate that this approach could facilitate the clinical application of engineered microbial therapeutics to accurately and effectively regulate host health.
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Affiliation(s)
- Meihui Cui
- School of Life Sciences, Tianjin University, Tianjin 300072, China
| | - Tao Sun
- Center for Biosafety Research and Strategy, Tianjin University, Tianjin 300072, China; Laboratory of Synthetic Microbiology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China
| | - Shubin Li
- Laboratory of Synthetic Microbiology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China
| | - Huizhuo Pan
- School of Life Sciences, Tianjin University, Tianjin 300072, China
| | - Jing Liu
- School of Life Sciences, Tianjin University, Tianjin 300072, China
| | - Xinyu Zhang
- School of Life Sciences, Tianjin University, Tianjin 300072, China
| | - Lianyue Li
- School of Life Sciences, Tianjin University, Tianjin 300072, China
| | - Shanshan Li
- School of Mechanical Engineering, Hebei University of Technology, Tianjin 300401, China
| | - Chunyang Wei
- School of Mechanical Engineering, Hebei University of Technology, Tianjin 300401, China
| | - Chengzhuang Yu
- School of Mechanical Engineering, Hebei University of Technology, Tianjin 300401, China
| | - Chun Yang
- School of Life Sciences, Tianjin University, Tianjin 300072, China
| | - Ning Ma
- School of Life Sciences, Tianjin University, Tianjin 300072, China
| | - Binglin Ma
- School of Life Sciences, Tianjin University, Tianjin 300072, China
| | - Shenjunjie Lu
- School of Life Sciences, Tianjin University, Tianjin 300072, China
| | - Jin Chang
- School of Life Sciences, Tianjin University, Tianjin 300072, China
| | - Weiwen Zhang
- Center for Biosafety Research and Strategy, Tianjin University, Tianjin 300072, China; Laboratory of Synthetic Microbiology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China
| | - Hanjie Wang
- School of Life Sciences, Tianjin University, Tianjin 300072, China.
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Grimnes G, Bhoelan S, Hindberg K, Davids M, Nieuwdorp M, Mollnes TE, Michelsen AE, Ueland T, Brækkan SK, Hansen JB, Tichelaar V. Impact of a Vancomycin-Induced Shift of the Gut Microbiome in a Gram-Negative Direction on Plasma Factor VIII:C Levels: Results from a Randomized Controlled Trial. Thromb Haemost 2021; 122:540-551. [PMID: 34428832 DOI: 10.1055/s-0041-1733906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
RATIONALE Inflammation is present in several conditions associated with risk of venous thromboembolism. The gut microbiome might be a source of systemic inflammation and activation of coagulation, by translocation of lipopolysaccharides from gram-negative bacteria to the systemic circulation. OBJECTIVE To investigate whether a vancomycin-induced shift of the gut microbiome in a gram-negative direction influences systemic inflammation and plasma factor (F) VIII procoagulant activity (FVIII:C). METHODS AND RESULTS We performed a randomized controlled trial including 43 healthy volunteers aged 19 to 37 years. Twenty-one were randomized to 7 days of oral vancomycin intake and 22 served as controls. Feces and blood were sampled at baseline, the day after the end of intervention, and 3 weeks after intervention. Gut microbiome composition was assessed by amplicon sequencing. FVIII C was measured using an activated partial thromboplastin time-based assay, cytokines were measured using multiplex technology, complement activation was measured using the enzyme-linked immunosorbent assay, and high-sensitivity C-reactive protein (CRP) was measured by an immunoturbidimetric assay. Vancomycin intake reduced gut microbiome diversity and increased the abundance of gram-negative bacteria. Change in FVIII:C in the intervention group was +4 IU/dL versus -6 IU/dL (p = 0.01) in the control group. A similar change was observed for log-transformed CRP (+0.21 mg/dL vs. -0.25 mg/dL, p = 0.04). The cytokines and complement activation markers remained similar in the two groups. CONCLUSION The found slight increases in FVIII:C and CRP levels might support the hypothesis that a vancomycin-induced gram-negative shift in the gut microbiome could induce increased systemic inflammation and thereby a procoagulant state.
