|
1
|
Lau RI, Su Q, Ng SC. Long COVID and gut microbiome: insights into pathogenesis and therapeutics. Gut Microbes 2025; 17:2457495. [PMID: 39854158 PMCID: PMC11776476 DOI: 10.1080/19490976.2025.2457495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 01/15/2025] [Accepted: 01/17/2025] [Indexed: 01/26/2025] Open
Abstract
Post-acute coronavirus disease 2019 syndrome (PACS), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19), is typically characterized by long-term debilitating symptoms affecting multiple organs and systems. Unfortunately, there is currently a lack of effective treatment strategies. Altered gut microbiome has been proposed as one of the plausible mechanisms involved in the pathogenesis of PACS; extensive studies have emerged to bridge the gap between the persistent symptoms and the dysbiosis of gut microbiome. Recent clinical trials have indicated that gut microbiome modulation using probiotics, prebiotics, and fecal microbiota transplantation (FMT) led to improvements in multiple symptoms related to PACS, including fatigue, memory loss, difficulty in concentration, gastrointestinal upset, and disturbances in sleep and mood. In this review, we highlight the latest evidence on the key microbial alterations observed in PACS, as well as the use of microbiome-based therapeutics in managing PACS symptoms. These novel findings altogether shed light on the treatment of PACS and other chronic conditions.
Collapse
Affiliation(s)
- Raphaela I. Lau
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong KongSAR, China
- Microbiota I-Center (MagIC), Hong KongSAR, China
| | - Qi Su
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong KongSAR, China
- Microbiota I-Center (MagIC), Hong KongSAR, China
| | - Siew C. Ng
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong KongSAR, China
- Microbiota I-Center (MagIC), Hong KongSAR, China
- Li Ka Shing Institute of Health Sciences, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong KongSAR, China
| |
Collapse
|
|
2
|
Hetta HF, Ahmed R, Ramadan YN, Fathy H, Khorshid M, Mabrouk MM, Hashem M. Gut virome: New key players in the pathogenesis of inflammatory bowel disease. World J Methodol 2025; 15:92592. [DOI: 10.5662/wjm.v15.i2.92592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 05/28/2024] [Accepted: 07/23/2024] [Indexed: 11/27/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory illness of the intestine. While the mechanism underlying the pathogenesis of IBD is not fully understood, it is believed that a complex combination of host immunological response, environmental exposure, particularly the gut microbiota, and genetic susceptibility represents the major determinants. The gut virome is a group of viruses found in great frequency in the gastrointestinal tract of humans. The gut virome varies greatly among individuals and is influenced by factors including lifestyle, diet, health and disease conditions, geography, and urbanization. The majority of research has focused on the significance of gut bacteria in the progression of IBD, although viral populations represent an important component of the microbiome. We conducted this review to highlight the viral communities in the gut and their expected roles in the etiopathogenesis of IBD regarding published research to date.
Collapse
Affiliation(s)
- Helal F Hetta
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
- Division of Microbiology, Immunology and Biotechnology, Faculty of pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Rehab Ahmed
- Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia
| | - Yasmin N Ramadan
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Hayam Fathy
- Department of Internal Medicine, Division Hepatogastroenterology, Assiut University, Assiut 71515, Egypt
| | - Mohammed Khorshid
- Department of Clinical Research, Egyptian Developers of Gastroenterology and Endoscopy Foundation, Cairo 11936, Egypt
| | - Mohamed M Mabrouk
- Department of Internal Medicine, Faculty of Medicine. Tanta University, Tanta 31527, Egypt
| | - Mai Hashem
- Department of Tropical Medicine, Gastroenterology and Hepatology, Assiut University Hospital, Assiut 71515, Egypt
| |
Collapse
|
|
3
|
Wu H, Liu Z, Li Y. Intestinal microbiota and respiratory system diseases: Relationships with three common respiratory virus infections. Microb Pathog 2025; 203:107500. [PMID: 40139334 DOI: 10.1016/j.micpath.2025.107500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 03/19/2025] [Accepted: 03/21/2025] [Indexed: 03/29/2025]
Abstract
In recent years, the role of the intestinal microbiota in regulating host health and immune balance has attracted widespread attention. This study provides an in-depth analysis of the close relationship between the intestinal microbiota and respiratory system diseases, with a focus on three common respiratory virus infections, including respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and influenza virus. The research indicates that during RSV infection, there is a significant decrease in intestinal microbial diversity, suggesting the impact of the virus on the intestinal ecosystem. In SARS-CoV-2 infection, there are evident alterations in the intestinal microbiota, which are positively correlated with the severity of the disease. Similarly, influenza virus infection is associated with dysbiosis of the intestinal microbiota, and studies have shown that the application of specific probiotics exhibits beneficial effects against influenza virus infection. Further research indicates that the intestinal microbiota exerts a wide and profound impact on the occurrence and development of respiratory system diseases through various mechanisms, including modulation of the immune system and production of short-chain fatty acids (SCFAs). This article comprehensively analyzes these research advances, providing new perspectives and potential strategies for the prevention and treatment of future respiratory system diseases. This study not only deepens our understanding of the relationship between the intestinal microbiota and respiratory system diseases but also offers valuable insights for further exploring the role of host-microbiota interactions in the development of diseases.
Collapse
Affiliation(s)
- Haonan Wu
- Department of Respiratory, Children's Medical Center, The First Hospital of Jilin University, Changchun, China; Clinical Research Center for Child Health, The First Hospital of Jilin University, Changchun, China
| | - Ziyu Liu
- The First Hospital of Jilin University, Changchun, China.
| | - Yanan Li
- Department of Respiratory, Children's Medical Center, The First Hospital of Jilin University, Changchun, China; Clinical Research Center for Child Health, The First Hospital of Jilin University, Changchun, China.
| |
Collapse
|
|
4
|
Yang Y, Wang D, Li L, Song J, Yang X, Li J. Evolution of enteric viruses in the progression of colorectal cancer via the adenoma-carcinoma sequence pathway. Virus Res 2025; 355:199569. [PMID: 40180222 PMCID: PMC12005302 DOI: 10.1016/j.virusres.2025.199569] [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: 09/13/2024] [Revised: 03/22/2025] [Accepted: 03/31/2025] [Indexed: 04/05/2025]
Abstract
The global incidence of colorectal cancer (CRC) is increasing. In the majority of CRC cases, colon cancer develops from alterations in the adenoma-carcinoma sequence pathway. Currently, there are few studies regarding the effects of enteric viruses on the adenoma-carcinoma sequence pathway, and subsequently, the progression and development of the CRC. Here, fecal and tissue samples from a normal control group, an adenomatous polyp group, and a colorectal adenocarcinoma group were collected to gain a deeper understanding of the variations in enteric viruses in CRC patients and to analyze their significance. With the progression of CRC from adenoma to adenocarcinoma, the number of DNA viruses in the virus-like particles (VLPs) of fecal and tissue samples gradually increased, and there were distinct differences in the composition of enteric viruses among the different groups. Multiple species correlation analysis revealed extensive interactions among viruses, bacteria, and fungi in fecal and tissue samples. Functional analysis also revealed that the functional pathways in fecal and tissue samples also underwent significant changes. In conclusion, the changes in the composition and function of enteric viruses in the progression of CRC via adenoma-carcinoma sequence pathway were analyzed in this study, and these changes hold certain importance for exploring the role of enteric viruses in the occurrence of this disease; however, their mode of action and specific mechanisms require further investigation.
Collapse
Affiliation(s)
- Ying Yang
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Dan Wang
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China; Department of Gastroenterology, Pidu District People's Hospital, Chengdu, Sichuan, China
| | - Longlin Li
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Jieyu Song
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China
| | - Xianglan Yang
- Pengzhou Branch of the First Affiliated Hospital of Chengdu Medical College, Pengzhou Second People's Hospital, Chengdu, China
| | - Jun Li
- Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
| |
Collapse
|
|
5
|
Gaspar BS, Roşu OA, Enache RM, Manciulea Profir M, Pavelescu LA, Creţoiu SM. Gut Mycobiome: Latest Findings and Current Knowledge Regarding Its Significance in Human Health and Disease. J Fungi (Basel) 2025; 11:333. [PMID: 40422666 DOI: 10.3390/jof11050333] [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: 03/05/2025] [Revised: 04/16/2025] [Accepted: 04/21/2025] [Indexed: 05/28/2025] Open
Abstract
The gut mycobiome, the fungal component of the gut microbiota, plays a crucial role in health and disease. Although fungi represent a small fraction of the gut ecosystem, they influence immune responses, gut homeostasis, and disease progression. The mycobiome's composition varies with age, diet, and host factors, and its imbalance has been linked to conditions such as inflammatory bowel disease (IBD) and metabolic disorders. Advances in sequencing have expanded our understanding of gut fungi, but challenges remain due to methodological limitations and high variability between individuals. Emerging therapeutic strategies, including antifungals, probiotics, fecal microbiota transplantation, and dietary interventions, show promise but require further study. This review highlights recent discoveries on the gut mycobiome, its interactions with bacteria, its role in disease, and potential clinical applications. A deeper understanding of fungal contributions to gut health will help develop targeted microbiome-based therapies.
Collapse
Affiliation(s)
- Bogdan Severus Gaspar
- Department of Surgery, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Surgery Clinic, Bucharest Emergency Clinical Hospital, 014461 Bucharest, Romania
| | - Oana Alexandra Roşu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Robert-Mihai Enache
- Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Monica Manciulea Profir
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Department of Oncology, Elias University Emergency Hospital, 011461 Bucharest, Romania
| | - Luciana Alexandra Pavelescu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Sanda Maria Creţoiu
- Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
| |
Collapse
|
|
6
|
Xie Q, Ni J, Guo W, Ding C, Wang F, Wu Y, Zhao Y, Zhu L, Xu K, Chen Y. Two-year follow-up of gut microbiota alterations in patients after COVID-19: from the perspective of gut enterotype. Microbiol Spectr 2025; 13:e0277424. [PMID: 40207964 PMCID: PMC12054050 DOI: 10.1128/spectrum.02774-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 02/24/2025] [Indexed: 04/11/2025] Open
Abstract
Gut microbiota dysbiosis plays a role in the pathogenesis of post-acute coronavirus disease (COVID-19); however, the long-term recovery of the gut microbiota following SARS-CoV-2 infection remains insufficiently understood. In this study, 239 fecal samples were collected from 87 COVID-19 patients during the acute phase, and at 6 months, 1 year, and 2 years post-discharge. An additional 48 fecal samples from non-COVID-19 controls were also analyzed. Gut enterotypes were determined through 16S rRNA sequencing, and dynamic changes from the acute phase through recovery were assessed. Correlations between enterotypes and clinical characteristics were also examined. Two distinct enterotypes were identified: a Blautia-dominated enterotype (Enterotype-B) and a Streptococcus-dominated enterotype (Enterotype-S). Species diversity and richness were significantly higher in Enterotype-B. Enterotype-S, associated with inflammation, was more prevalent during the acute phase. Six months post-discharge, the ratio of Enterotype-B to Enterotype-S approached normal levels. Patients with Enterotype-S at admission had a higher incidence of severe cases during hospitalization and a longer duration of nasopharyngeal viral shedding compared with those with Enterotype-B. Furthermore, at 6 months post-discharge, residual pulmonary Computed Tomography (CT) abnormalities were more common in patients with Enterotype-S (55%) than in those with Enterotype-B (20%, P = 0.046). An index, B/S, representing the ratio of Blautia and Bifidobacterium to Streptococcus, was introduced and found to correlate closely with clinical characteristics. The Streptococcus-dominated enterotype is associated with inflammation and appears to influence both the severity of illness during the acute phase and cardiopulmonary recovery. IMPORTANCE This study sheds new light on the intricate process of rehabilitating the gut microbiota following disruptions caused by COVID-19. Our approach, which examines the dynamics from the vantage point of enterotypes, reveals a more rapid recovery than previously reported, with the majority of the microbiota rebounding within a 6-month timeframe. Furthermore, our findings underscore the importance of the Blautia-dominated enterotype as a marker of gut health, which plays a pivotal role in mitigating the risk of severe progression and lingering effects post-SARS-CoV-2 infection. By scrutinizing these enterotypes, we can now foresee the potential severity and aftermath of COVID-19, offering a valuable tool for prognosis and intervention.
Collapse
Affiliation(s)
- Qianhan Xie
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiali Ni
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Wanru Guo
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Cheng Ding
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Fengjiao Wang
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China
| | - Yechen Wu
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China
| | - Yuxi Zhao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Lingxiao Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Kaijin Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| | - Yanfei Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
| |
Collapse
|
|
7
|
El Jaddaoui I, Sehli S, Al Idrissi N, Bakri Y, Belyamani L, Ghazal H. The Gut Mycobiome for Precision Medicine. J Fungi (Basel) 2025; 11:279. [PMID: 40278100 PMCID: PMC12028274 DOI: 10.3390/jof11040279] [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: 03/08/2025] [Revised: 03/29/2025] [Accepted: 03/31/2025] [Indexed: 04/26/2025] Open
Abstract
The human gastrointestinal tract harbors a vast array of microorganisms, which play essential roles in maintaining metabolic balance and immune function. While bacteria dominate the gut microbiome, fungi represent a much smaller, often overlooked fraction. Despite their relatively low abundance, fungi may significantly influence both health and disease. Advances in next-generation sequencing, metagenomics, metatranscriptomics, metaproteomics, metabolomics, and computational biology have provided novel opportunities to study the gut mycobiome, shedding light on its composition, functional genes, and metabolite interactions. Emerging evidence links fungal dysbiosis to various diseases, including inflammatory bowel disease, colorectal cancer, metabolic disorders, and neurological conditions. The gut mycobiome also presents a promising avenue for precision medicine, particularly in biomarker discovery, disease diagnostics, and targeted therapeutics. Nonetheless, significant challenges remain in effectively integrating gut mycobiome knowledge into clinical practice. This review examines gut fungal microbiota, highlighting analytical methods, associations with human diseases, and its potential role in precision medicine. It also discusses pathways for clinical translation, particularly in diagnosis and treatment, while addressing key barriers to implementation.
Collapse
Affiliation(s)
- Islam El Jaddaoui
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, University Mohammed V, Rabat 10000, Morocco; (I.E.J.); (Y.B.)
- Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat 10000, Morocco
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
| | - Sofia Sehli
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
| | - Najib Al Idrissi
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
| | - Youssef Bakri
- Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, University Mohammed V, Rabat 10000, Morocco; (I.E.J.); (Y.B.)
- Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, University Mohammed V, Rabat 10000, Morocco
| | - Lahcen Belyamani
- School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco;
| | - Hassan Ghazal
- Laboratory of Precision Medicine & One Health (MedPreOne), School of Medicine, Mohammed VI University of Sciences & Health, Casablanca 82403, Morocco; (S.S.); (N.A.I.)
- Laboratory of Sports Sciences and Performance Optimization, Royal Institute of Executive Management, Salé 10102, Morocco
- National Center for Scientific and Technical Research, Rabat 10102, Morocco
| |
Collapse
|
|
8
|
Krivonos DV, Fedorov DE, Klimina KM, Veselovsky VA, Kovalchuk SN, Pavlenko AV, Yanushevich OO, Andreev DN, Sokolov FS, Fomenko AK, Devkota MK, Andreev NG, Zaborovsky AV, Tsaregorodtsev SV, Evdokimov VV, Krikheli NI, Bely PA, Levchenko OV, Maev IV, Govorun VM, Ilina EN. Gut Mycobiome Changes During COVID-19 Disease. J Fungi (Basel) 2025; 11:194. [PMID: 40137232 PMCID: PMC11943151 DOI: 10.3390/jof11030194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Revised: 02/07/2025] [Accepted: 02/28/2025] [Indexed: 03/27/2025] Open
Abstract
The majority of metagenomic studies are based on the study of bacterial biota. At the same time, the COVID-19 pandemic has prompted interest in the study of both individual fungal pathogens and fungal communities (i.e., the mycobiome) as a whole. Here, in this work, we investigated the human gut mycobiome during COVID-19. Stool samples were collected from patients at two time points: at the time of admission to the hospital (the first time point) and at the time of discharge from the hospital (the second time point). The results of this study revealed that Geotrichum sp. is more represented in a group of patients with COVID-19. Therefore, Geotrichum sp. is elevated in patients at the time of admission to the hospital and underestimated at the time of discharge. Additionally, the influence of factors associated with the diversity of fungal gut microbiota was separately studied, including disease severity and age factors.
Collapse
Affiliation(s)
- Danil V. Krivonos
- Research Institute for Systems Biology and Medicine (RISBM), 18, Nauchniy Proezd, 117246 Moscow, Russia
- Department of Molecular and Translational Medicine, Moscow Institute of Physics and Technology, State University, 141700 Dolgoprudny, Russia
| | - Dmitry E. Fedorov
- Research Institute for Systems Biology and Medicine (RISBM), 18, Nauchniy Proezd, 117246 Moscow, Russia
| | - Ksenia M. Klimina
- Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, ul. Malaya Pirogovskaya, 1s3, 119435 Moscow, Russia
| | - Vladimir A. Veselovsky
- Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency, ul. Malaya Pirogovskaya, 1s3, 119435 Moscow, Russia
| | - Svetlana N. Kovalchuk
- Research Institute for Systems Biology and Medicine (RISBM), 18, Nauchniy Proezd, 117246 Moscow, Russia
| | - Alexander V. Pavlenko
- Research Institute for Systems Biology and Medicine (RISBM), 18, Nauchniy Proezd, 117246 Moscow, Russia
| | - Oleg O. Yanushevich
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Dmitry N. Andreev
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Filipp S. Sokolov
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Aleksey K. Fomenko
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Mikhail K. Devkota
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Nikolai G. Andreev
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Andrey V. Zaborovsky
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Sergei V. Tsaregorodtsev
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Vladimir V. Evdokimov
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Natella I. Krikheli
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Petr A. Bely
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Oleg V. Levchenko
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Igor V. Maev
- Federal State Budgetary Educational Institution of Higher Education “Russian University of Medicine” of the Ministry of Health of the Russian Federation, 127006 Moscow, Russia (F.S.S.); (A.K.F.); (S.V.T.)
| | - Vadim M. Govorun
- Research Institute for Systems Biology and Medicine (RISBM), 18, Nauchniy Proezd, 117246 Moscow, Russia
| | - Elena N. Ilina
- Research Institute for Systems Biology and Medicine (RISBM), 18, Nauchniy Proezd, 117246 Moscow, Russia
| |
Collapse
|
|
9
|
Nai S, Song J, Su W, Liu X. Bidirectional Interplay Among Non-Coding RNAs, the Microbiome, and the Host During Development and Diseases. Genes (Basel) 2025; 16:208. [PMID: 40004537 PMCID: PMC11855195 DOI: 10.3390/genes16020208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 01/24/2025] [Accepted: 01/29/2025] [Indexed: 02/27/2025] Open
Abstract
It is widely known that the dysregulation of non-coding RNAs (ncRNAs) and dysbiosis of the gut microbiome play significant roles in host development and the progression of various diseases. Emerging evidence has highlighted the bidirectional interplay between ncRNAs and the gut microbiome. This article aims to review the current understanding of the molecular mechanisms underlying the crosstalk between ncRNAs, especially microRNA (miRNA), and the gut microbiome in the context of development and diseases, such as colorectal cancer, inflammatory bowel diseases, neurological disorders, obesity, and cardiovascular disease. Ultimately, this review seeks to provide a foundation for exploring the potential roles of ncRNAs and gut microbiome interactions as biomarkers and therapeutic targets for clinical diagnosis and treatment, such as ncRNA mimics, antisense oligonucleotides, and small-molecule compounds, as well as probiotics, prebiotics, and diets.
Collapse
Affiliation(s)
| | | | | | - Xiaoqian Liu
- State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China; (S.N.); (J.S.); (W.S.)
| |
Collapse
|
|
10
|
Straume Z, Krūmiņa N, Elbere I, Rozenberga M, Erts R, Rudzīte D, Proskurina A, Krumina A. Impact of Vitamins, Antibiotics, Probiotics, and History of COVID-19 on the Gut Microbiome in Ulcerative Colitis Patients: A Cross-Sectional Study. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:284. [PMID: 40005401 PMCID: PMC11857389 DOI: 10.3390/medicina61020284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 02/02/2025] [Accepted: 02/04/2025] [Indexed: 02/27/2025]
Abstract
Background and Objectives: The human gut microbiome is essential for the health of the host and is affected by antibiotics and coronavirus disease 2019 (COVID-19). The gut microbiome is recognized as a contributing factor in the development of ulcerative colitis. Specific vitamins and probiotics have been demonstrated to positively influence the microbiome by enhancing the prevalence of expected beneficial microorganisms. Materials and Methods: Forty-nine ulcerative colitis (UC) outpatients from Riga East Clinical University Hospital were enrolled in this cross-sectional study from June 2021 to December 2021. All patients were divided into groups based on history of COVID-19 (COVID-19 positive vs. COVID-19 negative) in the last six months. Information about antibiotic, probiotic, and vitamin intake were outlined, and faecal samples were collected. The MetaPhlAn v.2.6.0 tool was used for the taxonomic classification of the gut microbiome metagenome data. Statistical analysis was performed using R 4.2.1. Results: Of the 49 patients enrolled, 31 (63%) were male and 18 (37%) were female. Coronavirus disease 2019 was found in 14 (28.6%) patients in the last 6 months. Verrucomicrobia was statistically significantly lower in the COVID-19 positive group (M = 0.05; SD = 0.11) compared to the COVID-19 negative group (M = 0.5; SD = 1.22), p = 0.03. Antibiotic non-users had more Firmicutes in their microbiome than antibiotic users (p = 0.008). The most used vitamin supplement was vitamin D (N = 18), fifteen (42.9%) of the patients were COVID-19 negative and 3 (21.4%) were COVID-19 positive over the last six months (p > 0.05). Vitamin C users had more Firmicutes in their gut microbiome compared to non-users (Md = 72.8 [IQR: 66.6; 78.7] vs. Md = 60.1 [IQR: 42.4; 67.7]), p = 0.01. Conclusions: Antibiotic non-users had more Firmicutes than antibiotic users in their gut microbiome. Only vitamin C had statistically significant results; in users, more Firmicutes were observed. A mild course of COVID-19 may not influence ulcerative colitis patients' gut microbiome.
Collapse
Affiliation(s)
- Zane Straume
- Gastroenterology, Hepatology and Nutrition Clinic, Riga East Clinical University Hospital, LV-1038 Riga, Latvia;
- Department of Internal Diseases, Riga Stradins University, LV-1007 Riga, Latvia; (N.K.); (A.P.); (A.K.)
| | - Nikola Krūmiņa
- Department of Internal Diseases, Riga Stradins University, LV-1007 Riga, Latvia; (N.K.); (A.P.); (A.K.)
| | - Ilze Elbere
- Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia; (I.E.); (M.R.)
| | - Maija Rozenberga
- Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia; (I.E.); (M.R.)
| | - Renārs Erts
- The Faculty of Medicine and Life Sciences, University of Latvia, LV-1004 Riga, Latvia;
| | - Dace Rudzīte
- Gastroenterology, Hepatology and Nutrition Clinic, Riga East Clinical University Hospital, LV-1038 Riga, Latvia;
| | - Anna Proskurina
- Department of Internal Diseases, Riga Stradins University, LV-1007 Riga, Latvia; (N.K.); (A.P.); (A.K.)
- Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia
| | - Angelika Krumina
- Department of Internal Diseases, Riga Stradins University, LV-1007 Riga, Latvia; (N.K.); (A.P.); (A.K.)
| |
Collapse
|
|
11
|
Huang Z, Liu Y, Philips A, Zhang F, Zuo T. Varied prevalence and asymptomatic carriage of Cryptococcus gattii in the gut of Chinese populations. THE LANCET. MICROBE 2025:101086. [PMID: 39923780 DOI: 10.1016/j.lanmic.2025.101086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 01/18/2025] [Accepted: 01/21/2025] [Indexed: 02/11/2025]
Affiliation(s)
- Ziyu Huang
- Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510000, China; Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Clinical Research Center for Digestive Diseases, Guangzhou, Guangdong, China
| | - Yunyun Liu
- Jiangsu Province (Suqian) Hospital, Nanjing Medical University Suqian, Jiangsu, China
| | - Anna Philips
- Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
| | - Fen Zhang
- College of Life Science and Technology, Jinan University, Guangzhou, China
| | - Tao Zuo
- Key Laboratory of Human Microbiome and Chronic Diseases, Sun Yat-sen University, Ministry of Education, Guangzhou 510000, China; Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Clinical Research Center for Digestive Diseases, Guangzhou, Guangdong, China.
| |
Collapse
|
|
12
|
Zhou X, Wu Y, Zhu Z, Lu C, Zhang C, Zeng L, Xie F, Zhang L, Zhou F. Mucosal immune response in biology, disease prevention and treatment. Signal Transduct Target Ther 2025; 10:7. [PMID: 39774607 PMCID: PMC11707400 DOI: 10.1038/s41392-024-02043-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 09/05/2024] [Accepted: 10/27/2024] [Indexed: 01/11/2025] Open
Abstract
The mucosal immune system, as the most extensive peripheral immune network, serves as the frontline defense against a myriad of microbial and dietary antigens. It is crucial in preventing pathogen invasion and establishing immune tolerance. A comprehensive understanding of mucosal immunity is essential for developing treatments that can effectively target diseases at their entry points, thereby minimizing the overall impact on the body. Despite its importance, our knowledge of mucosal immunity remains incomplete, necessitating further research. The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored the critical role of mucosal immunity in disease prevention and treatment. This systematic review focuses on the dynamic interactions between mucosa-associated lymphoid structures and related diseases. We delve into the basic structures and functions of these lymphoid tissues during disease processes and explore the intricate regulatory networks and mechanisms involved. Additionally, we summarize novel therapies and clinical research advances in the prevention of mucosal immunity-related diseases. The review also addresses the challenges in developing mucosal vaccines, which aim to induce specific immune responses while maintaining tolerance to non-pathogenic microbes. Innovative therapies, such as nanoparticle vaccines and inhalable antibodies, show promise in enhancing mucosal immunity and offer potential for improved disease prevention and treatment.
Collapse
Affiliation(s)
- Xiaoxue Zhou
- School of Medicine, Hangzhou City University, Hangzhou, China
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China
| | - Yuchen Wu
- The First School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhipeng Zhu
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China
| | - Chu Lu
- The First Affiliated Hospital, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China
| | - Chunwu Zhang
- The First School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Linghui Zeng
- School of Medicine, Hangzhou City University, Hangzhou, China
| | - Feng Xie
- The First Affiliated Hospital, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
| | - Long Zhang
- MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, China.
- The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China.
| | - Fangfang Zhou
- The First Affiliated Hospital, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
| |
Collapse
|
|
13
|
Wei G. Insights into gut fungi in pigs: A comprehensive review. J Anim Physiol Anim Nutr (Berl) 2025; 109:96-112. [PMID: 39154229 DOI: 10.1111/jpn.14036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Revised: 06/17/2024] [Accepted: 08/04/2024] [Indexed: 08/19/2024]
Abstract
Fungi in the gut microbiota of mammals play a crucial role in host physiological regulation, including intestinal homeostasis and host immune regulation. However, our understanding of gut fungi in mammals remains limited, especially in economically valuable animals, such as pigs. Therefore, this review first describes the classification and characterisation of fungi, provides insights into the methods used to study gut fungi, and summarises the recent progress on pig gut fungi. Additionally, it discusses the challenges in the study of pig gut fungi and highlights potential perspectives. The aim of this review is to serve as a valuable reference for advancing our knowledge of gut fungi in animals.
Collapse
Affiliation(s)
- Guanyue Wei
- National Key Laboratory of Pig Genetic Improvement and Germplasm Innovation, Jiangxi Agricultural University, Nanchang, China
| |
Collapse
|
|
14
|
An Y, He L, Xu X, Piao M, Wang B, Liu T, Cao H. Gut microbiota in post-acute COVID-19 syndrome: not the end of the story. Front Microbiol 2024; 15:1500890. [PMID: 39777148 PMCID: PMC11703812 DOI: 10.3389/fmicb.2024.1500890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to major global health concern. However, the focus on immediate effects was assumed as the tip of iceberg due to the symptoms following acute infection, which was defined as post-acute COVID-19 syndrome (PACS). Gut microbiota alterations even after disease resolution and the gastrointestinal symptoms are the key features of PACS. Gut microbiota and derived metabolites disorders may play a crucial role in inflammatory and immune response after SARS-CoV-2 infection through the gut-lung axis. Diet is one of the modifiable factors closely related to gut microbiota and COVID-19. In this review, we described the reciprocal crosstalk between gut and lung, highlighting the participation of diet and gut microbiota in and after COVID-19 by destroying the gut barrier, perturbing the metabolism and regulating the immune system. Therefore, bolstering beneficial species by dietary supplements, probiotics or prebiotics and fecal microbiota transplantation (FMT) may be a novel avenue for COVID-19 and PACS prevention. This review provides a better understanding of the association between gut microbiota and the long-term consequences of COVID-19, which indicates modulating gut dysbiosis may be a potentiality for addressing this multifaceted condition.
