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Martí JM, Kok CR, Thissen JB, Mulakken NJ, Avila-Herrera A, Jaing CJ, Allen JE, Be NA. Addressing the dynamic nature of reference data: a new nucleotide database for robust metagenomic classification. mSystems 2025; 10:e0123924. [PMID: 40111052 PMCID: PMC12013259 DOI: 10.1128/msystems.01239-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Accepted: 02/14/2025] [Indexed: 03/22/2025] Open
Abstract
Accurate metagenomic classification relies on comprehensive, up-to-date, and validated reference databases. While the NCBI BLAST Nucleotide (nt) database, encompassing a vast collection of sequences from all domains of life, represents an invaluable resource, its massive size-currently exceeding 1012 nucleotides-and exponential growth pose significant challenges for researchers seeking to maintain current nt-based indices for metagenomic classification. Recognizing that no current nt-based indices exist for the widely used Centrifuge classifier, and the last public version currently available was released in 2018, we addressed this critical gap by leveraging advanced high-performance computing resources. We present new Centrifuge-compatible nt databases, meticulously constructed using a novel pipeline incorporating different quality control measures, including reference decontamination and filtering. These measures demonstrably reduce spurious classifications, as shown through our reanalysis of published metagenomic data where Plasmodium annotations were dramatically reduced using our decontaminated database, highlighting how database quality can significantly impact research conclusions. Through temporal comparisons, we also reveal how our approach minimizes inconsistencies in taxonomic assignments stemming from asynchronous updates between public sequence and taxonomy databases. These discrepancies are particularly evident in taxa such as Listeria monocytogenes and Naegleria fowleri, where classification accuracy varied significantly across database versions. These new databases, made available as pre-built Centrifuge indexes, respond to the need for an open, robust, nt-based pipeline for taxonomic classification in metagenomics. Applications such as environmental metagenomics, forensics, and clinical metagenomics, which require comprehensive taxonomic coverage, will benefit from this resource. Our work highlights the importance of treating reference databases as dynamic entities, subject to ongoing quality control and validation akin to software development best practices. This approach is crucial for ensuring accuracy and reliability of metagenomic analysis, especially as databases continue to expand in size and complexity. IMPORTANCE Accurately identifying the diverse microbes present in a sample, whether from the human gut, a soil sample, or a crime scene, is crucial for fields ranging from medicine to environmental science. Researchers rely on comprehensive DNA databases to match sequenced DNA fragments to known microbial species. However, the widely used NCBI nt database, while vast, poses significant challenges. Its massive size makes it difficult for many researchers to use effectively with taxonomic classifiers, and inconsistencies and contamination within the database can impact the accuracy of microbial identification. This work addresses these challenges by providing cleaned, updated, and validated nt-based databases specifically optimized for the widely used Centrifuge classification tool. This new resource demonstrably reduces errors and improves the reliability of microbial identification across diverse taxonomic groups. Moreover, by providing readily usable indexes, we overcome the size barrier, enabling researchers to leverage the full potential of the nt database for metagenomic analysis. Our findings underscore the need to treat reference databases as dynamic entities, emphasizing continuous quality control and versioning as essential practices for robust and reproducible metagenomics research.
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Affiliation(s)
- Jose Manuel Martí
- Global Security Computing Applications Division, Lawrence Livermore National Laboratory, Livermore, California, USA
| | - Car Reen Kok
- Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California, USA
| | - James B. Thissen
- Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California, USA
| | - Nisha J. Mulakken
- Global Security Computing Applications Division, Lawrence Livermore National Laboratory, Livermore, California, USA
| | - Aram Avila-Herrera
- Global Security Computing Applications Division, Lawrence Livermore National Laboratory, Livermore, California, USA
| | - Crystal J. Jaing
- Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California, USA
| | - Jonathan E. Allen
- Global Security Computing Applications Division, Lawrence Livermore National Laboratory, Livermore, California, USA
| | - Nicholas A. Be
- Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California, USA
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2
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Hosseininasab SSM, Ebrahimi R, Yaghoobpoor S, Kazemi K, Khakpour Y, Hajibeygi R, Mohamadkhani A, Fathi M, Vakili K, Tavasol A, Tutunchian Z, Fazel T, Fathi M, Hajiesmaeili M. Alzheimer's disease and infectious agents: a comprehensive review of pathogenic mechanisms and microRNA roles. Front Neurosci 2025; 18:1513095. [PMID: 39840010 PMCID: PMC11747386 DOI: 10.3389/fnins.2024.1513095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 12/02/2024] [Indexed: 01/23/2025] Open
Abstract
Alzheimer's Disease (AD) is the most prevalent type of dementia and is characterized by the presence of senile plaques and neurofibrillary tangles. There are various theories concerning the causes of AD, but the connection between viral and bacterial infections and their potential role in the pathogenesis of AD has become a fascinating area of research for the field. Various viruses such as Herpes simplex virus 1 (HSV-1), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), influenza viruses, and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), as well as bacteria such as Chlamydia pneumoniae (CP), Helicobacter pylori (HP), Porphyromonas gingivalis (P. gingivalis), Spirochetes and eukaryotic unicellular parasites (e.g., Toxoplasma gondii), have been linked to AD due to their ability to activate the immune system, induce inflammation and increase oxidative stress, thereby leading to cognitive decline and AD. In addition, microRNAs (miRNAs) might play a crucial role in the pathogenesis mechanisms of these pathogens since they are utilized to target various protein-coding genes, allowing for immune evasion, maintaining latency, and suppressing cellular signaling molecules. Also, they can regulate gene expression in human cells. This article provides an overview of the association between AD and various infectious agents, with a focus on the mechanisms by which these pathogens may be related to the pathogenesis of AD. These findings suggest important areas for further research to be explored in future studies.
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Affiliation(s)
- Seyyed Sam Mehdi Hosseininasab
- Critical Care Quality Improvement Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rasoul Ebrahimi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shirin Yaghoobpoor
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kiarash Kazemi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Yaser Khakpour
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ramtin Hajibeygi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Ashraf Mohamadkhani
- Liver and Pancreatobiliary Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Mobina Fathi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Kimia Vakili
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arian Tavasol
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zohreh Tutunchian
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tara Fazel
- Student Research Committee, School of International Campus, Guilan University of Medical Sciences, Tehran, Iran
| | - Mohammad Fathi
- Department of Anesthesiology, Critical Care Quality Improvement Research Center, Shahid Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Hajiesmaeili
- Critical Care Quality Improvement Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Zhao M, Wang B, Zhou F, Fang C, Zhu B, Zhou M, Ye X, Chen Y, Ding Z. Modeling "Two-Hit" Severe Pneumonia in Mice: Pathological Characteristics and Mechanistic Studies. Inflammation 2024:10.1007/s10753-024-02136-w. [PMID: 39212889 DOI: 10.1007/s10753-024-02136-w] [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: 06/13/2024] [Revised: 08/21/2024] [Accepted: 08/22/2024] [Indexed: 09/04/2024]
Abstract
Severe pneumonia is one of the most common critical diseases in clinical practice. Existing models for severe pneumonia have limitations, leading to limited clinical translation. In this study, a two-hit severe pneumonia mouse model was established by inducing primary pneumonia through intratracheal instillation of 800 μg lipopolysaccharide (LPS), followed by intraperitoneal injection of 10 mg/kg LPS. The effectiveness of various inflammatory indicators and the lung tissue damage during the time course of this model were confirmed and evaluated. At 3 h post two-hit, the IL-6, TNF-α levels in peripheral blood and bronchoalveolar lavage fluid (BALF), and the white blood cells, neutrophils, and lymphocytes in BALF notably exhibited the most pronounced elevation. At 12 h post two-hit, the white blood cells and neutrophils in peripheral blood significantly increased, accompanied by notable alterations in splenic immune cells and worsened pulmonary histopathological damage. Transcriptomics of lung tissue, microbiota analysis of lung and gut, as well as plasma metabolomics analyses further indicated changes in transcriptional profiles, microbial composition, and metabolites due to the two-hit modeling. These results validate that the two-hit model mimics the clinical presentation of severe pneumonia and serves as a robust experimental tool for studying the pathogenesis of severe pneumonia and developing and assessing treatment strategies.