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Affiliation(s)
- Gro Grimnes
- Department of Clinical Medicine, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT-The Arctic University of Norway, Tromsø, Norway.,Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
| | - Soerajja Bhoelan
- Department of Clinical Medicine, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT-The Arctic University of Norway, Tromsø, Norway.,Division of Haemostasis and Thrombosis, Department of Haematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Kristian Hindberg
- Department of Clinical Medicine, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT-The Arctic University of Norway, Tromsø, Norway
| | - Mark Davids
- Department of Vascular Medicine, Amsterdam University Medical Centers-location AMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Max Nieuwdorp
- Department of Vascular Medicine, Amsterdam University Medical Centers-location AMC, University of Amsterdam, Amsterdam, The Netherlands.,Department of Internal Medicine, Diabetes Center, Amsterdam University Medical Centers-location VUmc, Amsterdam, The Netherlands.,Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden
| | - Tom E Mollnes
- Department of Clinical Medicine, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT-The Arctic University of Norway, Tromsø, Norway.,Research Laboratory, Nordland Hospital, Bodø, Norway.,Department of Immunology, Oslo University Hospital and K.G. Jebsen IRC, University of Oslo, Oslo, Norway
| | - Annika E Michelsen
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Thor Ueland
- Department of Clinical Medicine, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT-The Arctic University of Norway, Tromsø, Norway.,Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Sigrid K Brækkan
- Department of Clinical Medicine, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT-The Arctic University of Norway, Tromsø, Norway.,Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
| | - John-Bjarne Hansen
- Department of Clinical Medicine, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT-The Arctic University of Norway, Tromsø, Norway.,Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
| | - Vladimir Tichelaar
- Department of Clinical Medicine, K. G. Jebsen Thrombosis Research and Expertise Center (TREC), UiT-The Arctic University of Norway, Tromsø, Norway.,Division of Haemostasis and Thrombosis, Department of Haematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.,Certe Thrombosis Service, Groningen, The Netherlands
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Ashraf MF, Tageldin O, Nassar Y, Batool A. Fecal Microbiota Transplantation in Patients With Recurrent Clostridium difficile Infection: A Four-Year Single-Center Retrospective Review. Gastroenterology Res 2021; 14:237-243. [PMID: 34527093 PMCID: PMC8425798 DOI: 10.14740/gr1436] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 07/13/2021] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Clostridium difficile infection (CDI) is a common cause of hospital and community-acquired diarrhea with an annual incidence of 453,000 cases in the USA. The white race, female gender, and age over 65 years are known risk factors. Recurrence of CDI is a major problem in patients taking antibiotics for prolonged periods. These patients are observed to have reduced diversity of the intestinal microbiome. Fecal microbiota transplantation (FMT) can restore the healthy flora in the gut, thus breaking the cycle of recurrent infection. Our study aimed to analyze the efficacy of FMT and the recurrence of CDI after FMT. We also aimed to investigate the effects of comorbidities on the outcome of FMT. METHODS After obtaining approval from the institutional review board, we included 64 patients who had received FMT at our institution from October 2015 to November 2019. All the patients over 16 years of age in both inpatient and outpatient settings were included. Patients under 16 years of age and patients treated without FMT were excluded. Frozen stool from a standardized stool bank (OpenBiome) was used. The thawed specimen was instilled into the terminal ileum or the cecum. Patients were followed up for the next 1 year for analysis of improvement in symptoms, recurrence, and repeat FMT. RESULTS On the 2-months follow-up, 75% of patients reported symptomatic improvement, 15.6% reported no improvement while 9.4% did not follow up. Twenty-six (40.6%) patients had CDI recurrence in the following year; and 69.2% of patients with recurrence underwent a repeat FMT. There was no statistically significant correlation between CDI recurrence and the age (P value = 0.68), gender (P value = 0.61), previous use of proton pump inhibitors (PPIs, P value = 0.11) or antibiotics (P value = 0.45). There was a statistically significant correlation noted with the use of immunosuppressants and recurrence (P value = 0.04). CONCLUSIONS FMT is a successful treatment modality for refractory and recurrent CDI. Repeat treatments can be beneficial if there is a lack of initial response. Being immunosuppressed with medications is associated with the risk of recurrence.