Collapse
Affiliation(s)
| | | | | | | | | | - Tianyu Liu
- Tianjin Key Laboratory of Digestive Diseases, Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, National Key Clinical Specialty, General Hospital, Tianjin Medical University, Tianjin, China
| | - Hailong Cao
- Tianjin Key Laboratory of Digestive Diseases, Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, National Key Clinical Specialty, General Hospital, Tianjin Medical University, Tianjin, China
| |
Collapse
|
|
15
|
Reyes Z, Stovall MC, Punyamurthula S, Longo M, Maraganore D, Solch-Ottaiano RJ. The impact of gut microbiome and diet on post-acute sequelae of SARS-CoV-2 infection. J Neurol Sci 2024; 467:123295. [PMID: 39550783 DOI: 10.1016/j.jns.2024.123295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 10/21/2024] [Accepted: 11/05/2024] [Indexed: 11/19/2024]
Abstract
Long COVID, also known as Post COVID-19 condition by the World Health Organization or Post-Acute Sequelae of SARS-CoV-2 infection (PASC), is defined as the development of symptoms such as post-exertional malaise, dysgeusia, and partial or full anosmia three months after initial SARS-CoV-2 infection. The multisystem effects of PASC make it difficult to distinguish from its mimickers. Further, a comprehensive evaluation of the gut microbiome, nutrition, and PASC has yet to be studied. The gut-brain axis describes bidirectional immune, neural, endocrine, and humoral modulatory interactions between the gut microbiome and brain function. We explore recent studies that support an association between alterations in gut microbiome diversity and the severity of acute-phase COVID-19, and how these may be affected by diets rich in antioxidants and fiber. The Mediterranean Diet (MeDi) has demonstrated promising neuroprotective effects through its anti-inflammatory processes. Further, diets rich in fiber increase gut diversity and increase the amount of short-chain fatty acids (SCFAs) within the body-both shown to protect from acute COVID-19 complications. Long-term changes to the gut microbiome persist after acute infection and may increase susceptibility to PASC. This study builds on existing knowledge of determinants of PASC and highlights a relationship between nutrition, gut microbiome, acute-phase COVID-19, and, subsequently, PASC susceptibility.
Collapse
Affiliation(s)
- Zabrina Reyes
- Department of Neurology, Tulane University School of Medicine, New Orleans, LA 70112, United States of America
| | - Mary Catherine Stovall
- Department of Neurology, Tulane University School of Medicine, New Orleans, LA 70112, United States of America
| | - Sanjana Punyamurthula
- Department of Neurology, Tulane University School of Medicine, New Orleans, LA 70112, United States of America
| | - Michele Longo
- Department of Neurology, Tulane University School of Medicine, New Orleans, LA 70112, United States of America
| | - Demetrius Maraganore
- Department of Neurology, Tulane University School of Medicine, New Orleans, LA 70112, United States of America; Clinical Neuroscience Research Center, Tulane University School of Medicine, New Orleans, LA 70112, United States of America; Tulane Brain Institute, Tulane University, New Orleans, LA 70112, United States of America
| | - Rebecca J Solch-Ottaiano
- Department of Neurology, Tulane University School of Medicine, New Orleans, LA 70112, United States of America; Clinical Neuroscience Research Center, Tulane University School of Medicine, New Orleans, LA 70112, United States of America; Tulane Brain Institute, Tulane University, New Orleans, LA 70112, United States of America.
| |
Collapse
|
|
16
|
Lee KH, Kim YO, Dho SH, Yong JJH, Oh HS, Lee JH, Yang SJ, Cha I, Chun J, Lee EH, Jeong SJ, Woo W, Choi JP, Han SH, Choi GB, Huh JR, Kim LK, Song YG. Altered gut microbiome in convalescent patients with coronavirus disease 2019. Front Cell Infect Microbiol 2024; 14:1455295. [PMID: 39669269 PMCID: PMC11634865 DOI: 10.3389/fcimb.2024.1455295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Accepted: 11/07/2024] [Indexed: 12/14/2024] Open
Abstract
Introduction Coronavirus disease 2019 (COVID-19) alters the gut microbiome. This study aimed to assess the association between the disease severity of COVID-19 and changes in stool microbes through a seven-month follow-up of stool collection. Methods We conducted a multicentre, prospective longitudinal study of 58 COVID-19 patients and 116 uninfected controls. Differences in the gut microbiota were analysed using 16S ribosomal RNA sequencing. The first stool samples were collected at an early convalescent phase of COVID-19, and the second sample was collected at least seven months after COVID-19 infection. Results and discussion At the order level, Eubacteriales and Bifidobacteriales decreased, while Bacteroidales and Burkholderiales increased in the COVID-19 group compared to the controls. Alpha diversity also decreased in COVID-19 patients compared to controls, with imperfect recovery of the gut microbiome after seven months. The compositional change in the gut microbiome between the early and late convalescent phases was largest in the moderate and severe groups. The severity of COVID-19 was the most influential clinical variable for microbiome composition (Sum of Sqs = 0.686, P = 0.006), and its effect persisted even after partialling out other effects such as antibiotic use and age. Thus, our study indicates a possible interaction between respiratory viral infection and the composition of the gut microbiota community, warranting future mechanistic and prospective longitudinal studies. Additionally, we were able to detect microbiome changes in patients who were re-infected with SARS-CoV-2. Notably, the dominant bacteria in the re-infected group were Lachnospiraceae and Faecalimonas umbilicata, compared to the one-time infected group.
Collapse
Affiliation(s)
- Kyoung Hwa Lee
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yeong Ouk Kim
- CJ Bioscience, Inc., Seoul, Republic of Korea
- Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea
| | - So Hee Dho
- Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jen J. H. Yong
- Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, United States
| | | | - Je Hee Lee
- CJ Bioscience, Inc., Seoul, Republic of Korea
| | | | - Inseong Cha
- CJ Bioscience, Inc., Seoul, Republic of Korea
| | | | - Eun Hwa Lee
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Su Jin Jeong
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Wonjin Woo
- Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae-Phil Choi
- Division of Infectious Diseases, Department of Internal Medicine, Seoul Medical Center, Seoul, Republic of Korea
| | - Sang Hoon Han
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Gloria B. Choi
- The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States
| | - Jun R. Huh
- Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, United States
- Bio2Q, Keio University, Tokyo, Japan
| | - Lark Kyun Kim
- Department of Biomedical Sciences, Graduate School of Medical Science, Brain Korea 21 Project, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Young Goo Song
- Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
17
|
King LR. Gastrointestinal manifestations of long COVID. Life Sci 2024; 357:123100. [PMID: 39357795 DOI: 10.1016/j.lfs.2024.123100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 09/15/2024] [Accepted: 09/28/2024] [Indexed: 10/04/2024]
Abstract
Long COVID is estimated to have affected 6.9 % of US adults, 17.8 million people in the US alone, as of early 2023. While SARS-CoV-2 is primarily considered a respiratory virus, gastrointestinal (GI) symptoms are also frequent in patients with coronavirus disease 2019 (COVID-19) and in patients with Long COVID. The risk of developing GI symptoms is increased with increasing severity of COVID-19, the presence of GI symptoms in the acute infection, and psychological distress both before and after COVID-19. Persistence of the virus in the GI tract, ensuing inflammation, and alteration of the microbiome are all likely mediators of the effects of SARS Co-V-2 virus on the gut. These factors may all increase intestinal permeability and systemic inflammation. GI inflammation and dysbiosis can change the absorption and metabolism of tryptophan, an important neurotransmitter. Long COVID GI symptoms resemble a Disorder of Gut Brain Interaction (DGBI) such as post infection Irritable Bowel Syndrome (IBS). Current standards of treatment for IBS can guide our treatment of Long COVID patients. Dysautonomia, a frequent Long COVID condition affecting the autonomic nervous system, can also affect the GI tract, and must be considered in Long COVID patients with GI symptoms. Long COVID symptoms fall within the broader category of Infection Associated Chronic Conditions (IACCs). Research into the GI symptoms of Long COVID may further our understanding of other post infection chronic GI conditions, and elucidate the roles of therapeutic options including antivirals, probiotics, neuromodulators, and treatments of dysautonomia.
Collapse
Affiliation(s)
- Louise R King
- University of North Carolina School of Medicine, Department of Medicine, Division of General Medicine and Clinical Epidemiology, 5034 Old Clinic Building, 101 Manning Drive, Chapel Hill, NC 27599, United States of America.
| |
Collapse
|
|
18
|
Caldarelli M, Rio P, Giambra V, Palucci I, Gasbarrini A, Gambassi G, Cianci R. SARS-CoV-2 and Environmental Changes: The Perfect Storm. Curr Issues Mol Biol 2024; 46:11835-11852. [PMID: 39590297 PMCID: PMC11592541 DOI: 10.3390/cimb46110703] [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: 09/25/2024] [Revised: 10/20/2024] [Accepted: 10/22/2024] [Indexed: 11/28/2024] Open
Abstract
The COVID-19 pandemic has had a significant impact on the global economy. It also provided insights into how the looming global climate crisis might be addressed, as there are several similarities between the challenges proposed by COVID-19 and those expected from the coming climate emergency. COVID-19 is an immediate health threat, but climate change represents a more gradual and insidious risk that will lead to long-term consequences for human health. Research shows that climate change, air pollution and the pandemics have a negative impact on health. Recent studies show that COVID-19 mortality increases with climate extremes. The goal of our review is to analyze the clinical findings of COVID-19 and how they are affected by the climate change, while also providing insight into the emergence of new variants and their ability to evade the immune system. We selected and synthesized data from primary studies, reviews, meta-analyses, and systematic reviews. Selection was based on rigorous methodological and relevance criteria. Indeed, a new variant of SARS-CoV-2, named JN.1, has emerged as the dominant, first in the United States and then worldwide; the variant has specific mutations in its spike proteins that increase its transmissibility. According to the World Health Organization (WHO), JN.1 is currently the most reported variant of interest (VOI), having been identified in 132 countries. We highlight the link between climate change and pandemics, emphasizing the need for global action, targeted medical approaches and scientific innovation.
Collapse
Affiliation(s)
- Mario Caldarelli
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, 00168 Rome, Italy; (M.C.); (P.R.); (A.G.); (G.G.)
- Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy;
| | - Pierluigi Rio
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, 00168 Rome, Italy; (M.C.); (P.R.); (A.G.); (G.G.)
- Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy;
| | - Vincenzo Giambra
- Institute for Stem Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy;
| | - Ivana Palucci
- Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy;
- Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie-Sezione di Microbiologia, Catholic University of Sacred Heart, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, 00168 Rome, Italy; (M.C.); (P.R.); (A.G.); (G.G.)
- Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy;
| | - Giovanni Gambassi
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, 00168 Rome, Italy; (M.C.); (P.R.); (A.G.); (G.G.)
- Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy;
| | - Rossella Cianci
- Department of Translational Medicine and Surgery, Catholic University of Sacred Heart, 00168 Rome, Italy; (M.C.); (P.R.); (A.G.); (G.G.)
- Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy;
| |
Collapse
|
|
19
|
Bistagnino F, Pizzi D, Mantovani F, Antonino JR, Tovani-Palone MR. Long COVID and gut candidiasis: What is the existing relationship? World J Gastroenterol 2024; 30:4104-4114. [DOI: 10.3748/wjg.v30.i37.4104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 08/30/2024] [Accepted: 09/13/2024] [Indexed: 09/26/2024] Open
Abstract
Since the beginning of the coronavirus disease (COVID) 2019 pandemic, thousands of articles on the topic have been published, and although there is a growing trend of research on another associated condition, long coronavirus disease, important points still remain to be clarified in this respect. Robust evidence has suggested a relevant link between new clinical discoveries and molecular mechanisms that could be associated with the manifestations of different signs and symptoms involving cases of long COVID. However, one of the existing gaps that requires further investigation concerns a possible relationship between gut candidiasis and long COVID. While recent studies also suggest an interplay between the occurrence of these two conditions, it is not yet fully clear how this may happen, as well as the specifics regarding the possible pathophysiological mechanisms involved. In this connection and with the advent of a potential strengthening of the body of evidence supporting the hypothesis of a link between gut candidiasis and long COVID, a better understanding of the clinical presentation, pathophysiology and clinical management of such a relationship should be essential and useful for both, additional advances towards more targeted research and appropriate case management. Knowing more about the signs, symptoms, and complications associated with cases of long COVID is essential in order to more effectively mitigate the related burden and provide a higher quality of care and life for the affected population. In light of this and the need for better outcomes, here we review and discuss the content on different aspects of long COVID, including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis, as well as suggest propositions for future related research.
Collapse
Affiliation(s)
- Filippo Bistagnino
- Department of Medical Biotechnology and Translational Medicine, International Medical School, Università degli Studi di Milano, Milan 20054, Italy
| | - Davide Pizzi
- Department of Medical Biotechnology and Translational Medicine, International Medical School, Università degli Studi di Milano, Milan 20054, Italy
| | - Filippo Mantovani
- Department of Medical Biotechnology and Translational Medicine, International Medical School, Università degli Studi di Milano, Milan 20054, Italy
| | - Jacopo Rosso Antonino
- Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan 20133, Italy
| | - Marcos Roberto Tovani-Palone
- Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, India
| |
Collapse
|
|
20
|
Zhu W, Chi J, Zhang Y, Wu D, Xia X, Liao X, Xu K, Shi W, Hu H, Wang W, Lu Z, Zhang Z, Liu Y. Global hotspots and trends in gut mycological research: a visual analytics and bibliometric approach. Front Immunol 2024; 15:1457913. [PMID: 39416793 PMCID: PMC11479889 DOI: 10.3389/fimmu.2024.1457913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 08/27/2024] [Indexed: 10/19/2024] Open
Abstract
Background Recent findings highlight the significant impact of intestinal fungi on the complex makeup of the gut microbiota and human health, challenging past oversights. However, a lack of thorough systematic and quantitative analyses remains. This study aims to address this gap by thoroughly examining the current research on gut fungi. Through analyzing developments and unique features in this area, our goal is to foster a deeper understanding and identify future research pathways. Methods We performed an extensive bibliometric analysis on documents from 2000 to 2023, sourced from the Web of Science Core Collection (WoSCC). Utilizing advanced visualization tools such as VOSviewer, CiteSpace, and Bibliometrix R, we meticulously examined and illustrated the data in scientific landscapes and networks. Results A total of 1434 papers were analyzed, revealing a substantial increase in publication volume over the past two decades, particularly in 2020. Contributions came from 67 countries, 2178 institutions, and 8,479 authors. China led in publication output with 468 articles, followed by the University of California with 84 articles, and ZHANG F as the most prolific author with 17 articles. Emerging research areas such as "Fungal-Bacteria Interactions," "Gut Fungus and Gut-Brain Axis," and "Gut Fungus and Immunity" are expected to attract growing interest in the future. Conclusion This extensive bibliometric analysis offers a current overview of scholarly efforts concerning intestinal fungi, highlighting the predominant landscape in this field. These insights can assist scholars in identifying appropriate publication avenues, forming collaborative relationships, and enhancing understanding of key themes and emerging areas, thereby stimulating future research endeavors.