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Affiliation(s)
- Mengjia Zhao
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Bixu Wang
- Ningbo Yinzhou Center for Disease Control and Prevention, Ningbo, 315199, China
| | - Fangmei Zhou
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Chengnan Fang
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Bingqi Zhu
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Mingyuan Zhou
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Xiaoqing Ye
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Yuchi Chen
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
| | - Zhishan Ding
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
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Jiang Z, Yang L, Qian X, Su K, Huang Y, Qu Y, Zhang Z, Liu W. Tongue coating microbiome composition reflects disease severity in patients with COVID-19 in Nanjing, China. J Oral Microbiol 2023; 15:2236429. [PMID: 37483641 PMCID: PMC10360987 DOI: 10.1080/20002297.2023.2236429] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 07/02/2023] [Accepted: 07/11/2023] [Indexed: 07/25/2023] Open
Abstract
Our purpose is to investigate the relationship between the microbiota of patients' tongue coating microbiota and the severity of COVID-19, and to identify the severity of COVID-19 patients' condition as early as possible. The participants were categorized into three groups: healthy controls (Con group) consisting of 37 individuals, patients with mild to moderate symptoms (M group) comprising 49 individuals, and patients with severe and critical symptoms (S-C group) consisting of 44 individuals. We collected oral swabs from all participants and performed 16S rRNA gene sequencing to analyze the microbiome. The α and β diversity differences were assessed respectively. Additionally, we employed the Linear Discriminant Analysis Effect Size (LEfSe) analysis to evaluate taxonomic differences among the three groups. Our findings revealed a significantly higher richness of tongue coating microbiota in both the S-C group and M group compared to the Con group. When compared with Con group, decreased Prevotella, Neisseria, Fusobacterium and Alloprevotella, and over-expressed Streptococcus and Rothia in M and S-C group were identified. LEfSe analysis indicated a greater abundance of Pseudomonas, Acinetbacter, Lactobacillus, Corynebacterium, Rothia in S-C group. Our study suggests a potential association between tongue coating microbiome and the severity of COVID-19 patients.
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Affiliation(s)
- Zongdan Jiang
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Lu Yang
- Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medical Hospital, Nanjing, China
| | - Xuetian Qian
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Kunhan Su
- Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medical Hospital, Nanjing, China
| | - Yuzhen Huang
- Department of Gastroenterology, Nanjing Integrated Traditional Chinese and Western Medical Hospital, Nanjing, China
| | - Yi Qu
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Zhenyu Zhang
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Wanli Liu
- Department of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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Durairajan SSK, Singh AK, Saravanan UB, Namachivayam M, Radhakrishnan M, Huang JD, Dhodapkar R, Zhang H. Gastrointestinal Manifestations of SARS-CoV-2: Transmission, Pathogenesis, Immunomodulation, Microflora Dysbiosis, and Clinical Implications. Viruses 2023; 15:1231. [PMID: 37376531 PMCID: PMC10304713 DOI: 10.3390/v15061231] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 05/12/2023] [Accepted: 05/15/2023] [Indexed: 06/29/2023] Open
Abstract
The clinical manifestation of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in the respiratory system of humans is widely recognized. There is increasing evidence suggesting that SARS-CoV-2 possesses the capability to invade the gastrointestinal (GI) system, leading to the manifestation of symptoms such as vomiting, diarrhea, abdominal pain, and GI lesions. These symptoms subsequently contribute to the development of gastroenteritis and inflammatory bowel disease (IBD). Nevertheless, the pathophysiological mechanisms linking these GI symptoms to SARS-CoV-2 infection remain unelucidated. During infection, SARS-CoV-2 binds to angiotensin-converting enzyme 2 and other host proteases in the GI tract during the infection, possibly causing GI symptoms by damaging the intestinal barrier and stimulating inflammatory factor production, respectively. The symptoms of COVID-19-induced GI infection and IBD include intestinal inflammation, mucosal hyperpermeability, bacterial overgrowth, dysbiosis, and changes in blood and fecal metabolomics. Deciphering the pathogenesis of COVID-19 and understanding its exacerbation may provide insights into disease prognosis and pave the way for the discovery of potential novel targets for disease prevention or treatment. Besides the usual transmission routes, SARS-CoV-2 can also be transmitted via the feces of an infected person. Hence, it is crucial to implement preventive and control measures in order to mitigate the fecal-to-oral transmission of SARS-CoV-2. Within this context, the identification and diagnosis of GI tract symptoms during these infections assume significance as they facilitate early detection of the disease and the development of targeted therapeutics. The present review discusses the receptors, pathogenesis, and transmission of SARS-CoV-2, with a particular focus on the induction of gut immune responses, the influence of gut microbes, and potential therapeutic targets against COVID-19-induced GI infection and IBD.
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Affiliation(s)
| | - Abhay Kumar Singh
- Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur 610005, India
| | - Udhaya Bharathy Saravanan
- Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur 610005, India
| | - Mayurikaa Namachivayam
- Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur 610005, India
| | - Moorthi Radhakrishnan
- Department of Microbiology, School of Life Sciences, Central University of Tamil Nadu, Tiruvarur 610005, India
| | - Jian-Dong Huang
- Department of Biochemistry, School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong 999077, China
- CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Rahul Dhodapkar
- Department of Microbiology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Government of India, Puducherry 605006, India
| | - Hongjie Zhang
- School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong 999077, China
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6
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Ralli T, Saifi Z, Rathee A, Aeri V, Kohli K. Decoding the bidirectional relationship between gut microbiota and COVID-19. Heliyon 2023; 9:e13801. [PMID: 36811017 PMCID: PMC9936796 DOI: 10.1016/j.heliyon.2023.e13801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 02/09/2023] [Accepted: 02/13/2023] [Indexed: 02/19/2023] Open
Abstract
From late 2019, whole world has been facing COVID-19 pandemic which is caused by SARS-CoV-2 virus. This virus primarily attacks the respiratory tract and enter host cell by binding with angiotensin 2 converting enzyme receptors present on alveoli of the lungs. Despite its binding in the lungs, many patients have reported gastrointestinal symptoms and indeed, RNA of the virus have been found in faecal sample of patients. This observation gave a clue of the involvement of gut-lung axis in this disease development and progression. From several studies reported in past two years, intestinal microbiome has shown to have bidirectional link with lungs i.e., gut dysbiosis increases the tendency of infection with COVID-19 and coronavirus can also cause perturbations in intestinal microbial composition. Thus, in this review we have tried to figure out the mechanisms by which disturbances in the gut composition can increase the susceptibility to COVID-19. Understanding these mechanisms can play a crucial role in decreasing the disease outcomes by manipulating the gut microbiome using prebiotics, probiotics, or combination of two. Even, faecal microbiota transplantation can also show better results, but intensive clinical trials need to be done first.
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Affiliation(s)
- Tanya Ralli
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi 110062, India
| | - Zoya Saifi
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi 110062, India
| | - Anjali Rathee
- Department of Pharmacognosy, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi 110062, India
| | - Vidhu Aeri
- Lloyd Institute of Management and Technology, Plot No-11, Knowledge Park-II, Greater Noida, Uttar Pradesh 201306, India
| | - Kanchan Kohli
- Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi 110062, India
- Research and Publications, Llyod Institute of Management and Technology, Knowledge Park II, Greater Noida, Uttar Pradesh, India
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7
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Yu L, Abd Ghani MK, Aghemo A, Barh D, Bassetti M, Catena F, Gallo G, Gholamrezanezhad A, Kamal MA, Lal A, Sahu KK, Saxena SK, Elmore U, Rahimi F, Robba C, Song Y, Xia Z, Yu B. SARS-CoV-2 Infection, Inflammation, Immunonutrition, and Pathogenesis of COVID-19. Curr Med Chem 2023; 30:4390-4408. [PMID: 36998130 DOI: 10.2174/0929867330666230330092725] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 01/25/2023] [Accepted: 02/16/2023] [Indexed: 04/01/2023]
Abstract
The COVID-19 pandemic, caused by the coronavirus, SARS-CoV-2, has claimed millions of lives worldwide in the past two years. Fatalities among the elderly with underlying cardiovascular disease, lung disease, and diabetes have particularly been high. A bibliometrics analysis on author's keywords was carried out, and searched for possible links between various coronavirus studies over the past 50 years, and integrated them. We found keywords like immune system, immunity, nutrition, malnutrition, micronutrients, exercise, inflammation, and hyperinflammation were highly related to each other. Based on these findings, we hypothesized that the human immune system is a multilevel super complex system, which employs multiple strategies to contain microorganism infections and restore homeostasis. It was also found that the behavior of the immune system is not able to be described by a single immunological theory. However, one main strategy is "self-destroy and rebuild", which consists of a series of inflammatory responses: 1) active self-destruction of damaged/dysfunctional somatic cells; 2) removal of debris and cells; 3) rebuilding tissues. Thus, invading microorganisms' clearance could be only a passive bystander response to this destroy-rebuild process. Microbial infections could be self-limiting and promoted as an indispensable essential nutrition for the vast number of genes existing in the microorganisms. The transient nutrition surge resulting from the degradation of the self-destroyed cell debris coupled with the existing nutrition state in the patient may play an important role in the pathogenesis of COVID-19. Finally, a few possible coping strategies to mitigate COVID-19, including vaccination, are discussed.
