Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 16 de 16
Filter
1.
Cells ; 11(5)2022 03 07.
Article in English | MEDLINE | ID: covidwho-1742341

ABSTRACT

The mucosal immune system of the respiratory tract possesses an effective "defense barrier" against the invading pathogenic microorganisms; therefore, the lungs of healthy organisms are considered to be sterile for a long time according to the strong pathogens-eliminating ability. The emergence of next-generation sequencing technology has accelerated the studies about the microbial communities and immune regulating functions of lung microbiota during the past two decades. The acquisition and maturation of respiratory microbiota during childhood are mainly determined by the birth mode, diet structure, environmental exposure and antibiotic usage. However, the formation and development of lung microbiota in early life might affect the occurrence of respiratory diseases throughout the whole life cycle. The interplay and crosstalk between the gut and lung can be realized by the direct exchange of microbial species through the lymph circulation, moreover, the bioactive metabolites produced by the gut microbiota and lung microbiota can be changed via blood circulation. Complicated interactions among the lung microbiota, the respiratory viruses, and the host immune system can regulate the immune homeostasis and affect the inflammatory response in the lung. Probiotics, prebiotics, functional foods and fecal microbiota transplantation can all be used to maintain the microbial homeostasis of intestinal microbiota and lung microbiota. Therefore, various kinds of interventions on manipulating the symbiotic microbiota might be explored as novel effective strategies to prevent and control respiratory diseases.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Probiotics , Fecal Microbiota Transplantation , Gastrointestinal Microbiome/physiology , Lung , Microbiota/physiology , Probiotics/therapeutic use
2.
mSphere ; 6(6): e0071121, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1546463

ABSTRACT

The COVID-19 pandemic has highlighted the need to identify additional antiviral small molecules to complement existing therapies. Although increasing evidence suggests that metabolites produced by the human microbiome have diverse biological activities, their antiviral properties remain poorly explored. Using a cell-based SARS-CoV-2 infection assay, we screened culture broth extracts from a collection of phylogenetically diverse human-associated bacteria for the production of small molecules with antiviral activity. Bioassay-guided fractionation uncovered three bacterial metabolites capable of inhibiting SARS-CoV-2 infection. This included the nucleoside analogue N6-(Δ2-isopentenyl)adenosine, the 5-hydroxytryptamine receptor agonist tryptamine, and the pyrazine 2,5-bis(3-indolylmethyl)pyrazine. The most potent of these, N6-(Δ2-isopentenyl)adenosine, had a 50% inhibitory concentration (IC50) of 2 µM. These natural antiviral compounds exhibit structural and functional similarities to synthetic drugs that have been clinically examined for use against COVID-19. Our discovery of structurally diverse metabolites with anti-SARS-CoV-2 activity from screening a small fraction of the bacteria reported to be associated with the human microbiome suggests that continued exploration of phylogenetically diverse human-associated bacteria is likely to uncover additional small molecules that inhibit SARS-CoV-2 as well as other viral infections. IMPORTANCE The continued prevalence of COVID-19 and the emergence of new variants has once again put the spotlight on the need for the identification of SARS-CoV-2 antivirals. The human microbiome produces an array of small molecules with bioactivities (e.g., host receptor ligands), but its ability to produce antiviral small molecules is relatively underexplored. Here, using a cell-based screening platform, we describe the isolation of three microbiome-derived metabolites that are able to prevent SARS-CoV-2 infection in vitro. These molecules display structural similarities to synthetic drugs that have been explored for the treatment of COVID-19, and these results suggest that the microbiome may be a fruitful source of the discovery of small molecules with antiviral activities.


Subject(s)
Antiviral Agents/pharmacology , Bacteria/metabolism , Culture Media/chemistry , Metabolic Networks and Pathways , Microbiota/physiology , SARS-CoV-2/drug effects , Symbiosis/physiology , Bacteria/chemistry , Bacteria/classification , Bacteria/growth & development , Biological Assay , Cell Line, Tumor , Culture Media/pharmacology , Humans , Molecular Docking Simulation , Protease Inhibitors/pharmacology , Protein Binding
3.
Exp Biol Med (Maywood) ; 247(5): 409-415, 2022 03.
Article in English | MEDLINE | ID: covidwho-1511670