Collapse
Affiliation(s)
- Wenhao Zhu
- Medical School of Southeast University, Nanjing, China
| | - Jiayu Chi
- Medical School of Southeast University, Nanjing, China
| | - Yongde Zhang
- Department of Gastroenterology and Endoscopy Center, Xining Hospital of Traditional Chinese Medicine, Xining, China
| | - Dongliang Wu
- Department of Gastroenterology and Endoscopy Center, Binhai County Second People’s Hospital, Yanchen, China
| | - Xinyu Xia
- College of Textile and Clothing Engineering, Soochow University, Suzhou, Jiangsu, China
| | - Xingyu Liao
- Medical School of Southeast University, Nanjing, China
- Beijing Jishuitan Hospital, Beijing, China
| | - Kexin Xu
- Medical School of Southeast University, Nanjing, China
| | - Wenying Shi
- Medical School of Southeast University, Nanjing, China
| | - Haowen Hu
- Medical School of Southeast University, Nanjing, China
| | - Wei Wang
- Medical School of Southeast University, Nanjing, China
| | - Zhiyuan Lu
- Medical School of Southeast University, Nanjing, China
| | - Zixu Zhang
- Medical School of Southeast University, Nanjing, China
| | - Yang Liu
- Medical School of Southeast University, Nanjing, China
- Department of Gastroenterology and Endoscopy Center, Xining Hospital of Traditional Chinese Medicine, Xining, China
- Department of Gastroenterology and Endoscopy Center, Binhai County Second People’s Hospital, Yanchen, China
- Department of Gastroenterology and Endoscopy Center, Pukou People’s Hospital, Nanjing, China
- Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, China
| |
Collapse
|
|
21
|
Puray-Chavez M, Eschbach JE, Xia M, LaPak KM, Zhou Q, Jasuja R, Pan J, Xu J, Zhou Z, Mohammed S, Wang Q, Lawson DQ, Djokic S, Hou G, Ding S, Brody SL, Major MB, Goldfarb D, Kutluay SB. A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models. Nat Commun 2024; 15:8394. [PMID: 39333139 PMCID: PMC11437049 DOI: 10.1038/s41467-024-52803-7] [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: 01/07/2024] [Accepted: 09/22/2024] [Indexed: 09/29/2024] Open
Abstract
Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism of the type I/III IFN-pathway in productively infected cells. Pharmacological inhibition of STING in primary airway cells enhances SARS-CoV-2 replication and reduces virus-induced innate immune activation. Together, our study highlights that tonic activation of the cGAS-STING and IFN pathways can impact SARS-CoV-2 cellular tropism in a manner dependent on ACE2 expression levels.
Collapse
Affiliation(s)
- Maritza Puray-Chavez
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Jenna E Eschbach
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Ming Xia
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Kyle M LaPak
- Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Qianzi Zhou
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Ria Jasuja
- Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Jiehong Pan
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Jian Xu
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Zixiang Zhou
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Shawn Mohammed
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Qibo Wang
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Dana Q Lawson
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Sanja Djokic
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Gaopeng Hou
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Siyuan Ding
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Steven L Brody
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Michael B Major
- Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, USA
| | - Dennis Goldfarb
- Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA
- Institute for Informatics, Data Science & Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
| | - Sebla B Kutluay
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA.
| |
Collapse
|
|
22
|
Liu S, Yu C, Tu Q, Zhang Q, Fu Z, Huang Y, He C, Yao L. Bacterial co-infection in COVID-19: a call to stay vigilant. PeerJ 2024; 12:e18041. [PMID: 39308818 PMCID: PMC11416760 DOI: 10.7717/peerj.18041] [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: 09/22/2023] [Accepted: 08/13/2024] [Indexed: 09/25/2024] Open
Abstract
Co-infection with diverse bacteria is commonly seen in patients infected with the novel coronavirus, SARS-CoV-2. This type of co-infection significantly impacts the occurrence and development of novel coronavirus infection. Bacterial co-pathogens are typically identified in the respiratory system and blood culture, which complicates the diagnosis, treatment, and prognosis of COVID-19, and even exacerbates the severity of disease symptoms and increases mortality rates. However, the status and impact of bacterial co-infections during the COVID-19 pandemic have not been properly studied. Recently, the amount of literature on the co-infection of SARS-CoV-2 and bacteria has gradually increased, enabling a comprehensive discussion on this type of co-infection. In this study, we focus on bacterial infections in the respiratory system and blood of patients with COVID-19 because these infection types significantly affect the severity and mortality of COVID-19. Furthermore, the progression of COVID-19 has markedly elevated the antimicrobial resistance among specific bacteria, such as Klebsiella pneumoniae, in clinical settings including intensive care units (ICUs). Grasping these resistance patterns is pivotal for the optimal utilization and stewardship of antibiotics, including fluoroquinolones. Our study offers insights into these aspects and serves as a fundamental basis for devising effective therapeutic strategies. We primarily sourced our articles from PubMed, ScienceDirect, Scopus, and Google Scholar. We queried these databases using specific search terms related to COVID-19 and its co-infections with bacteria or fungi, and selectively chose relevant articles for inclusion in our review.
Collapse
Affiliation(s)
- Shengbi Liu
- Department of Clinical Laboratory, Guiqian International General Hospital, Guiyang, People’s Republic of China
| | - Chao Yu
- Department of Clinical Laboratory, Guiqian International General Hospital, Guiyang, People’s Republic of China
| | - Qin Tu
- Department of Clinical Laboratory, Guiqian International General Hospital, Guiyang, People’s Republic of China
| | - Qianming Zhang
- Department of Clinical Laboratory, Guiqian International General Hospital, Guiyang, People’s Republic of China
| | - Zuowei Fu
- Department of Clinical Laboratory, Guiqian International General Hospital, Guiyang, People’s Republic of China
| | - Yifeng Huang
- Department of Clinical Laboratory, Guiqian International General Hospital, Guiyang, People’s Republic of China
| | - Chuan He
- Department of Clinical Laboratory, Guiqian International General Hospital, Guiyang, People’s Republic of China
| | - Lei Yao
- Department of Clinical Laboratory, Guiqian International General Hospital, Guiyang, People’s Republic of China
| |
Collapse
|
|
23
|
Puray-Chavez M, Eschbach JE, Xia M, LaPak KM, Zhou Q, Jasuja R, Pan J, Xu J, Zhou Z, Mohammed S, Wang Q, Lawson DQ, Djokic S, Hou G, Ding S, Brody SL, Major MB, Goldfarb D, Kutluay SB. A basally active cGAS-STING pathway limits SARS-CoV-2 replication in a subset of ACE2 positive airway cell models. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.01.07.574522. [PMID: 38260460 PMCID: PMC10802478 DOI: 10.1101/2024.01.07.574522] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/24/2024]
Abstract
Host factors that define the cellular tropism of SARS-CoV-2 beyond the cognate ACE2 receptor are poorly defined. Here we report that SARS-CoV-2 replication is restricted at a post-entry step in a number of ACE2-positive airway-derived cell lines due to tonic activation of the cGAS-STING pathway mediated by mitochondrial DNA leakage and naturally occurring cGAS and STING variants. Genetic and pharmacological inhibition of the cGAS-STING and type I/III IFN pathways as well as ACE2 overexpression overcome these blocks. SARS-CoV-2 replication in STING knockout cell lines and primary airway cultures induces ISG expression but only in uninfected bystander cells, demonstrating efficient antagonism of the type I/III IFN-pathway in productively infected cells. Pharmacological inhibition of STING in primary airway cells enhances SARS-CoV-2 replication and reduces virus-induced innate immune activation. Together, our study highlights that tonic activation of the cGAS-STING and IFN pathways can impact SARS-CoV-2 cellular tropism in a manner dependent on ACE2 expression levels.
Collapse
Affiliation(s)
- Maritza Puray-Chavez
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Jenna E. Eschbach
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Ming Xia
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Kyle M. LaPak
- Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Qianzi Zhou
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Ria Jasuja
- Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Jiehong Pan
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Jian Xu
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Zixiang Zhou
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Shawn Mohammed
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Qibo Wang
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Dana Q. Lawson
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Sanja Djokic
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Gaopeng Hou
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Siyuan Ding
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| | - Steven L. Brody
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Michael B. Major
- Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA
- Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, USA
| | - Dennis Goldfarb
- Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA
- Institute for Informatics, Data Science & Biostatistics, Washington University School of Medicine, St. Louis, MO, USA
| | - Sebla B. Kutluay
- Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
| |
Collapse
|
|
24
|
Bai X, Sönnerborg A, Nowak P. Elite controllers microbiome: unraveling the mystery of association and causation. Curr Opin HIV AIDS 2024; 19:261-267. [PMID: 38874425 DOI: 10.1097/coh.0000000000000867] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2024]
Abstract
PURPOSE OF REVIEW To unravel the current knowledge and possible link between the gut microbiome and HIV-1 virological control in elite controllers (EC), who can suppress viral replication in the absence of antiretroviral therapy. In addition, to discuss the limitations of current research and propose future research directions. RECENT FINDINGS EC possess a different gut bacterial microbiota profile in composition and functionality from that of treatment-naive HIV-1 viremic progressors (VP). Specifically, EC have a richer bacterial microbiota as compared to VP, which closely resembles the microbiota in HIV-1 negative healthy controls (HC). Differentially abundant bacteria are found between EC and VP or HC, though results vary among the few existing studies. These data imply that the gut microbiome could contribute to the natural suppression of HIV-1 infection. SUMMARY An association between the gut microbiome and HIV-1 virological control is evidenced by recent studies. Yet, there are substantial knowledge gaps, and the underlying mechanism of how the microbiome influences the EC phenotype is far from clarified. Future research should consider diverse microbial communities, the complex microbe-host interactions, as well as yet-unidentified causal links between microbiome alterations and HIV-1 disease progression.
Collapse
Affiliation(s)
- Xiangning Bai
- Department of Microbiology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway
- Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm
| | - Anders Sönnerborg
- Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm
- Department of Infectious Diseases, Karolinska University Hospital, Huddinge, Sweden
| | - Piotr Nowak
- Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm
- Department of Infectious Diseases, Karolinska University Hospital, Huddinge, Sweden
| |
Collapse
|
|
25
|
Bai X, Nielsen SD, Kunisaki KM, Trøseid M. Pulmonary comorbidities in people with HIV- the microbiome connection. Curr Opin HIV AIDS 2024; 19:246-252. [PMID: 38935049 DOI: 10.1097/coh.0000000000000871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/28/2024]
Abstract
PURPOSE OF REVIEW To report recent evidence on associations between human microbiome, particularly airway and gut, and pulmonary comorbidities in people with HIV (PWH). Furthermore, we explore how changes in the microbiome may contribute to pulmonary immune dysregulation and higher rates of pulmonary comorbidities among PWH. Finally, we propose future directions in the field. RECENT FINDINGS Increased risk of pulmonary comorbidities and rapid lung function decline have been reported in even well treated PWH. Altered microbiota profiles have been reported in PWH with pulmonary comorbidities and rapid lung function decline as compared to those without. The most consistent data have been the association between HIV-related pulmonary comorbidities, lung and oral microbiota dysbiosis, which has been also associated with distinct respiratory mucosal inflammatory profiles and short-term mortality. However, a possible causal link remains to be elucidated. SUMMARY Associations between the lung and oral microbiome, HIV-associated pulmonary comorbidities and rapid lung function decline have been reported in recent studies. Yet the underlying mechanism underpinning the observed associations is largely unknown and substantial knowledge gaps remain. Future research is warranted to unveil the role and mechanism of human microbiome from different anatomical compartments in relation to pulmonary comorbidities in PWH.
Collapse
Affiliation(s)
- Xiangning Bai
- Department of Microbiology, Division of Laboratory Medicine, Oslo University Hospital, Oslo, Norway
- Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Susanne Dam Nielsen
- Viro-Immunology Research Unit, Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen
- Department of Surgical Gastroenterology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Ken M Kunisaki
- Minneapolis Veterans Affairs Healthcare System
- University of Minnesota, Minneapolis, Minnesota, USA
| | - Marius Trøseid
- Institute of Clinical Medicine, University of Oslo
- Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation
- Section of Clinical Immunology and Infectious Diseases, Department of Rheumatology, Dermatology and Infectious Diseases, Oslo University Hospital, Oslo, Norway
| |
Collapse
|
|
26
|
Herrera-Quintana L, Vázquez-Lorente H, Lopez-Garzon M, Cortés-Martín A, Plaza-Diaz J. Cancer and the Microbiome of the Human Body. Nutrients 2024; 16:2790. [PMID: 39203926 PMCID: PMC11357655 DOI: 10.3390/nu16162790] [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: 08/03/2024] [Revised: 08/16/2024] [Accepted: 08/20/2024] [Indexed: 09/03/2024] Open
Abstract
Cancer remains a public health concern worldwide, with its incidence increasing worldwide and expected to continue growing during the next decades. The microbiome has emerged as a central factor in human health and disease, demonstrating an intricate relationship between the microbiome and cancer. Although some microbiomes present within local tissues have been shown to restrict cancer development, mainly by interacting with cancer cells or the host immune system, some microorganisms are harmful to human health and risk factors for cancer development. This review summarizes the recent evidence concerning the microbiome and some of the most common cancer types (i.e., lung, head and neck, breast, gastric, colorectal, prostate, and cervix cancers), providing a general overview of future clinical approaches and perspectives.
