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Leon-Derecho CMPD. Microbiome-based therapeutics. HUMAN MICROBIOME DRUG TARGETS 2025:233-244. [DOI: 10.1016/b978-0-443-15435-5.00017-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Zhang JT, Zhang N, Dong XT, Wang XR, Ma HW, Liu YD, Li MR. Efficacy and safety of fecal microbiota transplantation for treatment of ulcerative colitis: A post-consensus systematic review and meta-analysis. World J Clin Cases 2024; 12:4691-4702. [PMID: 39070844 PMCID: PMC11235499 DOI: 10.12998/wjcc.v12.i21.4691] [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: 03/27/2024] [Revised: 05/28/2024] [Accepted: 06/19/2024] [Indexed: 06/30/2024] Open
Abstract
BACKGROUND Numerous studies have assessed the efficacy and safety of fecal microbiota transplantation (FMT) as a therapy for ulcerative colitis (UC). However, the treatment processes and outcomes of these studies vary. AIM To evaluate the efficacy and safety of FMT for treating UC by conducting a systematic meta-analysis. METHODS The inclusion criteria involved reports of adult patients with UC treated with FMT, while studies that did not report clinical outcomes or that included patients with infection were excluded. Clinical remission (CR) and endoscopic remission (ER) were the primary and secondary outcomes, respectively. RESULTS We included nine studies retrieved from five electronic databases. The FMT group had better CR than the control group [relative risk (RR) = 1.53; 95% confidence interval (CI): 1.19-1.94; P < 0.0008]. ER was statistically significantly different between the two groups (RR = 2.80; 95%CI: 1.93-4.05; P < 0.00001). Adverse events did not differ significantly between the two groups. CONCLUSION FMT demonstrates favorable performance and safety; however, well-designed randomized clinical trials are still needed before the widespread use of FMT can be recommended. Furthermore, standardizing the FMT process is urgently needed for improved safety and efficacy.
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Affiliation(s)
- Jin-Tao Zhang
- Department of Clinical Medicine, School of Medicine, Nankai University, Tianjin 300071, China
| | - Nan Zhang
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
| | - Xue-Tao Dong
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
| | - Xiao-Ran Wang
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
| | - Hong-Wen Ma
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
| | - Yan-Di Liu
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
| | - Mu-Ran Li
- Department of Gastroenterology, Tianjin Union Medical Center, Tianjin 300122, China
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Malakar S, Sutaoney P, Madhyastha H, Shah K, Chauhan NS, Banerjee P. Understanding gut microbiome-based machine learning platforms: A review on therapeutic approaches using deep learning. Chem Biol Drug Des 2024; 103:e14505. [PMID: 38491814 DOI: 10.1111/cbdd.14505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Revised: 02/21/2024] [Accepted: 03/04/2024] [Indexed: 03/18/2024]
Abstract
Human beings possess trillions of microbial cells in a symbiotic relationship. This relationship benefits both partners for a long time. The gut microbiota helps in many bodily functions from harvesting energy from digested food to strengthening biochemical barriers of the gut and intestine. But the changes in microbiota composition and bacteria that can enter the gastrointestinal tract can cause infection. Several approaches like culture-independent techniques such as high-throughput and meta-omics projects targeting 16S ribosomal RNA (rRNA) sequencing are popular methods to investigate the composition of the human gastrointestinal tract microbiota and taxonomically characterizing microbial communities. The microbiota conformation and diversity should be provided by whole-genome shotgun metagenomic sequencing of site-specific community DNA associating genome mapping, gene inventory, and metabolic remodelling and reformation, to ease the functional study of human microbiota. Preliminary examination of the therapeutic potency for dysbiosis-associated diseases permits investigation of pharmacokinetic-pharmacodynamic changes in microbial communities for escalation of treatment and dosage plan. Gut microbiome study is an integration of metagenomics which has influenced the field in the last two decades. And the incorporation of artificial intelligence and deep learning through "omics-based" methods and microfluidic evaluation enhanced the capability of identification of thousands of microbes.
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Affiliation(s)
- Shilpa Malakar
- Department of Microbiology, Kalinga University, Raipur, Chhattisgarh, India
| | - Priya Sutaoney
- Department of Microbiology, Kalinga University, Raipur, Chhattisgarh, India
| | - Harishkumar Madhyastha
- Department of Cardiovascular Physiology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
| | - Kamal Shah
- Institute of Pharmaceutical Research, GLA University, Mathura, Uttar Pradesh, India
| | - Nagendra Singh Chauhan
- Department of Medical education, Drugs Testing Laboratory Avam Anusandhan Kendra, Raipur, Chhattisgarh, India
| | - Paromita Banerjee
- Department of Cardiology, AIIMS Rishikesh, Rishikesh, Uttarkhand, India
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Higinbotham AS, Kilbane CW. The gastrointestinal tract and Parkinson's disease. Front Cell Infect Microbiol 2024; 13:1158986. [PMID: 38292855 PMCID: PMC10825967 DOI: 10.3389/fcimb.2023.1158986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 12/14/2023] [Indexed: 02/01/2024] Open
Affiliation(s)
- Alissa S. Higinbotham
- Parkinson's disease and Movement Disorders Center, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Camilla W. Kilbane
- Parkinson's disease and Movement Disorders Center, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, United States
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Zhang X, Tang B, Guo J. Parkinson's disease and gut microbiota: from clinical to mechanistic and therapeutic studies. Transl Neurodegener 2023; 12:59. [PMID: 38098067 PMCID: PMC10722742 DOI: 10.1186/s40035-023-00392-8] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Accepted: 11/27/2023] [Indexed: 12/17/2023] Open
Abstract
Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases. The typical symptomatology of PD includes motor symptoms; however, a range of nonmotor symptoms, such as intestinal issues, usually occur before the motor symptoms. Various microorganisms inhabiting the gastrointestinal tract can profoundly influence the physiopathology of the central nervous system through neurological, endocrine, and immune system pathways involved in the microbiota-gut-brain axis. In addition, extensive evidence suggests that the gut microbiota is strongly associated with PD. This review summarizes the latest findings on microbial changes in PD and their clinical relevance, describes the underlying mechanisms through which intestinal bacteria may mediate PD, and discusses the correlations between gut microbes and anti-PD drugs. In addition, this review outlines the status of research on microbial therapies for PD and the future directions of PD-gut microbiota research.
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Affiliation(s)
- Xuxiang Zhang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Beisha Tang
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 410008, China
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, 410008, China
- Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008, China
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Jifeng Guo
- Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, China.
- Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, 410008, China.
- Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, 410008, China.
- Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008, China.
- Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, 410008, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China.
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Alam MZ, Markantonis JE, Fallon JT. Host Immune Responses to Clostridioides difficile Infection and Potential Novel Therapeutic Approaches. Trop Med Infect Dis 2023; 8:506. [PMID: 38133438 PMCID: PMC10747268 DOI: 10.3390/tropicalmed8120506] [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: 10/30/2023] [Revised: 11/17/2023] [Accepted: 11/19/2023] [Indexed: 12/23/2023] Open
Abstract
Clostridioides difficile infection (CDI) is a leading nosocomial infection, posing a substantial public health challenge within the United States and globally. CDI typically occurs in hospitalized elderly patients who have been administered antibiotics; however, there has been a rise in the occurrence of CDI in the community among young adults who have not been exposed to antibiotics. C. difficile releases toxins, which damage large intestinal epithelium, leading to toxic megacolon, sepsis, and even death. Unfortunately, existing antibiotic therapies do not always prevent these consequences, with up to one-third of treated patients experiencing a recurrence of the infection. Host factors play a crucial role in the pathogenesis of CDI, and accumulating evidence shows that modulation of host immune responses may potentially alter the disease outcome. In this review, we provide an overview of our current knowledge regarding the role of innate and adaptive immune responses on CDI outcomes. Moreover, we present a summary of non-antibiotic microbiome-based therapies that can effectively influence host immune responses, along with immunization strategies that are intended to tackle both the treatment and prevention of CDI.
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Affiliation(s)
- Md Zahidul Alam
- Department of Pathology and Laboratory Medicine, Brody School of Medicine, East Carolina University, 600 Moye Boulevard, Greenville, NC 27834, USA; (J.E.M.); (J.T.F.)
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Alsulaiman RM, Al-Quorain AA, Al-Muhanna FA, Piotrowski S, Kurdi EA, Vatte C, Alquorain AA, Alfaraj NH, Alrezuk AM, Robinson F, Dowdell AK, Alamri TA, Hamilton L, Lad H, Gao H, Gandla D, Keating BJ, Meng R, Piening B, Al-Ali AK. Gut microbiota analyses of inflammatory bowel diseases from a representative Saudi population. BMC Gastroenterol 2023; 23:258. [PMID: 37507685 PMCID: PMC10375692 DOI: 10.1186/s12876-023-02904-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 07/25/2023] [Indexed: 07/30/2023] Open
Abstract
BACKGROUND Crohn's diseases and ulcerative colitis, both of which are chronic immune-mediated disorders of the gastrointestinal tract are major contributors to the overarching Inflammatory bowel diseases. It has become increasingly evident that the pathological processes of IBDs results from interactions between genetic and environmental factors, which can skew immune responses against normal intestinal flora. METHODS The aim of this study is to assess and analyze the taxa diversity and relative abundances in CD and UC in the Saudi population. We utilized a sequencing strategy that targets all variable regions in the 16 S rRNA gene using the Swift Amplicon 16 S rRNA Panel on Illumina NovaSeq 6000. RESULTS The composition of stool 16 S rRNA was analyzed from 219 patients with inflammatory bowel disease and from 124 healthy controls. We quantified the abundance of microbial communities to examine any significant differences between subpopulations of samples. At the genus level, two genera in particular, Veillonella and Lachnoclostridium showed significant association with CD versus controls. There were significant differences between subjects with CD versus UC, with the top differential genera spanning Akkermansia, Harryflintia, Maegamonas and Phascolarctobacterium. Furthermore, statistically significant taxa diversity in microbiome composition was observed within the UC and CD groups. CONCLUSIONS In conclusion we have shown that there are significant differences in gut microbiota between UC, CD and controls in a Saudi Arabian inflammatory bowel disease cohort. This reinforces the need for further studies in large populations that are ethnically and geographically diverse. In addition, our results show the potential to develop classifiers that may have add additional richness of context to clinical diagnosis of UC and CD with larger inflammatory bowel disease cohorts.