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Affiliation(s)
| | - Omar Tageldin
- Department of Internal Medicine, Albany Medical Center, Albany, NY, USA
| | - Yousef Nassar
- Department of Gastroenterology, Albany Medical Center, Albany, NY, USA
| | - Asra Batool
- Department of Gastroenterology, Albany Medical Center, Albany, NY, USA
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Jiang G, Zhang X, Gao W, Ji C, Wang Y, Feng P, Feng Y, Zhang Z, Li L, Zhao F. Transport stress affects the fecal microbiota in healthy donkeys. J Vet Intern Med 2021; 35:2449-2457. [PMID: 34331476 PMCID: PMC8478045 DOI: 10.1111/jvim.16235] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 07/20/2021] [Accepted: 07/21/2021] [Indexed: 11/28/2022] Open
Abstract
Background With the development of large‐scale donkey farming in China, long‐distance transportation has become common practice, and the incidence of intestinal diseases after transportation has increased. The intestinal microbiota is important in health and disease, and whether or not transportation disturbs the intestinal microbiota in donkeys has not been investigated. Objectives To determine the effects of transportation on the fecal microbiota of healthy donkeys using 16S rRNA sequencing. Animals Fecal and blood samples were collected from 12 Dezhou donkeys before and after transportation. Methods Prospective controlled study. Cortisol, ACTH, and heat‐shock protein 90 (HSP90) concentrations were measured. Sequencing of 16S rRNA was used to assess the microbial composition. Alpha diversity and beta diversity were assessed. Results Results showed significant (P < .05) increases in cortisol (58.1 ± 14.6 to 71.1 ± 9.60 ng/mL), ACTH (163.8 ± 31.9 to 315.8 ± 27.9 pg/mL), and HSP90 (10.8 ± 1.67 to 14.6 ± 1.75 ng/mL) on the day of arrival. A significantly lower (P = .04) level of bacterial richness was found in fecal samples after transportation, compared with that before transportation without distinct changes in diversity. Most notably, donkeys had significant decreases in Atopostipes, Eubacterium, Streptococcus, and Coriobacteriaceae. Conclusions and Clinical Importance Transportation can induce stress in healthy donkeys and have some effect on the composition of the in fecal microbiota. Additional studies are required to understand the potential effect of these microbiota changes, especially significantly decreased bacteria, on the development intestinal diseases in donkeys during recovery from transportation.
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Affiliation(s)
- Guimiao Jiang
- Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, China.,National Engineering Research Center for Gelatin-based TCM, Dong-E E-Jiao Co., Ltd, Liaocheng, Shandong Province, China
| | - Xinhao Zhang
- National Engineering Research Center for Gelatin-based TCM, Dong-E E-Jiao Co., Ltd, Liaocheng, Shandong Province, China.,College of Animal Science and Technology, Shangdong Agricultural University, Taian, China
| | - Weiping Gao
- National Engineering Research Center for Gelatin-based TCM, Dong-E E-Jiao Co., Ltd, Liaocheng, Shandong Province, China
| | - Chuanliang Ji
- National Engineering Research Center for Gelatin-based TCM, Dong-E E-Jiao Co., Ltd, Liaocheng, Shandong Province, China
| | - Yantao Wang
- National Engineering Research Center for Gelatin-based TCM, Dong-E E-Jiao Co., Ltd, Liaocheng, Shandong Province, China
| | - Peixiang Feng
- National Engineering Research Center for Gelatin-based TCM, Dong-E E-Jiao Co., Ltd, Liaocheng, Shandong Province, China
| | - Yulong Feng
- National Engineering Research Center for Gelatin-based TCM, Dong-E E-Jiao Co., Ltd, Liaocheng, Shandong Province, China
| | - Zhiping Zhang
- The College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou, China
| | - Lin Li
- Key Laboratory of Zoonosis of Liaoning Province, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, China
| | - Fuwei Zhao
- National Engineering Research Center for Gelatin-based TCM, Dong-E E-Jiao Co., Ltd, Liaocheng, Shandong Province, China.,College of Veterinary Medicine, Yangzhou University, Yangzhou, China
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Cui J, Lin Z, Tian H, Yang B, Zhao D, Ye C, Li N, Qin H, Chen Q. Long-Term Follow-Up Results of Fecal Microbiota Transplantation for Irritable Bowel Syndrome: A Single-Center, Retrospective Study. Front Med (Lausanne) 2021; 8:710452. [PMID: 34395484 PMCID: PMC8362996 DOI: 10.3389/fmed.2021.710452] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 06/29/2021] [Indexed: 12/12/2022] Open
Abstract