Collapse
Affiliation(s)
- Lourdes Herrera-Quintana
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | - Héctor Vázquez-Lorente
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (L.H.-Q.); (H.V.-L.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | - Maria Lopez-Garzon
- Biomedical Group (BIO277), Department of Physical Therapy, Health Sciences Faculty, University of Granada, 18171 Granada, Spain;
| | - Adrián Cortés-Martín
- PROmoting FITness and Health through Physical Activity Research Group (PROFITH), Sport and Health University Research Institute (iMUDS), University of Granada, 18016 Granada, Spain;
- APC Microbiome Ireland, School of Microbiology, University College Cork, T12 YT20 Cork, Ireland
| | - Julio Plaza-Diaz
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
- Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada
| |
Collapse
|
|
27
|
Shen J, Shen X, Zhao F, Yao J. Pneumomediastinum and pneumoretroperitoneum after COVID-19: concealed intestinal perforation. BMC Infect Dis 2024; 24:801. [PMID: 39118012 PMCID: PMC11308679 DOI: 10.1186/s12879-024-09720-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 08/05/2024] [Indexed: 08/10/2024] Open
Abstract
BACKGROUND With the prevalence of coronavirus disease 2019 (COVID-19), many severe cases have been discovered worldwide. Here, a case of concurrent pneumomediastinum, pneumoretroperitoneum, and intestinal perforation was reported. This case was the first report on COVID-19-induced related complications. CASE PRESENTATION A 74-year-old female patient was hospitalized for COVID-19. Air leakage was unexpectedly found during imaging reexamination. Considering the unobvious subjective feeling of the patient, a conservative treatment was given at the early stage, and finally, sigmoid colon perforation was surgically confirmed. The family gave up the treatment at last, because the patient could not be taken off the ventilator. Coincidentally, the patient also had abnormal renal anatomical position. This situation led to an abnormal air leakage direction and the atypical manifestations of peritonitis. It was also one of the important reasons for the delayed diagnosis and treatment of the disease. CONCLUSIONS Clinicians should be vigilant for spontaneous gastrointestinal perforation in patients with COVID-19, particularly those undergoing treatment with glucocorticoids and tocilizumab. The case is shared to highlight this rare and fatal extrapulmonary manifestation of COVID-19 and further assist clinicians to raise their awareness and timely implement imaging investigation and multidisciplinary intervention so as to facilitate early discovery, diagnosis and treatment and reduce the mortality.
Collapse
Affiliation(s)
- Jiaying Shen
- Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang, China
| | - Xiaoyong Shen
- Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang, China
| | - Feimin Zhao
- Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang, China
| | - Jianping Yao
- Huzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Zhejiang, China.
| |
Collapse
|
|
28
|
McMillan P, Turner AJ, Uhal BD. Mechanisms of Gut-Related Viral Persistence in Long COVID. Viruses 2024; 16:1266. [PMID: 39205240 PMCID: PMC11360392 DOI: 10.3390/v16081266] [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: 07/01/2024] [Revised: 07/31/2024] [Accepted: 08/03/2024] [Indexed: 09/04/2024] Open
Abstract
Long COVID (post-acute sequelae of COVID-19-PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances, skeletal muscle abnormalities, complement dysregulation, novel abzymes, and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that long-term dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.
Collapse
Affiliation(s)
| | - Anthony J. Turner
- School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK;
| | - Bruce D. Uhal
- Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
| |
Collapse
|
|
29
|
Windyaswari AS, Nugraha MFI, Hartati R, Elfahmi. Isolation and antimicrobial activity of secondary metabolites of pothos tener wall. Nat Prod Res 2024:1-9. [PMID: 39102533 DOI: 10.1080/14786419.2024.2384081] [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: 03/21/2024] [Revised: 07/08/2024] [Accepted: 07/18/2024] [Indexed: 08/07/2024]
Abstract
The Pothos genus is extensively utilised in traditional medicine in China and India. An underexplored species of Pothos tener Wall was identified in Sulawesi, Indonesia. Antimicrobial activity was assessed using microdilutions and streak plates against Staphylococcus aureus, Eschericia coli, Aeromonas hydrophila, Aspergillus niger, and Candida albicans. Significant effectiveness was observed in the methanol extract, as indicated by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values for three different extracts (methanol, ethyl acetate, and n-hexane) of P. tener. The isolates obtained were structurally analysed using Ultraviolet (UV)-spectroscopy, Fourier-transform Infra Red-Spectroscopy (FT-IR), Mass Spectroscopy (MS), Nuclear Magnetic Resonance (NMR), and antimicrobial testing after undergoing fractionation and subfractionation. The isolate obtained was stigmasterol with moderate antimicrobial activity against A. niger and A. hydrophila, with MIC equivalent to MBC of 500 µg/ml. The first report of stigmasterol from P. tener has potent antimicrobial properties, bolstering empirical data in this field.
Collapse
Affiliation(s)
- Ari Sri Windyaswari
- Department of Pharmaceutical Biology, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia
- Department of Biology Pharmacy, Faculty of Pharmacy, University of Jenderal Achmad Yani, Cimahi, Indonesia
| | - Media Fitri Isma Nugraha
- Research Centre for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency, Cibinong, Indonesia
| | - Rika Hartati
- Department of Pharmaceutical Biology, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia
| | - Elfahmi
- Department of Pharmaceutical Biology, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia
- University Centre of Excellence for Nutraceuticals, Bioscience and Biotechnology Research Centre, Bandung Institute of Technology, Bandung, Indonesia
| |
Collapse
|
|
30
|
Sey EA, Warris A. The gut-lung axis: the impact of the gut mycobiome on pulmonary diseases and infections. OXFORD OPEN IMMUNOLOGY 2024; 5:iqae008. [PMID: 39193472 PMCID: PMC11316619 DOI: 10.1093/oxfimm/iqae008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 06/12/2024] [Accepted: 06/13/2024] [Indexed: 08/29/2024] Open
Abstract
The gastrointestinal tract contains a diverse microbiome consisting of bacteria, fungi, viruses and archaea. Although these microbes usually reside as commensal organisms, it is now well established that higher abundance of specific bacterial or fungal species, or loss of diversity in the microbiome can significantly affect development, progression and outcomes in disease. Studies have mainly focused on the effects of bacteria, however, the impact of other microbes, such as fungi, has received increased attention in the last few years. Fungi only represent around 0.1% of the total gut microbial population. However, key fungal taxa such as Candida, Aspergillus and Wallemia have been shown to significantly impact health and disease. The composition of the gut mycobiome has been shown to affect immunity at distal sites, such as the heart, lung, brain, pancreas, and liver. In the case of the lung this phenomenon is referred to as the 'gut-lung axis'. Recent studies have begun to explore and unveil the relationship between gut fungi and lung immunity in diseases such as asthma and lung cancer, and lung infections caused by viruses, bacteria and fungi. In this review we will summarize the current, rapidly growing, literature describing the impact of the gut mycobiome on respiratory disease and infection.
Collapse
Affiliation(s)
- Emily A Sey
- Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, EX4 4QD, UK
| | - Adilia Warris
- Medical Research Council Centre for Medical Mycology, University of Exeter, Exeter, EX4 4QD, UK
| |
Collapse
|
|
31
|
Folliero V, Ferravante C, Dell’Annunziata F, Brancaccio RN, D’Agostino Y, Giurato G, Manente R, Terenzi I, Greco R, Boccia G, Pagliano P, Weisz A, Franci G, Rizzo F. Influence of Mycobiota in the Nasopharyngeal Tract of COVID-19 Patients. Microorganisms 2024; 12:1468. [PMID: 39065235 PMCID: PMC11279359 DOI: 10.3390/microorganisms12071468] [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: 06/27/2024] [Revised: 07/10/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
The nasopharyngeal tract contains a complex microbial community essential to maintaining host homeostasis. Recent studies have shown that SARS-CoV-2 infection changes the microbial composition of the nasopharynx. Still, little is known about how it affects the fungal microbiome, which could provide valuable insights into disease pathogenesis. Nasopharyngeal swabs were collected from 55 patients, during three distinct COVID-19 waves that occurred in the Campania Region (southern Italy). An RNA-seq-based analysis was performed to evaluate changes in mycobiota diversity, showing variations depending on the disease's severity and the sample collection wave. The phyla Basidiomycota and Ascomycota were shown to have higher abundance in patients with severe symptoms. Furthermore, the diversity of the fungal population was greater in the second wave. Conclusion: According to our research, COVID-19 induces significant dysbiosis of the fungal microbiome, which may contribute to disease pathogenesis, and understanding its underlying mechanisms could contribute to developing effective treatments.
Collapse
Affiliation(s)
- Veronica Folliero
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (V.F.); (F.D.); (R.M.); (G.B.); (P.P.)
| | - Carlo Ferravante
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (C.F.); (R.N.B.); (Y.D.); (G.G.); (I.T.); (A.W.)
- Medical Genomics Program, AOU ‘S. Giovanni di Dio e Ruggi d’Aragona’, University of Salerno, 84131 Salerno, Italy
| | - Federica Dell’Annunziata
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (V.F.); (F.D.); (R.M.); (G.B.); (P.P.)
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Rosario Nicola Brancaccio
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (C.F.); (R.N.B.); (Y.D.); (G.G.); (I.T.); (A.W.)
| | - Ylenia D’Agostino
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (C.F.); (R.N.B.); (Y.D.); (G.G.); (I.T.); (A.W.)
- Medical Genomics Program, AOU ‘S. Giovanni di Dio e Ruggi d’Aragona’, University of Salerno, 84131 Salerno, Italy
| | - Giorgio Giurato
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (C.F.); (R.N.B.); (Y.D.); (G.G.); (I.T.); (A.W.)
- Genome Research Center for Health—CRGS, Campus of Medicine, University of Salerno, 84081 Salerno, Italy
| | - Roberta Manente
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (V.F.); (F.D.); (R.M.); (G.B.); (P.P.)
- Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Ilaria Terenzi
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (C.F.); (R.N.B.); (Y.D.); (G.G.); (I.T.); (A.W.)
| | - Rita Greco
- UOC Microbiologia e Virologia, AORN S. Anna e S. Sebastiano, 81100 Caserta, Italy;
| | - Giovanni Boccia
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (V.F.); (F.D.); (R.M.); (G.B.); (P.P.)
- UOC Igiene Ospedaliera ed Epidemiologia, DAI Igiene Sanitaria e Valutativa, San Giovanni di Dio e Ruggi D’Aragona, University of Salerno, 84131 Salerno, Italy
| | - Pasquale Pagliano
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (V.F.); (F.D.); (R.M.); (G.B.); (P.P.)
- Infectious Disease Unit, San Giovanni di Dio e Ruggi D’Aragona, University of Salerno, 84131 Salerno, Italy
| | - Alessandro Weisz
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (C.F.); (R.N.B.); (Y.D.); (G.G.); (I.T.); (A.W.)
- Medical Genomics Program, AOU ‘S. Giovanni di Dio e Ruggi d’Aragona’, University of Salerno, 84131 Salerno, Italy
- Genome Research Center for Health—CRGS, Campus of Medicine, University of Salerno, 84081 Salerno, Italy
| | - Gianluigi Franci
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (V.F.); (F.D.); (R.M.); (G.B.); (P.P.)
- Clinical Pathology and Microbiology Unit, San Giovanni di Dio e Ruggi D’Aragona, University of Salerno, 84131 Salerno, Italy
| | - Francesca Rizzo
- Laboratory of Molecular Medicine and Genomics, Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Salerno, Italy; (C.F.); (R.N.B.); (Y.D.); (G.G.); (I.T.); (A.W.)
- Genome Research Center for Health—CRGS, Campus of Medicine, University of Salerno, 84081 Salerno, Italy
| |
Collapse
|
|
32
|
Orosz L, Burián K. The "COVID effect" in culture-based clinical microbiology: Changes induced by COVID-19 pandemic in a Hungarian tertiary care center. J Infect Public Health 2024; 17:102453. [PMID: 38820897 DOI: 10.1016/j.jiph.2024.05.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 05/03/2024] [Accepted: 05/14/2024] [Indexed: 06/02/2024] Open
Abstract
BACKGROUND The presence of bacterial and fungal coinfections plays an important role in the mortality of patients with coronavirus 2019 (COVID-19). We compared data from the 3 years before and 3 years after the COVID-19 pandemic outbreak to evaluate its effect on the traits of bacterial and fungal diseases. METHODS We retrospectively collected and analyzed data on positive respiratory tract samples (n = 13,133 samples from 7717 patients) and blood cultures (n = 23,652 from 9653 patients) between 2017 and 2022 from the Clinical Center of the University of Szeged, Hungary. We also evaluated antimicrobial susceptibility test results derived from 169,020 respiratory samples and 549,729 blood cultures to gain insight into changes in antimicrobial resistance. RESULTS The most common respiratory pathogen in the pre-COVID era was Pseudomonas aeruginosa, whereas Candida albicans was the most frequent during the pandemic. The number of respiratory isolates of Acinetobacter baumannii was also markedly increased. In blood cultures, Staphylococcus epidermidis, Escherichia coli, and S. aureus were dominant during the study period, and A. baumannii was widespread in blood cultures during the pandemic years. Resistance to ofloxacin, penicillin, piperacillin-tazobactam, ceftazidime, cefepime, imipenem, ceftolozane-tazobactam, and itraconazole increased significantly in the COVID era. CONCLUSIONS During the COVID-19 pandemic, there were changes in the prevalence of respiratory and blood culture pathogens at the Clinical Center of the University of Szeged. C. albicans became the predominant respiratory pathogen, and the number of A. baumannii isolates increased dramatically. Additionally, antimicrobial resistance notably increased during this period.
Collapse
Affiliation(s)
- László Orosz
- Department of Medical Microbiology, University of Szeged, H-6725 Szeged Semmelweis str. 6/b., Hungary.
| | - Katalin Burián
- Department of Medical Microbiology, University of Szeged, H-6725 Szeged Semmelweis str. 6/b., Hungary
| |
Collapse
|
|
33
|
Lyu J, Wang H, Rai TS, Zheng H. Random Forest Approach to Identifying Microbial Biomarkers Relating to COVID-19 Severity. 2024 35TH IRISH SIGNALS AND SYSTEMS CONFERENCE (ISSC) 2024:1-6. [DOI: 10.1109/issc61953.2024.10602829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
- Jialin Lyu
- School of Computing, Ulster University,Belfast,UK
| | - Haiying Wang
- School of Computing, Ulster University,Belfast,UK
| | | | - Huiru Zheng
- School of Computing, Ulster University,Belfast,UK
| |
Collapse
|
|
34
|
Yan Q, Li S, Yan Q, Huo X, Wang C, Wang X, Sun Y, Zhao W, Yu Z, Zhang Y, Guo R, Lv Q, He X, Yao C, Li Z, Chen F, Ji Q, Zhang A, Jin H, Wang G, Feng X, Feng L, Wu F, Ning J, Deng S, An Y, Guo DA, Martin FM, Ma X. A genomic compendium of cultivated human gut fungi characterizes the gut mycobiome and its relevance to common diseases. Cell 2024; 187:2969-2989.e24. [PMID: 38776919 DOI: 10.1016/j.cell.2024.04.043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 02/17/2024] [Accepted: 04/29/2024] [Indexed: 05/25/2024]
Abstract
The gut fungal community represents an essential element of human health, yet its functional and metabolic potential remains insufficiently elucidated, largely due to the limited availability of reference genomes. To address this gap, we presented the cultivated gut fungi (CGF) catalog, encompassing 760 fungal genomes derived from the feces of healthy individuals. This catalog comprises 206 species spanning 48 families, including 69 species previously unidentified. We explored the functional and metabolic attributes of the CGF species and utilized this catalog to construct a phylogenetic representation of the gut mycobiome by analyzing over 11,000 fecal metagenomes from Chinese and non-Chinese populations. Moreover, we identified significant common disease-related variations in gut mycobiome composition and corroborated the associations between fungal signatures and inflammatory bowel disease (IBD) through animal experimentation. These resources and findings substantially enrich our understanding of the biological diversity and disease relevance of the human gut mycobiome.
Collapse
Affiliation(s)
- Qiulong Yan
- Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China; Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, School of Pharmacy, Dalian Medical University, Dalian 116044, China; College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
| | - Shenghui Li
- Puensum Genetech Institute, Wuhan 430076, China; Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100091, China
| | - Qingsong Yan
- Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China
| | - Xiaokui Huo
- Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China
| | - Chao Wang
- Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China; Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, School of Pharmacy, Dalian Medical University, Dalian 116044, China; First Affiliated Hospital, Dalian Medical University, Dalian 116044, China.
| | - Xifan Wang
- Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing 100091, China; Department of Obstetrics and Gynecology, Columbia University, New York, NY 10027, USA
| | - Yan Sun
- Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China
| | - Wenyu Zhao
- Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, School of Pharmacy, Dalian Medical University, Dalian 116044, China
| | - Zhenlong Yu
- Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, School of Pharmacy, Dalian Medical University, Dalian 116044, China
| | - Yue Zhang
- Puensum Genetech Institute, Wuhan 430076, China
| | - Ruochun Guo
- Puensum Genetech Institute, Wuhan 430076, China
| | - Qingbo Lv
- Puensum Genetech Institute, Wuhan 430076, China
| | - Xin He
- Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, School of Pharmacy, Dalian Medical University, Dalian 116044, China; Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China
| | - Changliang Yao
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China
| | | | - Fang Chen
- College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
| | - Qianru Ji
- Puensum Genetech Institute, Wuhan 430076, China
| | - Aiqin Zhang
- Puensum Genetech Institute, Wuhan 430076, China
| | - Hao Jin
- Puensum Genetech Institute, Wuhan 430076, China
| | - Guangyang Wang
- College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
| | - Xiaoying Feng
- Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China
| | - Lei Feng
- Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China
| | - Fan Wu
- Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China
| | - Jing Ning
- Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, School of Pharmacy, Dalian Medical University, Dalian 116044, China
| | - Sa Deng
- Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, School of Pharmacy, Dalian Medical University, Dalian 116044, China
| | - Yue An
- Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China
| | - De-An Guo
- Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201210, China.
| | - Francis M Martin
- Université de Lorraine, Institut national de recherche pour l'agriculture, l'alimentation et l'environnement, UMR Interactions Arbres/Microorganismes, Centre INRAE Grand Est-Nancy, Champenoux 54280, France; Beijing Advanced Innovation Center for Tree Breeding by Molecular Design, Beijing Forestry University, Beijing 100091, China.
| | - Xiaochi Ma
- Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China; Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, School of Pharmacy, Dalian Medical University, Dalian 116044, China.
| |
Collapse
|
|
35
|
Jiang C, Chen Z, Liao W, Zhang R, Chen G, Ma L, Yu H. The Medicinal Species of the Lycium Genus (Goji Berries) in East Asia: A Review of Its Effect on Cell Signal Transduction Pathways. PLANTS (BASEL, SWITZERLAND) 2024; 13:1531. [PMID: 38891336 PMCID: PMC11174690 DOI: 10.3390/plants13111531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 05/06/2024] [Accepted: 05/07/2024] [Indexed: 06/21/2024]
Abstract
Natural plants contain numerous chemical compounds that are beneficial to human health. The berries from the Lycium genus are widely consumed and are highly nutritious. Moreover, their chemical constituents have attracted attention for their health-promoting properties. In East Asia, there are three varieties of the Lycium genus (Lycium barbarum L., Lycium chinense Miller, and L. ruthenicum Murray) that possess medicinal value and are commonly used for treating chronic diseases and improving metabolic disorders. These varieties are locally referred to as "red Goji berries" or "black Goji berries" due to their distinct colors, and they differ in their chemical compositions, primarily in terms of carotenoid and anthocyanin content. The pharmacological functions of these berries include anti-aging, antioxidant, anti-inflammatory, and anti-exercise fatigue effects. This review aims to analyze previous and recent studies on the active ingredients and pharmacological activities of these Lycium varieties, elucidating their signaling pathways and assessing their impact on the gut microbiota. Furthermore, the potential prospects for using these active ingredients in the treatment of COVID-19 are evaluated. This review explores the potential targets of these Lycium varieties in the treatment of relevant diseases, highlighting their potential value in drug development.
Collapse
Affiliation(s)
| | | | | | | | | | - Lijuan Ma
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China; (C.J.); (Z.C.); (W.L.); (R.Z.); (G.C.)
| | - Haijie Yu
- Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China; (C.J.); (Z.C.); (W.L.); (R.Z.); (G.C.)
| |
Collapse
|
|
36
|
Al-Kenani HQM, Shaheed OM. Evaluation of some immunological markers in co-infection of COVID-19 with thrush candidiasis. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2024; 70:e20230845. [PMID: 38747876 PMCID: PMC11095970 DOI: 10.1590/1806-9282.20230845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 12/29/2023] [Indexed: 05/18/2024]
Abstract
OBJECTIVE COVID-19 infection poses significant risks, including life-threatening consequences and fungus synchronization, making it a significant concern. This study seeks to assess the effect of concurrent infection of COVID-19 with Thrush Candida albicans on the patient's health state by measuring the proportion of immune cells and certain interleukins such as IL-8, -10, -17, and -33. METHODS The study involved 70 patients (30 patients with COVID-19, 17 patients with thrush candidiasis, and 23 patients with Thrush Candida albicans) and 50 healthy individuals as a control group. COVID-19 was identified using RT-PCR, while C. albicans were identified through culture media, biochemical testing, and oral swabs. Ruby equipment and ELISA kits were used for blood counts and interleukin detection. RESULTS COVID-19, thrush candidiasis, and Thrush Candida albicans infections occur in a wide range of age groups (4-80 years), with no significant differences between sexes (p>0.05). Immunologically, our study found that Thrush Candida albicans patients had the highest rate of neutrophils (89.6%) and basophils (2.01%), while corona patients had the highest percentage of lymphocytes (70.12%) and eosinophils (7.11%), and patients with thrush candidiasis had the highest percentage of monocytes. Thrush Candida albicans patients showed increased IL-8 (56.7 pg/mL) and IL-17 (101.1 pg/mL) concentrations, with the greatest concentration of IL-33 (200.5 pg/mL) in COVID-19, and a decrease in the level of IL-10 in patient groups compared with controls. CONCLUSION Patient groups showed increased neutrophils, lymphocytes, monocytes, and IL-8 levels, with a significant linear association between proinflammatory interleukins and these cells.
Collapse
Affiliation(s)
| | - Orass Madhi Shaheed
- University of Al-Qadisiyah, College of Medicine, Department of Medical Microbiology – Diwaniya, Iraq
| |
Collapse
|
|
37
|
Çaklovica Küçükkaya I, Orhun G, Çağatay AA, Kalaycı S, Esen F, Şahin F, Ağaçfidan A, Erturan Z. Comparison of Candida colonization in intensive care unit patients with and without COVID-19: First prospective cohort study from Turkey. Med Mycol 2024; 62:myae035. [PMID: 38592959 PMCID: PMC11491735 DOI: 10.1093/mmy/myae035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 03/15/2024] [Accepted: 04/08/2024] [Indexed: 04/11/2024] Open
Abstract
Candida species are the primary cause of fungal infections in intensive care units (ICUs). Despite the increasing prevalence of Candida-related infections, monitoring the progression of these infections from colonization in COVID-19 ICU patients lacks sufficient information. This study aims prospectively to compare 62 COVID-19 and 60 non-COVID-19 ICU patients from admission to discharge in terms of colonization development, rates, isolated Candida species, risk factors, and Candida infections during hospitalization. A total of 1464 samples were collected at specific time intervals from various body sites [mouth, skin (axilla), rectal, and urine]. All samples were inoculated onto CHROMagar Candida and CHROMagar Candida Plus media, and isolates identified using MALDI-TOF MS. COVID-19 patients exhibited significantly higher colonization rates in oral, rectal, and urine samples compared to non-COVID-19 patients, (p < 0.05). Among the Candida species, non-albicans Candida was more frequently detected in COVID-19 patients, particularly in oral (75.8%-25%; p < 0.001) and rectal regions (74.19% - 46.66%; p < 0.05). Colonization with mixed Candida species was also more prevalent in the oropharyngeal region (p < 0.05). Mechanical ventilation and corticosteroid use emerged as elevated risk factors among COVID-19 patients (p < 0.05). Despite the colonization prevalence, both COVID-19-positive and negative patients exhibited low incidences of Candida infections, with rates of 9.67% (n = 6/62) and 6.67% (n = 3/60), respectively. Consequently, although Candida colonization rates were higher in COVID-19 ICU patients, there was no significant difference in Candida infection development compared to the non-COVID-19 group. However, the elevated rate of non-albicans Candida isolates highlights potential future infections, particularly given their intrinsic resistance in prophylactic or empirical treatments if needed. Additionally, the high rate of mixed colonization emphasizes the importance of using chromogenic media for routine evaluation.
Collapse
Affiliation(s)
- Ilvana Çaklovica Küçükkaya
- Istanbul University Istanbul Faculty of Medicine, Department of Medical Microbiology, 34093, Istanbul, Turkey
| | - Günseli Orhun
- Istanbul University Istanbul Faculty of Medicine, Department of Anesthesiology and Reanimation, 34093, Istanbul, Turkey
| | - Arif Atahan Çağatay
- Istanbul University Istanbul Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, 34093, Istanbul, Turkey
| | - Sadık Kalaycı
- Yeditepe University Faculty of Engineering, Department of Genetics and Bioengineering,
34755, Istanbul, Turkey
| | - Figen Esen
- Istanbul University Istanbul Faculty of Medicine, Department of Anesthesiology and Reanimation, 34093, Istanbul, Turkey
| | - Fikrettin Şahin
- Istanbul University Istanbul Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, 34093, Istanbul, Turkey
| | - Ali Ağaçfidan
- Istanbul University Istanbul Faculty of Medicine, Department of Medical Microbiology, 34093, Istanbul, Turkey
| | - Zayre Erturan
- Istanbul University Istanbul Faculty of Medicine, Department of Medical Microbiology, 34093, Istanbul, Turkey
| |
Collapse
|
|
38
|
Ramezanalipour Z, Hashemi SJ, Daie Ghazvini R, Shenagari M, Sharifdini M, Salehiniya H, Keivanlou MH, Ashrafi K, Roostaei D, Mansour Ghanaei F, Sasani E, Rafat Z. Assessment of species distribution and virulence factors of oral fungal carriage among hospitalized patients with COVID-19: a case-control study. Ann Med Surg (Lond) 2024; 86:2458-2466. [PMID: 38694283 PMCID: PMC11060290 DOI: 10.1097/ms9.0000000000001956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 02/29/2024] [Indexed: 05/04/2024] Open
Abstract
Background The COVID-19 pandemic highlighted the need to study oral fungal carriage and its potential impact. In oral fungal environments, factors like changes in respiratory epithelium, increased pathogen attachment, local inflammation, and virulence factors could influence COVID-19 severity. The authors conducted a study to explore oral fungal carriage in COVID-19 patients and compare it to a healthy control group. Methods The authors executed a case-control investigation including 144 COVID-19 patients and an equivalent number of 144 healthy controls. The matching criteria encompassed age, sex, body mass index, and the history of antibiotic and antiviral medication intake. This research was performed over a span of 12 months from May 2021 to May 2022. The mouth area was sampled with a cotton-tipped swab. Subsequently, all the samples underwent fungal culture and PCR-sequencing procedures. Results In COVID-19 patients, oral fungal carriage was three times higher compared to healthy controls. Candida was the exclusive genus found in both groups, with Candida albicans being the most frequently isolated species (90.79%). Among COVID-19 patients, Candida species showed significantly higher esterase, proteinase, and hemolysin activity compared to healthy individuals. Both groups exhibited elevated levels of C. albicans virulence factors compared to non-albicans species. Conclusions It is crucial to understand the way that virulence factors of oral fungal carriage act in COVID-19 patients in order to come up with novel antifungal medications, identify the contributing factors to drug resistance, and manage clinical outcomes.
Collapse
Affiliation(s)
- Zahra Ramezanalipour
- Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran
| | - Seyed Jamal Hashemi
- Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran
| | - Roshanak Daie Ghazvini
- Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran
| | | | | | - Hamid Salehiniya
- Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand
| | | | | | | | - Fariborz Mansour Ghanaei
- Gastrointestinal and Liver Diseases Research Center
- GI Cancer Screening and Prevention Research Center, Guilan University of Medical Sciences, Rasht
| | - Elahe Sasani
- Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | | |
Collapse
|
|
39
|
Yousef M, Rob M, Varghese S, Rao S, Zamir F, Paul P, Chaari A. The effect of microbiome therapy on COVID-19-induced gut dysbiosis: A narrative and systematic review. Life Sci 2024; 342:122535. [PMID: 38408636 DOI: 10.1016/j.lfs.2024.122535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2023] [Revised: 02/20/2024] [Accepted: 02/22/2024] [Indexed: 02/28/2024]
Abstract
AIMS Emerging evidence highlights the role of COVID-19 in instigating gut dysbiosis, with repercussions on disease severity and bidirectional gut-organ communication involving the lung, heart, brain, and liver. This study aims to evaluate the efficacy of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) in addressing gut dysbiosis associated with COVID-19, as well as their impact on related disease severity and clinical outcomes. MATERIALS AND METHODS We systematically review 27 studies exploring the efficacy of different microbiome-modulating therapies: probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as potential interventions for COVID-19. KEY FINDINGS The probiotics and synbiotics investigated encompassed a spectrum of eight bacterial and fungal genera, namely Lactobacillus, Bifidobacterium, Streptococcus, Enterococcus, Pediococcus, Bacillus, Saccharomyces, and Kluyveromyces. Noteworthy prebiotics employed in these studies included chestnut tannin, galactooligosaccharides, fructooligosaccharides, xylooligosaccharide, and resistant dextrin. The majority of the investigated biotics exhibited positive effects on COVID-19 patients, manifesting in symptom alleviation, inflammation reduction, and notable decreases in mortality rates. Five studies reported death rates, showing an average mortality ranging from 0 % to 11 % in the intervention groups, as compared to 3 % to 30 % in the control groups. Specifically, probiotics, prebiotics, and synbiotics demonstrated efficacy in diminishing the duration and severity of symptoms while significantly accelerating viral and symptomatic remission. FMT emerged as a particularly effective strategy, successfully restoring gut microbiota and ameliorating gastrointestinal disorders. SIGNIFICANCE The insights gleaned from this review significantly contribute to our broader comprehension of the therapeutic potential of biotics in addressing COVID-19-related gut dysbiosis and mitigating secondary multi-organ complications.
Collapse
Affiliation(s)
- Mahmoud Yousef
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Mlaak Rob
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Sanish Varghese
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Shrinidhi Rao
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Fahad Zamir
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Pradipta Paul
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar
| | - Ali Chaari
- Weill Cornell Medicine-Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha, Qatar.
| |
Collapse
|
|
40
|
Boorgula SY, Yelamanchili S, Sistla SK, Saher L, Gujjarlapudi D, E. S, V. SD, Duvvur NR. An Experience in Laboratory Diagnosis of Fungal Infections in COVID -19 Patients. Int Arch Otorhinolaryngol 2024; 28:e180-e187. [PMID: 38618586 PMCID: PMC11008951 DOI: 10.1055/s-0043-1768140] [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: 05/25/2022] [Accepted: 02/24/2023] [Indexed: 04/16/2024] Open
Abstract
Introduction Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has cast a gloom spell on healthcare worldwide, infecting millions of people. Objective The aim of the present study is to determine the prevalence and review the contributing comorbidities and the precipitating factors leading to the emergence of the fungal infections in COVID-19-affected patients. To assess the utility of different laboratory techniques for confirmation of fungal infections. To assess the strengths and limitations of the diagnostic methods. Methods We have studied 252 clinical samples obtained from 121 COVID-positive patients. Results Among the 121 patients clinically diagnosed with fungal infections, 88 had diabetes and were given steroids for treatment ( p -value = 0.001). Ninety-five patients (78.5%) had a positive laboratory diagnosis (either culture positive, potassium hydroxide [KOH]-positive or positive histopathology report). Fungal culture was positive in 75 (61.9%) patients and histopathology report was positive in 62 (51.2%). Histopathology was positive in 7 (5.8%) patients in whom culture and KOH were negative. Conclusion Aggressive treatment methods, administration of immune suppressants, and antibiotics, with an intention to salvage, have made patients susceptible to the benign fungus, causing it to evade the host immunity, thus leading to invasive infections. Applying different laboratory modalities would not only aid in providing fast and valuable information but also help in understanding the pathology which would assist the clinician in selecting the correct treatment for the patient.
Collapse
Affiliation(s)
| | | | | | - Lubna Saher
- Department of Microbiology, AIG Hospitals, Hyderabad, Telangana, India
| | | | - Shalini E.
- Department of Microbiology, AIG Hospitals, Hyderabad, Telangana, India
| | - Sindhu Devi V.
- Department of Microbiology, AIG Hospitals, Hyderabad, Telangana, India
| | | |
Collapse
|
|
41
|
Zhang Y, Zhang H, Xu T, Zeng L, Liu F, Huang X, Liu Q. Interactions among microorganisms open up a new world for anti-infectious therapy. FEBS J 2024; 291:1615-1631. [PMID: 36527169 DOI: 10.1111/febs.16705] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 11/12/2022] [Accepted: 12/15/2022] [Indexed: 12/23/2022]
Abstract
The human microbiome, containing bacteria, fungi, and viruses, is a community that coexists peacefully with humans most of the time, but with the potential to cause disease under certain conditions. When the environment changes or certain stimuli are received, microbes may interact with each other, causing or increasing the severity of disease in a host. With the appropriate methods, we can make these microbiota work for us, creating new applications for human health. This review discusses the wide range of interactions between microorganisms that result in an increase in susceptibility to, severity of, and mortality of diseases, and also briefly introduces how microorganisms interact with each other directly or indirectly. The study of microbial interactions and their mechanisms has revealed a new world of treatments for infectious disease. The regulation of the balance between intestinal flora, the correct application of probiotics, and the development of effective drugs by symbiosis all demonstrate the great contributions of the microbiota to human health and its powerful potential value. Consequently, the study of interactions between microorganisms plays an essential role in identifying the causes of diseases and the development of treatments.
Collapse
Affiliation(s)
- Yejia Zhang
- Department of Medical Microbiology, School of Medicine, Jiangxi Medical College, Nanchang University, China
| | - Hanchi Zhang
- Department of Medical Microbiology, School of Medicine, Jiangxi Medical College, Nanchang University, China
- The First Clinical Medical College, Nanchang University, China
| | - Tian Xu
- Department of Medical Microbiology, School of Medicine, Jiangxi Medical College, Nanchang University, China
| | - Lingbing Zeng
- Department of Medical Microbiology, School of Medicine, Jiangxi Medical College, Nanchang University, China
- The First Clinical Medical College, Nanchang University, China
| | - Fadi Liu
- The Department of Clinical Laboratory, Children's Hospital of Jiangxi Province, Nanchang, China
| | - Xiaotian Huang
- Department of Medical Microbiology, School of Medicine, Jiangxi Medical College, Nanchang University, China
| | - Qiong Liu
- Department of Medical Microbiology, School of Medicine, Jiangxi Medical College, Nanchang University, China
| |
Collapse
|
|
42
|
Zeng Z, Tang W. Gut microbiota: A potential player in psychiatric symptoms during COVID-19. World J Biol Psychiatry 2024; 25:267-280. [PMID: 38607962 DOI: 10.1080/15622975.2024.2342846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 04/04/2024] [Indexed: 04/14/2024]
Abstract
OBJECTIVES This study aims to explore the potential interconnections among gut microbiota, COVID-19 infection, depression and anxiety disorder. Additionally, it tries to assess potential therapeutic interventions that may improve the dysbiosis of gut microbiota. METHODS To achieve these objectives, we reviewed existing literature, encompassing studies and critical reviews that intersect the domains of gut microbiota, COVID-19, depression and anxiety disorders. RESULTS The findings highlight a notable correlation between the dysbiosis of gut microbiota and psychiatric symptoms in the context of COVID-19. Specifically, there is a marked reduction in the populations of bacteria that generate anti-inflammatory short-chain fatty acids (SCFAs), alongside a rise in the prevalence of gut bacterial clusters linked to inflammatory processes. Furthermore, several potential treatment strategies were summarised for improving the dysbiosis. CONCLUSIONS Gut microbiota plays a significant role in psychiatric symptoms during COVID-19, which has significant implications for the study and prevention of psychiatric symptoms in major epidemic diseases.
Collapse
Affiliation(s)
- Zijie Zeng
- Department of Psychology, School of Public Health, Southern Medical University, Guangzhou, China
| | | |
Collapse
|
|
43
|
Ren Y, Chen L, Guo R, Ma S, Li S, Zhang Y, Jiang H, Shi H, Zhang P. Altered gut mycobiome in patients with end-stage renal disease and its correlations with serum and fecal metabolomes. J Transl Med 2024; 22:202. [PMID: 38403655 PMCID: PMC10894479 DOI: 10.1186/s12967-024-05004-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 02/18/2024] [Indexed: 02/27/2024] Open
Abstract
BACKGROUND The relationship between the gut mycobiome and end-stage renal disease (ESRD) remains largely unexplored. METHODS In this study, we compared the gut fungal populations of 223 ESRD patients and 69 healthy controls (HCs) based on shotgun metagenomic sequencing data, and analyzed their associations with host serum and fecal metabolites. RESULTS Our findings revealed that ESRD patients had a higher diversity in the gut mycobiome compared to HCs. Dysbiosis of the gut mycobiome in ESRD patients was characterized by a decrease of Saccharomyces cerevisiae and an increase in various opportunistic pathogens, such as Aspergillus fumigatus, Cladophialophora immunda, Exophiala spinifera, Hortaea werneckii, Trichophyton rubrum, and others. Through multi-omics analysis, we observed a substantial contribution of the gut mycobiome to host serum and fecal metabolomes. The opportunistic pathogens enriched in ESRD patients were frequently and positively correlated with the levels of creatinine, homocysteine, and phenylacetylglycine in the serum. The populations of Saccharomyces, including the HC-enriched Saccharomyces cerevisiae, were frequently and negatively correlated with the levels of various toxic metabolites in the feces. CONCLUSIONS Our results provided a comprehensive understanding of the associations between the gut mycobiome and the development of ESRD, which had important implications for guiding future therapeutic studies in this field.
Collapse
Affiliation(s)
- Yi Ren
- Department of Critical Care Nephrology and Blood Purification, the First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, People's Republic of China
- Department of Nephrology, People's Hospital of Longhua, Shenzhen, 518109, People's Republic of China
| | - Lei Chen
- Department of Critical Care Nephrology and Blood Purification, the First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, People's Republic of China
| | - Ruochun Guo
- Puensum Genetech Institute, Wuhan, 430076, People's Republic of China
| | - Shiyang Ma
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi, People's Republic of China
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an, 710004, Shaanxi, People's Republic of China
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Xi'an, 710004, Shaanxi, People's Republic of China
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, 710004, People's Republic of China
| | - Shenghui Li
- Puensum Genetech Institute, Wuhan, 430076, People's Republic of China
| | - Yue Zhang
- Puensum Genetech Institute, Wuhan, 430076, People's Republic of China
| | - Hongli Jiang
- Department of Critical Care Nephrology and Blood Purification, the First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, People's Republic of China.
| | - Haitao Shi
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi, People's Republic of China.
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an, 710004, Shaanxi, People's Republic of China.
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Xi'an, 710004, Shaanxi, People's Republic of China.
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, 710004, People's Republic of China.
| | - Pan Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, 710004, Shaanxi, People's Republic of China.
- Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an, 710004, Shaanxi, People's Republic of China.
- Shaanxi Provincial Clinical Research Center for Gastrointestinal Diseases, Xi'an, 710004, Shaanxi, People's Republic of China.
- Digestive Disease Quality Control Center of Shaanxi Province, Xi'an, 710004, People's Republic of China.
| |
Collapse
|
|
44
|
Rhodes RH, Love GL, Da Silva Lameira F, Sadough Shahmirzadi M, Fox SE, Vander Heide RS. Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains. Diagn Pathol 2024; 19:33. [PMID: 38360666 PMCID: PMC10870569 DOI: 10.1186/s13000-024-01445-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 01/16/2024] [Indexed: 02/17/2024] Open
Abstract
BACKGROUND Hypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evidence of direct SARS-CoV-2 brain infection in COVID-19 patients. METHODS Brain histopathology of 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied along with findings from contemporary and pre-pandemic historical control groups. Immunostaining for serum and blood cell proteins and for complement components was employed. Microcirculatory wall complement deposition in the COVID-19 cohort was compared to historical control cases. Comparisons also included other relevant clinicopathological and microcirculatory findings in the COVID-19 cohort and control groups. RESULTS The COVID-19 cohort and both the contemporary and historical control groups had the same rate of hypertension, diabetes mellitus, and obesity. The COVID-19 cohort had varying amounts of acute neutrophilic vasculitis with leukocytoclasia in the microcirculation of the brain in all cases. Prominent vascular neutrophilic transmural migration was found in several cases and 25 cases had acute perivasculitis. Paravascular microhemorrhages and petechial hemorrhages (small brain parenchymal hemorrhages) had a slight tendency to be more numerous in cohort cases that displayed less acute neutrophilic vasculitis. Tissue burden of acute neutrophilic vasculitis with leukocytoclasia was the same in control cases as a group, while it was significantly higher in COVID-19 cases. Both the tissue burden of acute neutrophilic vasculitis and the activation of complement components, including membrane attack complex, were significantly higher in microcirculatory channels in COVID-19 cohort brains than in historical controls. CONCLUSIONS Acute neutrophilic vasculitis with leukocytoclasia, acute perivasculitis, and associated paravascular blood extravasation into brain parenchyma constitute the first phase of an immune-related, acute small-vessel inflammatory condition often termed type 3 hypersensitivity vasculitis or leukocytoclastic vasculitis. There is a higher tissue burden of acute neutrophilic vasculitis and an increased level of activated complement components in microcirculatory walls in COVID-19 cases than in pre-pandemic control cases. These findings are consistent with a more extensive small-vessel immune-related vasculitis in COVID-19 cases than in control cases. The pathway(s) and mechanism for these findings are speculative.
Collapse
Affiliation(s)
- Roy H Rhodes
- Department of Pathology, Louisiana State University Health Sciences Center, 7th Floor, 2021 Perdido Street, New Orleans, Louisiana, 70112, USA.
| | - Gordon L Love
- Department of Pathology, Louisiana State University Health Sciences Center, 7th Floor, 2021 Perdido Street, New Orleans, Louisiana, 70112, USA
| | - Fernanda Da Silva Lameira
- Department of Pathology, Louisiana State University Health Sciences Center, 7th Floor, 2021 Perdido Street, New Orleans, Louisiana, 70112, USA
- Department of Pathology, Virginia Commonwealth University, Norfolk, Virginia, 23510, USA
| | - Maryam Sadough Shahmirzadi
- Department of Pathology, Louisiana State University Health Sciences Center, 7th Floor, 2021 Perdido Street, New Orleans, Louisiana, 70112, USA
| | - Sharon E Fox
- Department of Pathology, Louisiana State University Health Sciences Center, 7th Floor, 2021 Perdido Street, New Orleans, Louisiana, 70112, USA
- Pathology and Laboratory Medicine Services, Southeast Louisiana Veterans Healthcare System, New Orleans, Louisiana, 70112, USA
| | - Richard S Vander Heide
- Department of Pathology, Louisiana State University Health Sciences Center, 7th Floor, 2021 Perdido Street, New Orleans, Louisiana, 70112, USA
- Marshfield Clinic Health System, Marshfield, Wisconsin, 54449, USA
| |
Collapse
|
|
45
|
Sendid B, Cornu M, Cordier C, Bouckaert J, Colombel JF, Poulain D. From ASCA breakthrough in Crohn's disease and Candida albicans research to thirty years of investigations about their meaning in human health. Autoimmun Rev 2024; 23:103486. [PMID: 38040100 DOI: 10.1016/j.autrev.2023.103486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 11/23/2023] [Indexed: 12/03/2023]
Abstract
Anti-Saccharomyces cerevisiae antibodies (ASCA) are human antibodies that can be detected using an enzyme-linked immunosorbent assay involving a mannose polymer (mannan) extracted from the cell wall of the yeast S. cerevisiae. The ASCA test was developed in 1993 with the aim of differentiating the serological response in two forms of inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis. The test, which is based on the detection of anti-oligomannosidic antibodies, has been extensively performed worldwide and there have been hundreds of publications on ASCA. The earlier studies concerned the initial diagnostic indications of ASCA and investigations then extended to many human diseases, generally in association with studies on intestinal microorganisms and the interaction of the micro-mycobiome with the immune system. The more information accumulates, the more the mystery of the meaning of ASCA deepens. Many fundamental questions remain unanswered. These questions concern the heterogeneity of ASCA, the mechanisms of their generation and persistence, the existence of self-antigens, and the relationship between ASCA and inflammation and autoimmunity. This review aims to discuss the gray areas concerning the origin of ASCA from an analysis of the literature. Structured around glycobiology and the mannosylated antigens of S. cerevisiae and Candida albicans, this review will address these questions and will try to clarify some lines of thought. The importance of the questions relating to the pathophysiological significance of ASCA goes far beyond IBD, even though these diseases remain the preferred models for their understanding.
Collapse
Affiliation(s)
- Boualem Sendid
- INSERM U1285, CNRS UMR 8576, Glycobiology in Fungal Pathogenesis and Clinical Applications, Université de Lille, F-59000 Lille, France; Pôle de Biologie-Pathologie-Génétique, Institut de Microbiologie, Service de Parasitologie-Mycologie, CHU Lille, F-59000 Lille, France.
| | - Marjorie Cornu
- INSERM U1285, CNRS UMR 8576, Glycobiology in Fungal Pathogenesis and Clinical Applications, Université de Lille, F-59000 Lille, France; Pôle de Biologie-Pathologie-Génétique, Institut de Microbiologie, Service de Parasitologie-Mycologie, CHU Lille, F-59000 Lille, France
| | - Camille Cordier
- INSERM U1285, CNRS UMR 8576, Glycobiology in Fungal Pathogenesis and Clinical Applications, Université de Lille, F-59000 Lille, France; Pôle de Biologie-Pathologie-Génétique, Institut de Microbiologie, Service de Parasitologie-Mycologie, CHU Lille, F-59000 Lille, France
| | - Julie Bouckaert
- CNRS UMR 8576, Computational Molecular Systems Biology, Université de Lille, F-59000 Lille, France
| | - Jean Frederic Colombel
- Department of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
| | - Daniel Poulain
- INSERM U1285, CNRS UMR 8576, Glycobiology in Fungal Pathogenesis and Clinical Applications, Université de Lille, F-59000 Lille, France.
| |
Collapse
|
|
46
|
Mario-Vasquez JE, Bagal UR, Lowe E, Morgulis A, Phan J, Sexton DJ, Shiryev S, Slatkevičius R, Welsh R, Litvintseva AP, Blumberg M, Agarwala R, Chow NA. Finding Candida auris in public metagenomic repositories. PLoS One 2024; 19:e0291406. [PMID: 38241320 PMCID: PMC10798454 DOI: 10.1371/journal.pone.0291406] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 01/04/2024] [Indexed: 01/21/2024] Open
Abstract
Candida auris is a newly emerged multidrug-resistant fungus capable of causing invasive infections with high mortality. Despite intense efforts to understand how this pathogen rapidly emerged and spread worldwide, its environmental reservoirs are poorly understood. Here, we present a collaborative effort between the U.S. Centers for Disease Control and Prevention, the National Center for Biotechnology Information, and GridRepublic (a volunteer computing platform) to identify C. auris sequences in publicly available metagenomic datasets. We developed the MetaNISH pipeline that uses SRPRISM to align sequences to a set of reference genomes and computes a score for each reference genome. We used MetaNISH to scan ~300,000 SRA metagenomic runs from 2010 onwards and identified five datasets containing C. auris reads. Finally, GridRepublic has implemented a prospective C. auris molecular monitoring system using MetaNISH and volunteer computing.
Collapse
Affiliation(s)
- Jorge E. Mario-Vasquez
- Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | | | - Elijah Lowe
- General Dynamics Information Technology Inc., Atlanta, Georgia, United States of America
| | - Aleksandr Morgulis
- National Center for Biotechnology Information, Bethesda, Maryland, United States of America
| | - John Phan
- General Dynamics Information Technology Inc., Atlanta, Georgia, United States of America
| | - D. Joseph Sexton
- Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Sergey Shiryev
- National Center for Biotechnology Information, Bethesda, Maryland, United States of America
| | | | - Rory Welsh
- Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Anastasia P. Litvintseva
- Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| | - Matthew Blumberg
- GridRepublic, Cambridge, Massachusetts, United States of America
| | - Richa Agarwala
- National Center for Biotechnology Information, Bethesda, Maryland, United States of America
| | - Nancy A. Chow
- Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
| |
Collapse
|
|
47
|
Righi E, Dalla Vecchia I, Auerbach N, Morra M, Górska A, Sciammarella C, Lambertenghi L, Gentilotti E, Mirandola M, Tacconelli E, Sartor A. Gut Microbiome Disruption Following SARS-CoV-2: A Review. Microorganisms 2024; 12:131. [PMID: 38257958 PMCID: PMC10820238 DOI: 10.3390/microorganisms12010131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 12/22/2023] [Accepted: 12/29/2023] [Indexed: 01/24/2024] Open
Abstract
COVID-19 has been associated with having a negative impact on patients' gut microbiome during both active disease and in the post-acute phase. In acute COVID-19, rapid alteration of the gut microbiome composition was observed, showing on one side a reduction in beneficial symbionts (e.g., Roseburia, Lachnospiraceae) and on the other side an increase in opportunistic pathogens such as Enterococcus and Proteobacteria. Alpha diversity tends to decrease, especially initially with symptom onset and hospital admission. Although clinical recovery appears to align with improved gut homeostasis, this process could take several weeks, even in mild infections. Moreover, patients with COVID-19 post-acute syndrome showed changes in gut microbiome composition, with specific signatures associated with decreased respiratory function up to 12 months following acute disease. Potential treatments, especially probiotic-based therapy, are under investigation. Open questions remain on the possibility to use gut microbiome data to predict disease progression and on potential confounders that may impair result interpretation (e.g., concomitant therapies in the acute phase; reinfection, vaccines, and occurrence of novel conditions or diseases in the post-acute syndrome). Understanding the relationships between gut microbiome dynamics and disease progression may contribute to better understanding post-COVID syndrome pathogenesis or inform personalized treatment that can affect specific targets or microbiome markers.
Collapse
Affiliation(s)
- Elda Righi
- IMID Laboratory, Department of Diagnostics and Public Health, Infectious Diseases Division, University of Verona, 37134 Verona, Italy (A.G.); (C.S.); (E.T.)
| | - Ilaria Dalla Vecchia
- IMID Laboratory, Department of Diagnostics and Public Health, Infectious Diseases Division, University of Verona, 37134 Verona, Italy (A.G.); (C.S.); (E.T.)
| | - Nina Auerbach
- IMID Laboratory, Department of Diagnostics and Public Health, Infectious Diseases Division, University of Verona, 37134 Verona, Italy (A.G.); (C.S.); (E.T.)
| | - Matteo Morra
- IMID Laboratory, Department of Diagnostics and Public Health, Infectious Diseases Division, University of Verona, 37134 Verona, Italy (A.G.); (C.S.); (E.T.)
| | - Anna Górska
- IMID Laboratory, Department of Diagnostics and Public Health, Infectious Diseases Division, University of Verona, 37134 Verona, Italy (A.G.); (C.S.); (E.T.)
| | - Concetta Sciammarella
- IMID Laboratory, Department of Diagnostics and Public Health, Infectious Diseases Division, University of Verona, 37134 Verona, Italy (A.G.); (C.S.); (E.T.)
| | - Lorenza Lambertenghi
- IMID Laboratory, Department of Diagnostics and Public Health, Infectious Diseases Division, University of Verona, 37134 Verona, Italy (A.G.); (C.S.); (E.T.)
| | - Elisa Gentilotti
- IMID Laboratory, Department of Diagnostics and Public Health, Infectious Diseases Division, University of Verona, 37134 Verona, Italy (A.G.); (C.S.); (E.T.)
| | - Massimo Mirandola
- IMID Laboratory, Department of Diagnostics and Public Health, Infectious Diseases Division, University of Verona, 37134 Verona, Italy (A.G.); (C.S.); (E.T.)
| | - Evelina Tacconelli
- IMID Laboratory, Department of Diagnostics and Public Health, Infectious Diseases Division, University of Verona, 37134 Verona, Italy (A.G.); (C.S.); (E.T.)
| | - Assunta Sartor
- Microbiology Unit, Udine University Hospital, 33100 Udine, Italy;
| |
Collapse
|
|
48
|
Scheithauer TPM, Montijn RC, Mieremet A. Gut microbe-host interactions in post-COVID syndrome: a debilitating or restorative partnership? Gut Microbes 2024; 16:2402544. [PMID: 39287023 PMCID: PMC11409505 DOI: 10.1080/19490976.2024.2402544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2024] [Revised: 08/14/2024] [Accepted: 09/04/2024] [Indexed: 09/19/2024] Open
Abstract
Post-COVID syndrome (PCS) patients have reported a wide range of symptoms, including fatigue, shortness of breath, and diarrhea. Particularly, the presence of gastrointestinal symptoms has led to the hypothesis that the gut microbiome is involved in the development and severity of PCS. The objective of this review is to provide an overview of the role of the gut microbiome in PCS by describing the microbial composition and microbial metabolites in COVID-19 and PCS. Moreover, host-microbe interactions via the microbiota-gut-brain (MGB) and the microbiota-gut-lung (MGL) axes are described. Furthermore, we explore the potential of therapeutically targeting the gut microbiome to support the recovery of PCS by reviewing preclinical model systems and clinical studies. Overall, current studies provide evidence that the gut microbiota is affected in PCS; however, diversity in symptoms and highly individual microbiota compositions suggest the need for personalized medicine. Gut-targeted therapies, including treatments with pre- and probiotics, have the potential to improve the quality of life of affected individuals.
Collapse
Affiliation(s)
- Torsten P M Scheithauer
- Department of Microbiology and Systems Biology, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, The Netherlands
| | - Roy C Montijn
- Department of Microbiology and Systems Biology, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, The Netherlands
| | - Arnout Mieremet
- Department of Microbiology and Systems Biology, Netherlands Organisation for Applied Scientific Research (TNO), Leiden, The Netherlands
| |
Collapse
|
|
49
|
Mir TUG, Manhas S, Khurshid Wani A, Akhtar N, Shukla S, Prakash A. Alterations in microbiome of COVID-19 patients and its impact on forensic investigations. Sci Justice 2024; 64:81-94. [PMID: 38182316 DOI: 10.1016/j.scijus.2023.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 11/12/2023] [Accepted: 12/11/2023] [Indexed: 01/07/2024]
Abstract
The human microbiome is vital for maintaining human health and has garnered substantial attention in recent years, particularly in the context of the coronavirus disease 2019 (COVID-19) outbreak. Studies have underscored significant alterations in the microbiome of COVID-19 patients across various body niches, including the gut, respiratory tract, oral cavity, skin, and vagina. These changes manifest as shifts in microbiota composition, characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. Such microbiome transformations may play a pivotal role in influencing the course and severity of COVID-19, potentially contributing to the inflammatory response. This ongoing relationship between COVID-19 and the human microbiome serves as a compelling subject of research, underscoring the necessity for further investigations into the underlying mechanisms and their implications for patient health. Additionally, these alterations in the microbiome may have significant ramifications for forensic investigations, given the microbiome's potential in establishing individual characteristics. Consequently, changes in the microbiome could introduce a level of complexity into forensic determinations. As research progresses, a more profound understanding of the human microbiome within the context of COVID-19 may offer valuable insights into disease prevention, treatment strategies, and its potential applications in forensic science. Consequently, this paper aims to provide an overarching review of microbiome alterations due to COVID-19 and the associated impact on forensic applications, bridging the gap between the altered microbiome of COVID-19 patients and the challenges forensic investigations may encounter when analyzing this microbiome as a forensic biomarker.
Collapse
Affiliation(s)
- Tahir Ul Gani Mir
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India; State Forensic Science Laboratory, Srinagar, Jammu and Kashmir 190001, India.
| | - Sakshi Manhas
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Atif Khurshid Wani
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Nahid Akhtar
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India
| | - Saurabh Shukla
- School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India.
| | - Ajit Prakash
- Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA
| |
Collapse
|
|
50
|
Beurel E. Stress in the microbiome-immune crosstalk. Gut Microbes 2024; 16:2327409. [PMID: 38488630 PMCID: PMC10950285 DOI: 10.1080/19490976.2024.2327409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Accepted: 03/04/2024] [Indexed: 03/19/2024] Open
Abstract
The gut microbiota exerts a mutualistic interaction with the host in a fragile ecosystem and the host intestinal, neural, and immune cells. Perturbations of the gastrointestinal track composition after stress have profound consequences on the central nervous system and the immune system. Reciprocally, brain signals after stress affect the gut microbiota highlighting the bidirectional communication between the brain and the gut. Here, we focus on the potential role of inflammation in mediating stress-induced gut-brain changes and discuss the impact of several immune cells and inflammatory molecules of the gut-brain dialogue after stress. Understanding the impact of microbial changes on the immune system after stress might provide new avenues for therapy.
Collapse
Affiliation(s)
- Eléonore Beurel
- Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, USA
- Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA
| |
Collapse
|