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Affiliation(s)
- Raed M Alsulaiman
- Department of Internal Medicine, King Fahd Hospital of the University, Alkhobar, Imam Abdulrahman bin Faisal University, Dammam, 31441, Saudi Arabia
| | - Abdulaziz A Al-Quorain
- Department of Internal Medicine, King Fahd Hospital of the University, Alkhobar, Imam Abdulrahman bin Faisal University, Dammam, 31441, Saudi Arabia
| | - Fahad A Al-Muhanna
- Department of Internal Medicine, King Fahd Hospital of the University, Alkhobar, Imam Abdulrahman bin Faisal University, Dammam, 31441, Saudi Arabia
| | - Stanley Piotrowski
- Earle A Chiles Research Institute, Robert W. Franz Cancer Center, Portland, Oregon, OR, 97213, USA
| | | | - Chittibabu Vatte
- Department of Clinical Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia
| | - Ahmed A Alquorain
- Department of Internal Medicine, King Fahd Hospital of the University, Alkhobar, Imam Abdulrahman bin Faisal University, Dammam, 31441, Saudi Arabia
| | | | - Abdulaziz M Alrezuk
- Department of Internal Medicine, King Fahd Hospital of the University, Alkhobar, Imam Abdulrahman bin Faisal University, Dammam, 31441, Saudi Arabia
| | - Fred Robinson
- Earle A Chiles Research Institute, Robert W. Franz Cancer Center, Portland, Oregon, OR, 97213, USA
| | - Alexa K Dowdell
- Earle A Chiles Research Institute, Robert W. Franz Cancer Center, Portland, Oregon, OR, 97213, USA
| | - Turki A Alamri
- Department of Internal Medicine, King Fahd Hospital of the University, Alkhobar, Imam Abdulrahman bin Faisal University, Dammam, 31441, Saudi Arabia
| | - Lauren Hamilton
- Earle A Chiles Research Institute, Robert W. Franz Cancer Center, Portland, Oregon, OR, 97213, USA
| | - Hetal Lad
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, 19104, USA
| | - Hui Gao
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, 19104, USA
| | - Divya Gandla
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, 19104, USA
| | - Brendan J Keating
- Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Pennsylvania, PA, 19104, USA
| | - Ryan Meng
- Earle A Chiles Research Institute, Robert W. Franz Cancer Center, Portland, Oregon, OR, 97213, USA
| | - Brian Piening
- Earle A Chiles Research Institute, Robert W. Franz Cancer Center, Portland, Oregon, OR, 97213, USA
| | - Amein K Al-Ali
- Department of Clinical Biochemistry, College of Medicine, Imam Abdulrahman bin Faisal University, Dammam, Saudi Arabia.
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Sheykhsaran E, Abbasi A, Ebrahimzadeh Leylabadlo H, Sadeghi J, Mehri S, Naeimi Mazraeh F, Feizi H, Bannazadeh Baghi H. Gut microbiota and obesity: an overview of microbiota to microbial-based therapies. Postgrad Med J 2023; 99:384-402. [PMID: 35140178 DOI: 10.1136/postgradmedj-2021-141311] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Accepted: 01/15/2022] [Indexed: 12/14/2022]
Abstract
The increasing prevalence of obesity and overweight is a significant public concern throughout the world. Obesity is a complex disorder involving an excessive amount of body fat. It is not just a cosmetic concern. It is a medical challenge that increases the risk of other diseases and health circumstances, such as diabetes, heart disease, high blood pressure and certain cancers. Environmental and genetic factors are involved in obesity as a significant metabolic disorder along with diabetes. Gut microbiota (GM) has a high potential for energy harvesting from the diet. In the current review, we aim to consider the role of GM, gut dysbiosis and significant therapies to treat obesity. Dietary modifications, probiotics, prebiotics, synbiotics compounds, using faecal microbiota transplant, and other microbial-based therapies are the strategies to intervene in obesity reducing improvement. Each of these factors serves through various mechanisms including a variety of receptors and compounds to control body weight. Trial and animal investigations have indicated that GM can affect both sides of the energy-balancing equation; first, as an influencing factor for energy utilisation from the diet and also as an influencing factor that regulates the host genes and energy storage and expenditure. All the investigated articles declare the clear and inevitable role of GM in obesity. Overall, obesity and obesity-relevant metabolic disorders are characterised by specific modifications in the human microbiota's composition and functions. The emerging therapeutic methods display positive and promising effects; however, further research must be done to update and complete existing knowledge.
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Affiliation(s)
- Elham Sheykhsaran
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amin Abbasi
- Student Research Committee, Department of Food Sciences and Technology Research Institute, Faculty of Nutrition Sciences and food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Javid Sadeghi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Samaneh Mehri
- Department of Biochemistry and structural Biology, University of Alabama, Birmingham, Alabama, USA
| | - Fariba Naeimi Mazraeh
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hadi Feizi
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hossein Bannazadeh Baghi
- Immunology Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Microbiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Miri AH, Kamankesh M, Rad-Malekshahi M, Yadegar A, Banar M, Hamblin MR, Haririan I, Aghdaei HA, Zali MR. Factors associated with treatment failure, and possible applications of probiotic bacteria in the arsenal against Helicobacter pylori. Expert Rev Anti Infect Ther 2023; 21:617-639. [PMID: 37171213 DOI: 10.1080/14787210.2023.2203382] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
INTRODUCTION Helicobacter pylori is a widespread helical Gram-negative bacterium, which causes a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. This microbe frequently colonizes the mucosal layer of the human stomach and survives in the inhospitable microenvironment, by adapting to this hostile milieu. AREAS COVERED In this extensive review, we describe conventional antibiotic treatment regimens used against H. pylori including, empirical, tailored, and salvage therapies. Then, we present state-of-the-art information about reasons for treatment failure against H. pylori. Afterward, the latest advances in the use of probiotic bacteria against H. pylori infection are discussed. Finally, we propose a polymeric bio-platform to provide efficient delivery of probiotics for H. pylori infection. EXPERT OPINION For effective probiotic delivery systems, it is necessary to avoid the early release of probiotics at the acidic stomach pH, to protect them against enzymes and antimicrobials, and precisely target H. pylori bacteria which have colonized the antrum area of the stomach (basic pH).
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Affiliation(s)
- Amir Hossein Miri
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mojtaba Kamankesh
- Polymer Chemistry Department, School of Science, University of Tehran, Tehran, Iran
| | - Mazda Rad-Malekshahi
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, 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
| | - Maryam Banar
- Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg Doornfontein, Johannesburg, South Africa
| | - Ismaeil Haririan
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran 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
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Claudino Dos Santos JC, Lima MPP, Brito GADC, Viana GSDB. Role of enteric glia and microbiota-gut-brain axis in parkinson disease pathogenesis. Ageing Res Rev 2023; 84:101812. [PMID: 36455790 DOI: 10.1016/j.arr.2022.101812] [Citation(s) in RCA: 36] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 11/24/2022] [Accepted: 11/25/2022] [Indexed: 11/30/2022]
Abstract
The microbiota-gut-brain axis or simple gut-brain axis (GBA) is a complex and interactive bidirectional communication network linking the gut to the brain. Alterations in the composition of the gut microbiome have been linked to GBA dysfunction, central nervous system (CNS) inflammation, and dopaminergic degeneration, as those occurring in Parkinson's disease (PD). Besides inflammation, the activation of brain microglia is known to play a central role in the damage of dopaminergic neurons. Inflammation is attributed to the toxic effect of aggregated α-synuclein, in the brain of PD patients. It has been suggested that the α-synuclein misfolding might begin in the gut and spread "prion-like", via the vagus nerve into the lower brainstem and ultimately to the midbrain, known as the Braak hypothesis. In this review, we discuss how the microbiota-gut-brain axis and environmental influences interact with the immune system to promote a pro-inflammatory state that is involved in the initiation and progression of misfolded α-synuclein proteins and the beginning of the early non-motor symptoms of PD. Furthermore, we describe a speculative bidirectional model that explains how the enteric glia is involved in the initiation and spreading of inflammation, epithelial barrier disruption, and α-synuclein misfolding, finally reaching the central nervous system and contributing to neuroinflammatory processes involved with the initial non-motor symptoms of PD.
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Affiliation(s)
- Júlio César Claudino Dos Santos
- Medical School of the Christus University Center - UNICHRISTUS, Fortaleza, CE, Brazil; Graduate Program in Morphofunctional Sciences, Federal University of Ceará - UFC, Fortaleza, CE, Brazil.
| | | | - Gerly Anne de Castro Brito
- Physiology and Pharmacology Department of the Federal University of Ceará - UFC, Fortaleza, CE, Brazil; Morphology Department of the Federal University of Ceará - UFC, Fortaleza, CE, Brazil
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Salim S, Ahmad F, Banu A, Mohammad F. Gut microbiome and Parkinson's disease: Perspective on pathogenesis and treatment. J Adv Res 2022:S2090-1232(22)00242-9. [PMID: 36332796 PMCID: PMC10403695 DOI: 10.1016/j.jare.2022.10.013] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 09/26/2022] [Accepted: 10/26/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Parkinson's disease (PD) is a disease of ⍺-synuclein aggregation-mediated dopaminergic neuronal loss in the substantia nigra pars compacta, which leads to motor and non-motor symptoms. Through the last two decades of research, there has been growing consensus that inflammation-mediated oxidative stress, mitochondrial dysfunction, and cytokine-induced toxicity are mainly involved in neuronal damage and loss associated with PD. However, it remains unclear how these mechanisms relate to sporadic PD, a more common form of PD. Both enteric and central nervous systems have been implicated in the pathogenesis of sporadic PD, thus highlighting the crosstalk between the gut and brain. AIM of Review: In this review, we summarize how alterations in the gut microbiome can affect PD pathogenesis. We highlight various mechanisms increasing/decreasing the risk of PD development. Based on the previous supporting evidence, we suggest how early interventions could protect against PD development and how controlling specific factors, including our diet, could modify our perspective on disease mechanisms and therapeutics. We explain the strong relationship between the gut microbiota and the brain in PD subjects, by delineating the multiple mechanisms involved inneuroinflammation and oxidative stress. We conclude that the neurodetrimental effects of western diet (WD) and the neuroprotective effects of Mediterranean diets should be further exploredin humans through clinical trials. Key Scientific Concepts of Review: Alterations in the gut microbiome and associated metabolites may contribute to pathogenesis in PD. In some studies, probiotics have been shown to exert anti-oxidative effects in PD via improved mitochondrial dynamics and homeostasis, thus reducing PD-related consequences. However, there is a significant unmet need for randomized clinical trials to investigate the effectiveness of microbial products, probiotic-based supplementation, and dietary intervention in reversing gut microbial dysbiosis in PD.