ABSTRACT

The upper respiratory tract is inhabited by diverse range of commensal microbiota which plays a role in protecting the mucosal surface from pathogens. Alterations of the bacterial community from respiratory viral infections could increase the susceptibility to secondary infections and disease severities. We compared the upper respiratory bacterial profiles among Thai patients with influenza or COVID-19 by using 16S rDNA high-throughput sequencing based on MiSeq platform. The Chao1 richness was not significantly different among groups, whereas the Shannon diversity of Flu A and Flu B groups were significantly lower than Non-Flu & COVID-19 group. The beta diversity revealed that the microbial communities of influenza (Flu A and Flu B), COVID-19, and Non-Flu & COVID-19 were significantly different; however, the comparison of the community structure was similar between Flu A and Flu B groups. The bacterial classification revealed that Enterobacteriaceae was predominant in influenza patients, while Staphylococcus and Pseudomonas were significantly enriched in the COVID-19 patients. These implied that respiratory viral infections might be related to alteration of upper respiratory bacterial community and susceptibility to secondary bacterial infections. Moreover, the bacteria that observed in Non-Flu & COVID-19 patients had high abundance of Streptococcus, Prevotella, Veillonella, and Fusobacterium. This study provides the basic knowledge for further investigation of the relationship between upper respiratory microbiota and respiratory disease which might be useful for better understanding the mechanism of viral infectious diseases.


Subject(s)
Bacteria/genetics , COVID-19/microbiology , Influenza, Human/microbiology , Microbiota/physiology , Nasopharynx/microbiology , Adolescent , Adult , Humans , Microbiota/genetics , Middle Aged , Retrospective Studies , Young Adult
4.
Cytokine ; 149: 155757, 2022 01.
Article in English | MEDLINE | ID: covidwho-1499766

ABSTRACT

BACKGROUND: To determine and compare nasopharyngeal microbiota (NM) composition, in vitro basal (Nil tube), provoked (Mitogen tube) production of cytokines at the early stage of COVID-19. METHODS: This cross-sectional study included 4 age and sex-matched study groups; group 1 (recovered COVID-19) (n = 26), group 2 (mild COVID-19) (n = 24), group 3 (severe COVID-19) (n = 25), and group 4 (healthy controls) (n = 25). The study parameters obtained from the COVID-19 (group 2, and 3) at the early phase of hospital admission. RESULTS: The results from the reaserch deoicted that the Mean ± SD age was 53.09 ± 14.51 years. Some of the in vitro cytokines production was significantly different between the study groups. Some of the findinggs on cytokines depicted a significant differences between study groups were interleukin (IL)-1ß Nil, IL-1ß Mitogen, and their subtraction (i.e Mitogen-Nil). Regarding IL-10, and IL-17a levels, Mitogen, and Mitogen-Nil tube production levels were significantly different between the groups. Surprisingly, most of these measures were lowest in the severe COVID-19 patients' group. Using discriminant analysis effect size (LEfSe), Taxa of NM with significant abundance was determined. About 20 taxa with an LDA score > 4 were identified as candidate biomarkers. Some of these taxa showed a significant correlation with IL-1ß and IL-10 Mitogen and Mitogen- Nil levels (R > 0.3 or < -0.3, p < 0.05). CONCLUSIONS: The findings of this perticular study regarting the early stage of COVID-19 showed that in vitro cytokines production, studies might be more useful than the ordinary cytokines' blood level measurement. Besides, the study identified some NM species that could be candidate biomarkers in managing this infection. However, further detailed studies are needed in these fields.


Subject(s)
COVID-19/metabolism , COVID-19/microbiology , Cytokines/metabolism , Microbiota/physiology , Nasopharynx/microbiology , Nasopharynx/virology , COVID-19/virology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged
5.
Nat Commun ; 12(1): 6243, 2021 10 29.
Article in English | MEDLINE | ID: covidwho-1493101

ABSTRACT

Understanding the pathology of COVID-19 is a global research priority. Early evidence suggests that the respiratory microbiome may be playing a role in disease progression, yet current studies report contradictory results. Here, we examine potential confounders in COVID-19 respiratory microbiome studies by analyzing the upper (n = 58) and lower (n = 35) respiratory tract microbiome in well-phenotyped COVID-19 patients and controls combining microbiome sequencing, viral load determination, and immunoprofiling. We find that time in the intensive care unit and type of oxygen support, as well as associated treatments such as antibiotic usage, explain the most variation within the upper respiratory tract microbiome, while SARS-CoV-2 viral load has a reduced impact. Specifically, mechanical ventilation is linked to altered community structure and significant shifts in oral taxa previously associated with COVID-19. Single-cell transcriptomics of the lower respiratory tract of COVID-19 patients identifies specific oral bacteria in physical association with proinflammatory immune cells, which show higher levels of inflammatory markers. Overall, our findings suggest confounders are driving contradictory results in current COVID-19 microbiome studies and careful attention needs to be paid to ICU stay and type of oxygen support, as bacteria favored in these conditions may contribute to the inflammatory phenotypes observed in severe COVID-19 patients.