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Affiliation(s)
- Ligen Yu
- Talent Recruitment and Career Support (TRACS) Office, Nanyang Technological University, N2.1 B4-01, 76 Nanyang Drive, 637331, Singapore
| | - Mohd Khanapi Abd Ghani
- Biomedical Computing and Engineering Technologies (BIOCORE) Applied Research Group, Faculty of Information and Communication Technology, Universiti Teknikal Malaysia Melaka, Durian Tunggal, 76100, Melaka, Malaysia
| | | | - Debmalya Barh
- Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur WB, India
- Departamento de Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
| | - Matteo Bassetti
- Infectious Diseases Clinic, Department of Health Sciences, University of Genoa and Policlinico San Martino Hospital - IRCCS, Genoa, Italy
| | - Fausto Catena
- Azienda Ospedaliero - Universitaria di Parma, Parma, Italy
| | | | - Ali Gholamrezanezhad
- Keck School of Medicine, University of Southern California (USC), Los Angeles, California, USA
| | | | - Amos Lal
- Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, 55902, USA
| | | | - Shailendra K Saxena
- Center for Advanced Research, King George's Medical University (KGMU), Lucknow-226003, India
| | - Ugo Elmore
- Department of Gastrointestinal Surgery, IRCCS San Raffaele Scientific Institute, San Raffaele Vita-Salute University, Milan, Italy
| | - Farid Rahimi
- Division of Biomedical Science and Biochemistry, Research School of Biology, The Australian National University, Ngunnawal and Ngambri Country, Canberra, ACT 2600, Australia
| | - Chiara Robba
- Anesthesia and Intensive Care, Policlinico San Martino, Largo Rosanna Benzi 15, 16100 Genova, Italy
| | - Yuanlin Song
- Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, P.R. China
| | - Zhengyuan Xia
- Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
| | - Boxuan Yu
- School of Computer Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore
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Iesanu MI, Zahiu CDM, Dogaru IA, Chitimus DM, Pircalabioru GG, Voiculescu SE, Isac S, Galos F, Pavel B, O’Mahony SM, Zagrean AM. Melatonin-Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions. Antioxidants (Basel) 2022; 11:2244. [PMID: 36421432 PMCID: PMC9686962 DOI: 10.3390/antiox11112244] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/07/2022] [Accepted: 11/09/2022] [Indexed: 08/27/2023] Open
Abstract
Melatonin is a pineal indolamine, allegedly known as a circadian rhythm regulator, and an antioxidative and immunomodulatory molecule. In both experimental and clinical trials, melatonin has been shown to have positive effects in various pathologies, as a modulator of important biochemical pathways including inflammation, oxidative stress, cell injury, apoptosis, and energy metabolism. The gut represents one of melatonin's most abundant extra pineal sources, with a 400-times-higher concentration than the pineal gland. The importance of the gut microbial community-namely, the gut microbiota, in multiple critical functions of the organism- has been extensively studied throughout time, and its imbalance has been associated with a variety of human pathologies. Recent studies highlight a possible gut microbiota-modulating role of melatonin, with possible implications for the treatment of these pathologies. Consequently, melatonin might prove to be a valuable and versatile therapeutic agent, as it is well known to elicit positive functions on the microbiota in many dysbiosis-associated conditions, such as inflammatory bowel disease, chronodisruption-induced dysbiosis, obesity, and neuropsychiatric disorders. This review intends to lay the basis for a deeper comprehension of melatonin, gut microbiota, and host-health subtle interactions.
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Affiliation(s)
- Mara Ioana Iesanu
- Department of Functional Sciences, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Pediatrics, Marie Curie Emergency Children’s Hospital, 041451 Bucharest, Romania
| | - Carmen Denise Mihaela Zahiu
- Department of Functional Sciences, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Ioana-Alexandra Dogaru
- Department of Functional Sciences, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Diana Maria Chitimus
- Department of Functional Sciences, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Gratiela Gradisteanu Pircalabioru
- Section Earth, Environmental and Life Sciences, Research Institute of the University of Bucharest, 050663 Bucharest, Romania
- Academy of Romanian Scientists, 54 Splaiul Independentei Street, District 5, 050094 Bucharest, Romania
| | - Suzana Elena Voiculescu
- Department of Functional Sciences, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Sebastian Isac
- Department of Functional Sciences, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Anesthesiology and Intensive Care I, ‘Fundeni’ Clinical Institute, 022328 Bucharest, Romania
| | - Felicia Galos
- Department of Pediatrics, Marie Curie Emergency Children’s Hospital, 041451 Bucharest, Romania
- Department of Pediatrics, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Bogdan Pavel
- Department of Functional Sciences, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Siobhain M. O’Mahony
- Department of Anatomy and Neuroscience, University College Cork, T12 XF62 Cork, Ireland
- APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland
| | - Ana-Maria Zagrean
- Department of Functional Sciences, Carol Davila University of Medicine and Pharmacy, 020021 Bucharest, Romania
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Zeinali T, Faraji N, Joukar F, Khan Mirzaei M, Kafshdar Jalali H, Shenagari M, Mansour-Ghanaei F. Gut bacteria, bacteriophages, and probiotics: Tripartite mutualism to quench the SARS-CoV2 storm. Microb Pathog 2022; 170:105704. [PMID: 35948266 PMCID: PMC9357283 DOI: 10.1016/j.micpath.2022.105704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Revised: 07/19/2022] [Accepted: 08/01/2022] [Indexed: 11/30/2022]
Abstract
Patients with SARS-CoV-2 infection, exhibit various clinical manifestations and severity including respiratory and enteric involvements. One of the main reasons for death among covid-19 patients is excessive immune responses directed toward cytokine storm with a low chance of recovery. Since the balanced gut microbiota could prepare health benefits by protecting against pathogens and regulating immune homeostasis, dysbiosis or disruption of gut microbiota could promote severe complications including autoimmune disorders; we surveyed the association between the imbalanced gut bacteria and the development of cytokine storm among COVID-19 patients, also the impact of probiotics and bacteriophages on the gut bacteria community to alleviate cytokine storm in COVID-19 patients. In present review, we will scrutinize the mechanism of immunological signaling pathways which may trigger a cytokine storm in SARS-CoV2 infections. Moreover, we are explaining in detail the possible immunological signaling pathway-directing by the gut bacterial community. Consequently, the specific manipulation of gut bacteria by using probiotics and bacteriophages for alleviation of the cytokine storm will be investigated. The tripartite mutualistic cooperation of gut bacteria, probiotics, and phages as a candidate prophylactic or therapeutic approach in SARS-CoV-2 cytokine storm episodes will be discussed at last.
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Affiliation(s)
- Tahereh Zeinali
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Niloofar Faraji
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Farahnaz Joukar
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammadali Khan Mirzaei
- Institute of Virology, Helmholtz Center Munich and Technical University of Munich, 85764, Neuherberg, Germany
| | - Hossnieh Kafshdar Jalali
- Department of Microbiology, Faculty of Science, Lahijan Branch, Islamic Azad University, Lahijan, Iran
| | - Mohammad Shenagari
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran; Department of Microbiology, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
| | - Fariborz Mansour-Ghanaei
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran; Caspian Digestive Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.
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10
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Badi SA, Khatami S, Siadat SD. Tripartite communication in COVID-19 infection: SARS-CoV-2 pathogenesis, gut microbiota and ACE2. Future Virol 2022. [PMID: 35910851 PMCID: PMC9313525 DOI: 10.2217/fvl-2021-0231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 07/07/2022] [Indexed: 11/25/2022]
Affiliation(s)
- Sara Ahmadi Badi
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, 1316943551, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, 1316943551, Iran
| | - Shohreh Khatami
- Biochemistry Department, Pasteur Institute of Iran, Tehran, 1316943551, Iran
| | - Seyed Davar Siadat
- Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, 1316943551, Iran
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, 1316943551, Iran
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11
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Kumari R, Yadav Y, Misra R, Das U, Das Adhikari U, Malakar P, Dubey GP. Emerging frontiers of antibiotics use and their impacts on the human gut microbiome. Microbiol Res 2022; 263:127127. [PMID: 35914416 DOI: 10.1016/j.micres.2022.127127] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 04/17/2022] [Accepted: 07/11/2022] [Indexed: 02/07/2023]
Abstract
Antibiotics, the primary drugs used to cure bacterial diseases, are increasingly becoming ineffective due to the emergence of multiple drug resistance (MDR) leading to recurrence of previously sensitive pathogens. Human gut microbiome (GM), known to play an important role in various physiological processes, consists of pool of diverse microbes. Indiscriminate use of antibiotics during the life span of an individual may lead to development of resistant microbes e.g. Vibrio, Acinetobacter, Escherichia, Klebsiella, Clostridia, etc. in the human GM. Transmission of antibiotic resistant genes (ARGs) between pathogenic and commensal bacteria occurs more frequently in microbiome communities wherein bacteria communicate and exchange cellular constituents both among themselves and with the host. Additionally, co-factors like 'early vs. late' exposure, type of antibiotics and duration of treatment modulate the adverse effects of antibiotics on GM maturation. Furthermore, factors like mode of birth, ethnicity, malnutrition, demography, diet, lifestyle, etc., which influence GM composition, can also indirectly alter the host response to antibiotics. Currently, advanced 'omics' and culturomics approaches are revealing novel avenues to study the interplay between antibiotics and the microbiome and to identify resistant genes in these bacterial communities. Here, we discuss the recent developments that have given insights into the effects of antibiotics on the homeostatic balance of the gut microbiome and thus on human health.