Objective: This study aimed to investigate the long-term efficacy of fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS). Study Methods: In this single-center long-term follow-up study, FMT treatment was administered to patients with moderate to severe IBS (IBS severity scoring system (IBS-SSS) > 175). After 1 year of treatment, it was decided whether to repeat FMT based on IBS-SSS score (IBS-SSS > 175). Baseline characteristics before and after FMT and questionnaires were completed at 1, 3, 6, 12, 24, 36, 48, and 60 months after FMT. The study outcomes included treatment efficacy rates, change of IBS-SSS, IBS-specific quality of life and fatigue, effect on stool frequency, Bristol Stool Scale for IBS-C and IBS-D, and side effects. Results: A total of 227 patients (47.58% IBS-C, 39.21% IBS-D, and 13.22% IBS-M) were recruited (142 females and 85 males with a mean age of 41.89 ± 13.57 years). The efficacy rates were 108 (51.92%), 147 (74.62%), 125 (74.41 %), 88 (71.54%), 78 (75.00%), 65 (73.03%), 45 (61.64%), and 37 (62.71%) at different follow-up time points. The total IBS-SSS score was 321.37 ± 73.89 before FMT, which significantly decreased after 1 month. The IBS-specific quality of life (IBS-QoL) score was 40.24 ± 11.34 before FMT, increased gradually, and was significantly higher at 3 months compared to before FMT. The total Fatigue Assessment Scale (FAS) score was 47 ± 8.64 before FMT and was significantly lower at 3 months. During follow-up, 89 (39.21%) side effects occurred that were alleviated by symptomatic treatment, and no serious adverse events were detected. Conclusion: Based on 60 months of long-term follow-up, the safety and efficacy of FMT for IBS was established. However, as the treatment effect declines over time, periodic and repetitive FMT is required for a sustained effect.
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Affiliation(s)
- Jiaqu Cui
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, China
| | - Zhiliang Lin
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, China
| | - Hongliang Tian
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, China
| | - Bo Yang
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, China
| | - Di Zhao
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, China
| | - Chen Ye
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, China
| | - Ning Li
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, China
| | - Huanlong Qin
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, China
| | - Qiyi Chen
- Intestinal Microenvironment Treatment Center of General Surgery, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai, China
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Tariq R, Hayat M, Pardi D, Khanna S. Predictors of failure after fecal microbiota transplantation for recurrent Clostridioides difficile infection: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis 2021; 40:1383-1392. [PMID: 33496893 DOI: 10.1007/s10096-021-04163-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 01/11/2021] [Indexed: 01/20/2023]
Abstract
Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI), with ~15% 1-year recurrence rate. Small studies have identified variable risk factors associated with FMT failure. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of FMT failure. A systematic search of Medline, Embase, and Web of Science was performed from January 2013 up to June 2020. Meta-analyses were performed using random-effects models and pooled adjusted odds ratios for risk factors reported in ≥2 studies were calculated. Overall, 2671 patients with recurrent CDI who underwent FMT in 12 studies were included. FMT failure occurred in 454 patients (16.9%) with median follow-up of 3 months (range 2-7.7 months). A total of 9 risk factors were identified in ≥2 studies. Meta-analysis showed that use of non- CDI antibiotics, presence of inflammatory bowel disease, poor quality of bowel preparation, CDI-related hospitalization before FMT, inpatient FMT, and severe CDI were associated with statistically significant increased risk of failure after FMT. Increasing age, female gender, and immunocompromised status were not associated with increased risk for FMT failure. Several risk factors (both modifiable and non-modifiable) are associated with FMT failure. Lower use of antibiotics in the post-FMT period and good bowel preparation at the time of FMT are associated with lower risk of failure after FMT. Additionally, patients with non-modifiable risk factors should be counseled to be particularly alert about recurrent symptoms after FMT.
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Affiliation(s)
- Raseen Tariq
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
- Department of Internal Medicine, Rochester General Hospital, Rochester, NY, USA
| | - Maham Hayat
- Department of Internal Medicine, University of Oklahoma, Norman, OK, USA
| | - Darrell Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Sahil Khanna
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
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50
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Munshi S. A depressed gut makes for a depressed brain via vagal transmission. Brain Behav Immun 2021; 95:15-16. [PMID: 33766699 DOI: 10.1016/j.bbi.2021.03.017] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 03/17/2021] [Indexed: 02/06/2023] Open
Affiliation(s)
- Soumyabrata Munshi
- Tulane Brain Institute, Department of Cell and Molecular Biology, Tulane University, 6823 St. Charles Avenue, New Orleans, LA 70118, United States of America.
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