Subject(s)
COVID-19/microbiology , Gastrointestinal Microbiome/genetics , Gastrointestinal Microbiome/physiology , Humans , Microbiota/physiology , SARS-CoV-2/pathogenicity , Transcriptome/genetics
6.
mBio ; 12(5): e0214421, 2021 10 26.
Article in English | MEDLINE | ID: covidwho-1440802

ABSTRACT

Ecology and evolution, especially of microbes, have never been more relevant than in our global fight against SARS-CoV-2, the virus that causes COVID-19. Understanding how populations of SARS-CoV-2 grow, disperse, and evolve is of critical importance to managing the COVID-19 pandemic, and these questions are fundamentally ecological and evolutionary in nature. We compiled data from bioRxiv and medRxiv preprint abstracts and US National Institutes of Health Research Project grant abstracts to visualize the impact that the pivot to COVID-19 research has had on the study of microbes across biological disciplines. Finding that the pivot appears weaker in ecology and evolutionary biology than in other areas of biology, we discuss why the ecology and evolution of microbes, both pathogenic and otherwise, need renewed attention and investment going forward.


Subject(s)
Biological Evolution , COVID-19/epidemiology , Ecology , Microbiota/physiology , Humans , Pandemics
7.
Cells ; 10(6)2021 06 10.
Article in English | MEDLINE | ID: covidwho-1264420

ABSTRACT

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients.


Subject(s)
COVID-19/diagnosis , Leukocytes, Mononuclear/microbiology , Lung/microbiology , Microbiota/physiology , Bronchoalveolar Lavage Fluid/microbiology , Bronchoalveolar Lavage Fluid/virology , COVID-19/immunology , COVID-19/microbiology , COVID-19/virology , Case-Control Studies , Humans , Leukocytes, Mononuclear/virology , Liquid Biopsy , Lung/pathology , Lung/virology , Microbiota/genetics , Microbiota/immunology , Prognosis , RNA, Bacterial/analysis , RNA, Fungal/analysis , RNA-Seq , SARS-CoV-2/physiology
8.
Gut Microbes ; 13(1): 1-7, 2021.
Article in English | MEDLINE | ID: covidwho-1219896

ABSTRACT

Mortality and morbidity from SARS-CoV2 (COVID-19) infections in children remains low, including an exceedingly low rate of horizontal and vertical transmission. However, unforeseen complications to childhood health have emerged secondary to the pandemic. Few studies to date have examined unintended complications of the pandemic in newborns and infants. In this Commentary, we discuss the impact that COVID-19 may have on inheritance of the newborn microbiome and its assembly throughout the first years of life. In the early stages of the pandemic when vertical transmission of COVID-19 was poorly understood, several studies reported increased rates of C-sections in COVID-19 positive women. Initial recommendations discouraged COVID-19 positive mothers from breastfeeding and participating in skin-to-skin care, advising them to isolate during their window of infectivity. These shifts in perinatal care can adversely impact microbial colonization during the first 1000 days of life. While obstetrical and neonatal management have evolved to reflect our current knowledge of perinatal transmission, we are observing other changes in early life exposures of infants, including increased attention to hygiene, fewer social interactions, and decreased global travel, all of which are major drivers of early-life gut colonization. Composition of the gut microbiota in adults directly impacts severity of infection, suggesting a role of microbial communities in modulating immune responses to COVID-19. Conversely, the role of the intestinal microbiome in susceptibility and severity of COVID-19 in newborns and children remains unknown. The onset of adulthood diseases is related to the establishment of a healthy gut microbiome during childhood. As we continue to define COVID-19 biology, further research is necessary to understand how acquisition of the neonatal microbiome is affected by the pandemic. Furthermore, infection control measures must be balanced with strategies that promote microbial diversity to impart optimal health outcomes and potentially modulate susceptibility of children to COVID-19.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Gastrointestinal Microbiome/physiology , Infectious Disease Transmission, Vertical , Microbiota/physiology , Pregnancy Complications, Infectious/etiology , Pregnancy Complications, Infectious/physiopathology , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Pregnancy , SARS-CoV-2
9.
Mediators Inflamm ; 2021: 6611222, 2021.
Article in English | MEDLINE | ID: covidwho-1201585