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Affiliation(s)
- Rekha Kumari
- Department of Zoology, Miranda House, University of Delhi, Delhi 110007, India.
| | - Yasha Yadav
- Department of Zoology, Miranda House, University of Delhi, Delhi 110007, India
| | - Richa Misra
- Department of Zoology, Sri Venkateswara College, University of Delhi, Delhi 1100021, India
| | - Utpal Das
- Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
| | - Upasana Das Adhikari
- The Ragon Institute of MGH, MIT and Harvard, 400 Technology Square Cambridge, MA 02139, USA
| | - Pushkar Malakar
- Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
| | - Gyanendra P Dubey
- Molecular Microbial Pathogenesis Unit, Institut Pasteur, 28 rue du Docteur Roux, 75724 Cedex 15 Paris, France.
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12
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Chakraborty C, Sharma AR, Bhattacharya M, Dhama K, Lee SS. Altered gut microbiota patterns in COVID-19: Markers for inflammation and disease severity. World J Gastroenterol 2022; 28:2802-2822. [PMID: 35978881 PMCID: PMC9280735 DOI: 10.3748/wjg.v28.i25.2802] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/19/2022] [Accepted: 05/14/2022] [Indexed: 02/06/2023] Open
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to a severe respiratory illness and alters the gut microbiota, which dynamically interacts with the human immune system. Microbiota alterations include decreased levels of beneficial bacteria and augmentation of opportunistic pathogens. Here, we describe critical factors affecting the microbiota in coronavirus disease 2019 (COVID-19) patients. These include, such as gut microbiota imbalance and gastrointestinal symptoms, the pattern of altered gut microbiota composition in COVID-19 patients, and crosstalk between the microbiome and the gut-lung axis/gut-brain-lung axis. Moreover, we have illustrated the hypoxia state in COVID-19 associated gut microbiota alteration. The role of ACE2 in the digestive system, and control of its expression using the gut microbiota is discussed, highlighting the interactions between the lungs, the gut, and the brain during COVID-19 infection. Similarly, we address the gut microbiota in elderly or co-morbid patients as well as gut microbiota dysbiosis of in severe COVID-19. Several clinical trials to understand the role of probiotics in COVID-19 patients are listed in this review. Augmented inflammation is one of the major driving forces for COVID-19 symptoms and gut microbiome disruption and is associated with disease severity. However, understanding the role of the gut microbiota in immune modulation during SARS-CoV-2 infection may help improve therapeutic strategies for COVID-19 treatment.
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Affiliation(s)
| | - Ashish Ranjan Sharma
- Institute for Skeletal Aging & Orthopaedic Surgery, Hallym University, Chuncheon-si 24252, South Korea
| | | | - Kuldeep Dhama
- Division of Pathology, Indian Council of Agricultural Research (ICAR)-Indian Veterinary Research Institute (IVRI), Bareilly 243122, Uttar Pradesh, India
| | - Sang-Soo Lee
- Institute for Skeletal Aging & Orthopedic Surgery, Hallym University, Chuncheon-si 24252, South Korea
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13
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Ziyaei K, Ataie Z, Mokhtari M, Adrah K, Daneshmehr MA. An insight to the therapeutic potential of algae-derived sulfated polysaccharides and polyunsaturated fatty acids: Focusing on the COVID-19. Int J Biol Macromol 2022; 209:244-257. [PMID: 35306019 PMCID: PMC8924028 DOI: 10.1016/j.ijbiomac.2022.03.063] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 03/07/2022] [Accepted: 03/11/2022] [Indexed: 01/07/2023]
Abstract
Covid-19 pandemic severely affected human health worldwide. The rapidly increasing COVID-19 cases and successive mutations of the virus have made it a major challenge for scientists to find the best and efficient drug/vaccine/strategy to counteract the virus pathogenesis. As a result of research in scientific databases, regulating the immune system and its responses with nutrients and nutritional interventions is the most critical solution to prevent and combat this infection. Also, modulating other organs such as the intestine with these compounds can lead to the vaccines' effectiveness. Marine resources, mainly algae, are rich sources of nutrients and bioactive compounds with known immunomodulatory properties and the gut microbiome regulations. According to the purpose of the review, algae-derived bioactive compounds with immunomodulatory activities, sulfated polysaccharides, and polyunsaturated fatty acids have a good effect on the immune system. In addition, they have probiotic/prebiotic properties in the intestine and modulate the gut microbiomes; therefore, they can increase the effectiveness of vaccines produced. Thus, they with respectable safety, immune regulation, and modulation of microbiota have potential therapeutic against infections, especially COVID-19. They can also be employed as promising candidates for the prevention and treatment of viral infections, such as COVID-19.
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Affiliation(s)
- Kobra Ziyaei
- Department of Fisheries, Faculty of Natural Resources, University of Tehran, Karaj, Iran
| | - Zahra Ataie
- Evidence-based Phytotherapy & Complementary Medicine Research Center, Alborz University of Medical Sciences, Karaj, Iran; Department of Pharmaceutics, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran
| | - Majid Mokhtari
- Department of Medical Bioinformatics, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran; Laboratory of System Biology and Bioinformatics (LBB), Department of Bioinformatics, Kish International Campus, University of Tehran, Kish Island, Iran
| | - Kelvin Adrah
- Food and Nutritional Sciences Program, North Carolina Agricultural and Technical State University, Greensboro, NC 27411, USA
| | - Mohammad Ali Daneshmehr
- Department of Medicinal Chemistry, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
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14
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Mashaqi S, Kallamadi R, Matta A, Quan SF, Patel SI, Combs D, Estep L, Lee-Iannotti J, Smith C, Parthasarathy S, Gozal D. Obstructive Sleep Apnea as a Risk Factor for COVID-19 Severity-The Gut Microbiome as a Common Player Mediating Systemic Inflammation via Gut Barrier Dysfunction. Cells 2022; 11:1569. [PMID: 35563874 PMCID: PMC9101605 DOI: 10.3390/cells11091569] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 04/30/2022] [Accepted: 05/03/2022] [Indexed: 02/04/2023] Open
Abstract
The novel corona virus that is now known as (SARS-CoV-2) has killed more than six million people worldwide. The disease presentation varies from mild respiratory symptoms to acute respiratory distress syndrome and ultimately death. Several risk factors have been shown to worsen the severity of COVID-19 outcomes (such as age, hypertension, diabetes mellitus, and obesity). Since many of these risk factors are known to be influenced by obstructive sleep apnea, this raises the possibility that OSA might be an independent risk factor for COVID-19 severity. A shift in the gut microbiota has been proposed to contribute to outcomes in both COVID-19 and OSA. To further evaluate the potential triangular interrelationships between these three elements, we conducted a thorough literature review attempting to elucidate these interactions. From this review, it is concluded that OSA may be a risk factor for worse COVID-19 clinical outcomes, and the shifts in gut microbiota associated with both COVID-19 and OSA may mediate processes leading to bacterial translocation via a defective gut barrier which can then foster systemic inflammation. Thus, targeting biomarkers of intestinal tight junction dysfunction in conjunction with restoring gut dysbiosis may provide novel avenues for both risk detection and adjuvant therapy.
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Affiliation(s)
- Saif Mashaqi
- Department of Pulmonary, Allergy, Critical Care and Sleep Medicine, The University of Arizona College of Medicine, Tucson, AZ 85719, USA; (S.F.Q.); (S.I.P.); (D.C.); (L.E.); (S.P.)
| | - Rekha Kallamadi
- Department of Internal Medicine, The University of North Dakota School of Medicine, Grand Forks, ND 58203, USA; (R.K.); (A.M.)
| | - Abhishek Matta
- Department of Internal Medicine, The University of North Dakota School of Medicine, Grand Forks, ND 58203, USA; (R.K.); (A.M.)
| | - Stuart F. Quan
- Department of Pulmonary, Allergy, Critical Care and Sleep Medicine, The University of Arizona College of Medicine, Tucson, AZ 85719, USA; (S.F.Q.); (S.I.P.); (D.C.); (L.E.); (S.P.)
- Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital and Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115, USA
| | - Salma I. Patel
- Department of Pulmonary, Allergy, Critical Care and Sleep Medicine, The University of Arizona College of Medicine, Tucson, AZ 85719, USA; (S.F.Q.); (S.I.P.); (D.C.); (L.E.); (S.P.)
| | - Daniel Combs
- Department of Pulmonary, Allergy, Critical Care and Sleep Medicine, The University of Arizona College of Medicine, Tucson, AZ 85719, USA; (S.F.Q.); (S.I.P.); (D.C.); (L.E.); (S.P.)
| | - Lauren Estep
- Department of Pulmonary, Allergy, Critical Care and Sleep Medicine, The University of Arizona College of Medicine, Tucson, AZ 85719, USA; (S.F.Q.); (S.I.P.); (D.C.); (L.E.); (S.P.)
| | - Joyce Lee-Iannotti
- Department of Sleep Medicine, The University of Arizona College of Medicine, Phoenix, AZ 85006, USA;
| | - Charles Smith
- The Intermountain Healthcare, Merrill Gappmayer Family Medicine Center, Provo, UT 84604, USA;
| | - Sairam Parthasarathy
- Department of Pulmonary, Allergy, Critical Care and Sleep Medicine, The University of Arizona College of Medicine, Tucson, AZ 85719, USA; (S.F.Q.); (S.I.P.); (D.C.); (L.E.); (S.P.)
| | - David Gozal
- Department of Child Health, University of Missouri School of Medicine, Columbia, MO 65201, USA;
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15
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Farsi Y, Tahvildari A, Arbabi M, Vazife F, Sechi LA, Shahidi Bonjar AH, Jamshidi P, Nasiri MJ, Mirsaeidi M. Diagnostic, Prognostic, and Therapeutic Roles of Gut Microbiota in COVID-19: A Comprehensive Systematic Review. Front Cell Infect Microbiol 2022; 12:804644. [PMID: 35310853 PMCID: PMC8930898 DOI: 10.3389/fcimb.2022.804644] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 02/07/2022] [Indexed: 12/14/2022] Open
Abstract
Introduction The Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) emerged in late December 2019. Considering the important role of gut microbiota in maturation, regulation, and induction of the immune system and subsequent inflammatory processes, it seems that evaluating the composition of gut microbiota in COVID-19 patients compared with healthy individuals may have potential value as a diagnostic and/or prognostic biomarker for the disease. Also, therapeutic interventions affecting gut microbial flora may open new horizons in the treatment of COVID-19 patients and accelerating their recovery. Methods A systematic search was conducted for relevant studies published from December 2019 to December 2021 using Pubmed/Medline, Embase, and Scopus. Articles containing the following keywords in titles or abstracts were selected: "SARS-CoV-2" or "COVID-19" or "Coronavirus Disease 19" and "gastrointestinal microbes" or "dysbiosis" or "gut microbiota" or "gut bacteria" or "gut microbes" or "gastrointestinal microbiota". Results Out of 1,668 studies, 22 articles fulfilled the inclusion criteria and a total of 1,255 confirmed COVID-19 patients were examined. All included studies showed a significant association between COVID-19 and gut microbiota dysbiosis. The most alteration in bacterial composition of COVID-19 patients was depletion in genera Ruminococcus, Alistipes, Eubacterium, Bifidobacterium, Faecalibacterium, Roseburia, Fusicathenibacter, and Blautia and enrichment of Eggerthella, Bacteroides, Actinomyces, Clostridium, Streptococcus, Rothia, and Collinsella. Also, some gut microbiome alterations were associated with COVID-19 severity and poor prognosis including the increment of Bacteroides, Parabacteroides, Clostridium, Bifidobacterium, Ruminococcus, Campylobacter, Rothia, Corynebacterium, Megasphaera, Enterococcus, and Aspergillus spp. and the decrement of Roseburia, Eubacterium, Lachnospira, Faecalibacterium, and the Firmicutes/Bacteroidetes ratio. Conclusion Our study showed a significant change of gut microbiome composition in COVID-19 patients compared with healthy individuals. This great extent of impact has proposed the gut microbiota as a potential diagnostic, prognostic, and therapeutic strategy for COVID-19. There is much evidence about this issue, and it is expected to be increased in near future.
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Affiliation(s)
- Yeganeh Farsi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azin Tahvildari
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahta Arbabi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fateme Vazife
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Leonardo A. Sechi
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
- Struttura Complessa (SC), Microbiologia e Virologia, Azienda Ospedaliera Universitaria, Sassari, Italy
| | - Amir Hashem Shahidi Bonjar
- Clinician Scientist of Dental Materials and Restorative Dentistry, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parnian Jamshidi
- Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Javad Nasiri
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Mirsaeidi
- Division of Pulmonary and Critical Care, College of Medicine-Jacksonville, University of Florida, Jacksonville, FL, United States
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16
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Gumenyuk LN, Golod MV, Silaeva NV, Sorokina LE, Ilyasov SS, Androschyuk NA, Krivoshapko OR, Velilyaev AM, Asanova LN. Gut microbiota alterations and their relationship to the disease severity and some cytokine profile indicators in patients with COVID-19. BULLETIN OF RUSSIAN STATE MEDICAL UNIVERSITY 2022. [DOI: 10.24075/brsmu.2022.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Gut microbiota is an essential element of maintaining the immune homeostasis, including in individuals with COVID-19. The study was aimed to assess taxonomic changes in the gut microbiota and their relationship with the disease severity and the levels of IL6, IL10, IL17, and TNFα in patients with COVID-19. A total of 110 patients with COVID-19 (index group) and 98 individuals with no COVID-19 (control group) were enrolled to the comparative cross-sectional study. The gut micribiota composition was determined by shotgun sequencing. Blood serum levels of IL6, IL10, IL17, and TNFα were assessed by enzyme-linked immunosorbent assay. The following significant changes in the gut microbiota composition were observed in patients with COVID-19 in contrast to controls: decreased abundance of B. adolescentis (p = 0.048), E. rectale (p = 0.036), F. prausnitzi (p = 0.0002), B. dorei (p < 0.001), and increased abundance of R. gnavus (p = 0.012), Сl. hathewayi (p = 0.003), E. faecium (p = 0.0003). Correlations were established between the abundance of B. dorei and the IL6 levels (r = 0.49; p = 0.034), the abundance of F. prausnitzii and the levels of IL10, IL17 (r = 0.44; p = 0.001 and r = –0.52; p < 0.001, respectively). The abundance of R. gnavus correlated with the TNFα levels, and the abundance of E. faecium was related to the levels of IL6 (r = 0.47; p = 0.002) and TNFα (r = 0.56; p = 0.001). The relationship between the abundance of B. dorei, F. prausnitzii, E. faecium and the higher SHOKS-COVID clinical assessment scale scores was also revealed (r = –0.54; p = 0.001, r = –0.60; p < 0.001 and r = 0.67; p = 0.005, respectively). Targeted correction of gut microbiota may improve the COVID-19 treatment efficacy.
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Affiliation(s)
- LN Gumenyuk
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - MV Golod
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - NV Silaeva
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - LE Sorokina
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - SS Ilyasov
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - NA Androschyuk
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - OR Krivoshapko
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - AM Velilyaev
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
| | - LN Asanova
- V.I. Vernadsky Crimean Federal University, Simferopol, Russia
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17
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Mousa WK, Chehadeh F, Husband S. Recent Advances in Understanding the Structure and Function of the Human Microbiome. Front Microbiol 2022; 13:825338. [PMID: 35185849 PMCID: PMC8851206 DOI: 10.3389/fmicb.2022.825338] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 01/11/2022] [Indexed: 12/11/2022] Open
Abstract
Trillions of microbes live within our bodies in a deep symbiotic relationship. Microbial populations vary across body sites, driven by differences in the environment, immunological factors, and interactions between microbial species. Major advances in genome sequencing enable a better understanding of microbiome composition. However, most of the microbial taxa and species of the human microbiome are still unknown. Without revealing the identity of these microbes as a first step, we cannot appreciate their role in human health and diseases. A shift in the microbial balance, termed dysbiosis, is linked to a broad range of diseases from simple colitis and indigestion to cancer and dementia. The last decade has witnessed an explosion in microbiome research that led to a better understanding of the microbiome structure and function. This understanding leads to potential opportunities to develop next-generation microbiome-based drugs and diagnostic biomarkers. However, our understanding is limited given the highly personalized nature of the microbiome and its complex and multidirectional interactions with the host. In this review, we discuss: (1) our current knowledge of microbiome structure and factors that shape the microbial composition, (2) recent associations between microbiome dysbiosis and diseases, and (3) opportunities of new microbiome-based therapeutics. We analyze common themes, promises, gaps, and challenges of the microbiome research.
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Affiliation(s)
- Walaa K. Mousa
- College of Pharmacy, Al Ain University of Science and Technology, Al Ain, United Arab Emirates
- Department of Biology, Whitman College, Walla Walla, WA, United States
- College of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Fadia Chehadeh
- Department of Biology, Whitman College, Walla Walla, WA, United States
| | - Shannon Husband
- Department of Biology, Whitman College, Walla Walla, WA, United States
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18
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Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients: a retrospective cohort study in a Mediterranean area. J Infect 2021; 84:329-336. [PMID: 34963638 PMCID: PMC8709923 DOI: 10.1016/j.jinf.2021.12.030] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 12/08/2021] [Accepted: 12/21/2021] [Indexed: 12/11/2022]
Abstract
This study aimed to analyse the diversity and taxonomic composition of the nasopharyngeal microbiota, to determine its association with COVID-19 clinical outcome. To study the microbiota, we utilized 16S rRNA sequencing of 177 samples that came from a retrospective cohort of COVID-19 hospitalized patients. Raw sequences were processed by QIIME2. The associations between microbiota, invasive mechanical ventilation (IMV), and all-cause mortality were analysed by multiple logistic regression, adjusted for age, gender, and comorbidity. The microbiota α diversity indexes were lower in patients with a fatal outcome, whereas the β diversity analysis showed a significant clustering in these patients. After multivariate adjustment, the presence of Selenomonas spp., Filifactor spp., Actinobacillus spp., or Chroococcidiopsis spp., was associated with a reduction of more than 90% of IMV. Higher diversity and the presence of certain genera in the nasopharyngeal microbiota seem to be early biomarkers of a favourable clinical evolution in hospitalized COVID-19 patients.
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19
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Roy K, Agarwal S, Banerjee R, Paul MK, Purbey PK. COVID-19 and gut immunomodulation. World J Gastroenterol 2021; 27:7925-7942. [PMID: 35046621 PMCID: PMC8678818 DOI: 10.3748/wjg.v27.i46.7925] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 06/09/2021] [Accepted: 11/29/2021] [Indexed: 02/06/2023] Open
Abstract
The disease coronavirus disease 2019 (COVID-19) is a severe respiratory illness that has emerged as a devastating health problem worldwide. The disease outcome is heterogeneous, and severity is likely dependent on the immunity of infected individuals and comorbidities. Although symptoms of the disease are primarily associated with respiratory problems, additional infection or failure of other vital organs are being reported. Emerging reports suggest a quite common co-existence of gastrointestinal (GI) tract symptoms in addition to respiratory symptoms in many COVID-19 patients, and some patients show just the GI symptoms. The possible cause of the GI symptoms could be due to direct infection of the epithelial cells of the gut, which is supported by the fact that (1) The intestinal epithelium expresses a high level of angiotensin-converting enzyme-2 and transmembrane protease serine 2 protein that are required for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry into the cells; (2) About half of the severe COVID-19 patients show viral RNA in their feces and various parts of the GI tract; and (3) SARS-CoV-2 can directly infect gut epithelial cells in vitro (gut epithelial cells and organoids) and in vivo (rhesus monkey). The GI tract seems to be a site of active innate and adaptive immune responses to SARS-CoV-2 as clinically, stool samples of COVID-19 patients possess proinflammatory cytokines (interleukin 8), calprotectin (neutrophils activity), and immunoglobulin A antibodies. In addition to direct immune activation by the virus, impairment of GI epithelium integrity can evoke immune response under the influence of systemic cytokines, hypoxia, and changes in gut microbiota (dysbiosis) due to infection of the respiratory system, which is confirmed by the observation that not all of the GI symptomatic patients are viral RNA positive. This review comprehensively summarizes the possible GI immunomodulation by SARS-CoV-2 that could lead to GI symptoms, their association with disease severity, and potential therapeutic interventions.
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Affiliation(s)
- Koushik Roy
- Microbiology and Immunology, Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT 84112, United States
| | - Sidra Agarwal
- Department of Gastroenterology, Shadan Institute of Medical Sciences, Peeramcheru 500086, Telangana, India
| | - Rajib Banerjee
- Department of Electronics and Communication Engineering, Dr. B. C. Roy Engineering College, Durgapur 713206, West Bengal, India
| | - Manash K Paul
- Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States
| | - Prabhat K Purbey
- Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, United States
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20
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Kariyawasam JC, Jayarajah U, Riza R, Abeysuriya V, Seneviratne SL. Gastrointestinal manifestations in COVID-19. Trans R Soc Trop Med Hyg 2021; 115:1362-1388. [PMID: 33728439 PMCID: PMC7989191 DOI: 10.1093/trstmh/trab042] [Citation(s) in RCA: 87] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 02/15/2021] [Accepted: 02/18/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19), a respiratory viral infection, has affected more than 78 million individuals worldwide as of the end of December 2020. Previous studies reported that severe acute respiratory syndrome coronavirus 1 and Middle East respiratory syndrome-related coronavirus infections may affect the gastrointestinal (GI) system. In this review we outline the important GI manifestations of COVID-19 and discuss the possible underlying pathophysiological mechanisms and their diagnosis and management. GI manifestations are reported in 11.4-61.1% of individuals with COVID-19, with variable onset and severity. The majority of COVID-19-associated GI symptoms are mild and self-limiting and include anorexia, diarrhoea, nausea, vomiting and abdominal pain/discomfort. A minority of patients present with an acute abdomen with aetiologies such as acute pancreatitis, acute appendicitis, intestinal obstruction, bowel ischaemia, haemoperitoneum or abdominal compartment syndrome. Severe acute respiratory syndrome coronavirus 2 RNA has been found in biopsies from all parts of the alimentary canal. Involvement of the GI tract may be due to direct viral injury and/or an inflammatory immune response and may lead to malabsorption, an imbalance in intestinal secretions and gut mucosal integrity and activation of the enteric nervous system. Supportive and symptomatic care is the mainstay of therapy. However, a minority may require surgical or endoscopic treatment for acute abdomen and GI bleeding.
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Affiliation(s)
- Jayani C Kariyawasam
- Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo, Sri Lanka
| | - Umesh Jayarajah
- Postgraduate Institute of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Rishdha Riza
- Colombo South Teaching Hospital, Colombo, Sri Lanka
| | - Visula Abeysuriya
- Nawaloka Hospital Research and Education Foundation, Nawaloka Hospitals, Colombo, Sri Lanka
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21
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Singla RK, He X, Chopra H, Tsagkaris C, Shen L, Kamal MA, Shen B. Natural Products for the Prevention and Control of the COVID-19 Pandemic: Sustainable Bioresources. Front Pharmacol 2021; 12:758159. [PMID: 34925017 PMCID: PMC8671886 DOI: 10.3389/fphar.2021.758159] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Accepted: 10/27/2021] [Indexed: 02/05/2023] Open
Abstract
Background: The world has been unprecedentedly hit by a global pandemic which broke the record of deadly pandemics that faced humanity ever since its existence. Even kids are well-versed in the terminologies and basics of the SARS-CoV-2 virus and COVID-19 now. The vaccination program has been successfully launched in various countries, given that the huge global population of concern is still far behind to be vaccinated. Furthermore, the scarcity of any potential drug against the COVID-19-causing virus forces scientists and clinicians to search for alternative and complementary medicines on a war-footing basis. Aims and Objectives: The present review aims to cover and analyze the etiology and epidemiology of COVID-19, the role of intestinal microbiota and pro-inflammatory markers, and most importantly, the natural products to combat this deadly SARS-CoV-2 virus. Methods: A primary literature search was conducted through PubMed and Google Scholar using relevant keywords. Natural products were searched from January 2020 to November 2020. No timeline limit has been imposed on the search for the biological sources of those phytochemicals. Interactive mapping has been done to analyze the multi-modal and multi-target sources. Results and Discussion: The intestinal microbiota and the pro-inflammatory markers that can serve the prognosis, diagnosis, and treatment of COVID-19 were discussed. The literature search resulted in yielding 70 phytochemicals and ten polyherbal formulations which were scientifically analyzed against the SARS-CoV-2 virus and its targets and found significant. Retrospective analyses led to provide information about 165 biological sources that can also be screened if not done earlier. Conclusion: The interactive analysis mapping of biological sources with phytochemicals and targets as well as that of phytochemical class with phytochemicals and COVID-19 targets yielded insights into the multitarget and multimodal evidence-based complementary medicines.
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Affiliation(s)
- Rajeev K. Singla
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- iGlobal Research and Publishing Foundation, New Delhi, India
| | - Xuefei He
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Hitesh Chopra
- Chitkara College of Pharmacy, Chitkara University, Rajpura, India
| | | | - Li Shen
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
| | - Mohammad Amjad Kamal
- West China School of Nursing/Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Enzymoics; Novel Global Community Educational Foundation, Hebersham, NSW, Australia
| | - Bairong Shen
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China
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22
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Li Z, Li Y, Li L, Mo X, Li S, Xie M, Zhan Y, Lin Y, Li Z, Xie M, Chen Z, Zhu A, Ying R, Yu L, Zhao J, Li SC, Cai W, Ye F. Alteration of the respiratory microbiome in COVID-19 patients with different severities. J Genet Genomics 2021; 49:258-261. [PMID: 34798357 PMCID: PMC8595322 DOI: 10.1016/j.jgg.2021.11.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 11/01/2021] [Accepted: 11/03/2021] [Indexed: 12/12/2022]
Affiliation(s)
- Zhengtu Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, 510120, China
| | - Yinhu Li
- Department of Computer Sciences, City University of Hong Kong, Hong Kong, 999077, China
| | - Linghua Li
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, China
| | - Xiaoneng Mo
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, China
| | - Shaoqiang Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, 510120, China
| | - Mingzhou Xie
- Beijing YuanShengKangTai (ProtoDNA) Genetech Co. Ltd., Beijing, 100190, China
| | - Yangqing Zhan
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, 510120, China
| | - Ye Lin
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, 510120, China
| | - Zhun Li
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, 510120, China
| | - Min Xie
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, China
| | - Zhaoming Chen
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, 510120, China
| | - Airu Zhu
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, 510120, China
| | - Ruosu Ying
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, China
| | - Le Yu
- Beijing YuanShengKangTai (ProtoDNA) Genetech Co. Ltd., Beijing, 100190, China
| | - Jincun Zhao
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, 510120, China
| | - Shuai Cheng Li
- Department of Computer Sciences, City University of Hong Kong, Hong Kong, 999077, China.
| | - Weiping Cai
- Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, 510060, China.
| | - Feng Ye
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, 510120, China.
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23
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Skrajnowska D, Brumer M, Kankowska S, Matysek M, Miazio N, Bobrowska-Korczak B. Covid 19: Diet Composition and Health. Nutrients 2021; 13:2980. [PMID: 34578858 PMCID: PMC8472186 DOI: 10.3390/nu13092980] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 08/09/2021] [Accepted: 08/26/2021] [Indexed: 12/29/2022] Open
Abstract
The virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the disease coronavirus disease 2019 (COVID-19). The cumulative number of cases reported globally is now nearly 197 million and the number of cumulative deaths is 4.2 million (26 July to 1 August 2021). Currently we are focusing primarily on keeping a safe distance from others, washing our hands, and wearing masks, and the question of the effects of diet and diet-dependent risk factors remains outside the center of attention. Nevertheless, numerous studies indicate that diet can play an important role in the course of COVID-19. In this paper, based on select scientific reports, we discuss the structure and replication cycle of SARS-CoV-2, risk factors, dietary standards for sick patients, and the roles of the microbiome and dietary components supporting the immune system in preventing COVID-19.
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Affiliation(s)
| | | | | | | | | | - Barbara Bobrowska-Korczak
- Department of Bromatology, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland; (D.S.); (M.B.); (S.K.); (M.M.); (N.M.)
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24
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Tang G, Zhang L, Huang W, Wei Z. Could Immunonutrition Help in the Fight against COVID-19 in Cancer Patient? Nutr Cancer 2021; 74:1203-1212. [PMID: 34309463 DOI: 10.1080/01635581.2021.1957128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The rapid and widespread global pandemic of 2019 coronavirus disease (COVID-19) has had unprecedented negative health and economic impacts. Immune responses play a key role in the development of COVID-19, including the disruption of immune balance and cytokine storms caused by excessive inflammatory responses. Due to the effects of cancer itself and treatment, patients often accompanied by immunosuppression appear to be a susceptible population for COVID-19. Worryingly, COVID-19 with cancer is associated with a poor prognosis. Cancer patients are a vulnerable group, threatened by COVID-19, finding a way to combat COVID-19 for them is urgent. Immunonutrition is closely related to balance and strong immune function. Supplementary immunonutrition can improve the immune function and inflammatory response of cancer patients after surgery, which provides evidence for the role of immunonutrition in combating COVID-19. We reviewed possible mechanisms of immunonutrition against COVID-19, including enhancing immune cell function, increasing immune cell count, ameliorating excessive inflammatory response, and regulating gut microbiota. Immunonutrition supplementation in cancer patients may be beneficial to enhance immune function in the early stage of COVID-19 infection and control excessive inflammatory response in the late stage. Therefore, immunonutrition is a potential strategy for the prevention and treatment of COVID-19 in cancer.
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Affiliation(s)
- Gang Tang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Linyu Zhang
- Department of Clinical Medicine, Chongqing Medical University, Chongqing, China
| | - Wang Huang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhengqiang Wei
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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25
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van der Lelie D, Oka A, Taghavi S, Umeno J, Fan TJ, Merrell KE, Watson SD, Ouellette L, Liu B, Awoniyi M, Lai Y, Chi L, Lu K, Henry CS, Sartor RB. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nat Commun 2021; 12:3105. [PMID: 34050144 PMCID: PMC8163890 DOI: 10.1038/s41467-021-23460-x] [Citation(s) in RCA: 115] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 04/29/2021] [Indexed: 12/12/2022] Open
Abstract
Environmental factors, mucosal permeability and defective immunoregulation drive overactive immunity to a subset of resident intestinal bacteria that mediate multiple inflammatory conditions. GUT-103 and GUT-108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients, address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. GUT-103, composed of 17 strains that synergistically provide protective and sustained engraftment in the IBD inflammatory environment, prevented and treated chronic immune-mediated colitis. Therapeutic application of GUT-108 reversed established colitis in a humanized chronic T cell-mediated mouse model. It decreased pathobionts while expanding resident protective bacteria; produced metabolites promoting mucosal healing and immunoregulatory responses; decreased inflammatory cytokines and Th-1 and Th-17 cells; and induced interleukin-10-producing colonic regulatory cells, and IL-10-independent homeostatic pathways. We propose GUT-108 for treating and preventing relapse for IBD and other inflammatory conditions characterized by unbalanced microbiota and mucosal permeability.
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Affiliation(s)
| | - Akihiko Oka
- Departments of Medicine, Microbiology and Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Internal Medicine II, Shimane University Faculty of Medicine, Shimane, Japan
| | | | - Junji Umeno
- Departments of Medicine, Microbiology and Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Fukuoka, Japan
| | | | | | | | | | - Bo Liu
- Departments of Medicine, Microbiology and Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Muyiwa Awoniyi
- Departments of Medicine, Microbiology and Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Yunjia Lai
- Department of Environmental Sciences and Engineering, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Liang Chi
- Department of Environmental Sciences and Engineering, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Kun Lu
- Department of Environmental Sciences and Engineering, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | | | - R Balfour Sartor
- Departments of Medicine, Microbiology and Immunology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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26
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Interplay between severities of COVID-19 and the gut microbiome: implications of bacterial co-infections? Gut Pathog 2021; 13:14. [PMID: 33632296 PMCID: PMC7906082 DOI: 10.1186/s13099-021-00407-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 02/16/2021] [Indexed: 01/07/2023] Open
Abstract
COVID-19 is an acute respiratory distress syndrome and is often accompanied by gastrointestinal symptoms. The SARS-CoV-2 has been traced not only in nasopharyngeal and mid-nasal swabs but also in stool and rectal swabs of COVID-19 patients. The gut microbiota is important for an effective immune response as it ensures that unfavorable immune reactions in lungs and other vital organs are regulated. The human gut-lung microbiota interplay provides a framework for therapies in the treatment and management of several pulmonary diseases and infections. Here, we have collated data from COVID-19 studies, which suggest that bacterial co-infections as well as the gut-lung cross talk may be important players in COVID-19 disease prognosis. Our analyses suggests a role of gut microbiome in pathogen infections as well as in an array of excessive immune reactions during and post COVID-19 infection recovery period.
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27
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Devaux CA, Lagier JC, Raoult D. New Insights Into the Physiopathology of COVID-19: SARS-CoV-2-Associated Gastrointestinal Illness. Front Med (Lausanne) 2021; 8:640073. [PMID: 33681266 PMCID: PMC7930624 DOI: 10.3389/fmed.2021.640073] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 01/20/2021] [Indexed: 12/17/2022] Open
Abstract
Although SARS-CoV-2 is considered a lung-tropic virus that infects the respiratory tract through binding to the ACE2 cell-surface molecules present on alveolar lungs epithelial cells, gastrointestinal symptoms have been frequently reported in COVID-19 patients. What can be considered an apparent paradox is that these symptoms (e.g., diarrhea), sometimes precede the development of respiratory tract illness as if the breathing apparatus was not its first target during viral dissemination. Recently, evidence was reported that the gut is an active site of replication for SARS-CoV-2. This replication mainly occurs in mature enterocytes expressing the ACE2 viral receptor and TMPRSS4 protease. In this review we question how SARS-CoV-2 can cause intestinal disturbances, whether there are pneumocyte-tropic, enterocyte-tropic and/or dual tropic strains of SARS-CoV-2. We examine two major models: first, that of a virus directly causing damage locally (e.g., by inducing apoptosis of infected enterocytes); secondly, that of indirect effect of the virus (e.g., by inducing changes in the composition of the gut microbiota followed by the induction of an inflammatory process), and suggest that both situations probably occur simultaneously in COVID-19 patients. We eventually discuss the consequences of the virus replication in brush border of intestine on long-distance damages affecting other tissues/organs, particularly lungs.