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12
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Biazzo M, Allegra M, Deidda G. Clostridioides difficile and neurological disorders: New perspectives. Front Neurosci 2022; 16:946601. [PMID: 36203814 PMCID: PMC9530032 DOI: 10.3389/fnins.2022.946601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 08/24/2022] [Indexed: 12/02/2022] Open
Abstract
Despite brain physiological functions or pathological dysfunctions relying on the activity of neuronal/non-neuronal populations, over the last decades a plethora of evidence unraveled the essential contribution of the microbial populations living and residing within the gut, called gut microbiota. The gut microbiota plays a role in brain (dys)functions, and it will become a promising valuable therapeutic target for several brain pathologies. In the present mini-review, after a brief overview of the role of gut microbiota in normal brain physiology and pathology, we focus on the role of the bacterium Clostridioides difficile, a pathogen responsible for recurrent and refractory infections, in people with neurological diseases, summarizing recent correlative and causative evidence in the scientific literature and highlighting the potential of microbiota-based strategies targeting this pathogen to ameliorate not only gastrointestinal but also the neurological symptoms.
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Affiliation(s)
- Manuele Biazzo
- The BioArte Limited, Life Sciences Park, San Gwann, Malta
- SienabioACTIVE, University of Siena, Siena, Italy
| | - Manuela Allegra
- Neuroscience Institute, National Research Council (IN-CNR), Padua, Italy
| | - Gabriele Deidda
- Department of Biomedical Sciences, University of Padua, Padua, Italy
- *Correspondence: Gabriele Deidda
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Biazzo M, Deidda G. Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases. J Clin Med 2022; 11:jcm11144119. [PMID: 35887883 PMCID: PMC9320118 DOI: 10.3390/jcm11144119] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/08/2022] [Accepted: 07/12/2022] [Indexed: 02/01/2023] Open
Abstract
The human body is home to a variety of micro-organisms. Most of these microbial communities reside in the gut and are referred to as gut microbiota. Over the last decades, compelling evidence showed that a number of human pathologies are associated with microbiota dysbiosis, thereby suggesting that the reinstatement of physiological microflora balance and composition might ameliorate the clinical symptoms. Among possible microbiota-targeted interventions, pre/pro-biotics supplementations were shown to provide effective results, but the main limitation remains in the limited microbial species available as probiotics. Differently, fecal microbiota transplantation involves the transplantation of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient's gut microbial composition aiming to confer a health benefit. Firstly used in the 4th century in traditional Chinese medicine, nowadays, it has been exploited so far to treat recurrent Clostridioides difficile infections, but accumulating data coming from a number of clinical trials clearly indicate that fecal microbiota transplantation may also carry the therapeutic potential for a number of other conditions ranging from gastrointestinal to liver diseases, from cancer to inflammatory, infectious, autoimmune diseases and brain disorders, obesity, and metabolic syndrome. In this review, we will summarize the commonly used preparation and delivery methods, comprehensively review the evidence obtained in clinical trials in different human conditions and discuss the variability in the results and the pivotal importance of donor selection. The final aim is to stimulate discussion and open new therapeutic perspectives among experts in the use of fecal microbiota transplantation not only in Clostridioides difficile infection but as one of the first strategies to be used to ameliorate a number of human conditions.
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Affiliation(s)
- Manuele Biazzo
- The BioArte Limited, Life Sciences Park, Triq San Giljan, SGN 3000 San Gwann, Malta;
- SienabioACTIVE, University of Siena, Via Aldo Moro 1, 53100 Siena, Italy
| | - Gabriele Deidda
- Department of Biomedical Sciences, University of Padua, Via U. Bassi 58/B, 35131 Padova, Italy
- Correspondence: ; Tel.: +39-049-827-6125
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Chen C, Liang H, Wang J, Ren G, Li R, Cui ZG, Zhang C. Heterophyllin B an Active Cyclopeptide Alleviates Dextran Sulfate Sodium-induced Colitis by Modulating Gut Microbiota and Repairing Intestinal Mucosal Barrier via AMPK Activation. Mol Nutr Food Res 2022; 66:e2101169. [PMID: 35796402 DOI: 10.1002/mnfr.202101169] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 05/12/2022] [Indexed: 12/07/2022]
Abstract
SCOPE Advances in pathology broaden our perception of the intimate interaction between gut microbiota dysbiosis and the pathogenesis of ulcerative colitis (UC), but the potential modulating roles remain to be elucidated. METHODS AND RESULTS DSS-induced colitis was used to investigate the effect of Heterophyllin B (HB), a typical active cyclopeptide extracted from Pseudostellaria heterophylla, on colitis and gut microbiota. Administration of HB substantially mitigated the symptoms of UC as evidenced by increasing body weight and colon length, as well as decreased macrophages infiltration in the colon. Meanwhile, HB significantly alleviated intestinal mucosal barrier dysfunction by reducing the production of inflammatory cytokines, while all the mentioned beneficial effects were significantly eliminated by co-treatment with compound C, a selective AMPK inhibitor. In addition, 16S rDNA gene analyses and fecal microbiota transplantation also revealed that HB dramatically prevented against UC by reshaping intestinal dysbiosis, especially elevated the relative abundance of Akkermansia muciniphila. CONCLUSION These findings illustrated that HB prominently improved intestinal epithelial homeostasis via activating AMPK and ameliorated the colonic inflammation in a gut microbiota-dependent manner, which provide evidence for microbial contribution to UC pathogenesis and suggesting a novel approach for colitis prevention. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Ce Chen
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, China.,Sino-Jan Joint Lab of Natural Health Products Research, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, China
| | - Han Liang
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, China
| | - Jiaoyang Wang
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, China
| | - Guoqing Ren
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, China
| | - Renshi Li
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, China.,Sino-Jan Joint Lab of Natural Health Products Research, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, China
| | - Zheng-Guo Cui
- Department of Environmental Health, University of Fukui School of Medical Science, 23-3 Matsuoka Shimoaizuki, Eiheiji, Fukui, 910-1193, Japan
| | - Chaofeng Zhang
- State Key Laboratory of Natural Medicines, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, China.,Sino-Jan Joint Lab of Natural Health Products Research, School of Traditional Chinese Medicines, China Pharmaceutical University, Nanjing, China
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15
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Miri AH, Kamankesh M, Llopis-Lorente A, Liu C, Wacker MG, Haririan I, Asadzadeh Aghdaei H, Hamblin MR, Yadegar A, Rad-Malekshahi M, Zali MR. The Potential Use of Antibiotics Against Helicobacter pylori Infection: Biopharmaceutical Implications. Front Pharmacol 2022; 13:917184. [PMID: 35833028 PMCID: PMC9271669 DOI: 10.3389/fphar.2022.917184] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 05/31/2022] [Indexed: 11/13/2022] Open
Abstract
Helicobacter pylori (H. pylori) is a notorious, recalcitrant and silent germ, which can cause a variety of debilitating stomach diseases, including gastric and duodenal ulcers and gastric cancer. This microbe predominantly colonizes the mucosal layer of the human stomach and survives in the inhospitable gastric microenvironment, by adapting to this hostile milieu. In this review, we first discuss H. pylori colonization and invasion. Thereafter, we provide a survey of current curative options based on polypharmacy, looking at pharmacokinetics, pharmacodynamics and pharmaceutical microbiology concepts, in the battle against H. pylori infection.
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Affiliation(s)
- Amir Hossein Miri
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mojtaba Kamankesh
- Polymer Chemistry Department, School of Science, University of Tehran, Tehran, Iran
| | - Antoni Llopis-Lorente
- Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands
| | - Chenguang Liu
- College of Marine Life Science, Ocean University of China, Qingdao, China
| | - Matthias G. Wacker
- Department of Pharmacy, National University of Singapore, Singapore, Singapore
| | - Ismaeil Haririan
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran 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
| | - Michael R. Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mazda Rad-Malekshahi
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran 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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16
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Dong S, Sun M, He C, Cheng H. Brain-gut-microbiota axis in Parkinson's disease: a historical review and future perspective. Brain Res Bull 2022; 183:84-93. [PMID: 35245613 DOI: 10.1016/j.brainresbull.2022.02.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 02/15/2022] [Accepted: 02/22/2022] [Indexed: 01/03/2023]
Affiliation(s)
- Siyu Dong
- Department of Neurology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Mei Sun
- Department of Neurology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Chuan He
- Department of Rehabilitation Medicine, the Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou, 215228, China.
| | - Hong Cheng
- Department of Neurology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
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Watts AE, Sninsky JA, Richey MM, Donovan K, Dougherty MK, McGill SK. Family Stool Donation Predicts Failure of Fecal Microbiota Transplant for Clostridioides difficile Infection. GASTRO HEP ADVANCES 2022; 1:141-146. [PMID: 39131119 PMCID: PMC11307599 DOI: 10.1016/j.gastha.2021.11.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 11/15/2021] [Indexed: 08/13/2024]
Abstract
Background and Aims Fecal microbiota transplant (FMT) via colonoscopy is highly effective treatment for Clostridioides difficile infection (CDI). We aimed to determine baseline patient characteristics that predict failure to respond to colonoscopy-based FMT. Methods We evaluated adult patients who received FMT for CDI not responding to standard therapies at a single tertiary center between 2014 and 2018 in this retrospective cohort study. We defined clinical success as formed stool or C difficile-negative diarrhea at 2 months after FMT. If patients required a second FMT, follow-up was extended 2 months after repeat infusion. We performed multivariate logistic regression and a random forest model to identify variables predictive of response to FMT. Results Clinical success was attained in 87.3% of 103 patients who underwent FMT for CDI. In the multivariate model, the odds of FMT failure for family donation compared with stool bank were odds ratio 4.13 (1.00-7.01 P = .049). Diarrhea while taking anti-CDI antibiotics was common (37.8% of patients) and did not predict failure (odds ratio 0.64, 0.19-2.11 P = .46) in the univariate model. A machine learning model to predict response using clinical factors only achieved a sensitivity of 70%, specificity of 77%, and negative predictive value of 96%. Conclusion Colonoscopy-based FMT was highly effective for CDI, even in a population where immunosuppression and proton pump inhibitor use were common. Family stool donation was associated with FMT failure, compared with the use of a stool bank. The study suggests that the use of a stool bank may not only improve access to FMT but also its efficacy.
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Affiliation(s)
- Ariel E. Watts
- Division of Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
| | - Jared A. Sninsky
- Division of Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
| | - Morgan M. Richey
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Kevin Donovan
- Department of Biostatistics, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
| | - Michael K. Dougherty
- Division of Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
| | - Sarah K. McGill
- Division of Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina Chapel Hill, Chapel Hill, North Carolina
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18
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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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19
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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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20
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Deidda G, Biazzo M. Gut and Brain: Investigating Physiological and Pathological Interactions Between Microbiota and Brain to Gain New Therapeutic Avenues for Brain Diseases. Front Neurosci 2021; 15:753915. [PMID: 34712115 PMCID: PMC8545893 DOI: 10.3389/fnins.2021.753915] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 09/16/2021] [Indexed: 12/12/2022] Open
Abstract
Brain physiological functions or pathological dysfunctions do surely depend on the activity of both neuronal and non-neuronal populations. Nevertheless, over the last decades, compelling and fast accumulating evidence showed that the brain is not alone. Indeed, the so-called "gut brain," composed of the microbial populations living in the gut, forms a symbiotic superorganism weighing as the human brain and strongly communicating with the latter via the gut-brain axis. The gut brain does exert a control on brain (dys)functions and it will eventually become a promising valuable therapeutic target for a number of brain pathologies. In the present review, we will first describe the role of gut microbiota in normal brain physiology from neurodevelopment till adulthood, and thereafter we will discuss evidence from the literature showing how gut microbiota alterations are a signature in a number of brain pathologies ranging from neurodevelopmental to neurodegenerative disorders, and how pre/probiotic supplement interventions aimed to correct the altered dysbiosis in pathological conditions may represent a valuable future therapeutic strategy.
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Affiliation(s)
- Gabriele Deidda
- The BioArte Limited, Life Sciences Park, San Gwann, Malta
- Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
| | - Manuele Biazzo
- The BioArte Limited, Life Sciences Park, San Gwann, Malta
- SienabioACTIVE, University of Siena, Siena, Italy
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21
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Rinott E, Youngster I, Meir AY, Tsaban G, Kaplan A, Zelicha H, Rubin E, Koren O, Shai I. Autologous fecal microbiota transplantation can retain the metabolic achievements of dietary interventions. Eur J Intern Med 2021; 92:17-23. [PMID: 33883079 DOI: 10.1016/j.ejim.2021.03.038] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 03/24/2021] [Accepted: 03/26/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND We recently reported that autologous fecal microbiota transplantation (aFMT), derived from the time of maximal weight-loss and administrated in the regain-phase, might preserve weight loss and glycemic control in moderately obese subjects, and is associated with specific microbiome signatures. Here, we sought to explore the global effect of aFMT on adipokines, inflammatory markers and blood cholesterol and on the overall gut microbiome preservation. METHODS In the DIRECT-PLUS weight-loss trial, abdominally obese participants were randomized to three distinct weight-loss diets. Following the expected weight loss phase (0-6 m), 90 participants were randomized to receive their personal frozen fecal microbiota or placebo oral capsules (ten 1 g-capsules over ten sessions-total=100 g) during the expected weight regain phase (8-14 m). RESULTS Of the 90 participants (age=52 yr; 0-6 m weight loss=-8.3 kg), 95.6% ingested at least 80/100 oral aFMT/placebo capsules over 6 months. Overall, the gut microbiome community structure was associated with plasma levels of leptin, cholesterol and interleukin-6 at baseline and after 6 m, whereas 6 m (weight loss phase) changes in specific microbiome species associated with the dynamic of leptin and inflammatory biomarkers. Following the 8-14 m aFMT administration phase, aFMT maintained decreased levels of leptin (ΔaFMT=-3.54 ng/mL vs. Δplacebo=-0.82 ng/mL;P = 0.04), C-reactive-protein (ΔaFMT=-1.45 mg/L vs. Δplacebo=-0.66 mg/L;P = 0.009), Interleukin-6 (ΔaFMT=-0.03pg/mL vs. Δplacebo=1.11pg/mL;P = 0.03) and total cholesterol (ΔaFMT=2.2 mg/dl vs. Δplacebo=13.1 mg/dl;P = 0.04) achieved in the weight loss phase. Overall, aFMT induced a significant preservatory effect on personal gut microbiome global composition (P = 0.03;Jensen-Shannon distance), as compared to placebo. CONCLUSIONS aFMT treatment in the regain phase might retain weight-loss induced metabolic benefits. These findings may suggest a novel aFMT treatment approach for personal metabolic attainment preservation.
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Affiliation(s)
- Ehud Rinott
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Ilan Youngster
- Pediatric Division and Center for Microbiome Research, Shamir Medical Center, Be'er Ya'akov, Israel; Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Anat Yaskolka Meir
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Gal Tsaban
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Alon Kaplan
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Hila Zelicha
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Elad Rubin
- Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Omry Koren
- Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel
| | - Iris Shai
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
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22
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Wang Q, Luo Y, Chaudhuri KR, Reynolds R, Tan EK, Pettersson S. The role of gut dysbiosis in Parkinson's disease: mechanistic insights andtherapeutic options. Brain 2021; 144:2571-2593. [PMID: 33856024 DOI: 10.1093/brain/awab156] [Citation(s) in RCA: 148] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 01/23/2021] [Accepted: 03/23/2021] [Indexed: 12/02/2022] Open
Abstract
Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.
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Affiliation(s)
- Qing Wang
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China
| | - Yuqi Luo
- Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China
| | - K Ray Chaudhuri
- Parkinson Foundation International Centre of Excellence at King's College Hospital, and Kings College, Denmark Hill, London, SE5 9RS, UK
| | - Richard Reynolds
- Department of Brain Sciences, Imperial College London, Hammersmith Hospital Campus, Burlington Danes Building, Du Cane Road, London, W12 0NN, UK.,Centre for Molecular Neuropathology, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232
| | - Eng-King Tan
- Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore.,Duke-NUS Medical School, Singapore
| | - Sven Pettersson
- Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore.,Duke-NUS Medical School, Singapore.,LKC School of Medicine, NTU, Singapore.,Sunway University, Department of Medical Sciences, Kuala Lumpur, Malaysia
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23
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Mehta SR, Yen EF. Microbiota-based Therapies Clostridioides difficile infection that is refractory to antibiotic therapy. Transl Res 2021; 230:197-207. [PMID: 33278650 DOI: 10.1016/j.trsl.2020.11.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 11/05/2020] [Accepted: 11/29/2020] [Indexed: 11/27/2022]
Abstract
Clostridioides difficile infection (CDI) has had a devastating impact worldwide with significant rates of mortality, especially among the elderly. Despite effective antibiotics, the incidence of recurrent CDI (rCDI) is increasing and more difficult to treat with antibiotics alone. Fecal Microbiota Transplantation (FMT) has emerged as a consistently effective treatment for rCDI. Mechanisms for FMT are not entirely understood, but remain an area of active investigation. There have been recent safety reports with the use of FMT regarding transmission of pathogens in a few patients that have led to serious illness. With appropriate screening, FMT can be safely administered and continue to have a significant impact on eradication of rCDI and improve the lives of patients suffering from this disease. In this review, we summarize current treatments for CDI with a focus on microbiota-based therapies used for antibiotic refractory disease.
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Affiliation(s)
- Shama R Mehta
- NorthShore University HealthSystem, Division of Gastroenterology, 2650 Ridge Avenue, Suite G221, Evanston, IL 60201
| | - Eugene F Yen
- NorthShore University HealthSystem, Division of Gastroenterology, 2650 Ridge Avenue, Suite G221, Evanston, IL 60201.
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24
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Chen ZJ, Liang CY, Yang LQ, Ren SM, Xia YM, Cui L, Li XF, Gao BL. Association of Parkinson's Disease With Microbes and Microbiological Therapy. Front Cell Infect Microbiol 2021; 11:619354. [PMID: 33763383 PMCID: PMC7982661 DOI: 10.3389/fcimb.2021.619354] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Accepted: 01/28/2021] [Indexed: 12/11/2022] Open
Abstract
Parkinson's disease (PD) is the most common movement disorder in the world, affecting 1-2 per 1,000 of the population. The main pathological changes of PD are damage of dopaminergic neurons in substantia nigra of the central nervous system and formation of Lewy bodies. These pathological changes also occur in the intestinal tract and are strongly associated with changes in intestinal flora. By reviewing the research progress in PD and its association with intestinal flora in recent years, this review expounded the mechanism of action between intestinal flora and PD as well as the transmission mode of α - synuclein in neurons. In clinical studies, β diversity of intestinal flora in PD patients was found to change significantly, with Lactobacillusaceae and Verrucomicrobiaceae being significantly increased and Lachnospiraceae and Prevotellaceae being significantly decreased. In addition, a longer PD course was associated with fewer bacteria and probiotics producing short chain fatty acids, but more pathogenic bacteria. Moreover, the motor symptoms of PD patients may be related to Enterobacteriaceae and bacteria. Most importantly, catechol-O-methyltransferase inhibitors and anticholinergic drugs could change the intestinal flora of PD patients and increase the harmful flora, whereas other anti-PD drugs such as levodopa, dopamine agonist, monoamine oxidase inhibitors, and amantadine did not have these effects. Probiotics, prebiotics, and synbiotics treatment had some potential values in improving the constipation of PD patients, promoting the growth of probiotics, and improving the level of intestinal inflammation. At present, there were only a few case studies and small sample studies which have found certain clinical efficacy of fecal microbiome transplants. Further studies are necessary to elaborate the relationship of PD with microbes.
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Affiliation(s)
- Zhao-Ji Chen
- Department of Neurology, Affiliated Hospital of Hebei University, Baoding, China
| | - Cheng-Yu Liang
- Department of Neurology, Affiliated Hospital of Hebei University, Baoding, China
| | - Li-Qing Yang
- Department of Neurology, Affiliated Hospital of Hebei University, Baoding, China
| | - Si-Min Ren
- Department of Neurology, Affiliated Hospital of Hebei University, Baoding, China
| | - Yan-Min Xia
- Department of Neurology, Affiliated Hospital of Hebei University, Baoding, China
| | - Lei Cui
- Department of Neurology, Affiliated Hospital of Hebei University, Baoding, China
| | - Xiao-Fang Li
- Department of Neurology, Affiliated Hospital of Hebei University, Baoding, China
| | - Bu-Lang Gao
- Department of Neurology, Affiliated Hospital of Hebei University, Baoding, China
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Liu C, Huang S, Wu Z, Li T, Li N, Zhang B, Han D, Wang S, Zhao J, Wang J. Cohousing-mediated microbiota transfer from milk bioactive components-dosed mice ameliorate colitis by remodeling colonic mucus barrier and lamina propria macrophages. Gut Microbes 2021; 13:1-23. [PMID: 33789528 PMCID: PMC8018355 DOI: 10.1080/19490976.2021.1903826] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 03/07/2021] [Accepted: 03/09/2021] [Indexed: 02/08/2023] Open
Abstract
Human milk oligosaccharides (HMOs) and milk fat globule membrane (MFGM) are highly abundant in breast milk, and have been shown to exhibit potent immunomodulatory effects. Yet, their role in the gut microbiota modulation in relation to colitis remains understudied. Since the mixtures of fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS) perfectly mimic the properties and functions of HMOs, the combination of MFGM, FOS, and GOS (CMFG) has therefore been developed and used in this study. Here, CMFG were pre-fed to mice for three weeks to investigate its preventive effect on dextran sodium sulfate (DSS) induced colitis. Moreover, CMFG-treated and vehicle-treated mice were cohoused to further elucidate the preventive role of the gut microbiota transfer in colitis. At the end of the study, 16S rDNA gene amplicon sequencing, short-chain fatty acids (SCFAs) profiling, transcriptome sequencing, histological analysis, immunofluorescence staining and flow cytometry analysis were conducted. Our results showed that CMFG pre-supplementation alleviated DSS-induced colitis as evidenced by decreased disease activity index (DAI) score, reduced body weight loss, increased colon length and mucin secretion, and ameliorated intestinal damage. Moreover, CMFG reduced macrophages in the colon, resulting in decreased levels of IL-1β, IL-6, IL-8, TNF-α, and MPO in the colon and circulation. Furthermore, CMFG altered the gut microbiota composition and promoted SCFAs production in DSS-induced colitis. Markedly, the cohousing study revealed that transfer of gut microbiota from CMFG-treated mice largely improved the DSS-induced colitis as evidenced by reduced intestinal damage and decreased macrophages infiltration in the colon. Moreover, transfer of the gut microbiota from CMFG-treated mice protected against DSS-induced gut microbiota dysbiosis and promotes SCFAs production, which showed to be associated with colitis amelioration. Collectively, these findings demonstrate the beneficial role of CMFG in the gastrointestinal diseases, and further provide evidence for the rational design of effective prophylactic functional diets in both animals and humans.
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Affiliation(s)
- Cong Liu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shimeng Huang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Zhenhua Wu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Tiantian Li
- Academy of National Food and Strategic Reserves Administration, Beijing, China
| | - Na Li
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Bing Zhang
- Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Dandan Han
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shilan Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Jiangchao Zhao
- Department of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, AR, USA
| | - Junjun Wang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
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Oddi S, Huber P, Rocha Faria Duque AL, Vinderola G, Sivieri K. Breast-milk derived potential probiotics as strategy for the management of childhood obesity. Food Res Int 2020; 137:109673. [PMID: 33233250 DOI: 10.1016/j.foodres.2020.109673] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 08/10/2020] [Accepted: 09/06/2020] [Indexed: 12/18/2022]
Abstract
Obesity and overweight, and their concomitant metabolic diseases, emerge as one of the most severe health problems in the world. Prevention and management of obesity are proposed to begin early in childhood, when probiotics may have a role. The Simulator of the Human Intestinal Microbial Ecosystem (SHIME®), in a dynamic validated in vitro system able to simulate the different parts of the gastrointestinal tract, has proven to be useful in analyzing the human intestinal microbial community. L. plantarum 73a and B. animalis subsp. lactis INL1, two strains isolated from breast milk, were assayed in the SHIME® using the fecal microbiota of an obese child. L. plantarum 73a alone or in combination with B. animalis subsp. lactis INL1 demonstrated survival capacity in the SHIME® system. The administration of both strains increased the alpha diversity of the microbiota and reduced the levels of the phylum Proteobacteria. In particular, the genera Escherichia, Shigella, and Clostridium_sensu_stricto_1 were significantly reduced when both strains were administered. The increase of Proteobacteria phylum is generally associated with the microbiota of obese people. Escherichia and Shigellacan be involved in inflammation-dependent adiposity and insulin resistance. L. plantarum73a supplementation reduced ammonia production. L. plantarum 73a alone or in combination with B. animalis subsp. lactis INL1 are potential probiotic candidates for the management of infant obesity.
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Affiliation(s)
- S Oddi
- Instituto de Lactología Industrial (INLAIN, UNL-CONICET), Facultad de Ingeniería Química, Universidad Nacional del Litoral, Santa Fe, Argentina
| | - P Huber
- Laboratorio de Plancton, Instituto Nacional de Limnología (INALI, UNL-CONICET), Universidad Nacional del Litoral, Santa Fe, Argentina
| | - A L Rocha Faria Duque
- Department of Food and Nutrition, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 9 SP 14800-903, Brazil
| | - G Vinderola
- Instituto de Lactología Industrial (INLAIN, UNL-CONICET), Facultad de Ingeniería Química, Universidad Nacional del Litoral, Santa Fe, Argentina.
| | - K Sivieri
- Department of Food and Nutrition, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 9 SP 14800-903, Brazil
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Emerging role of microbiota in immunomodulation and cancer immunotherapy. Semin Cancer Biol 2020; 70:37-52. [PMID: 32580024 DOI: 10.1016/j.semcancer.2020.06.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 06/11/2020] [Accepted: 06/11/2020] [Indexed: 02/08/2023]
Abstract
Gut microbiota is emerging as a key modulator of the immune system. Alteration of gut microbiota impacts functioning of the immune system and pathophysiology of several diseases, including cancer. Growing evidence indicates that gut microbiota is not only involved in carcinogenesis but also has an impact on the efficacy and toxicity of cancer therapy. Recently, several pre-clinical and clinical studies across diverse cancer types reported the influence of gut microbiota on the host immune response to immunotherapy. Advancement in our understanding of the mechanism behind microbiota-mediated modulation of immune response is paramount for their utilization as cancer therapeutics. These microbial therapies in combination with conventional immunotherapeutic methods have the potential to transform the pre-existing treatment strategies to personalized cancer therapy. In this review, we have summarized the current status of research in the field and discussed the role of microbiota as an immune system modulator in context of cancer and their impact on immunotherapy.
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Chen L, Zhang L, Wang W, Qiu W, Liu L, Ning A, Cao J, Huang M, Zhong M. Polysaccharides isolated from Cordyceps Sinensis contribute to the progression of NASH by modifying the gut microbiota in mice fed a high-fat diet. PLoS One 2020; 15:e0232972. [PMID: 32512581 PMCID: PMC7279895 DOI: 10.1371/journal.pone.0232972] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 04/24/2020] [Indexed: 02/07/2023] Open
Abstract
Various dietary fibers are considered to prevent obesity by modulating the gut microbiota. Cordyceps sinensis polysaccharide (CSP) is a soluble dietary fiber known to have protective effects against obesity and related diseases, but whether these effects induce any side effects remains unknown. The function and safety of CSP were tested in high-fat diet (HFD)-feding C57BL/6J mice. The results revealed that even though CSP supplementation could prevent an increase in body weight, it aggravated liver fibrosis and steatosis as evidenced by increased inflammation, lipid metabolism markers, insulin resistance (IR) and alanine aminotransferase (ALT) in HFD-induced obesity. 16S rDNA gene sequencing was used to analyze the gut microbiota composition, and the relative abundance of the Actinobacteria phylum, including the Olsenella genus, was significantly higher in CSP-treated mice than in HFD-fed mice. CSP supplementation may increase the proportion of Actinobacteria, which can degrade CSP. The high level of Actinobacteria aggravated the disorder of the intestinal flora and contributed to the progression from obesity to nonalcoholic steatohepatitis (NASH) and related diseases.
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Affiliation(s)
- Lei Chen
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China
| | - Liangyu Zhang
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China
| | - Wendong Wang
- First Affiliated Hospital of Dalian Medical University, Dalian, PR China
| | - Wei Qiu
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China
| | - Lei Liu
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China
| | - Anhong Ning
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China
| | - Jing Cao
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China
| | - Min Huang
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China
| | - Mintao Zhong
- Department of Microbiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, PR China
- * E-mail:
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Quyushengxin Formula Causes Differences in Bacterial and Phage Composition in Ulcerative Colitis Patients. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:5859023. [PMID: 32454865 PMCID: PMC7240791 DOI: 10.1155/2020/5859023] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 02/24/2020] [Accepted: 03/13/2020] [Indexed: 12/14/2022]
Abstract
Background Ulcerative colitis (UC) is a chronic inflammatory disease that affects the colon and the rectum. Recently, some studies have shown that microorganisms in the gut play important roles in many chronic diseases such as UC. Methods To study the candidate viruses and bacteria involved in UC and to investigate the therapeutic mechanism of Quyushengxin formula (QYSX) in UC patients, metagenomic sequencing was performed on the feces from healthy donors and UC patients before and after QYSX treatment. Results QYSX improved the symptoms of UC. In all participants, Caudovirales and Herpesvirales were the most dominant viruses. The abundance of Caudovirales in UC patients was significantly higher than that in the normal controls, while QYSX restored Caudovirales abundance. Furthermore, the abundance of crAssphage was enhanced in UC patients compared with the normal control, while the diversity was then decreased after QYSX treatment. However, there was no significant difference (P > 0.05). Additionally, other non-crAssphage bacteriophages including phiST, SP-10, and phi17:2 were higher in UC patients and QYSX decreased these viruses, while the trends of MED4−213, P-HM1, and P−HM2 were adverse. Interestingly, PhiDP23.1 was only found in UC patients before and after QYSX treatment. In addition, Bifidobacterium, Bacteroidetes, Prevotellaceae, Actinobacteria, and Corynebacteriales were the biomarkers in UC patients after QYSX treatment due to their high abundance. GO terms and KEGG analysis showed that the identified gut microbiome was involved in many biological processes and pathways. Conclusions QYSX could regulate disordered gut microbiome and phages, indicating that QYSX has great therapeutic potential for UC.
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Abstract
Although the gut and brain are separate organs, they communicate with each other via trillions of intestinal bacteria that collectively make up one's gut microbiome. Findings from both humans and animals support a critical role of gut microbes in regulating brain function, mood, and behavior. Gut bacteria influence neural circuits that are notably affected in addiction-related behaviors. These include circuits involved in stress, reward, and motivation, with substance use influencing gut microbial abnormalities, suggesting significant gut-brain interactions in drug addiction. Given the overwhelming rates of opioid overdose deaths driven by abuse and addiction, it is essential to characterize mechanisms mediating the abuse potential of opioids. We discuss in this review the role of gut microbiota in factors that influence opioid addiction, including incentive salience, reward, tolerance, withdrawal, stress, and compromised executive function. We present clinical and preclinical evidence supporting a bidirectional relationship between gut microbiota and opioid-related behaviors by highlighting the effects of opioid use on gut bacteria, and the effects of gut bacteria on behavioral responses to opioids. Further, we discuss possible mechanisms of this gut-brain communication influencing opioid use. By clarifying the relationship between the gut microbiome and opioid-related behaviors, we improve understanding on mechanisms mediating reward-, motivation-, and stress-related behaviors and disorders, which may contribute to the development of effective, targeted therapeutic interventions in opioid dependence and addiction.
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Affiliation(s)
- Michelle Ren
- Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, USA,
| | - Shahrdad Lotfipour
- Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, USA,
- Department of Emergency Medicine, School of Medicine, University of California, Irvine, Irvine, CA, USA,
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Lv Q, Yang A, Shi W, Chen F, Liu Y, Liu Y, Wang D. Calcipotriol and iBRD9 reduce obesity in Nur77 knockout mice by regulating the gut microbiota, improving intestinal mucosal barrier function. Int J Obes (Lond) 2020; 44:1052-1061. [PMID: 32203112 PMCID: PMC7188666 DOI: 10.1038/s41366-020-0564-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 02/26/2020] [Accepted: 03/04/2020] [Indexed: 12/26/2022]
Abstract
Objective The orphan nuclear receptor Nur77 is an important factor regulating metabolism. Nur77 knockout mice become obese with age, but the cause of obesity in these mice has not been fully ascertained. We attempted to explain the cause of obesity in Nur77 knockout mice from the perspective of the gut microbiota and to investigate the inhibitory effect of calcipotriol combined with BRD9 inhibitor (iBRD9) on obesity. Methods Eight-week-old wild-type mice and Nur77 knockout C57BL/6J mice were treated with calcipotriol combined with iBRD9 for 12 weeks. Mouse feces were collected and the gut microbiota was assessed by analyzing 16S rRNA gene sequences. The bacterial abundance difference was analyzed, and the intestinal mucosal tight junction protein, antimicrobial peptide, and inflammatory cytokine mRNA levels of the colon and serum LPS and inflammatory cytokine levels were measured. Results Calcipotriol combined with iBRD9 treatment reduced the body weight and body fat percentage in Nur77 knockout mice. In the gut microbiota of Nur77 knockout mice, the relative abundances of Lachnospiraceae and Prevotellaceae decreased, and Rikenellaceae increased; while Rikenellaceae decreased after treatment (p < 0.05). Correspondingly, the mRNA levels of intestinal mucosal tight junction proteins (occludin (Ocln), claudin3 (Cldn3)) in the colons of Nur77 knockout mice were significantly decreased, and they increased significantly after treatment (p < 0.001). The mRNA levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β)) were significantly increased in Nur77 knockout mice, and TNF-α and IL-6 levels were significantly decreased after treatment (p < 0.05, <0.01, or <0.001). The levels of serum LPS, TNF-α, and IL-1β in Nur77 knockout mice were significantly increased (p < 0.05). Serum LPS, TNF-α, and IL-6 levels were significantly decreased after treatment (p < 0.05 or <0.01). Conclusions Calcipotriol combined with iBRD9 can regulate the gut microbiota, improve intestinal mucosal barrier function, reduce LPS absorption into the blood, and alleviate obesity in Nur77 knockout mice.
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Affiliation(s)
- Qingqing Lv
- Nutrition Department, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Aolin Yang
- Nutrition Department, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Wanying Shi
- Nutrition Department, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Feng Chen
- Department of Geriatric Endocrinology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yixuan Liu
- Department of Geriatric Endocrinology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Ying Liu
- Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning, China
| | - Difei Wang
- Department of Geriatric Endocrinology, The First Hospital of China Medical University, Shenyang, Liaoning, China.
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Singh SP, Chand HS, Banerjee S, Agarwal H, Raizada V, Roy S, Sopori M. Acetylcholinesterase Inhibitor Pyridostigmine Bromide Attenuates Gut Pathology and Bacterial Dysbiosis in a Murine Model of Ulcerative Colitis. Dig Dis Sci 2020; 65:141-149. [PMID: 31643033 PMCID: PMC6943409 DOI: 10.1007/s10620-019-05838-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Accepted: 09/10/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) is a Th2 inflammatory bowel disease characterized by increased IL-5 and IL-13 expression, eosinophilic/neutrophilic infiltration, decreased mucus production, impaired epithelial barrier, and bacterial dysbiosis of the colon. Acetylcholine and nicotine stimulate mucus production and suppress Th2 inflammation through nicotinic receptors in lungs but UC is rarely observed in smokers and the mechanism of the protection is unclear. METHODS In order to evaluate whether acetylcholine can ameliorate UC-associated pathologies, we employed a mouse model of dextran sodium sulfate (DSS)-induced UC-like conditions, and a group of mice were treated with Pyridostigmine bromide (PB) to increase acetylcholine availability. The effects on colonic tissue morphology, Th2 inflammatory factors, MUC2 mucin, and gut microbiota were analyzed. RESULTS DSS challenge damaged the murine colonic architecture, reduced the MUC2 mucin and the tight-junction protein ZO-1. The PB treatment significantly attenuated these DSS-induced responses along with the eosinophilic infiltration and the pro-Th2 inflammatory factors. Moreover, PB inhibited the DSS-induced loss of commensal Clostridia and Flavobacteria, and the gain of pathogenic Erysipelotrichia and Fusobacteria. CONCLUSIONS Together, these data suggest that in colons of a murine model, PB promotes MUC2 synthesis, suppresses Th2 inflammation and attenuates bacterial dysbiosis therefore, PB has a therapeutic potential in UC.
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Affiliation(s)
- Shashi P Singh
- Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr SE, Albuquerque, NM, 87108, USA
| | - Hitendra S Chand
- Department of Immunology and Nano-Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, 33199, USA
| | - Santanu Banerjee
- Department of Surgery and Sylvester Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, 33101, USA
| | - Hemant Agarwal
- University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA
| | - Veena Raizada
- University of New Mexico Health Sciences Center, Albuquerque, NM, 87131, USA
| | - Sabita Roy
- Department of Surgery and Sylvester Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, 33101, USA
| | - Mohan Sopori
- Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr SE, Albuquerque, NM, 87108, USA.
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Yahiro T, Hara T, Matsumoto T, Ikebe E, Fife-Koshinomi N, Xu Z, Hiratsuka T, Iha H, Inomata M. Long-Term Potable Effects of Alkalescent Mineral Water on Intestinal Microbiota Shift and Physical Conditioning. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2019; 2019:2710587. [PMID: 31827547 PMCID: PMC6885775 DOI: 10.1155/2019/2710587] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/20/2019] [Revised: 09/03/2019] [Accepted: 10/01/2019] [Indexed: 12/20/2022]
Abstract
BACKGROUND An alkalescent (pH 8.3) mineral water (AMW) of Hita basin, located in the northwestern part of Kyushu island in Japan, has been recognized for the unique quality of ingredients including highly concentrated silicic acid, sodium, potassium, and hydrogen carbonate. The biological effects of AMW intake were evaluated with a particular focus on its "antiobesity" properties through its modulation of the gut microbiota population. METHODS Two groups of C57BL6/J mice (8-week-old male) were maintained with a standard diet and tap water (control: TWC group) or AMW (AMW group) for 6 months and the following outputs were quantitated: (1) food and water intake, (2) body weight (weekly), (3) body fat measurements by CT scan (monthly), (4) sera biochemical values (TG, ALT, AST, and ALP), and (5) UCP-1 mRNA in fat tissues (terminal point). Two groups of ICR mice (7-week-old male) were maintained with the same method and their feces were collected at the 0, 1st, 3rd, and 6th month at which time the population rates of gut microbiota were quantitated using metagenomic sequencing analysis of 16S-rRNA. RESULTS Among all antiobesity testing items, even though a weekly dietary consumption was increased (p=0.012), both ratios of weight gain (p=1.21E - 10) and visceral fat accumulation (p=0.029) were significantly reduced in the AMW group. Other criteria including water intake (p=0.727), the amounts of total (p=0.1602), and subcutaneous fat accumulation (p=0.052) were within the margin of error and UCP-1 gene expression level (p=0.171) in the AMW group was 3.89-fold higher than that of TWC. Among 8 major gut bacteria families, Lactobacillaceae (increased, p=0.029) and Clostridiaceae (decreased, p=0.029) showed significant shift in the whole population. CONCLUSION We observed significantly reduced (1) weight gaining ratio (average -1.86%, up to -3.3%), (2) visceral fat accumulation ratio (average -4.30%, up to -9.1%), and (3) changes in gut microbiota population. All these consequences could support the "health benefit" functionality of AMW.
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Affiliation(s)
- Takaaki Yahiro
- Department of Microbiology, Oita University Faculty of Medicine, Oita, Japan
- Department of Pathology, Tsurumi Hospital, Beppu, Oita, Japan
| | - Takao Hara
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan
| | - Takashi Matsumoto
- Department of Microbiology, Oita University Faculty of Medicine, Oita, Japan
| | - Emi Ikebe
- Department of Microbiology, Oita University Faculty of Medicine, Oita, Japan
| | | | - Zhaojun Xu
- Environmental Medicine Research Center, Quanzhou Medical College, Quanzhou, Fujian 362011, China
| | - Takahiro Hiratsuka
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan
| | - Hidekatsu Iha
- Department of Microbiology, Oita University Faculty of Medicine, Oita, Japan
| | - Masafumi Inomata
- Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan
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Gazerani P. Probiotics for Parkinson's Disease. Int J Mol Sci 2019; 20:E4121. [PMID: 31450864 PMCID: PMC6747430 DOI: 10.3390/ijms20174121] [Citation(s) in RCA: 100] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 08/14/2019] [Accepted: 08/21/2019] [Indexed: 02/08/2023] Open
Abstract
Parkinson's disease (PD) is a complex neurological disorder classically characterized by impairments in motor system function associated with loss of dopaminergic neurons in the substantia nigra. After almost 200 years since the first description of PD by James Parkinson, unraveling the complexity of PD continues to evolve. It is now recognized that an interplay between genetic and environmental factors influences a diverse range of cellular processes, reflecting on other clinical features including non-motor symptoms. This has consequently highlighted the extensive value of early clinical diagnosis to reduce difficulties of later stage management of PD. Advancement in understanding of PD has made remarkable progress in introducing new tools and strategies such as stem cell therapy and deep brain stimulation. A link between alterations in gut microbiota and PD has also opened a new line. Evidence exists of a bidirectional pathway between the gastrointestinal tract and the central nervous system. Probiotics, prebiotics and synbiotics are being examined that might influence gut-brain axis by altering gut microbiota composition, enteric nervous system, and CNS. This review provides status on use of probiotics for PD. Limitations and future directions will also be addressed to promote further research considering use of probiotics for PD.
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Affiliation(s)
- Parisa Gazerani
- Biomedicine: Department of Health Science and Technology, Faculty of Medicine, Aalborg University，Frederik Bajers Vej 3B, 9220 Aalborg East, Denmark.
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Yang J, Yang H. Non-antibiotic therapy for Clostridioides difficile infection: a review. Crit Rev Clin Lab Sci 2019; 56:493-509. [PMID: 31411909 DOI: 10.1080/10408363.2019.1648377] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Clostridioides difficile infection (CDI) is a common infectious disease that is mainly caused by antibiotics. Antibiotic therapy is still the dominant treatment for CDI, although it is accompanied by side effects. Probiotics, fecal microbiota transplantation (FMT), engineered microorganisms, bacteriophages, diet, natural active substances, nanoparticles and compounds are examples of emerging non-antibiotic therapies that have received a great amount of attention. In this review, we collected data about different non-antibiotic therapies for CDI and provided a comprehensive analysis and detailed comparison of these therapies. The mechanism of action, therapeutic efficacy, and the strengths and weaknesses of these non-antibiotic therapies have been investigated to provide a basis for the reasonable alternative of non-antibiotic therapies for CDI. In summary, probiotics and FMT are currently the best choice for non-antibiotic therapy for CDI.
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Affiliation(s)
- Jingpeng Yang
- State Key Laboratory of Microbial Metabolism, and School of Life Science & Biotechnology, Shanghai Jiao Tong University , Shanghai , China
| | - Hong Yang
- State Key Laboratory of Microbial Metabolism, and School of Life Science & Biotechnology, Shanghai Jiao Tong University , Shanghai , China
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Moderate Traumatic Brain Injury Alters the Gastrointestinal Microbiome in a Time-Dependent Manner. Shock 2019; 52:240-248. [DOI: 10.1097/shk.0000000000001211] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Zhou Y, Xu H, Huang H, Li Y, Chen H, He J, Du Y, Chen Y, Zhou Y, Nie Y. Are There Potential Applications of Fecal Microbiota Transplantation beyond Intestinal Disorders? BIOMED RESEARCH INTERNATIONAL 2019; 2019:3469754. [PMID: 31467881 PMCID: PMC6699279 DOI: 10.1155/2019/3469754] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 06/04/2019] [Accepted: 06/17/2019] [Indexed: 02/07/2023]
Abstract
Intestinal microbial dysbiosis is associated with various intestinal and extraintestinal disorders. Fecal microbiota transplantation (FMT), a type of fecal bacteriotherapy, is considered an effective therapeutic option for recurrent Clostridium difficile infection (rCDI) and also has important value in other intestinal diseases including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). The purpose of this review is to discuss promising therapeutic value in extraintestinal diseases associated with gut microbial dysbiosis, including liver, metabolic, chronic kidney, neuropsychiatric, allergic, autoimmune, and hematological diseases as well as tumors.
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Affiliation(s)
- Youlian Zhou
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Haoming Xu
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Hongli Huang
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Yingfei Li
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Huiting Chen
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Jie He
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Yanlei Du
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Ye Chen
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
| | - Yongjian Zhou
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
| | - Yuqiang Nie
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510180, China
- Department of Gastroenterology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, China
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Giau VV, Lee H, An SSA, Hulme J. Recent advances in the treatment of C. difficile using biotherapeutic agents. Infect Drug Resist 2019; 12:1597-1615. [PMID: 31354309 PMCID: PMC6579870 DOI: 10.2147/idr.s207572] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2019] [Accepted: 05/03/2019] [Indexed: 12/12/2022] Open
Abstract
Clostridium difficile (C. difficile) is rapidly becoming one of the most prevalent health care–associated bacterial infections in the developed world. The emergence of new, more virulent strains has led to greater morbidity and resistance to standard therapies. The bacterium is readily transmitted between people where it can asymptomatically colonize the gut environment, and clinical manifestations ranging from frequent watery diarrhea to toxic megacolon can arise depending on the age of the individual or their state of gut dysbiosis. Several inexpensive approaches are shown to be effective against virulent C. difficile in research settings such as probiotics, fecal microbiota transfer and immunotherapies. This review aims to highlight the current advantages and limitations of the aforementioned approaches with an emphasis on recent studies.
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Affiliation(s)
- Vo Van Giau
- Department of BioNano Technology, Gachon University, Seongnam-si 461-701, Republic of Korea
| | - Hyon Lee
- Department of Neurology, Gachon University Gil Medical Center, Incheon, South Korea
| | - Seong Soo A An
- Department of BioNano Technology, Gachon University, Seongnam-si 461-701, Republic of Korea
| | - John Hulme
- Department of BioNano Technology, Gachon University, Seongnam-si 461-701, Republic of Korea
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Álvarez-Mercado AI, Navarro-Oliveros M, Robles-Sánchez C, Plaza-Díaz J, Sáez-Lara MJ, Muñoz-Quezada S, Fontana L, Abadía-Molina F. Microbial Population Changes and Their Relationship with Human Health and Disease. Microorganisms 2019; 7:68. [PMID: 30832423 PMCID: PMC6463060 DOI: 10.3390/microorganisms7030068] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 02/26/2019] [Accepted: 02/27/2019] [Indexed: 12/11/2022] Open
Abstract
Specific microbial profiles and changes in intestinal microbiota have been widely demonstrated to be associated with the pathogenesis of a number of extra-intestinal (obesity and metabolic syndrome) and intestinal (inflammatory bowel disease) diseases as well as other metabolic disorders, such as non-alcoholic fatty liver disease and type 2 diabetes. Thus, maintaining a healthy gut ecosystem could aid in avoiding the early onset and development of these diseases. Furthermore, it is mandatory to evaluate the alterations in the microbiota associated with pathophysiological conditions and how to counteract them to restore intestinal homeostasis. This review highlights and critically discusses recent literature focused on identifying changes in and developing gut microbiota-targeted interventions (probiotics, prebiotics, diet, and fecal microbiota transplantation, among others) for the above-mentioned pathologies. We also discuss future directions and promising approaches to counteract unhealthy alterations in the gut microbiota. Altogether, we conclude that research in this field is currently in its infancy, which may be due to the large number of factors that can elicit such alterations, the variety of related pathologies, and the heterogeneity of the population involved. Further research on the effects of probiotics, prebiotics, or fecal transplantations on the composition of the human gut microbiome is necessary.
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Affiliation(s)
- Ana Isabel Álvarez-Mercado
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain.
- Institute of Nutrition and Food Technology "José Mataix," Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain.
| | - Miguel Navarro-Oliveros
- Institute of Nutrition and Food Technology "José Mataix," Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain.
| | - Cándido Robles-Sánchez
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain.
- Institute of Nutrition and Food Technology "José Mataix," Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain.
| | - Julio Plaza-Díaz
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain.
- Institute of Nutrition and Food Technology "José Mataix," Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain.
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain.
| | - María José Sáez-Lara
- Department of Biochemistry and Molecular Biology I, School of Sciences, University of Granada, 18071 Granada, Spain.
| | - Sergio Muñoz-Quezada
- Departamento de Farmacia, Facultad de Química y de Farmacia, Pontificia Universidad Católica de Chile, Santiago 6094411, Chile.
- National Agency for Medicines (ANAMED), Public Health Institute, Santiago 7780050, Chile.
| | - Luis Fontana
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain.
- Institute of Nutrition and Food Technology "José Mataix," Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain.
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain.
| | - Francisco Abadía-Molina
- Institute of Nutrition and Food Technology "José Mataix," Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n. 18016 Armilla, Granada, Spain.
- Department of Cell Biology, School of Sciences, University of Granada, 18071 Granada, Spain.
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Moossavi S, Bishehsari F. Microbes: possible link between modern lifestyle transition and the rise of metabolic syndrome. Obes Rev 2019; 20:407-419. [PMID: 30548384 DOI: 10.1111/obr.12784] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Revised: 09/10/2018] [Accepted: 09/11/2018] [Indexed: 12/13/2022]
Abstract
The rapid decrease in infectious diseases globally has coincided with an increase in the prevalence of obesity and other components of metabolic syndrome. Insulin resistance is a common feature of metabolic syndrome and can be influenced by genetic and non-genetic/environmental factors. The emergence of metabolic syndrome epidemics over only a few decades suggests a more prominent role of the latter. Changes in our environment and lifestyle have indeed paralleled the rise in metabolic syndrome. Gastrointestinal tract microbiota, the composition of which plays a significant role in host physiology, including metabolism and energy homeostasis, are distinctly different within the context of metabolic syndrome. Among humans, recent lifestyle-related changes could be linked to changes in diversity and composition of 'ancient' microbiota. Given the co-adaptation and co-evolution of microbiota with the immune system over a long period of time, it is plausible that such lifestyle-related microbiota changes could trigger aberrant immune responses, thereby predisposing an individual to a variety of diseases. Here, we review current evidence supporting a role for gut microbiota in the ongoing rise of metabolic syndrome. We conclude that population-level shifts in microbiota can play a mediatory role between lifestyle factors and pathogenesis of insulin resistance and metabolic syndrome.
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Affiliation(s)
- S Moossavi
- Digestive Oncology Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.,Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada
| | - F Bishehsari
- Department of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, IL, USA
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Cani PD, Van Hul M, Lefort C, Depommier C, Rastelli M, Everard A. Microbial regulation of organismal energy homeostasis. Nat Metab 2019; 1:34-46. [PMID: 32694818 DOI: 10.1038/s42255-018-0017-4] [Citation(s) in RCA: 357] [Impact Index Per Article: 59.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 11/15/2018] [Indexed: 12/13/2022]
Abstract
The gut microbiome has emerged as a key regulator of host metabolism. Here we review the various mechanisms through which the gut microbiome influences the energy metabolism of its host, highlighting the complex interactions between gut microbes, their metabolites and host cells. Among the most important bacterial metabolites are short-chain fatty acids, which serve as a direct energy source for host cells, stimulate the production of gut hormones and act in the brain to regulate food intake. Other microbial metabolites affect systemic energy expenditure by influencing thermogenesis and adipose tissue browning. Both direct and indirect mechanisms of action are known for specific metabolites, such as bile acids, branched chain amino acids, indole propionic acid and endocannabinoids. We also discuss the roles of specific bacteria in the production of specific metabolites and explore how external factors, such as antibiotics and exercise, affect the microbiome and thereby energy homeostasis. Collectively, we present a large body of evidence supporting the concept that gut microbiota-based therapies can be used to modulate host metabolism, and we expect to see such approaches moving from bench to bedside in the near future.
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Affiliation(s)
- Patrice D Cani
- Metabolism and Nutrition Research Group, WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium.
| | - Matthias Van Hul
- Metabolism and Nutrition Research Group, WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
| | - Charlotte Lefort
- Metabolism and Nutrition Research Group, WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
| | - Clara Depommier
- Metabolism and Nutrition Research Group, WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
| | - Marialetizia Rastelli
- Metabolism and Nutrition Research Group, WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
| | - Amandine Everard
- Metabolism and Nutrition Research Group, WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
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43
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McClements DJ. Feeding the World Inside Us: Our Gut Microbiomes, Diet, and Health. FUTURE FOODS 2019. [DOI: 10.1007/978-3-030-12995-8_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Bianchi F, Duque ALRF, Saad SMI, Sivieri K. Gut microbiome approaches to treat obesity in humans. Appl Microbiol Biotechnol 2018; 103:1081-1094. [PMID: 30554391 DOI: 10.1007/s00253-018-9570-8] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 12/06/2018] [Accepted: 12/06/2018] [Indexed: 02/08/2023]
Abstract
The rising worldwide prevalence of obesity has become a major concern having many implications for the public health and the economy. It is well known that many factors such as lifestyle, increased intake of foods high in fat and sugar and a host's genetic profile can lead to obesity. Besides these factors, recent studies have pointed to the gut microbiota composition as being responsible for the development of obesity. Since then, many efforts have been made to understand the link between the gut microbiota composition and obesity, as well as the role of food ingredients, such as pro- and prebiotics, in the modulation of the gut microbiota. Studies involving the gut microbiota composition of obese individuals are however still controversial, making it difficult to treat obesity. In this sense, this mini-review deals with obesity and the relationship with gut microbiota, summarising the principal findings on gut microbiome approaches for treating obesity in humans.
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Affiliation(s)
- Fernanda Bianchi
- Department of Food and Nutrition, School of Pharmaceutical Sciences, State University of São Paulo (UNESP), Araraquara, SP, Brazil
| | - Ana Luiza Rocha Faria Duque
- Department of Food and Nutrition, School of Pharmaceutical Sciences, State University of São Paulo (UNESP), Araraquara, SP, Brazil
| | - Susana Marta Isay Saad
- Department of Biochemical and Pharmaceutical Technology, University of São Paulo (USP), São Paulo, SP, Brazil.,Food Research Center, University of São Paulo (USP), São Paulo, SP, Brazil
| | - Katia Sivieri
- Department of Food and Nutrition, School of Pharmaceutical Sciences, State University of São Paulo (UNESP), Araraquara, SP, Brazil.
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Fang X. Microbial treatment: the potential application for Parkinson's disease. Neurol Sci 2018; 40:51-58. [PMID: 30415447 DOI: 10.1007/s10072-018-3641-6] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 11/07/2018] [Indexed: 02/07/2023]
Abstract
Alterations in the composition of the intestinal flora are associated with the pathophysiology of Parkinson's disease (PD). More importantly, the possible cause-effect links between gut flora and PD pathogenesis have been identified using PD animal models. Recent studies have found that probiotics improve the symptoms associated with constipation in PD patients. In addition, fecal microbiota transplantation (FMT) was recently shown to provide a protective effect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. Effective microbial therapy for PD includes probiotics and FMT. Therefore, microbial therapy may be a useful and novel approach for treatment of PD. In this review, I discuss the use of microbial treatment in PD.
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Affiliation(s)
- Xin Fang
- Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
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46
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Honey bees as models for gut microbiota research. Lab Anim (NY) 2018; 47:317-325. [PMID: 30353179 DOI: 10.1038/s41684-018-0173-x] [Citation(s) in RCA: 179] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 08/07/2018] [Indexed: 12/15/2022]
Abstract
The gut microbiota of the honey bee (Apis mellifera) offers several advantages as an experimental system for addressing how gut communities affect their hosts and for exploring the processes that determine gut community composition and dynamics. A small number of bacterial species dominate the honey bee gut community. These species are restricted to bee guts and can be grown axenically and genetically manipulated. Large numbers of microbiota-free hosts can be economically reared and then inoculated with single isolates or defined communities to examine colonization patterns and effects on host phenotypes. Honey bees have been studied extensively, due to their importance as agricultural pollinators and as models for sociality. Because of this history of bee research, the physiology, development, and behavior of honey bees is relatively well understood, and established behavioral and phenotypic assays are available. To date, studies on the honey bee gut microbiota show that it affects host nutrition, weight gain, endocrine signaling, immune function, and pathogen resistance, while perturbation of the microbiota can lead to reduced host fitness. As in humans, the microbiota is concentrated in the distal part of the gut, where it contributes to digestion and fermentation of plant cell wall components. Much like the human gut microbiota, many bee gut bacteria are specific to the bee gut and can be directly transmitted between individuals through social interaction. Although simpler than the human gut microbiota, the bee gut community presents opportunities to understand the processes that govern the assembly of specialized gut communities as well as the routes through which gut communities impact host biology.
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47
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de Carvalho Marchesin J, Celiberto LS, Orlando AB, de Medeiros AI, Pinto RA, Zuanon JAS, Spolidorio LC, dos Santos A, Taranto MP, Cavallini DCU. A soy-based probiotic drink modulates the microbiota and reduces body weight gain in diet-induced obese mice. J Funct Foods 2018. [DOI: 10.1016/j.jff.2018.07.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Filip M, Tzaneva V, Dumitrascu DL. Fecal transplantation: digestive and extradigestive clinical applications. CLUJUL MEDICAL (1957) 2018; 91:259-265. [PMID: 30093802 PMCID: PMC6082619 DOI: 10.15386/cjmed-946] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/05/2017] [Accepted: 12/06/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIM Fecal transplantation or fecal material transplantation (FMT) became a hot topic in gastroenterology in recent years. Therefore it is important to disseminate the up-to-date information on FMT. The aim of the paper is to review the knowledge on FMT and its clinical applications. METHODS An extensive review of the literature was carried out. Titles from Pubmed were searched and analyzed. A narrative review has been written with emphasis on indications of FMT in different conditions. RESULTS The guidelines recommend FMT in relapsing infection with Clostridium difficile. Several attempts to use FMT in other conditions have been analyzed. Attempts were recorded in other bowel disorders like IBD, IBS, chronic constipation and even colorectal cancer. The attempt to change the microbiota by FMT in diabetes and obesity represent challenges for the future. CONCLUSIONS Fecal transplantation represents an important therapeutic method, intensively investigated these years. Beside the indication for persistent and recurrent Clostridium difficile infection, several attempts were undertaken in other intestinal diseases and in metabolic conditions. The efficiency of these applications has to be demonstrated.
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Affiliation(s)
- Mihaela Filip
- 2nd Deptartment Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | | | - Dan L Dumitrascu
- 2nd Deptartment Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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49
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Wilkinson EM, Ilhan ZE, Herbst-Kralovetz MM. Microbiota–drug interactions: Impact on metabolism and efficacy of therapeutics. Maturitas 2018; 112:53-63. [DOI: 10.1016/j.maturitas.2018.03.012] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Revised: 03/23/2018] [Accepted: 03/29/2018] [Indexed: 02/06/2023]
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50
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Chen T, Zhou Q, Zhang D, Jiang F, Wu J, Zhou JY, Zheng X, Chen YG. Effect of Faecal Microbiota Transplantation for Treatment of Clostridium difficile Infection in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Cohort Studies. J Crohns Colitis 2018; 12:710-717. [PMID: 29528385 DOI: 10.1093/ecco-jcc/jjy031] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Evidence concerning the effect of faecal microbiota transplantation [FMT] in Clostridium difficile infection [CDI] patients with inflammatory bowel disease [IBD] has not been firmly established. Therefore, we performed a systematic review and meta-analysis to evaluate FMT treatment outcomes in patients with IBD treated for CDI. METHODS An electronic search of four databases was conducted until November 1, 2017. Cohort studies of FMT efficacy and safety in CDI patients with IBD were included. Pooled effect sizes were calculated with 95% confidence intervals [CI] using a random-effects model. RESULTS Nine cohort studies comprising a total of 346 CDI patients with IBD were included. The initial cure rate was 81% [95% CI = 76%-85%] and the overall cure rate was up to 89% [95% CI = 83%-93%], both with no significant heterogeneity. The recurrence rate was 19% [95% CI = 13%-27%] with moderate heterogeneity [Cochran's Q, p = 0.19; I2 = 33%]. There was no significant difference in the CDI cure rate after FMT in patients with and without IBD (risk ratio [RR] = 0.92; 95% CI = 0.81-1.05; Cochran's Q, p = 0.06; I2 = 53%). Subgroup analysis revealed a similar CDI treatment effects after FMT in patients with Crohn's disease and in those with ulcerative colitis [p = 0.1804]. Four studies reported adverse events of IBD flares. CONCLUSIONS FMT is an effective therapy for CDI in patients with IBD. Well-designed randomised controlled trials and well-conducted microbiological studies are needed to validate its efficacy and safety.
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Affiliation(s)
- Tuo Chen
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Qun Zhou
- Department of Anesthesiology, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu, China
| | - Dan Zhang
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Feng Jiang
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jing Wu
- Central Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jin-Yong Zhou
- Central Laboratory, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Xiao Zheng
- Department of Pharmacy, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yu-Gen Chen
- Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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