ABSTRACT

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is responsible for the outbreak of a new viral respiratory infection. It has been demonstrated that the microbiota has a crucial role in establishing immune responses against respiratory infections, which are controlled by a bidirectional cross-talk, known as the "gut-lung axis." The effects of microbiota on antiviral immune responses, including dendritic cell (DC) function and lymphocyte homing in the gut-lung axis, have been reported in the recent literature. Additionally, the gut microbiota composition affects (and is affected by) the expression of angiotensin-converting enzyme-2 (ACE2), which is the main receptor for SARS-CoV-2 and contributes to regulate inflammation. Several studies demonstrated an altered microbiota composition in patients infected with SARS-CoV-2, compared to healthy individuals. Furthermore, it has been shown that vaccine efficacy against viral respiratory infection is influenced by probiotics pretreatment. Therefore, the importance of the gut microbiota composition in the lung immune system and ACE2 expression could be valuable to provide optimal therapeutic approaches for SARS-CoV-2 and to preserve the symbiotic relationship of the microbiota with the host.


Subject(s)
Gastrointestinal Microbiome/physiology , Microbiota/physiology , COVID-19/microbiology , Humans , Probiotics/therapeutic use , SARS-CoV-2/pathogenicity
10.
Curr Opin Virol ; 49: 21-26, 2021 08.
Article in English | MEDLINE | ID: covidwho-1198681

ABSTRACT

Impacts of respiratory tract viruses have long been appreciated to highly heterogeneous both between and within various populations. The SARS-CoV-2 pandemic, which is the first time that a pathogen's spread across the globe has been extensively monitored by direct detection of the pathogen itself rather just than the morbidity left in its wake, indicates such heterogeneity is not limited to outcomes of infections but whether infection of a particular host occurs at all. This suggests an important role for yet to be discovered environmental (i.e. non-genetic) factors that influence whether an exposure to the virus initiates a productive infection and, moreover, the severity of disease that results. This article discusses the emerging hypothesis that the composition of a host's commensal microbial communities, that is, its 'microbiome', may be one such determinant that influences outcomes following encounters with respiratory viral pathogens in general and SARS-CoV-2 in particular. Specifically, we will review the rationales and evidence that supports this hypothesis and, moreover, speculate as to possible approaches to manipulate microbiota to ameliorate disease induced by respiratory viral pathogens.


Subject(s)
COVID-19/microbiology , COVID-19/therapy , Microbiota/physiology , Adaptive Immunity , COVID-19/epidemiology , COVID-19/immunology , Gastrointestinal Microbiome , Host-Pathogen Interactions , Humans , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Intestinal Mucosa/virology , Microbial Interactions , Respiratory Tract Infections/immunology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/virology , SARS-CoV-2
11.
J Microbiol Immunol Infect ; 54(5): 808-815, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1164098

ABSTRACT

BACKGROUND: In COVID-19 patients, information regarding superinfection, antimicrobial assessment, and the value of metagenomic sequencing (MS) could help develop antimicrobial stewardship. METHOD: This retrospective study analyzed 323 laboratory-confirmed COVID-19 patients for co-infection rate and antimicrobial usage in the Shanghai Public Health Clinical Center (SPHCC) from January 23rd to March 14th 2020. The microbiota composition was also investigated in patients with critically severe COVID-19. RESULTS: The total population co-infection rate was 17/323 (5.3%) and 0/229 (0), 4/78 (5.1%), and 13/16 (81.3%) for the mild, severe, and critically severe subgroups, respectively. Proven fungal infection was significantly associated with a higher mortality rate (p = 0.029). In critically severe patients, the rate of antimicrobials and carbapenem usage were 16/16 (100%) and 13/16 (81.3%), respectively, in which the preemptive and empiric antimicrobial days accounted for 51.6% and 30.1%, respectively. Targeted therapy only accounted for 18.3%. MS was implemented to detect non-COVID-19 virus co-existence and the semi-quantitative surveillance of bacteremia, with clear clinical benefit seen in cases with MS-based precision antimicrobial management. Airway microbiome analysis suggested that the microbiota compositions in critically severe COVID-19 patients were likely due to intubation and mechanical ventilation. CONCLUSIONS: In the SPHCC cohort, we observed a non-negligible rate of super-infection, especially for the critically ill COVID-19 patients. Fungal co-infection requires intensive attention due to the high risk of mortality, and the clinical benefit of MS in guiding antimicrobial management warrants further investigation.