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Affiliation(s)
- Christian A. Devaux
- Aix-Marseille University, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France
- CNRS, Marseille, France
| | - Jean-Christophe Lagier
- Aix-Marseille University, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France
| | - Didier Raoult
- Aix-Marseille University, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France
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28
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Dolatshahi M, Sabahi M, Aarabi MH. Pathophysiological Clues to How the Emergent SARS-CoV-2 Can Potentially Increase the Susceptibility to Neurodegeneration. Mol Neurobiol 2021; 58:2379-2394. [PMID: 33417221 PMCID: PMC7791539 DOI: 10.1007/s12035-020-02236-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Accepted: 11/25/2020] [Indexed: 12/20/2022]
Abstract
Along with emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, a myriad of neurologic symptoms, associated with structural brain changes, were reported. In this paper, we provide evidence to critically discuss the claim that the survived patients could possibly be at increased risk for neurodegenerative diseases via various mechanisms. This virus can directly invade the brain through olfactory bulb, retrograde axonal transport from peripheral nerve endings, or via hematogenous or lymphatic routes. Infection of the neurons along with peripheral leukocytes activation results in pro-inflammatory cytokine increment, rendering the brain to neurodegenerative changes. Also, occupation of the angiotensin-converting enzyme 2 (ACE-2) with the virus may lead to a decline in ACE-2 activity, which acts as a neuroprotective factor. Furthermore, acute respiratory distress syndrome (ARDS) and septicemia induce hypoxemia and hypoperfusion, which are locally exacerbated due to the hypercoagulable state and micro-thrombosis in brain vessels, leading to oxidative stress and neurodegeneration. Common risk factors for COVID-19 and neurodegenerative diseases, such as metabolic risk factors, genetic predispositions, and even gut microbiota dysbiosis, can contribute to higher occurrence of neurodegenerative diseases in COVID-19 survivors. However, it should be considered that severity of the infection, the extent of neurologic symptoms, and the persistence of viral infection consequences are major determinants of this association. Importantly, whether this pandemic will increase the overall incidence of neurodegeneration is not clear, as a high percentage of patients with severe form of COVID-19 might probably not survive enough to develop neurodegenerative diseases.
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Affiliation(s)
- Mahsa Dolatshahi
- Students' Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran. .,NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
| | - Mohammadmahdi Sabahi
- NeuroImaging Network (NIN), Universal Scientific Education and Research Network (USERN), Tehran, Iran.,Neurosurgery Research Group (NRG), Student Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mohammad Hadi Aarabi
- Department of Neuroscience, University of Padova, Padova, Italy.,Padova Neuroscience Center (PNC), University of Padova, Padova, Italy
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29
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Krishnan A, Hamilton JP, Alqahtani SA, Woreta TA. COVID-19: An overview and a clinical update. World J Clin Cases 2021; 9:8-23. [PMID: 33511168 PMCID: PMC7809683 DOI: 10.12998/wjcc.v9.i1.8] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 10/30/2020] [Accepted: 12/06/2020] [Indexed: 02/06/2023] Open
Abstract
The outbreak of coronavirus disease-2019 (COVID-19, previously known as 2019 nCoV) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Wuhan City, China, has spread rapidly around the world. Most patients from the first cluster had an epidemiological connection to the Wuhan's Huanan Seafood Wholesale Market. Available evidence has shown that SARS-CoV-2 can be easily transmitted from person to person through close contact and respiratory droplets, posing a substantial challenge to public health. At present, the research on SARS-CoV-2 is still in the primary stages. However, dexa-methasone and remdesivir are appeared to be promising medical therapies. Still, there is no definite specific treatment, and the mainstay of treatment is still focused on supportive therapies. Currently, over 150 vaccines are under investigation. It is necessary to understand the nature of the virus and its clinical characteristics in order to find effectively manage the disease. The knowledge about this virus is rapidly evolving, and clinicians must update themselves regularly. The present review comprehensively summarizes the epidemiology, pathogenesis, clinical characteristics, and management of COVID-19 based on the current evidence.
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Affiliation(s)
- Arunkumar Krishnan
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States
| | - James P Hamilton
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States
| | - Saleh A Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States
- Liver Transplant Center, King Faisal Specialist Hospital & Research Center, Riyadh 12713, Saudi Arabia
| | - Tinsay A Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States
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30
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Ferreira C, Viana SD, Reis F. Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update. Microorganisms 2020; 9:microorganisms9010053. [PMID: 33379162 PMCID: PMC7824665 DOI: 10.3390/microorganisms9010053] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 12/19/2020] [Accepted: 12/21/2020] [Indexed: 02/07/2023] Open
Abstract
The scientific knowledge already attained regarding the way severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells and the clinical manifestations and consequences for Coronavirus Disease 2019 (COVID-19) patients, especially the most severe cases, brought gut microbiota into the discussion. It has been suggested that intestinal microflora composition plays a role in this disease because of the following: (i) its relevance to an efficient immune system response; (ii) the fact that 5–10% of the patients present gastrointestinal symptoms; and (iii) because it is modulated by intestinal angiotensin-converting enzyme 2 (ACE2) (which is the virus receptor). In addition, it is known that the most severely affected patients (those who stay longer in hospital, who require intensive care, and who eventually die) are older people with pre-existing cardiovascular, metabolic, renal, and pulmonary diseases, the same people in which the prevalence of gut microflora dysbiosis is higher. The COVID-19 patients presenting poor outcomes are also those in which the immune system’s hyperresponsiveness and a severe inflammatory condition (collectively referred as “cytokine storm”) are particularly evident, and have been associated with impaired microbiota phenotype. In this article, we present the evidence existing thus far that may suggest an association between intestinal microbiota composition and the susceptibility of some patients to progress to severe stages of the disease.
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Affiliation(s)
- Carolina Ferreira
- Institute of Pharmacology & Experimental Therapeutics, & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (C.F.); (S.D.V.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), 3000-075 Coimbra, Portugal
| | - Sofia D. Viana
- Institute of Pharmacology & Experimental Therapeutics, & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (C.F.); (S.D.V.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), 3000-075 Coimbra, Portugal
- Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy, 3046-854 Coimbra, Portugal
| | - Flávio Reis
- Institute of Pharmacology & Experimental Therapeutics, & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal; (C.F.); (S.D.V.)
- Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal
- Clinical Academic Center of Coimbra (CACC), 3000-075 Coimbra, Portugal
- Correspondence: ; Tel.: +351-239-480-053
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31
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Abstract
Although the COVID-19 pandemic is caused by a single virus, the rest of the human microbiome appears to be involved in the disease and could influence vaccine responses while offering opportunities for microbiome-directed therapeutics. The newly formed Microbiome Centers Consortium (MCC) surveyed its membership and identified four ways to leverage the strengths and experience of microbiome centers in the response to the COVID-19 pandemic. Although the COVID-19 pandemic is caused by a single virus, the rest of the human microbiome appears to be involved in the disease and could influence vaccine responses while offering opportunities for microbiome-directed therapeutics. The newly formed Microbiome Centers Consortium (MCC) surveyed its membership and identified four ways to leverage the strengths and experience of microbiome centers in the response to the COVID-19 pandemic. To meet these needs, the MCC will provide a platform to coordinate clinical and environmental research, assist with practical obstacles, and help communicate the connections between the microbiome and COVID-19. We ask that microbiome researchers join us in these efforts to address the ongoing pandemic.
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Mantziari A, Salminen S, Szajewska H, Malagón-Rojas JN. Postbiotics against Pathogens Commonly Involved in Pediatric Infectious Diseases. Microorganisms 2020; 8:E1510. [PMID: 33008065 PMCID: PMC7601467 DOI: 10.3390/microorganisms8101510] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/22/2020] [Accepted: 09/29/2020] [Indexed: 02/08/2023] Open
Abstract
The Sustainable Development goals for 2020 included reducing all causes associated with infant and perinatal mortality in their priorities. The use of compounds with bioactive properties has been proposed as a therapeutic strategy due to their stimulating effect on the host's immune system. Additionally, biotherapeutic products such as postbiotics, tentatively defined as compounds produced during a fermentation process that support health and well-being, promote intestinal barrier integrity without posing considerable risks to children's health. Although this is a concept in development, there are increasing studies in the field of nutrition, chemistry, and health that aim to understand how postbiotics can help prevent different types of infections in priority populations such as minors under the age of five. The present review aims to describe the main mechanisms of action of postbiotics. In addition, it presents the available current evidence regarding the effects of postbiotics against pathogens commonly involved in pediatric infections. Postbiotics may constitute a safe alternative capable of modulating the cellular response and stimulating the host's humoral response.
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Affiliation(s)
- Anastasia Mantziari
- Functional Foods Forum, Faculty of Medicine, University of Turku, 20520 Turku, Finland;
| | - Seppo Salminen
- Functional Foods Forum, Faculty of Medicine, University of Turku, 20520 Turku, Finland;
| | - Hania Szajewska
- Department of Paediatrics at the Medical University of Warsaw, 02091 Warsaw, Poland;
| | - Jeadran Nevardo Malagón-Rojas
- Facultad de Medicina, Universidad El Bosque, 110121 Bogotá, Colombia;
- Instituto Nacional de Salud de Colombia, 111321 Bogotá, Colombia
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