Subject(s)
Anti-Bacterial Agents/therapeutic use , COVID-19 , Metagenomics , Microbiota/physiology , Respiratory System/microbiology , Superinfection/drug therapy , Adult , Aged , Aged, 80 and over , Antimicrobial Stewardship , China , Cohort Studies , Coinfection/drug therapy , Critical Illness , Female , High-Throughput Nucleotide Sequencing , Humans , Male , Microbiota/genetics , Middle Aged , Mycoses/drug therapy , Retrospective Studies , SARS-CoV-2
13.
Front Cell Infect Microbiol ; 10: 619075, 2020.
Article in English | MEDLINE | ID: covidwho-1084083

ABSTRACT

Albeit the lungs were thought to be sterile, recent scientific data reported a microbial microbiota in the lungs of healthy individuals. Apparently, new developments in technological approachesincluding genome sequencing methodologies contributed in the identification of the microbiota and shed light on the role of the gut and lung microbiomes in the development of respiratory diseases. Moreover, knowledge of the human microbiome in health may act as a tool for evaluating characteristic shifts in the case of disease. This review paper discusses the development of respiratory disease linked to the intestinal dysbiosis which influences the lung immunity and microbiome. The gastrointestinal-lung dialogue provides interesting aspects in the pathogenesis of the respiratory diseases. Lastly, we were further interested on the role of this interconnection in the progression and physiopathology of newly emergedCOVID-19.


Subject(s)
Bacteria/isolation & purification , Lung/immunology , Lung/microbiology , Microbiota/physiology , Bacteria/classification , COVID-19/pathology , Gastrointestinal Tract/microbiology , Humans , SARS-CoV-2/growth & development
14.
Microbiome ; 9(1): 2, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1067276

ABSTRACT

The inaugural "Microbiome for Mars" virtual workshop took place on July 13, 2020. This event assembled leaders in microbiome research and development to discuss their work and how it may relate to long-duration human space travel. The conference focused on surveying current microbiome research, future endeavors, and how this growing field could broadly impact human health and space exploration. This report summarizes each speaker's presentation in the order presented at the workshop.


Subject(s)
Astronauts , Delivery of Health Care/trends , Mars , Microbiota/physiology , Space Flight , Animals , Gastrointestinal Microbiome/genetics , Gastrointestinal Microbiome/physiology , Humans , Microbiota/genetics
15.
Gut Microbes ; 13(1): 1-20, 2021.
Article in English | MEDLINE | ID: covidwho-1057792

ABSTRACT

The last twenty years of seminal microbiome research has uncovered microbiota's intrinsic relationship with human health. Studies elucidating the relationship between an unbalanced microbiome and disease are currently published daily. As such, microbiome big data have become a reality that provide a mine of information for the development of new therapeutics. Machine learning (ML), a branch of artificial intelligence, offers powerful techniques for big data analysis and prediction-making, that are out of reach of human intellect alone. This review will explore how ML can be applied for the development of microbiome-targeted therapeutics. A background on ML will be given, followed by a guide on where to find reliable microbiome big data. Existing applications and opportunities will be discussed, including the use of ML to discover, design, and characterize microbiome therapeutics. The use of ML to optimize advanced processes, such as 3D printing and in silico prediction of drug-microbiome interactions, will also be highlighted. Finally, barriers to adoption of ML in academic and industrial settings will be examined, concluded by a future outlook for the field.


Subject(s)
Machine Learning , Microbiota/physiology , Artificial Intelligence , Precision Medicine
16.
J Med Virol ; 93(6): 3288-3293, 2021 06.
Article in English | MEDLINE | ID: covidwho-1008192

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by respiratory syndrome coronavirus qualified as SARS-CoV-2. Viral penetration requires binding of the viral spike (S) protein to a specific cellular receptor (ACE2) highly expressed in a nasal goblet and ciliated cells. In several countries, the COVID-19 evolution was relatively benign compared to others and despite noncompliance with health recommendations on several occasions. In this overview, we attempt to define the criteria that could explain such a difference. Among these criteria, the specificity of Lactobacillus genus strains, as a part of nasal microbiota, could play a role of a barrier against viral penetration and could strengthen the host's immune system in some populations rather than others. In fact, several studies have shown the role of lactic acid bacteria, including lactobacilli, in the prevention of viral respiratory infections. This could provide important information on a possible mechanism of the virus spreading.


Subject(s)
COVID-19/microbiology , COVID-19/prevention & control , Lactobacillus/physiology , Microbiota/physiology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Humans , Microbiota/immunology , SARS-CoV-2/isolation & purification , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL