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van Zanten GC, Madsen AL, Yde CC, Krych L, Yeung N, Saarinen MT, Kot W, Jensen HM, Rasmussen MA, Ouwehand AC, Nielsen DS. Randomised, Placebo-Controlled Investigation of the Impact of Probiotic Consumption on Gut Microbiota Diversity and the Faecal Metabolome in Seniors. Microorganisms 2024; 12:796. [PMID: 38674741 PMCID: PMC11052279 DOI: 10.3390/microorganisms12040796] [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: 03/20/2024] [Revised: 04/05/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
Aging has been associated with a changed composition and function of the gut microbiota (GM). Here, we investigate the effects of the multi-strain probiotic HOWARU® Restore on GM composition and function in seniors. Ninety-eight healthy adult volunteers aged ≥75 years were enrolled in a randomised, double-blinded intervention (NCT02207140), where they received HOWARU Restore (1010 CFU) or the placebo daily for 24 weeks, with 45 volunteers from each group completing the intervention. Questionnaires monitoring the effects on gastro-intestinal discomfort and bowel movements were collected. Faecal samples for GM characterisation (qPCR, 16S rRNA gene amplicon sequencing) and metabolomics (GC-FID, 1H NMR) were collected at the baseline and after 24 weeks. In the probiotic group, self-reported gastro-intestinal discomfort in the form of flatulence was significantly decreased during the intervention. At the baseline, 151 'core species' (present in ≥95% of samples) were identified. Most core species belonged to the Lachnospiraceae and Ruminococcaceae families. Neither alpha diversity nor beta diversity or faecal metabolites was affected by probiotic intake. On the contrary, we observed high intra-individual GM stability, with 'individual' accounting for 72-75% of variation. In conclusion, 24 weeks of HOWARU Restore intake reduced gastro-intestinal discomfort in the form of flatulence in healthy seniors without significantly influencing GM composition or activity.
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Affiliation(s)
- Gabriella C. van Zanten
- Department of Food Science, University of Copenhagen, 1958 Frederiksberg, Denmark; (G.C.v.Z.); (A.L.M.); (L.K.); (M.A.R.); (D.S.N.)
| | - Anne Lundager Madsen
- Department of Food Science, University of Copenhagen, 1958 Frederiksberg, Denmark; (G.C.v.Z.); (A.L.M.); (L.K.); (M.A.R.); (D.S.N.)
| | - Christian C. Yde
- IFF Enabling Technologies, Brabrand, 8220 Aarhus, Denmark; (C.C.Y.); (H.M.J.)
| | - Lukasz Krych
- Department of Food Science, University of Copenhagen, 1958 Frederiksberg, Denmark; (G.C.v.Z.); (A.L.M.); (L.K.); (M.A.R.); (D.S.N.)
| | - Nicolas Yeung
- IFF Health, 02460 Kantvik, Finland; (N.Y.); (M.T.S.)
| | | | - Witold Kot
- Department of Plant and Environmental Sciences, University of Copenhagen, 1871 Frederiksberg, Denmark;
| | - Henrik Max Jensen
- IFF Enabling Technologies, Brabrand, 8220 Aarhus, Denmark; (C.C.Y.); (H.M.J.)
| | - Morten A. Rasmussen
- Department of Food Science, University of Copenhagen, 1958 Frederiksberg, Denmark; (G.C.v.Z.); (A.L.M.); (L.K.); (M.A.R.); (D.S.N.)
- Copenhagen Studies on Asthma in Childhood, University of Copenhagen, 2820 Gentofte, Denmark
| | | | - Dennis S. Nielsen
- Department of Food Science, University of Copenhagen, 1958 Frederiksberg, Denmark; (G.C.v.Z.); (A.L.M.); (L.K.); (M.A.R.); (D.S.N.)
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Chetty A, Blekhman R. Multi-omic approaches for host-microbiome data integration. Gut Microbes 2024; 16:2297860. [PMID: 38166610 PMCID: PMC10766395 DOI: 10.1080/19490976.2023.2297860] [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: 07/19/2023] [Accepted: 12/18/2023] [Indexed: 01/05/2024] Open
Abstract
The gut microbiome interacts with the host through complex networks that affect physiology and health outcomes. It is becoming clear that these interactions can be measured across many different omics layers, including the genome, transcriptome, epigenome, metabolome, and proteome, among others. Multi-omic studies of the microbiome can provide insight into the mechanisms underlying host-microbe interactions. As more omics layers are considered, increasingly sophisticated statistical methods are required to integrate them. In this review, we provide an overview of approaches currently used to characterize multi-omic interactions between host and microbiome data. While a large number of studies have generated a deeper understanding of host-microbiome interactions, there is still a need for standardization across approaches. Furthermore, microbiome studies would also benefit from the collection and curation of large, publicly available multi-omics datasets.
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Affiliation(s)
- Ashwin Chetty
- Committee on Genetics, Genomics and Systems Biology, The University of Chicago, Chicago, IL, USA
| | - Ran Blekhman
- Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL, USA
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3
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Zabel B, Mäkelä SM, Nedveck D, Hibberd AA, Yeung N, Latvala S, Lehtoranta L, Junnila J, Walters KB, Morovic W, Lehtinen MJ. The Effect of Bifidobacterium animalis subsp. lactis Bl-04 on Influenza A Virus Infection in Mice. Microorganisms 2023; 11:2582. [PMID: 37894240 PMCID: PMC10609243 DOI: 10.3390/microorganisms11102582] [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: 09/11/2023] [Revised: 10/10/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
Influenza A virus infection is a major global disease requiring annual vaccination. Clinical studies indicate that certain probiotics may support immune function against influenza and other respiratory viruses, but direct molecular evidence is scarce. Here, mice were treated with a placebo or Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) orally via food (cereal) and also by gavage and exposed to Influenza A virus H1N1 (H1N1). The symptoms of the infection were observed, and tissues and digesta were collected for viral load RT-qPCR, transcriptomics, and microbiomics. The treatment decreased the viral load by 48% at day 3 post-infection in lungs and symptoms of infection at day 4 compared to placebo. Tissue transcriptomics showed differences between the Bl-04 and placebo groups in the genes in the Influenza A pathway in the intestine, blood, and lungs prior to and post-infection, but the results were inconclusive. Moreover, 16S rRNA gene profiling and qPCR showed the presence of Bl-04 in the intestine, but without major shifts in the microbiome. In conclusion, Bl-04 treatment may influence the host response against H1N1 in a murine challenge model; however, further studies are required to elucidate the mechanism of action.
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Affiliation(s)
- Bryan Zabel
- Health & Biosciences, International Flavors & Fragrances, 3329 Agriculture Dr., Madison, WI 53716, USA
| | - Sanna M Mäkelä
- Health & Biosciences, International Flavors & Fragrances, Sokeritehtaantie 20, 02460 Kantvik, Finland
| | - Derek Nedveck
- Health & Biosciences, International Flavors & Fragrances, 3329 Agriculture Dr., Madison, WI 53716, USA
| | - Ashley A Hibberd
- Health & Biosciences, International Flavors & Fragrances, 3329 Agriculture Dr., Madison, WI 53716, USA
| | - Nicolas Yeung
- Health & Biosciences, International Flavors & Fragrances, Sokeritehtaantie 20, 02460 Kantvik, Finland
| | - Sinikka Latvala
- Health & Biosciences, International Flavors & Fragrances, Sokeritehtaantie 20, 02460 Kantvik, Finland
| | - Liisa Lehtoranta
- Health & Biosciences, International Flavors & Fragrances, Sokeritehtaantie 20, 02460 Kantvik, Finland
| | | | - Kevin B Walters
- Department of Infectious Disease Research, Southern Research Institute, 431 Aviation Way, Frederick, MD 21701, USA
| | - Wesley Morovic
- Health & Biosciences, International Flavors & Fragrances, 3329 Agriculture Dr., Madison, WI 53716, USA
| | - Markus J Lehtinen
- Health & Biosciences, International Flavors & Fragrances, Sokeritehtaantie 20, 02460 Kantvik, Finland
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Ishizaka A, Koga M, Mizutani T, Uraki R, Yamayoshi S, Iwatsuki-Horimoto K, Yamamoto S, Imai M, Tsutsumi T, Suzuki Y, Kawaoka Y, Yotsuyanagi H. Research article antibody induction and immune response in nasal cavity by third dose of SARS-CoV-2 mRNA vaccination. Virol J 2023; 20:146. [PMID: 37443091 PMCID: PMC10339591 DOI: 10.1186/s12985-023-02113-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 07/03/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND The mucosa serves as the first defence against pathogens and facilitates the surveillance and elimination of symbiotic bacteria by mucosal immunity. Recently, the mRNA vaccine against SARS-CoV-2 has been demonstrated to induce secretory antibodies in the oral and nasal cavities in addition to a systemic immune response. However, the mechanism of induced immune stimulation effect on mucosal immunity and commensal bacteria profile remains unclear. METHODS Here, we longitudinally analysed the changing nasal microbiota and both systemic and nasal immune response upon SARS-CoV-2 mRNA vaccination, and evaluated how mRNA vaccination influenced nasal microbiota in 18 healthy participants who had received the third BNT162b. RESULTS The nasal S-RBD IgG level correlated significantly with plasma IgG levels until 1 month and the levels were sustained for 3 months post-vaccination. In contrast, nasal S-RBD IgA induction peaked at 1 month, albeit slightly, and correlated only with plasma IgA, but the induction level decreased markedly at 3 months post-vaccination. 16 S rRNA sequencing of the nasal microbiota post-vaccination revealed not an overall change, but a decrease in certain opportunistic bacteria, mainly Fusobacterium. The decrease in these bacteria was more pronounced in those who exhibited nasal S-RBD IgA induction, and those with higher S-RBD IgA induction had lower relative amounts of potentially pathogenic bacteria such as Pseudomonas pre-vaccination. In addition, plasma and mucosal S-RBD IgG levels correlated with decreased commensal pathogens such as Finegoldia. CONCLUSIONS These findings suggest that the third dose of SARS-CoV-2 mRNA vaccination induced S-RBD antibodies in the nasal mucosa and may have stimulated mucosal immunity against opportunistic bacterial pathogens. This effect, albeit probably secondary, may be considered one of the benefits of mRNA vaccination. Furthermore, our data suggest that a cooperative function of mucosal and systemic immunity in the reduction of bacteria and provides a better understanding of the symbiotic relationship between the host and bacteria in the nasal mucosa.
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Affiliation(s)
- Aya Ishizaka
- Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan
| | - Michiko Koga
- Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan
| | - Taketoshi Mizutani
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha Kashiwa 277, 8562, Chiba, Japan.
| | - Ryuta Uraki
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
| | - Seiya Yamayoshi
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
| | - Kiyoko Iwatsuki-Horimoto
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Shinya Yamamoto
- Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Masaki Imai
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
| | - Takeya Tsutsumi
- Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- Department of Infectious Diseases, The University of Tokyo, Tokyo, Japan
| | - Yutaka Suzuki
- Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha Kashiwa 277, 8562, Chiba, Japan
| | - Yoshihiro Kawaoka
- Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
- The Research Center for Global Viral Diseases, National Center for Global Health and Medicine Research Institute, Tokyo, Japan
- Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI, USA
- Pandemic Preparedness, Infection and Advanced Research Center, The University of Tokyo, Tokyo, Japan
| | - Hiroshi Yotsuyanagi
- Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan.
- Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
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Bustamante S, Yau Y, Boys V, Chang J, Paramsothy S, Pudipeddi A, Leong RW, Wasinger VC. Tryptophan Metabolism 'Hub' Gene Expression Associates with Increased Inflammation and Severe Disease Outcomes in COVID-19 Infection and Inflammatory Bowel Disease. Int J Mol Sci 2022; 23:14776. [PMID: 36499104 PMCID: PMC9737535 DOI: 10.3390/ijms232314776] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/16/2022] [Accepted: 11/22/2022] [Indexed: 11/29/2022] Open
Abstract
The epithelial barrier's primary role is to protect against entry of foreign and pathogenic elements. Both COVID-19 and Inflammatory Bowel Disease (IBD) show commonalities in symptoms and treatment with sensitization of the epithelial barrier inviting an immune response. In this study we use a multi-omics strategy to identify a common signature of immune disease that may be able to predict for more severe patient outcomes. Global proteomic approaches were applied to transcriptome and proteome. Further semi- and relative- quantitative targeted mass spectrometry methods were developed to substantiate the proteomic and metabolomics changes in nasal swabs from healthy, COVID-19 (24 h and 3 weeks post infection); serums from Crohn's disease patients (scored for epithelial leak), terminal ileum tissue biopsies (patient matched inflamed and non-inflamed regions, and controls). We found that the tryptophan/kynurenine metabolism pathway is a 'hub' regulator of canonical and non-canonical transcription, macrophage release of cytokines and significant changes in the immune and metabolic status with increasing severity and disease course. Significantly modified pathways include stress response regulator EIF2 signaling (p = 1 × 10-3); energy metabolism, KYNU (p = 4 × 10-4), WARS (p = 1 × 10-7); inflammation, and IDO activity (p = 1 × 10-6). Heightened levels of PARP1, WARS and KYNU are predictive at the acute stage of infection for resilience, while in contrast, levels remained high and are predictive of persistent and more severe outcomes in COVID disease. Generation of a targeted marker profile showed these changes in immune disease underlay resolution of epithelial barrier function and have the potential to define disease trajectory and more severe patient outcomes.
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Affiliation(s)
- Sonia Bustamante
- Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia
| | - Yunki Yau
- Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia
| | - Victoria Boys
- School of Medical Sciences, Faculty of Medicine, The University of New South Wales, Sydney, NSW 2052, Australia
| | - Jeff Chang
- Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia
| | - Sudarshan Paramsothy
- Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia
| | - Aviv Pudipeddi
- Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia
| | - Rupert W. Leong
- Department of Gastroenterology, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia
| | - Valerie C. Wasinger
- Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Centre, The University of New South Wales, Sydney, NSW 2052, Australia
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Microarray-Based Analyses of Rhinovirus Species-Specific Antibody Responses in Exacerbated Pediatric Asthma in a German Pediatric Cohort. Viruses 2022; 14:v14091857. [PMID: 36146664 PMCID: PMC9502376 DOI: 10.3390/v14091857] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 08/15/2022] [Accepted: 08/18/2022] [Indexed: 02/05/2023] Open
Abstract
Rhinoviruses (RV) account for a significant number of asthma exacerbations, and RV species C may be associated with a severe course in vulnerable patient groups. Despite important evidence on the role of RV reported by clinicians and life scientists, there are still unanswered questions regarding their influence on asthma exacerbation in young patients. Thus, we measured the RVspecies-specific IgG titers in our German pediatric exacerbation cohort using a microarray-based technology. For this approach, human sera of patients with exacerbated asthma and wheeze, as well as healthy control subjects (n = 136) were included, and correlation analyses were performed. Concordantly with previously published results, we observed significantly higher cumulative levels of RV species A-specific IgG (p = 0.011) and RV-C-specific IgG (p = 0.051) in exacerbated asthma group compared to age-matched controls. Moreover, atopic wheezers had increased RV-specific IgG levels for species A (p = 0.0011) and species C (p = 0.0009) compared to non-atopic wheezers. Hypothesizing that bacterial infection positively correlates with immune memory against RV, we included nasopharyngeal swab results in our analyses and detected limited correlations. Interestingly, the eosinophil blood titer positively correlated with RV-specific IgG levels. With these observations, we add important observations to the existing data regarding exacerbation in pediatric and adolescent medicine. We propose that scientists and clinicians should pay more attention to the relevance of RV species in susceptible pediatric patients.
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7
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Mancabelli L, Milani C, Fontana F, Lugli GA, Tarracchini C, Turroni F, van Sinderen D, Ventura M. Mapping bacterial diversity and metabolic functionality of the human respiratory tract microbiome. J Oral Microbiol 2022; 14:2051336. [PMID: 35309410 PMCID: PMC8933033 DOI: 10.1080/20002297.2022.2051336] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 02/25/2022] [Accepted: 03/07/2022] [Indexed: 02/07/2023] Open
Abstract
Background The Human Respiratory Tract (HRT) is colonized by various microbial taxa, known as HRT microbiota, in a manner that is indicative of mutualistic interaction between such microorganisms and their host. Aim To investigate the microbial composition of the HRT and its possible correlation with the different compartments of the respiratory tract. Methods In the current study, we performed an in-depth meta-analysis of 849 HRT samples from public shotgun metagenomic datasets obtained through several distinct collection methods. Results The statistical robustness provided by this meta-analysis allowed the identification of 13 possible HRT-specific Community State Types (CSTs), which appear to be specific to each anatomical region of the respiratory tract. Furthermore, functional characterization of the metagenomic datasets revealed specific microbial metabolic features correlating with the different compartments of the respiratory tract. Conclusion The meta-analysis here performed suggested that the variable presence of certain bacterial species seems to be linked to a location-related abundance gradient in the HRT and seems to be characterized by a specific microbial metabolic capability.
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Affiliation(s)
- Leonardo Mancabelli
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Christian Milani
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
- Interdepartmental Research Centre “Microbiome Research Hub”, University of Parma, Parma, Italy
| | - Federico Fontana
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Gabriele Andrea Lugli
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Chiara Tarracchini
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
| | - Francesca Turroni
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
- Interdepartmental Research Centre “Microbiome Research Hub”, University of Parma, Parma, Italy
| | - Douwe van Sinderen
- APC Microbiome Institute and School of Microbiology, Bioscience Institute, National University of Ireland, Cork, Ireland
| | - Marco Ventura
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy
- Interdepartmental Research Centre “Microbiome Research Hub”, University of Parma, Parma, Italy
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8
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Jackson DJ, Gern JE. Rhinovirus Infections and Their Roles in Asthma: Etiology and Exacerbations. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:673-681. [PMID: 35074599 DOI: 10.1016/j.jaip.2022.01.006] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Revised: 01/06/2022] [Accepted: 01/06/2022] [Indexed: 12/17/2022]
Abstract
Rhinovirus infections can cause wheezing illnesses in all age groups. In preschool children, rhinovirus infections frequently initiate acute wheezing illnesses. Children who wheeze with rhinoviruses are at increased risk to go on to develop asthma. Once asthma is established, rhinovirus infections are potent triggers for acute airway obstruction and exacerbations in children and adults. Paradoxically, for most individuals, rhinovirus infections commonly cause cold symptoms with little or no involvement of the lower airways. This paradox has led investigators to identify specific risk factors and mechanisms for rhinovirus wheezing, and this review will outline progress in 3 main areas. First, the 3 species of rhinoviruses have different patterns of infection and virulence. Second, personal factors such as lung function and immunity influence lower respiratory outcomes of rhinovirus infection. The mucosal immune response is critical, and the quality of the interferon response and allergic inflammation interacts to determine the risk for rhinovirus wheezing. Finally, rhinovirus infections can promote pathogen-dominated airway microbiota that increase the risk for wheezing. Although specific antivirals for rhinovirus are still not available, identifying risk factors for wheezing illnesses has provided several other potential targets and strategies for reducing the risk of rhinovirus-induced wheezing and exacerbations of asthma.
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Affiliation(s)
- David J Jackson
- Guy's Severe Asthma Centre, Guy's & St Thomas' NHS Trust, London, United Kingdom; School of Immunology & Microbial Sciences, King's College London, London, United Kingdom.
| | - James E Gern
- Departments of Pediatrics and Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis
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Shetty SA, van Beek J, Bijvank E, Groot J, Kuiling S, Bosch T, van Baarle D, Fuentes S. Associations and recovery dynamics of the nasopharyngeal microbiota during influenza-like illness in the aging population. Sci Rep 2022; 12:1915. [PMID: 35115596 PMCID: PMC8813934 DOI: 10.1038/s41598-022-05618-9] [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: 10/07/2021] [Accepted: 01/12/2022] [Indexed: 11/09/2022] Open
Abstract
Influenza-like illness (ILI), a disease caused by respiratory pathogens including influenza virus, is a major health concern in older adults. There is little information on changes and recovery dynamics of the nasopharyngeal (NP) microbiota of older adults associated with an ILI. Here, we compared the NP microbiota in older adults reporting (n = 240) or not (n = 157) ILI during the 2014-2015 influenza season at different times of the ILI event. A small but significant effect of the ILI was observed on the microbiota community composition and structure when compared to controls and samples collected at recovery. Corynebacterium was negatively associated with ILI and its abundance increased after recovery. Potential pathobionts such as Haemophilus, Porphyromonas and Gemella had higher abundances during acute-ILI. Stability and changes in the NP microbial community showed individual dynamics. Key core genera, Corynebacterium, Moraxella and Dolosigranulum exhibited higher inter-individual variability in acute-ILI, but showed comparable variability to controls after recovery. Participants in the ILI group with higher core microbiota abundances at the acute phase showed higher microbiota stability after recovery. Our findings demonstrate that acute-ILI is associated with alterations in the phylogenetic structure of the NP microbiota in older adults. The variation in the core microbiota suggests imbalances in the ecosystem, which could potentially play a role in the susceptibility and recovery of the NP microbiota after an ILI event.
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Affiliation(s)
- Sudarshan A Shetty
- Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
- Department of Medical Microbiology and Infection Prevention, Virology and Immunology Research Group, University Medical Center Groningen, Groningen, The Netherlands
| | - Josine van Beek
- Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Elske Bijvank
- Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - James Groot
- Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Sjoerd Kuiling
- Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Thijs Bosch
- Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Debbie van Baarle
- Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
- Department of Medical Microbiology and Infection Prevention, Virology and Immunology Research Group, University Medical Center Groningen, Groningen, The Netherlands
| | - Susana Fuentes
- Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
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10
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Gupta A, Karyakarte R, Joshi S, Das R, Jani K, Shouche Y, Sharma A. Nasopharyngeal microbiome reveals the prevalence of opportunistic pathogens in SARS-CoV-2 infected individuals and their association with host types. Microbes Infect 2022; 24:104880. [PMID: 34425246 PMCID: PMC8379005 DOI: 10.1016/j.micinf.2021.104880] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 08/03/2021] [Accepted: 08/06/2021] [Indexed: 02/09/2023]
Abstract
The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing a severe global health emergency owing to its highly infectious nature. Although the symptoms of SARS-CoV-2 are well known but its impact on nasopharyngeal microbiome is poorly studied. The present cross-sectional study was intended to understand the perturbation in the nasopharyngeal microbiome composition within the infected (n = 63) and non-infected (n = 26) individuals using 16S rRNA gene based targeted amplicon sequencing and their association with host types and the prevalence of opportunistic pathogens at the stage of infection. The results confirmed that number of OTUs were significantly (p < 0.05) decreased in the SARS-CoV-2 infected individuals in comparison to non-infected individuals. Pairwise Wilcoxon test showed a significant (p < 0.05) increase in the abundance of Proteobacteria in infected individuals compared to non-infected ones and vice-versa for Fusobacteria and Bacteroidetes. Similarity percentage (SIMPER) analysis showed the increment in the abundance of opportunistic pathogens (Haemophilus, Stenotrophomonas, Acinetobacter, Moraxella, Corynebacterium 1, Gemella, Ralstonia, and Pseudomonas) involved in secondary infection. Furthermore, this study highlighted the microbial community structure of individuals within and across the families. In this study, we also performed the assesment of microbiome associated with host types (age and genders) and COVID-19 conditions (symptomatic and asymptomatic). The data suggested that the host types/conditions during the COVID-19 infection are potential factors in enrichment of specific bacterial communities in upper respiratory tract.
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Affiliation(s)
- Abhishek Gupta
- DBT-National Centre for Cell Science, Pune, Maharashtra, 411007, India
| | - Rajesh Karyakarte
- Byramjee Jeejeebhoy Government Medical College, Pune, Maharashtra, 411001, India
| | - Suvarna Joshi
- Byramjee Jeejeebhoy Government Medical College, Pune, Maharashtra, 411001, India
| | - Rashmita Das
- Byramjee Jeejeebhoy Government Medical College, Pune, Maharashtra, 411001, India
| | - Kunal Jani
- DBT-National Centre for Cell Science, Pune, Maharashtra, 411007, India
| | - Yogesh Shouche
- DBT-National Centre for Cell Science, Pune, Maharashtra, 411007, India
| | - Avinash Sharma
- DBT-National Centre for Cell Science, Pune, Maharashtra, 411007, India.
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11
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Zhao Y, Chen J, Hao Y, Wang B, Wang Y, Liu Q, Zhao J, Li Y, Wang P, Wang X, Zhang P, Zhang L. Predicting the recurrence of chronic rhinosinusitis with nasal polyps using nasal microbiota. Allergy 2022; 77:540-549. [PMID: 34735742 DOI: 10.1111/all.15168] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Revised: 10/11/2021] [Accepted: 10/21/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Recent studies have revealed that the nasal microbiota in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is profoundly altered and is correlated with systemic inflammation. However, little is known regarding whether the microbiota can be utilized to predict nasal polyp recurrence. This study is aimed to determine whether altered nasal microbiota constituents could be used as biomarkers to predict CRSwNP recurrence. METHODS Nasal microbiota constituents were quantified and characterized using bacterial 16S ribosomal RNA gene sequencing. Selected features for least absolute shrinkage and selection operator regression-based predictors were the nasal microbiota community composition and CRSwNP patient clinical characteristics. The primary outcome was recurrence, which was determined post-admission. RESULTS By distinguishing recurrence-associated nasal microbiota taxa and exploiting the distinct nasal microbiota abundance between patients with recurrent and non-recurrent CRSwNP, we developed a predictive classifier for the diagnosis of nasal polyps' recurrence with 91.4% accuracy. CONCLUSIONS Key taxonomical features of the nasal microbiome could predict recurrence in CRSwNP patients. The nasal microbiome is an understudied source of clinical variation in CRSwNP and represents a novel therapeutic target for future prevention and treatment.
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Affiliation(s)
- Yan Zhao
- Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases and Beijing Laboratory of Allergic Diseases Beijing Institute of Otolaryngology Beijing China
| | - Junru Chen
- Reproductive and Genetic Hospital of CITIC‐Xiangya Changsha China
| | - Yun Hao
- Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical University Beijing China
| | - Boqian Wang
- Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical University Beijing China
| | - Yue Wang
- Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical University Beijing China
| | - Qinghua Liu
- Department of Otorhinolaryngology Head and Neck Surgery Fujian Provincial Hospital Fuzhou China
| | - Jinming Zhao
- Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical University Beijing China
| | - Ying Li
- Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases and Beijing Laboratory of Allergic Diseases Beijing Institute of Otolaryngology Beijing China
| | - Ping Wang
- Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases and Beijing Laboratory of Allergic Diseases Beijing Institute of Otolaryngology Beijing China
| | - Xiangdong Wang
- Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases and Beijing Laboratory of Allergic Diseases Beijing Institute of Otolaryngology Beijing China
| | - Peng Zhang
- Beijing Key Laboratory for Genetics of Birth Defects, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health Beijing China
| | - Luo Zhang
- Department of Otolaryngology Head and Neck Surgery Beijing Tongren HospitalCapital Medical University Beijing China
- Beijing Key Laboratory of Nasal Diseases and Beijing Laboratory of Allergic Diseases Beijing Institute of Otolaryngology Beijing China
- Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China
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12
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He Y, Yu W, Ning P, Luo Q, Zhao L, Xie Y, Yu Y, Ma X, Chen L, Zheng Y, Gao Z. Shared and Specific Lung Microbiota with Metabolic Profiles in Bronchoalveolar Lavage Fluid Between Infectious and Inflammatory Respiratory Diseases. J Inflamm Res 2022; 15:187-198. [PMID: 35046693 PMCID: PMC8760989 DOI: 10.2147/jir.s342462] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Accepted: 12/31/2021] [Indexed: 12/30/2022] Open
Abstract
Background Infiltration of the lower respiratory tract (LRT) microenvironment could be significantly associated with respiratory diseases. However, alterations in the LRT microbiome and metabolome in infectious and inflammatory respiratory diseases and their correlation with inflammation still need to be explored. Methods Bronchoalveolar lavage samples from 44 community-acquired pneumonia (CAP) patients, 29 connective tissue disease-associated interstitial disease (CTD-ILD) patients, and 30 healthy volunteers were used to detect microbiota and metabolites through 16S rRNA gene sequencing and untargeted high-performance liquid chromatography with mass spectrometry. Results The composition of the LRT microbial communities and metabolites differed in disease states. CAP patients showed a significantly low abundance and both diseases presented a depletion of some genera of the phylum Bacteroidetes, including Prevotella, Porphyromonas, and health-associated metabolites, such as sphingosine (d16:1), which were negatively correlated with infectious indicators. In contrast, Bacillus and Mycoplasma were both enriched in the disease groups. Streptococcus was specifically increased in CTD-ILD. In addition, co-elevated metabolites such as FA (22:4) and pyruvic acid represented hypoxia and inflammation in the diseases. Significantly increased levels of amino acids and succinate, as well as decreased itaconic acid levels, were observed in CAP patients, whereas CTD-ILD patients showed only a handful of specific metabolic alterations. Functions related to microbial lipid and amino acid metabolism were significantly altered, indicating the possible contributions of microbial metabolism. Dual omics analysis showed a moderate positive correlation between the microbiome and metabolome. The levels of L-isoleucine and L-arginine were negatively correlated with Streptococcus, and itaconic acid positively correlated with Streptococcus. Conclusion In the LRT microenvironment, shared and specific alterations occurred in CAP and CTD-ILD patients, which were associated with inflammatory and immune reactions, which may provide a new direction for future studies aiming to elucidate the mechanism, improve the diagnosis, and develop therapies for different respiratory diseases.
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Affiliation(s)
- Yukun He
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
| | - Wenyi Yu
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
| | - Pu Ning
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China
| | - Qiongzhen Luo
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
- Department of Respiratory & Critical Care Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China
| | - Lili Zhao
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
| | - Yu Xie
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
| | - Yan Yu
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
| | - Xinqian Ma
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
| | - Li Chen
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
| | - Yali Zheng
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
- Department of Respiratory, Critical Care, and Sleep Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China
- Correspondence: Yali Zheng Department of Respiratory, Critical Care, and Sleep Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China Email
| | - Zhancheng Gao
- Department of Respiratory and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China
- Department of Respiratory, Critical Care, and Sleep Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China
- Zhancheng Gao Department of Pulmonary and Critical Care Medicine, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China Email
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13
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Turner RB, Lehtoranta L, Hibberd A, Männikkö S, Zabel B, Yeung N, Huttunen T, Burns FR, Lehtinen MJ. Effect of Bifidobacterium animalis spp. lactis Bl-04 on Rhinovirus-Induced Colds: A Randomized, Placebo-Controlled, Single-Center, Phase II Trial in Healthy Volunteers. EClinicalMedicine 2022; 43:101224. [PMID: 34927036 PMCID: PMC8649651 DOI: 10.1016/j.eclinm.2021.101224] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 11/11/2021] [Accepted: 11/17/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND This study was designed to assess the efficacy of Bifidobacterium animalis ssp. lactis (Bl-04) for prevention of rhinovirus colds and to explore the interactions between the probiotic, the viral infection, the host response and the host microbiome. METHODS The effect of ingestion of the probiotic Bl-04 was evaluated in a randomized, double-blinded rhinovirus (RV) challenge study. Healthy volunteers recruited from a university community in USA were randomized 1:1 using a computer generated code to ingest either Bl-04 (n=165) or placebo (n=169) for 28 days and were then challenged with RV-A39, and followed for 14 days. All study interactions and sample collection occurred in dedicated clinical research space. The primary analysis was the effect of the probiotic on the incidence of RV-associated illness. (Trial registration: NCT02679807, study complete). FINDINGS The first cohort of volunteers was randomized on March 14, 2016 and the last (5th) cohort was randomized on March 12, 2018. Sixty-three (56%, 95% CI [47%; 66%]) of the 112 subjects in the active group and 60 (50%,95% CI [41%; 59%]) of the 120 subjects in the placebo group had a protocol-defined rhinovirus-associated illness (χ2=0·91, p=0·34). The point estimate of the difference in illness (active-placebo) is 6.3% (95% CI -6.7;19.1). There were no adverse events that were judged as definitely or probably related to the study product. INTERPRETATION In this study there was no effect of orally administered Bl-04 on the occurrence of RV-associated illness. FUNDING Danisco Sweeteners Oy (now IFF Health & Biosciences).
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Affiliation(s)
- Ronald B. Turner
- Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA
- Corresponding To: 512 Rosemont Drive, Charlottesville, VA 22903
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14
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Ren L, Wang Y, Zhong J, Li X, Xiao Y, Li J, Yang J, Fan G, Guo L, Shen Z, Kang L, Shi L, Li Q, Li J, Di L, Li H, Wang C, Wang Y, Wang X, Zou X, Rao J, Zhang L, Wang J, Huang Y, Cao B, Wang J, Li M. Dynamics of the Upper Respiratory Tract Microbiota and Its Association with Mortality in COVID-19. Am J Respir Crit Care Med 2021; 204:1379-1390. [PMID: 34534435 PMCID: PMC8865718 DOI: 10.1164/rccm.202103-0814oc] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Rationale Alteration of human respiratory microbiota had been observed in coronavirus disease (COVID-19). How the microbiota is associated with the prognosis in COVID-19 is unclear. Objectives To characterize the feature and dynamics of the respiratory microbiota and its associations with clinical features in patients with COVID-19. Methods We conducted metatranscriptome sequencing on 588 longitudinal oropharyngeal swab specimens collected from 192 patients with COVID-19 (including 39 deceased patients) and 95 healthy controls from the same geographic area. Meanwhile, the concentration of 27 cytokines and chemokines in plasma was measured for patients with COVID-19. Measurements and Main Results The upper respiratory tract (URT) microbiota in patients with COVID-19 differed from that in healthy controls, whereas deceased patients possessed a more distinct microbiota, both on admission and before discharge/death. The alteration of URT microbiota showed a significant correlation with the concentration of proinflammatory cytokines and mortality. Specifically, Streptococcus-dominated microbiota was enriched in recovered patients, and showed high temporal stability and resistance against pathogens. In contrast, the microbiota in deceased patients was more susceptible to secondary infections and became more deviated from the norm after admission. Moreover, the abundance of S. parasanguinis on admission was significantly correlated with prognosis in nonsevere patients (lower vs. higher abundance, odds ratio, 7.80; 95% CI, 1.70–42.05). Conclusions URT microbiota dysbiosis is a remarkable manifestation of COVID-19; its association with mortality suggests it may reflect the interplay between pathogens, symbionts, and the host immune status. Whether URT microbiota could be used as a biomarker for diagnosis and prognosis of respiratory diseases merits further investigation.
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Affiliation(s)
- Lili Ren
- NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, and.,Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yeming Wang
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, and.,Department of Respiratory Medicine, Capital Medical University, Beijing, China
| | - Jiaxin Zhong
- Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Xia Li
- Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Wuhan, China
| | - Yan Xiao
- NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, and.,Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie Li
- School of Life Sciences, Beijing Advanced Innovation Center for Structural Biology, and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China
| | - Jing Yang
- Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Guohui Fan
- Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China
| | - Li Guo
- NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, and.,Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zijie Shen
- Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Lu Kang
- Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Leisheng Shi
- Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Qiong Li
- School of Life Sciences, Beijing Advanced Innovation Center for Structural Biology, and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China
| | - Jizhou Li
- School of Life Sciences, Beijing Advanced Innovation Center for Structural Biology, and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China
| | - Lin Di
- Biomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, College of Chemistry, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
| | - Haibo Li
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, and.,Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China
| | - Conghui Wang
- NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, and
| | - Ying Wang
- NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, and
| | - Xinming Wang
- NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, and
| | - Xiaohui Zou
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, and.,Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China
| | - Jian Rao
- NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, and.,Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Zhang
- Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Jianbin Wang
- School of Life Sciences, Beijing Advanced Innovation Center for Structural Biology, and Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing, China
| | - Yanyi Huang
- Biomedical Pioneering Innovation Center, Beijing Advanced Innovation Center for Genomics, College of Chemistry, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.,Institute for Cell Analysis, Shenzhen Bay Laboratory, Guangdong, China
| | - Bin Cao
- Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, and.,Department of Respiratory Medicine, Capital Medical University, Beijing, China.,Institute of Respiratory Medicine, Chinese Academy of Medical Science, Beijing, China.,Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China; and
| | - Jianwei Wang
- NHC Key Laboratory of Systems Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, and.,Key Laboratory of Respiratory Disease Pathogenomics, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mingkun Li
- Beijing Institute of Genomics, Chinese Academy of Sciences, and China National Center for Bioinformation, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China.,Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, China
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15
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Jochems SP, Ferreira DM, Smits HH. Microbiota and compartment matter in the COVID-19 response. Nat Immunol 2021; 22:1350-1352. [PMID: 34675388 DOI: 10.1038/s41590-021-01041-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Simon P Jochems
- Department of Parasitology, Leiden University Medical Center, Leiden, the Netherlands.
| | - Daniela M Ferreira
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Hermelijn H Smits
- Department of Parasitology, Leiden University Medical Center, Leiden, the Netherlands
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16
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Kolhe R, Sahajpal NS, Vyavahare S, Dhanani AS, Adusumilli S, Ananth S, Mondal AK, Patterson GT, Kumar S, Rojiani AM, Isales CM, Fulzele S. Alteration in Nasopharyngeal Microbiota Profile in Aged Patients with COVID-19. Diagnostics (Basel) 2021; 11:diagnostics11091622. [PMID: 34573964 PMCID: PMC8467337 DOI: 10.3390/diagnostics11091622] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Revised: 08/26/2021] [Accepted: 08/30/2021] [Indexed: 02/07/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is an infectious virus that causes coronavirus disease 2019 (COVID-19) transmitted mainly through droplets and aerosol affecting the respiratory tract and lungs. Little is known regarding why some individuals are more susceptible than others and develop severe symptoms. In this study, we analyzed the nasopharyngeal microbiota profile of aged patients with COVID-19 (asymptomatic vs. symptomatic) vs. healthy individuals. We examined the nasopharynx swab of 84 aged-matched patients, out of which 27 were negative asymptomatic (NegA), 30 were positive asymptomatic (PA), and 27 patients were positive symptomatic (PSY). Our analysis revealed the presence of abundant Cyanobacterial taxa at phylum level in PA (p-value = 0.0016) and PSY (p-value = 0.00038) patients along with an upward trend in the population of Litoricola, Amylibacter, Balneola, and Aeromonas at the genus level. Furthermore, to know the relationship between the nasal microbiota composition and severity of COVID-19, we compared PA and PSY groups. Our data show that the nasal microbiota of PSY patients was significantly enriched with the signatures of two bacterial taxa: Cutibacterium (p-value = 0.045) and Lentimonas (p-value = 0.007). Furthermore, we also found a significantly lower abundance of five bacterial taxa, namely: Prevotellaceae (p-value = 7 × 10−6), Luminiphilus (p-value = 0.027), Flectobacillus (p-value = 0.027), Comamonas (p-value = 0.048), and Jannaschia (p-value = 0.012) in PSY patients. The dysbiosis of the nasal microbiota in COVID-19 positive patients might have a role in contributing to the severity of COVID-19. The findings of our study show that there is a strong correlation between the composition of the nasal microbiota and COVID-19 severity. Further studies are needed to validate our finding in large-scale samples and to correlate immune response (cytokine Strome) and nasal microbiota to identify underlying mechanisms and develop therapeutic strategies against COVID-19.
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Affiliation(s)
- Ravindra Kolhe
- Department of Pathology, Augusta University, Augusta, GA 30912, USA; (R.K.); (N.S.S.); (S.A.); (A.K.M.); (A.M.R.)
| | - Nikhil Shri Sahajpal
- Department of Pathology, Augusta University, Augusta, GA 30912, USA; (R.K.); (N.S.S.); (S.A.); (A.K.M.); (A.M.R.)
| | - Sagar Vyavahare
- Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA; (S.V.); (S.K.)
| | - Akhilesh S. Dhanani
- Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada;
| | - Satish Adusumilli
- Department of Pathology, University of Notre Dame, Notre Dame, IN 46556, USA;
| | - Sudha Ananth
- Department of Pathology, Augusta University, Augusta, GA 30912, USA; (R.K.); (N.S.S.); (S.A.); (A.K.M.); (A.M.R.)
| | - Ashis K. Mondal
- Department of Pathology, Augusta University, Augusta, GA 30912, USA; (R.K.); (N.S.S.); (S.A.); (A.K.M.); (A.M.R.)
| | - G. Taylor Patterson
- Department of Orthopedics, Augusta University, Augusta, GA 30912, USA; (G.T.P.); (C.M.I.)
| | - Sandeep Kumar
- Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA; (S.V.); (S.K.)
| | - Amyn M. Rojiani
- Department of Pathology, Augusta University, Augusta, GA 30912, USA; (R.K.); (N.S.S.); (S.A.); (A.K.M.); (A.M.R.)
- Department of Pathology, Penn State University, State College, PA 16802, USA
| | - Carlos M. Isales
- Department of Orthopedics, Augusta University, Augusta, GA 30912, USA; (G.T.P.); (C.M.I.)
- Department of Medicine, Augusta University, Augusta, GA 30912, USA
- Center for Healthy Aging, Augusta University, Augusta, GA 30912, USA
| | - Sadanand Fulzele
- Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA; (S.V.); (S.K.)
- Department of Orthopedics, Augusta University, Augusta, GA 30912, USA; (G.T.P.); (C.M.I.)
- Department of Medicine, Augusta University, Augusta, GA 30912, USA
- Center for Healthy Aging, Augusta University, Augusta, GA 30912, USA
- Correspondence:
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17
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Rhoades NS, Pinski AN, Monsibais AN, Jankeel A, Doratt BM, Cinco IR, Ibraim I, Messaoudi I. Acute SARS-CoV-2 infection is associated with an increased abundance of bacterial pathogens, including Pseudomonas aeruginosa in the nose. Cell Rep 2021; 36:109637. [PMID: 34433082 PMCID: PMC8361213 DOI: 10.1016/j.celrep.2021.109637] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 07/12/2021] [Accepted: 08/06/2021] [Indexed: 01/08/2023] Open
Abstract
Research conducted on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and coronavirus disease 2019 (COVID-19) generally focuses on the systemic host response, especially that generated by severely ill patients, with few studies investigating the impact of acute SARS-CoV-2 at the site of infection. We show that the nasal microbiome of SARS-CoV-2-positive patients (CoV+, n = 68) at the time of diagnosis is unique when compared to CoV− healthcare workers (n = 45) and CoV− outpatients (n = 21). This shift is marked by an increased abundance of bacterial pathogens, including Pseudomonas aeruginosa, which is also positively associated with viral RNA load. Additionally, we observe a robust host transcriptional response in the nasal epithelia of CoV+ patients, indicative of an antiviral innate immune response and neuronal damage. These data suggest that the inflammatory response caused by SARS-CoV-2 infection is associated with an increased abundance of bacterial pathogens in the nasal cavity that could contribute to increased incidence of secondary bacterial infections.
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Affiliation(s)
- Nicholas S Rhoades
- Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA
| | - Amanda N Pinski
- Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA
| | - Alisha N Monsibais
- Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA
| | - Allen Jankeel
- Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA
| | - Brianna M Doratt
- Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA
| | - Isaac R Cinco
- Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA
| | - Izabela Ibraim
- Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA
| | - Ilhem Messaoudi
- Department of Molecular Biology and Biochemistry, University of California Irvine, Irvine, CA, USA.
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18
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Velikova T, Snegarova V, Kukov A, Batselova H, Mihova A, Nakov R. Gastrointestinal mucosal immunity and COVID-19. World J Gastroenterol 2021; 27:5047-5059. [PMID: 34497434 PMCID: PMC8384742 DOI: 10.3748/wjg.v27.i30.5047] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 05/01/2021] [Accepted: 07/12/2021] [Indexed: 02/06/2023] Open
Abstract
As the gastrointestinal tract may also be a crucial entry or interaction site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the role of the gut mucosal immune system as a first-line physical and immunological defense is critical. Furthermore, gastrointestinal involvement and symptoms in coronavirus disease 2019 (COVID-19) patients have been linked to worse clinical outcomes. This review discusses recent data on the interactions between the virus and the immune cells and molecules in the mucosa during the infection. By carrying out appropriate investigations, the mucosal immune system role in SARS-CoV-2 infection in therapy and prevention can be established. In line with this, COVID-19 vaccines that stimulate mucosal immunity against the virus may have more advantages than the others.
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Affiliation(s)
- Tsvetelina Velikova
- Department of Clinical Immunology, University Hospital Lozenetz, Medical Faculty, Sofia University, St. Kliment Ohridski, Sofia 1407, Bulgaria
| | - Violeta Snegarova
- Clinic of Internal Diseases, Naval Hospital – Varna, Military Medical Academy, Medical Faculty, Medical University, Varna 9000, Bulgaria
| | - Alexander Kukov
- Department of Clinical Immunology, University Hospital Lozenetz, Medical Faculty, Sofia University, St. Kliment Ohridski, Sofia 1407, Bulgaria
| | - Hristiana Batselova
- Department of Epidemiology and Disaster Medicine, Medical University, Plovdiv, University Hospital "St George", Plovdiv 6000, Bulgaria
| | - Antoaneta Mihova
- Department of Clinical Immunology, University Hospital Lozenetz, Medical Faculty, Sofia University, St. Kliment Ohridski, Sofia 1407, Bulgaria
| | - Radislav Nakov
- Clinic of Gastroenterology, Tsaritsa Joanna University Hospital, Medical University of Sofia, Sofia 1527, Bulgaria
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19
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Ngo VL, Gewirtz AT. Microbiota as a potentially-modifiable factor influencing COVID-19. Curr Opin Virol 2021; 49:21-26. [PMID: 34000641 PMCID: PMC8059947 DOI: 10.1016/j.coviro.2021.04.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/12/2021] [Accepted: 04/13/2021] [Indexed: 12/11/2022]
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.
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Affiliation(s)
- Vu L Ngo
- Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
| | - Andrew T Gewirtz
- Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
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20
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Iorio A, Biazzo M, Gardini S, Muda AO, Perno CF, Dallapiccola B, Putignani L. Cross-correlation of virome-bacteriome-host-metabolome to study respiratory health. Trends Microbiol 2021; 30:34-46. [PMID: 34052095 DOI: 10.1016/j.tim.2021.04.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 04/29/2021] [Accepted: 04/30/2021] [Indexed: 12/13/2022]
Abstract
A comprehensive understanding of the microbiome-host relationship in respiratory diseases can be elucidated by exploring the landscape of virome-bacteriome-host metabolome data through unsupervised 'multi-omics' approaches. Here, we describe how the composition and function of airway and gut virome and bacteriome may contribute to pathogen establishment and propagation in airway districts and how the virome-bacteriome communities may react to respiratory diseases. A new systems medicine approach, including the characterization of respiratory and gut microbiome, may be crucial to demonstrate the likelihood and odds of respiratory disease pathophysiology, opening new avenues to the discovery of a chain of causation for key bacteria and viruses in disease severity.
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Affiliation(s)
- Andrea Iorio
- Department of Diagnostic and Laboratory Medicine, Unit of Parasitology and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Manuele Biazzo
- The BioArte Ltd, The Victoria Centre, Mosta, Malta; SienaBioActive, University of Siena, Siena, Italy
| | | | - Andrea Onetti Muda
- Department of Diagnostic and Laboratory Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Carlo Federico Perno
- Unit of Microbiology and Immunology, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
| | - Bruno Dallapiccola
- Scientific Directorate, Children's Hospital and Research Institute 'Bambino Gesù', IRCCS, Rome
| | - Lorenza Putignani
- Department of Diagnostic and Laboratory Medicine, Unit of Parasitology and Multimodal Laboratory Medicine Research Area, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
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21
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Yang M, Yang Y, He Q, Zhu P, Liu M, Xu J, Zhao M. Intestinal Microbiota-A Promising Target for Antiviral Therapy? Front Immunol 2021; 12:676232. [PMID: 34054866 PMCID: PMC8149780 DOI: 10.3389/fimmu.2021.676232] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 04/28/2021] [Indexed: 12/12/2022] Open
Abstract
The intestinal microbiota is thought to be an important biological barrier against enteric pathogens. Its depletion, however, also has curative effects against some viral infections, suggesting that different components of the intestinal microbiota can play both promoting and inhibitory roles depending on the type of viral infection. The two primary mechanisms by which the microbiota facilitates or inhibits viral invasion involve participation in the innate and adaptive immune responses and direct or indirect interaction with the virus, during which the abundance and composition of the intestinal microbiota might be changed by the virus. Oral administration of probiotics, faecal microbiota transplantation (FMT), and antibiotics are major therapeutic strategies for regulating intestinal microbiota balance. However, these three methods have shown limited curative effects in clinical trials. Therefore, the intestinal microbiota might represent a new and promising supplementary antiviral therapeutic target, and more efficient and safer methods for regulating the microbiota require deeper investigation. This review summarizes the latest research on the relationship among the intestinal microbiota, anti-viral immunity and viruses and the most commonly used methods for regulating the intestinal microbiota with the goal of providing new insight into the antiviral effects of the gut microbiota.
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Affiliation(s)
- Mengling Yang
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Yang Yang
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Qingnan He
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Ping Zhu
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Mengqi Liu
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Jiahao Xu
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Mingyi Zhao
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
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22
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Impact of human rhinoviruses on gene expression in pediatric patients with severe acute respiratory infection. Virus Res 2021; 300:198408. [PMID: 33878402 DOI: 10.1016/j.virusres.2021.198408] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 03/17/2021] [Accepted: 03/29/2021] [Indexed: 11/22/2022]
Abstract
Human rhinovirus (HRV) is one of the most common viruses, causing mild to severe respiratory tract infections in children and adults. Moreover, it can lead to patients' hospitalization. Nowadays, evaluation of gene expression alterations in host cells due to viral respiratory infections considered essential to understand the viral effects on cells. OBJECTIVE In this study, we aimed to find important differentially expressed genes (DEGs) related to rhinitis and asthma exacerbation stimulated with Poly (I: C) and then to validate their expression in clinical samples of children how were less than 5 years old, hospitalized with severe acute respiratory infection (SARI) due to HRV infection in comparison with healthy cases. METHODS Eight candidate genes involved in immunity, viral defense, inflammation, P53 pathway, and viral release processes were selected based on the analysis of a gene expression data set (GSE51392) and gene enrichment analysis. Then quantitative real-time PCR on cDNAs was performed for selected genes. The results were analyzed by Livak method and visualized by GraphPad prism software (8.4.3). RESULT CXCL10, CMPK2, RSAD2, SERPINA3, TNFAIP6, CXCL14, IVNS1AB, and ZMAT3 were selected based on the enrichment and topological analysis of the constructed protein-protein interaction (PPI) network. Laboratory validation by real-time PCR showed CXCL10, CMPK2, RSAD2, SERPINA3, and TNFAIP6 (belonged to immunity, inflammatory responses and viral defense) were up-regulated, whereas CXCL14 (related to immunity) and IVNS1AB, ZMAT3 (associated to Influenza and P53 pathway) were down-regulated. CONCLUSION Our results showed, that in children less than 5 years old affected by HRV and hospitalized with SARI, the inflammatory responses, antiviral defense, and type 1 interferon-signaling pathway have significantly affected by viral infection.
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23
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Heidari Z, Tajbakhsh A, Gheibi-Hayat SM, Moattari A, Razban V, Berenjian A, Savardashtaki A, Negahdaripour M. Probiotics/ prebiotics in viral respiratory infections: implication for emerging pathogens. Recent Pat Biotechnol 2021; 15:112-136. [PMID: 33874878 DOI: 10.2174/1872208315666210419103742] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 02/01/2021] [Accepted: 03/10/2021] [Indexed: 01/08/2023]
Abstract
BACKGROUND Viral respiratory infections could result in perturbation of the gut microbiota due to a probable cross-talk between lungs and gut microbiota. This can affect the pulmonary health and the gastrointestinal system. OBJECTIVE This review aimed to discuss the impact of probiotics/ prebiotics and supplements on the prevention and treatment of respiratory infections, especially emerging pathogens. METHODS The data were searched were searched in PubMed, Scopus, Google Scholar, Google Patents, and The Lens-Patent using keywords of probiotics and viral respiratory infections in the title, abstract, and keywords. RESULT Probiotics consumption could decrease the susceptibility to viral respiratory infections, such as COVID-19 and simultaneously enhance vaccine efficiency in infectious disease prevention through the immune system enhancement. Probiotics improve the gut microbiota and the immune system via regulating the innate system response and production of anti-inflammatory cytokines. Moreover, treatment with probiotics contributes to the intestinal homeostasis restitution under antibiotic pressure and decreasing the risk of secondary infections due to viral respiratory infections. Probiotics present varied performances in different conditions; thus, promoting their efficacy through combining with supplements (prebiotics, postbiotics, nutraceuticals, berberine, curcumin, lactoferrin, minerals, and vitamins) is important. Several supplements reported to enhance the probiotics' efficacy and their mechanisms as well as probiotics related patents are summarized in this review. Using nanotechnology and microencapsulation techniques can also improve probiotics efficiency. CONCLUSION Given the global challenge of COVID-19, probiotic/prebiotic and following nutritional guidelines should be regarded seriously. Additionally, their role as an adjuvant in vaccination for immune response augmentation needs attention.
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Affiliation(s)
- Zahra Heidari
- Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz. Iran
| | - Amir Tajbakhsh
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz. Iran
| | - Seyed Mohammad Gheibi-Hayat
- Department of Medical Biotechnology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd. Iran
| | - Afagh Moattari
- Department of Parasitology and Mycology, Shiraz University of Medical Sciences, Shiraz. Iran
| | - Vahid Razban
- Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz. Iran
| | - Aydin Berenjian
- School of Engineering, Faculty of Science and Engineering, The University of Waikato, Hamilton. New Zealand
| | - Amir Savardashtaki
- Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz. Iran
| | - Manica Negahdaripour
- Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz. Iran
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24
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Hsiao CJ, Paulson JN, Singh S, Mongodin EF, Carroll KC, Fraser CM, Rock P, Faraday N. Nasal Microbiota and Infectious Complications After Elective Surgical Procedures. JAMA Netw Open 2021; 4:e218386. [PMID: 33914049 PMCID: PMC8085724 DOI: 10.1001/jamanetworkopen.2021.8386] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
IMPORTANCE The association of the nasal microbiome with outcomes in surgical patients is poorly understood. OBJECTIVE To characterize the composition of nasal microbiota in patients undergoing clean elective surgical procedures and to examine the association between characteristics of preoperative nasal microbiota and occurrence of postoperative infection. DESIGN, SETTING, AND PARTICIPANTS Using a nested matched case-control design, 53 individuals who developed postoperative infection were matched (approximately 3:1 by age, sex, and surgical procedure) with 144 individuals who were not infected (ie, the control group). The 2 groups were selected from a prospective cohort of patients undergoing surgical procedures at 2 tertiary care university hospitals in Baltimore, Maryland, who were at high risk for postoperative infectious complications. Included individuals were aged 40 years or older; had no history of autoimmune disease, immunocompromised state, immune-modulating medication, or active infection; and were scheduled to undergo elective cardiac, vascular, spinal, or intracranial surgical procedure. Data were analyzed from October 2015 through September 2020. EXPOSURES Nasal microbiome cluster class served as the main exposure. An unsupervised clustering method (ie, grades of membership modeling) was used to classify nasal microbial samples into 2 groups based on features derived from 16S ribosomal RNA gene sequencing. The microbiome cluster groups were derived independently and agnostic of baseline clinical characteristics and infection status. MAIN OUTCOMES AND MEASURES Composite of surgical site infection, bacteremia, and pneumonia occurring within 6 months after surgical procedure. RESULTS Among 197 participants (mean [SD] age, 64.1 [10.6] years; 63 [37.7%] women), 553 bacterial taxa were identified from preoperative nasal swab samples. A 2-cluster model (with 167 patients in cluster 1 and 30 patients in cluster 2) accounted for the largest proportion of variance in microbial profiles using grades of membership modeling and was most parsimonious. After adjusting for potential confounders, the probability of assignment to cluster 2 was associated with 6-fold higher odds of infection after surgical procedure (odds ratio [OR], 6.18; 95% CI, 3.33-11.7; P < .001) independent of baseline clinical characteristics, including nasal carriage of Staphylococcus aureus. Intrasample (ie, α) diversity was inversely associated with infectious outcome in both clusters (OR, 0.57; 95% CI, 0.42-0.75; P < .001); however, probability of assignment to cluster 2 was associated with higher odds of infection independent of α diversity (OR, 4.61; 95% CI, 2.78-7.86; P < .001). CONCLUSIONS AND RELEVANCE These findings suggest that the nasal microbiome was an independent risk factor associated with infectious outcomes among individuals who underwent elective surgical procedures and may serve as a biomarker associated with infection susceptibility in this population.
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Affiliation(s)
| | - Joseph N. Paulson
- Product Development Biostatistics, Genentech, South San Francisco, California
| | - Sarabdeep Singh
- Center for Drug Evaluation and Research, Food and Drug Administration, White Oak, Maryland
| | - Emmanuel F. Mongodin
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore
- Lung Biology and Disease Program, Division of Lung Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
| | - Karen C. Carroll
- Division of Medical Microbiology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Claire M. Fraser
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore
| | - Peter Rock
- Department of Anesthesiology, University of Maryland School of Medicine, Baltimore
| | - Nauder Faraday
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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25
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Hurst JH, McCumber AW, Aquino JN, Rodriguez J, Heston SM, Lugo DJ, Rotta AT, Turner NA, Pfeiffer TS, Gurley TC, Moody MA, Denny TN, Rawls JF, Woods CW, Kelly MS. Age-related changes in the upper respiratory microbiome are associated with SARS-CoV-2 susceptibility and illness severity. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2021:2021.03.20.21252680. [PMID: 33791716 PMCID: PMC8010748 DOI: 10.1101/2021.03.20.21252680] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Children are less susceptible to SARS-CoV-2 and typically have milder illness courses than adults. We studied the nasopharyngeal microbiomes of 274 children, adolescents, and young adults with SARS-CoV-2 exposure using 16S rRNA gene sequencing. We find that higher abundances of Corynebacterium species are associated with SARS-CoV-2 infection and SARS-CoV-2-associated respiratory symptoms, while higher abundances of Dolosigranulum pigrum are present in SARS-CoV-2-infected individuals without respiratory symptoms. We also demonstrate that the abundances of these bacteria are strongly, and independently, associated with age, suggesting that the nasopharyngeal microbiome may be a potentially modifiable mechanism by which age influences SARS-CoV-2 susceptibility and severity. SUMMARY Evaluation of nasopharyngeal microbiome profiles in children, adolescents, and young adults with a SARS-CoV-2-infected close contact identified specific bacterial species that vary in abundance with age and are associated with SARS-CoV-2 susceptibility and the presence of SARS-CoV-2-associated respiratory symptoms.
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26
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Porto BN, Moraes TJ. The triad: respiratory microbiome - virus - immune response in the pathophysiology of pulmonary viral infections. Expert Rev Respir Med 2021; 15:635-648. [PMID: 33605840 DOI: 10.1080/17476348.2021.1893168] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The longstanding dogma that the healthy lung is sterile has been refuted by recent advances in culture-independent analyses of airway samples. The respiratory microbiome comprises all airway and lung tissue-associated microbes. These micro-organisms occur throughout the upper and lower respiratory tracts, with different populations and distinct burdens at specific sites and can be classified as pathogenic or commensal. AREAS COVERED The majority of studies investigating the respiratory microbiome have focused on bacteria; however, emerging evidence has revealed the composition of the lung virome, the global viral communities present in the lung tissue. In this review, we searched PubMed and used keywords such as airway microbiome. We restricted outputs to English language and did not limit by any dates. We summarize the up-to-date knowledge on how the microbiome interacts with the host immune system and influences the pathogenesis of pulmonary viral infections. EXPERT OPINION The relationship between colonizing microbes and the host is complex and various factors need to be considered in order to appreciate its pathophysiological consequences. Understanding these intricate mechanisms of interaction among the respiratory microbiome, viruses and the immune response may lead to the development of better therapies to treat or prevent respiratory viral infections.
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Affiliation(s)
- Bárbara N Porto
- Program in Translational Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Theo J Moraes
- Program in Translational Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.,Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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27
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Gallo O, Locatello LG, Mazzoni A, Novelli L, Annunziato F. The central role of the nasal microenvironment in the transmission, modulation, and clinical progression of SARS-CoV-2 infection. Mucosal Immunol 2021; 14:305-316. [PMID: 33244161 PMCID: PMC7690066 DOI: 10.1038/s41385-020-00359-2] [Citation(s) in RCA: 156] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 10/30/2020] [Accepted: 11/05/2020] [Indexed: 02/06/2023]
Abstract
The novel coronavirus SARS-CoV-2 enters into the human body mainly through the ACE2 + TMPRSS2+ nasal epithelial cells. The initial host response to this pathogen occurs in a peculiar immune microenvironment that, starting from the Nasopharynx-Associated Lymphoid Tissue (NALT) system, is the product of a long evolutionary process that is aimed to first recognize exogenous airborne agents. In the present work, we want to critically review the latest molecular and cellular findings on the mucosal response to SARS-CoV-2 in the nasal cavity and in NALT, and to analyze its impact in the subsequent course of COVID-19. Finally, we want to explore the possibility that the regulation of the systemic inflammatory network against the virus can be modulated starting from the initial phases of the nasal and nasopharyngeal response and this may have several clinical and epidemiological implications starting from a mucosal vaccine development.
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Affiliation(s)
- Oreste Gallo
- Department of Otorhinolaryngology, Careggi University Hospital, Largo Brambilla, 3, 50134, Florence, Italy
| | - Luca Giovanni Locatello
- Department of Otorhinolaryngology, Careggi University Hospital, Largo Brambilla, 3, 50134, Florence, Italy
| | - Alessio Mazzoni
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Luca Novelli
- Department of Pathology, Careggi University Hospital, Largo Brambilla, 3, 50134, Florence, Italy
| | - Francesco Annunziato
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy,Flow Cytometry and Immunotherapy Diagnostic Center, Careggi University Hospital, Largo Brambilla, 3, 50134, Florence, Italy
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28
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Shah V. Letter to the Editor: Microbiota in the Respiratory System-A Possible Explanation to Age and Sex Variability in Susceptibility to SARS-CoV-2. Microbiol Insights 2021; 14:1178636120988604. [PMID: 33519207 PMCID: PMC7818001 DOI: 10.1177/1178636120988604] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 12/16/2020] [Indexed: 12/21/2022] Open
Abstract
The Human respiratory tract is colonized by a variety of microbes and the microbiota change as we age. In this perspective, literature support is presented for the hypothesis that the respiratory system microbiota could explain the differential age and sex breakdown amongst COVID-19 patients. The number of patients in the older and elderly adult group is higher than the other age groups. The perspective presents the possibility that certain genera of bacteria present in the respiratory system microbiota in children and young adults could be directly or through eliciting an immune response from the host, prevent full-fledged infection of SARS-CoV-2. The possibility also exists that the microbiota in older adults and the elderly population have bacteria that make it easier for the virus to cause infection. I call upon the scientific community to investigate the link between human microbiota and SARS-CoV-2 susceptibility to further understand the viral pathogenesis.
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Affiliation(s)
- Vishal Shah
- College of the Sciences and Mathematics, West Chester University, PA, USA
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29
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Fakhroo AD, Al Thani AA, Yassine HM. Markers Associated with COVID-19 Susceptibility, Resistance, and Severity. Viruses 2020; 13:E45. [PMID: 33396584 PMCID: PMC7823574 DOI: 10.3390/v13010045] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 11/29/2020] [Accepted: 11/30/2020] [Indexed: 01/08/2023] Open
Abstract
In December 2019, the latest member of the coronavirus family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, leading to the outbreak of an unusual viral pneumonia known as coronavirus disease 2019 (COVID-19). COVID-19 was then declared as a pandemic in March 2020 by the World Health Organization (WHO). The initial mortality rate of COVID-19 declared by WHO was 2%; however, this rate has increased to 3.4% as of 3 March 2020. People of all ages can be infected with SARS-CoV-2, but those aged 60 or above and those with underlying medical conditions are more prone to develop severe symptoms that may lead to death. Patients with severe infection usually experience a hyper pro-inflammatory immune reaction (i.e., cytokine storm) causing acute respiratory distress syndrome (ARDS), which has been shown to be the leading cause of death in COVID-19 patients. However, the factors associated with COVID-19 susceptibility, resistance and severity remain poorly understood. In this review, we thoroughly explore the correlation between various host, viral and environmental markers, and SARS-CoV-2 in terms of susceptibility and severity.
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Affiliation(s)
- Aisha D. Fakhroo
- Research and Development Department, Barzan Holdings, Doha 7178, Qatar;
| | | | - Hadi M. Yassine
- Biomedical Research Center, Qatar University, Doha 2713, Qatar;
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30
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Di Stadio A, Costantini C, Renga G, Pariano M, Ricci G, Romani L. The Microbiota/Host Immune System Interaction in the Nose to Protect from COVID-19. Life (Basel) 2020; 10:life10120345. [PMID: 33322584 PMCID: PMC7763594 DOI: 10.3390/life10120345] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 12/03/2020] [Accepted: 12/10/2020] [Indexed: 12/12/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by variable clinical presentation that ranges from asymptomatic to fatal multi-organ damage. The site of entry and the response of the host to the infection affect the outcomes. The role of the upper airways and the nasal barrier in the prevention of infection is increasingly being recognized. Besides the epithelial lining and the local immune system, the upper airways harbor a community of microorganisms, or microbiota, that takes an active part in mucosal homeostasis and in resistance to infection. However, the role of the upper airway microbiota in COVID-19 is not yet completely understood and likely goes beyond protection from viral entry to include the regulation of the immune response to the infection. Herein, we discuss the hypothesis that restoring endogenous barriers and anti-inflammatory pathways that are defective in COVID-19 patients might represent a valid strategy to reduce infectivity and ameliorate clinical symptomatology.
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Affiliation(s)
- Arianna Di Stadio
- Department of Otolaryngology, University of Perugia, 06132 Perugia, Italy;
- Correspondence: (A.D.S.); (L.R.)
| | - Claudio Costantini
- Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy; (C.C.); (G.R.); (M.P.)
| | - Giorgia Renga
- Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy; (C.C.); (G.R.); (M.P.)
| | - Marilena Pariano
- Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy; (C.C.); (G.R.); (M.P.)
| | - Giampietro Ricci
- Department of Otolaryngology, University of Perugia, 06132 Perugia, Italy;
| | - Luigina Romani
- Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy; (C.C.); (G.R.); (M.P.)
- Correspondence: (A.D.S.); (L.R.)
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Lehtoranta L, Latvala S, Lehtinen MJ. Role of Probiotics in Stimulating the Immune System in Viral Respiratory Tract Infections: A Narrative Review. Nutrients 2020; 12:nu12103163. [PMID: 33081138 PMCID: PMC7602805 DOI: 10.3390/nu12103163] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 10/05/2020] [Accepted: 10/13/2020] [Indexed: 12/29/2022] Open
Abstract
Viral respiratory tract infection (RTI) is the most frequent cause of infectious illnesses including the common cold. Pharmacological solutions for treating or preventing viral RTIs are so far limited and thus several self-care products are available in the market. Some dietary supplements such as probiotics have been shown to modulate immune system function and their role in reducing the risk and the course of RTIs has been investigated extensively within the past decade. However, the mechanism of action and the efficacy of probiotics against viral RTIs remains unclear. We searched PubMed, Google Scholar, and Web of Knowledge for pre-clinical and clinical studies investigating the effect of probiotics on respiratory virus infections, immune response, and the course of upper and lower respiratory tract illness. The literature summarized in this narrative review points out that specific probiotic strains seem effective in pre-clinical models, through stimulating the immune system and inhibiting viral replication. Clinical studies indicate variable efficacy on upper respiratory illnesses and lack proof of diagnosed viral infections. However, meta-analyses of clinical studies indicate that probiotics could be beneficial in upper respiratory illnesses without specific etiology. Further studies aiming at discovering the mechanisms of action of probiotics and clinical efficacy are warranted.
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De Rudder C, Garcia-Tímermans C, De Boeck I, Lebeer S, Van de Wiele T, Calatayud Arroyo M. Lacticaseibacillus casei AMBR2 modulates the epithelial barrier function and immune response in a donor-derived nasal microbiota manner. Sci Rep 2020; 10:16939. [PMID: 33037304 PMCID: PMC7547715 DOI: 10.1038/s41598-020-73857-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 08/17/2020] [Indexed: 01/06/2023] Open
Abstract
Live biotherapeutic products (LBP) are emerging as alternative treatment strategies for chronic rhinosinusitis. The selection of interesting candidate LBPs often involves model systems that do not include the polymicrobial background (i.e. the host microbiota) in which they will be introduced. Here, we performed a screening in a simplified model system of upper respiratory epithelium to assess the effect of nasal microbiota composition on the ability to attach and grow of a potential LBP, Lacticaseibacillus casei AMBR2, in this polymicrobial background. After selecting the most permissive and least permissive donor, L. casei AMBR2 colonisation in their respective polymicrobial backgrounds was assessed in more physiologically relevant model systems. We examined cytotoxicity, epithelial barrier function, and cytokine secretion, as well as bacterial cell density and phenotypic diversity in differentiated airway epithelium based models, with or without macrophage-like cells. L. casei AMBR2 could colonize in the presence of both selected donor microbiota and increased epithelial barrier resistance in presence of donor-derived nasal bacteria, as well as anti-inflammatory cytokine secretion in the presence of macrophage-like cells. This study highlights the potential of L. casei AMBR2 as LBP and the necessity to employ physiologically relevant model systems to investigate host–microbe interaction in LBP research.
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Affiliation(s)
- Charlotte De Rudder
- Center for Microbial Ecology and Technology, Faculty of Bioscience Engineering, Coupure Links 653, Ghent University, 9000, Ghent, Belgium
| | - Cristina Garcia-Tímermans
- Center for Microbial Ecology and Technology, Faculty of Bioscience Engineering, Coupure Links 653, Ghent University, 9000, Ghent, Belgium
| | - Ilke De Boeck
- Research Group of Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
| | - Sarah Lebeer
- Research Group of Environmental Ecology and Applied Microbiology, Department of Bioscience Engineering, University of Antwerp, Antwerp, Belgium
| | - Tom Van de Wiele
- Center for Microbial Ecology and Technology, Faculty of Bioscience Engineering, Coupure Links 653, Ghent University, 9000, Ghent, Belgium.
| | - Marta Calatayud Arroyo
- Center for Microbial Ecology and Technology, Faculty of Bioscience Engineering, Coupure Links 653, Ghent University, 9000, Ghent, Belgium.,Group of Lactic Bacteria and Probiotics, Department of Biotechnology, Institute of Agrochemistry and Food Technology (IATA), Spanish Research Council (CSIC), Valencia, Spain
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Symbiotic microbiome Staphylococcus aureus from human nasal mucus modulates IL-33-mediated type 2 immune responses in allergic nasal mucosa. BMC Microbiol 2020; 20:301. [PMID: 33028252 PMCID: PMC7542126 DOI: 10.1186/s12866-020-01974-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 09/10/2020] [Indexed: 12/15/2022] Open
Abstract
Background The host-microbial commensalism can shape the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models. Results Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, ovalbumin-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice. Conclusion Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.
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34
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Durack J, Christophersen CT. Human Respiratory and Gut Microbiomes-Do They Really Contribute to Respiratory Health? Front Pediatr 2020; 8:528. [PMID: 33014929 PMCID: PMC7509439 DOI: 10.3389/fped.2020.00528] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Accepted: 07/24/2020] [Indexed: 12/19/2022] Open
Abstract
Human gastrointestinal and respiratory tracts are colonized by diverse polymicrobial communities shortly after birth, which are continuously molded by environmental exposure. The development of the resident microbiota in early life is a critical factor in the maturation of a healthy immune system. Disturbances to the intricate relationship between environmental exposure and maturation of the infant microbiome have been increasingly identified as a potential contributor to a range of childhood diseases. This review details recent evidence that implicates the contribution of gut and airway microbiome to pediatric respiratory health.
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Affiliation(s)
- Juliana Durack
- Symbiome Inc., San Francisco, CA, United States
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA, United States
| | - Claus T. Christophersen
- School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
- WA Human Microbiome Collaboration Centre, School of Molecular and Life Sciences, Curtin University, Perth, WA, Australia
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McMullen C, Alexander TW, Orsel K, Timsit E. Progression of nasopharyngeal and tracheal bacterial microbiotas of feedlot cattle during development of bovine respiratory disease. Vet Microbiol 2020; 248:108826. [PMID: 32891954 DOI: 10.1016/j.vetmic.2020.108826] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 08/13/2020] [Indexed: 01/04/2023]
Abstract
It is generally accepted that as bovine respiratory disease (BRD) develops, bacterial pathogens first proliferate in the nasopharynx and then colonize the lungs, leading to bronchopneumonia. However, such temporal changes have never been definitively demonstrated. Therefore, the objective was to describe the progression of the nasopharyngeal and tracheal bacterial microbiotas of feedlot cattle during development of BRD. Nasopharyngeal swabs and tracheal wash samples were collected from 24 heifers over 20 d after arrival at a feedlot. Heifers were assessed daily and sampled based on reticulo-rumen/rectal temperatures and development of clinical signs of BRD. The study end point for each heifer was either at BRD treatment (BRD group; n = 15) or day 20 if the heifer remained healthy or did not meet BRD treatment criteria (TOL group; n = 9). Total DNA was extracted from each sample and the 16S rRNA gene (V3-V4) sequenced. Alpha and beta diversity were compared between BRD-TOL groups and sampling locations over time. There were no common patterns of change over time in composition or diversity of either the nasopharyngeal or tracheal bacterial microbiotas of cattle that developed BRD. Health status affected bacterial composition (R2 = 0.043; < 0.001), though this effect was low compared to variation among individual animals (R2 = 0.335; < 0.001) and effects of days on feed (R2 = 0.082; < 0.001). Specific bacterial taxa (Moraxella and Mycoplasma dispar) nevertheless appeared to have a potential role in respiratory health.
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Affiliation(s)
| | - Trevor W Alexander
- Lethbridge Research and Development Center, Agriculture and Agri-Food Canada, Lethbridge, AB, Canada
| | - Karin Orsel
- Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada
| | - Edouard Timsit
- Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada; Simpson Ranch Chair in Beef Cattle Health and Wellness, University of Calgary, Calgary, AB, Canada; Ceva Santé Animale, Libourne, France.
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36
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Ramos-Sevillano E, Wade WG, Mann A, Gilbert A, Lambkin-Williams R, Killingley B, Nguyen-Van-Tam JS, Tang CM. The Effect of Influenza Virus on the Human Oropharyngeal Microbiome. Clin Infect Dis 2020; 68:1993-2002. [PMID: 30445563 PMCID: PMC6541733 DOI: 10.1093/cid/ciy821] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 10/04/2018] [Indexed: 12/27/2022] Open
Abstract
Background Secondary bacterial infections are an important cause of morbidity and mortality associated with influenza infections. As bacterial disease can be caused by a disturbance of the host microbiome, we examined the impact of influenza on the upper respiratory tract microbiome in a human challenge study. Methods The dynamics and ecology of the throat microbiome were examined following an experimental influenza challenge of 52 previously-healthy adult volunteers with influenza A/Wisconsin/67/2005 (H3N2) by intranasal inoculation; 35 healthy control subjects were not subjected to the viral challenge. Serial oropharyngeal samples were taken over a 30-day period, and the V1-V3 region of the bacterial 16S ribosomal RNA sequences were amplified and sequenced to determine the composition of the microbiome. The carriage of pathogens was also detected. Results Of the 52 challenged individuals, 43 developed proven influenza infections, 33 of whom became symptomatic. None of the controls developed influenza, although 22% reported symptoms. The diversity of bacterial communities remained remarkably stable following the acquisition of influenza, with no significant differences over time between individuals with influenza and those in the control group. Influenza infection was not associated with perturbation of the microbiome at the level of phylum or genus. There was no change in colonization rates with Streptococcus pneumoniae or Neisseria meningitidis. Conclusions The throat microbiota is resilient to influenza infection, indicating the robustness of the upper-airway microbiome.
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Affiliation(s)
| | | | - Alex Mann
- hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, United Kingdom
| | - Anthony Gilbert
- hVIVO Services Limited, Queen Mary BioEnterprises Innovation Centre, United Kingdom
| | | | - Ben Killingley
- Department of Infection and Acute Medicine, University College London Hospital, United Kingdom
| | | | - Christoph M Tang
- Sir William Dunn School of Pathology, University of Oxford, United Kingdom
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37
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Higgins TS, Wu AW, Illing EA, Sokoloski KJ, Weaver BA, Anthony BP, Hughes N, Ting JY. Intranasal Antiviral Drug Delivery and Coronavirus Disease 2019 (COVID-19): A State of the Art Review. Otolaryngol Head Neck Surg 2020; 163:682-694. [PMID: 32660339 DOI: 10.1177/0194599820933170] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To provide a state of the art review of intranasal antiviral drug delivery and to discuss current applications, adverse reactions, and future considerations in the management of coronavirus disease 2019 (COVID-19). DATA SOURCES PubMed, Embase, and Clinicaltrials.gov search engines. REVIEW METHODS A structured search of the current literature was performed of dates up to and including April 2020. Search terms were queried as related to topics of antiviral agents and intranasal applications. A series of video conferences was convened among experts in otolaryngology, infectious diseases, public health, pharmacology, and virology to review the literature and discuss relevant findings. CONCLUSIONS Intranasal drug delivery for antiviral agents has been studied for many years. Several agents have broad-spectrum antiviral activity, but they still require human safety and efficacy trials prior to implementation. Intranasal drug delivery has potential relevance for future clinical trials in the settings of disease spread prevention and treatment of SARS-CoV-2 and other viral diseases. IMPLICATIONS FOR PRACTICE Intranasal drug delivery represents an important area of research for COVID-19 and other viral diseases. The consideration of any potential adverse reactions is paramount.
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Affiliation(s)
- Thomas S Higgins
- Department of Otolaryngology-Head and Neck Surgery and Communica-tive Disorders, University of Louisville, Louisville, Kentucky, USA.,Rhinology, Sinus, and Skull Base, Kentuckiana Ear, Nose, and Throat, Louisville, Kentucky, USA
| | - Arthur W Wu
- Department of Otolaryngology-Head and Neck Surgery, Cedars Sinai, Los Angeles, California, USA
| | - Elisa A Illing
- Department of Otolaryngology-Head and Neck Surgery, Indiana University, Indianapolis, Indiana, USA
| | - Kevin J Sokoloski
- Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky, USA.,Center for Predictive Medicine and Emerging Infectious Diseases, University of Louisville, Louisville Kentucky, USA
| | - Bree A Weaver
- Division of Infectious Diseases, Departments of Internal Medicine and Pediatrics, School of Medicine, Indiana University, Indianapolis, Indiana, USA
| | - Benjamin P Anthony
- Department of Otolaryngology-Head and Neck Surgery, Indiana University, Indianapolis, Indiana, USA
| | - Nathan Hughes
- Pharmacy Operations, Kindred Healthcare Support Center, Louisville, Kentucky, USA
| | - Jonathan Y Ting
- Department of Otolaryngology-Head and Neck Surgery, Indiana University, Indianapolis, Indiana, USA
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Dose-Response Recovery of Probiotic Strains in Simulated Gastro-Intestinal Passage. Microorganisms 2020; 8:microorganisms8010112. [PMID: 31941108 PMCID: PMC7023332 DOI: 10.3390/microorganisms8010112] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Revised: 01/09/2020] [Accepted: 01/10/2020] [Indexed: 12/11/2022] Open
Abstract
The probiotic definition stipulates “adequate amounts”. Here, we investigated the metabolic output and recovery rate of probiotic strains using a simulated upper gastro-intestinal passage and colonic fermentation. Two different doses, 7 × 109 colony forming units (CFU) and 7 × 1010 CFU, of a probiotic mixture (Bifidobacterium lactis Bl-04, Lactobacillus acidophilus La-14, Lactobacillus paracasei Lpc-37, and Lactobacillus plantarum Lp-115) or placebo were tested. The four strains were quantified by qPCR and the metabolites analyzed by gas chromatography. There was a dose-response in the detection of all four strains. There was a slightly larger increase between the two doses for L. paracasei Lpc-37 as compared with the other strains; this may suggest a greater robustness of this strain. Compared with the placebo, the high dose simulations generated more propionic acid and a higher total of short chain fatty acids (SCFA). Higher doses of a species are required to reach measurable increases above the baseline level of this species.
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Salli K, Lehtinen MJ, Tiihonen K, Ouwehand AC. Xylitol's Health Benefits beyond Dental Health: A Comprehensive Review. Nutrients 2019; 11:nu11081813. [PMID: 31390800 PMCID: PMC6723878 DOI: 10.3390/nu11081813] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 07/28/2019] [Accepted: 07/31/2019] [Indexed: 12/16/2022] Open
Abstract
Xylitol has been widely documented to have dental health benefits, such as reducing the risk for dental caries. Here we report on other health benefits that have been investigated for xylitol. In skin, xylitol has been reported to improve barrier function and suppress the growth of potential skin pathogens. As a non-digestible carbohydrate, xylitol enters the colon where it is fermented by members of the colonic microbiota; species of the genus Anaerostipes have been reported to ferment xylitol and produce butyrate. The most common Lactobacillus and Bifidobacterium species do not appear to be able to grow on xylitol. The non-digestible but fermentable nature of xylitol also contributes to a constipation relieving effect and improved bone mineral density. Xylitol also modulates the immune system, which, together with its antimicrobial activity contribute to a reduced respiratory tract infection, sinusitis, and otitis media risk. As a low caloric sweetener, xylitol may contribute to weight management. It has been suggested that xylitol also increases satiety, but these results are not convincing yet. The benefit of xylitol on metabolic health, in addition to the benefit of the mere replacement of sucrose, remains to be determined in humans. Additional health benefits of xylitol have thus been reported and indicate further opportunities but need to be confirmed in human studies.
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Affiliation(s)
- Krista Salli
- Global Health & Nutrition Sciences, DuPont Nutrition & Biosciences, 02460 Kantvik, Finland
| | - Markus J Lehtinen
- Global Health & Nutrition Sciences, DuPont Nutrition & Biosciences, 02460 Kantvik, Finland
| | - Kirsti Tiihonen
- Global Health & Nutrition Sciences, DuPont Nutrition & Biosciences, 02460 Kantvik, Finland
| | - Arthur C Ouwehand
- Global Health & Nutrition Sciences, DuPont Nutrition & Biosciences, 02460 Kantvik, Finland.
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40
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Airaksinen K, Yeung N, Lyra A, Lahtinen SJ, Huttunen T, Shanahan F, Ouwehand AC. The effect of a probiotic blend on gastrointestinal symptoms in constipated patients: a double blind, randomised, placebo controlled 2-week trial. Benef Microbes 2019; 10:617-627. [PMID: 31131616 DOI: 10.3920/bm2018.0163] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Selected strains of lactobacilli and bifidobacteria are known to ameliorate constipation-related symptoms and have previously shown efficacy on digestive health. In this clinical trial, the safety and effectiveness of a probiotic blend containing lactobacilli and bifidobacteria were evaluated in adults with self-reported bloating and functional constipation. Constipation was diagnosed by the Rome III criteria. A total of 156 adults were randomised into this double-blind and placebo-controlled trial. Participants consumed the combination of Lactobacillus acidophilus NCFM (1010 cfu), Lactobacillus paracasei Lpc-37 (2.5×109 cfu), Bifidobacterium animalis subsp. lactis strains Bl-04 (2.5×109 cfu), Bi-07 (2.5×109 cfu) and HN019 (1010 cfu) (n=78), or placebo (microcrystalline cellulose) (n=78) for two weeks. After treatment the following were measured: primary outcome of bloating and secondary outcomes of colonic transit time, bowel movement frequency, stool consistency, other gastrointestinal symptoms (flatulence, abdominal pain, and burbling), constipation-related questionnaires (PAC-SYM and PAC-QoL) and product satisfaction. Faecal recovery of consumed strains was determined. The enrolled population was defined as constipated, however, the initial bloating severity was lower than in previous similar studies. No clinically significant observations related to the safety of the product were reported. Product efficacy was not shown in the primary analysis for bloating nor for the secondary efficacy analyses. The placebo functioned similarly as the probiotic product. In post-hoc analysis, a statistically significant decrease in flatulence in favour of the probiotic group was observed; day 7 (intention-to-treat (ITT): P=0.0313; per-protocol (PP): 0.0253) and on day 14 (ITT: P=0.0116; PP: P=0.0102) as measured by area under the curve (AUC) analysis. The mean AUC of all symptoms decreased in favour of the probiotic group, indicating less digestive discomfort. The study was registered at the ISRCTN registry (ISRCTN41607808).
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Affiliation(s)
- K Airaksinen
- DuPont Nutrition and Health, Global Health & Nutrition Science, Sokeritehtaantie 20, 02460 Kantvik, Finland
| | - N Yeung
- DuPont Nutrition and Health, Global Health & Nutrition Science, Sokeritehtaantie 20, 02460 Kantvik, Finland
| | - A Lyra
- DuPont Nutrition and Health, Global Health & Nutrition Science, Sokeritehtaantie 20, 02460 Kantvik, Finland
| | - S J Lahtinen
- DuPont Nutrition and Health, Global Health & Nutrition Science, Sokeritehtaantie 20, 02460 Kantvik, Finland
| | - T Huttunen
- 4Pharma Ltd, Tykistökatu 4, 20520 Turku, Finland
| | - F Shanahan
- Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
| | - A C Ouwehand
- DuPont Nutrition and Health, Global Health & Nutrition Science, Sokeritehtaantie 20, 02460 Kantvik, Finland
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Hernandez-Leyva A, Wilson NG, Kau AL. Breathe Soft, What Bugs through Early Windows Break? Cell Host Microbe 2019; 24:337-339. [PMID: 30212647 DOI: 10.1016/j.chom.2018.08.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022]
Abstract
In this issue of Cell Host & Microbe, Teo et al. (2018) explore the development of the upper airway microbiota over the first 5 years of life and provide evidence for a "critical window" of microbial exposure that contributes to chronic wheezing, a precursor to asthma.
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Affiliation(s)
- Ariel Hernandez-Leyva
- Department of Medicine, Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Naomi G Wilson
- Department of Medicine, Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Andrew L Kau
- Department of Medicine, Division of Allergy and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for Women's Infectious Disease Research, Washington University School of Medicine, St. Louis, MO 63110, USA.
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42
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Impact of Rhinovirus Infections in Children. Viruses 2019; 11:v11060521. [PMID: 31195744 PMCID: PMC6632063 DOI: 10.3390/v11060521] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2019] [Revised: 05/22/2019] [Accepted: 06/04/2019] [Indexed: 12/16/2022] Open
Abstract
Rhinovirus (RV) is an RNA virus that causes more than 50% of upper respiratory tract infections in humans worldwide. Together with Respiratory Syncytial Virus, RV is one of the leading causes of viral bronchiolitis in infants and the most common virus associated with wheezing in children aged between one and two years. Because of its tremendous genetic diversity (>150 serotypes), the recurrence of RV infections each year is quite typical. Furthermore, because of its broad clinical spectrum, the clinical variability as well as the pathogenesis of RV infection are nowadays the subjects of an in-depth examination and have been the subject of several studies in the literature. In fact, the virus is responsible for direct cell cytotoxicity in only a small way, and it is now clearer than ever that it may act indirectly by triggering the release of active mediators by structural and inflammatory airway cells, causing the onset and/or the acute exacerbation of asthmatic events in predisposed children. In the present review, we aim to summarize the RV infection's epidemiology, pathogenetic hypotheses, and available treatment options as well as its correlation with respiratory morbidity and mortality in the pediatric population.
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43
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Dubourg G, Edouard S, Raoult D. Relationship between nasopharyngeal microbiota and patient's susceptibility to viral infection. Expert Rev Anti Infect Ther 2019; 17:437-447. [PMID: 31106653 DOI: 10.1080/14787210.2019.1621168] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Introduction: The burden of respiratory viral infections is a global public health concern with significant mortality, morbidity, and economic impact. While Koch's postulate led to considering only the etiological agent, numerous works have demonstrated that commensal microbes could contribute to both the susceptibility and the severity of these infections, in particular those of the nasopharynx. Areas covered: Herein, we first propose to briefly recall the historical background that led to considering microbes inhabiting the nasopharyngeal microbiota as a potential contributor to human viral infections. We describe the evolution of the normal nasopharyngeal microbiota composition over time, especially during the first year of life. We aimed to resume the changes of the nasopharyngeal microbiota during viral respiratory infections. We also develop how nasopharyngeal microbiota could contribute to the acquisition of respiratory viral infections. We finally provide the potential therapeutic perspectives deriving from these findings. Expert opinion: Prospective studies focusing on children have identified that nasopharyngeal microbiota composition is associated with predisposition to acute respiratory illness and bronchiolitis, while data are scarce regarding adults. For the latter, further works are needed, in particular as a part of the multi-OMICS approach that should probably be performed in conjunction with gut microbiota studies.
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Affiliation(s)
- Grégory Dubourg
- a IRD, Assistance Publique Hôpitaux de Marseille (APHM), Microbes, Evolution, Phylogeny and Infection (MEPHI) , Aix Marseille University , Marseille , France.,b IHU-Méditerranée Infection , Marseille , France
| | - Sophie Edouard
- a IRD, Assistance Publique Hôpitaux de Marseille (APHM), Microbes, Evolution, Phylogeny and Infection (MEPHI) , Aix Marseille University , Marseille , France.,b IHU-Méditerranée Infection , Marseille , France
| | - Didier Raoult
- a IRD, Assistance Publique Hôpitaux de Marseille (APHM), Microbes, Evolution, Phylogeny and Infection (MEPHI) , Aix Marseille University , Marseille , France.,b IHU-Méditerranée Infection , Marseille , France
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Mbareche H, Veillette M, Pilote J, Létourneau V, Duchaine C. Bioaerosols Play a Major Role in the Nasopharyngeal Microbiota Content in Agricultural Environment. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16081375. [PMID: 30995814 PMCID: PMC6518280 DOI: 10.3390/ijerph16081375] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 04/09/2019] [Accepted: 04/13/2019] [Indexed: 12/21/2022]
Abstract
Background: Bioaerosols are a major concern for public health and sampling for exposure assessment purposes is challenging. The nasopharyngeal region could be a potent carrier of long-term bioaerosol exposure agents. This study aimed to evaluate the correlation between nasopharyngeal bacterial flora of swine workers and the swine barns bioaerosol biodiversity. Methods: Air samples from eight swine barns as well as nasopharyngeal swabs from pig workers (n = 25) and from a non-exposed control group (n = 29) were sequenced using 16S rRNA gene high-throughput sequencing. Wastewater treatment plants were used as the industrial, low-dust, non-agricultural environment control to validate the microbial link between the bioaerosol content (air) and the nasopharynxes of workers. Results: A multivariate analysis showed air samples and nasopharyngeal flora of pig workers cluster together, compared to the non-exposed control group. The significance was confirmed with the PERMANOVA statistical test (p-value of 0.0001). Unlike the farm environment, nasopharynx samples from wastewater workers did not cluster with air samples from wastewater treatment plants. The difference in the microbial community of nasopharynx of swine workers and a control group suggest that swine workers are carriers of germs found in bioaerosols. Conclusion: Nasopharynx sampling and microbiota could be used as a proxy of air sampling for exposure assessment studies or for the determination of exposure markers in highly contaminated agricultural environments.
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Affiliation(s)
- Hamza Mbareche
- Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec G1V 4G5, Canada.
- Département de Biochimie, de Microbiologie et de Bio-Informatique, Faculté des Sciences et de Génie, Université Laval, Québec G1V 0A6, Canada.
| | - Marc Veillette
- Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec G1V 4G5, Canada.
| | - Jonathan Pilote
- Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec G1V 4G5, Canada.
- Département de Biochimie, de Microbiologie et de Bio-Informatique, Faculté des Sciences et de Génie, Université Laval, Québec G1V 0A6, Canada.
| | - Valérie Létourneau
- Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec G1V 4G5, Canada.
| | - Caroline Duchaine
- Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec G1V 4G5, Canada.
- Département de Biochimie, de Microbiologie et de Bio-Informatique, Faculté des Sciences et de Génie, Université Laval, Québec G1V 0A6, Canada.
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Girkin J, Maltby S, Singanayagam A, Bartlett N, Mallia P. In vivo experimental models of infection and disease. RHINOVIRUS INFECTIONS 2019. [PMCID: PMC7149593 DOI: 10.1016/b978-0-12-816417-4.00008-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Human and animal models continue to play a crucial role in research to understand host immunity to rhinovirus (RV) and identify disease mechanisms. Human models have provided direct evidence that RV infection is capable of exacerbating chronic respiratory diseases and identified immunological processes that correlate with clinical disease outcomes. Mice are the most commonly used nonhuman experimental RV infection model. Although semipermissive, under defined experimental conditions sufficient replication occurs to induce host immune responses that recapitulate immunity and disease during human infection. The capacity to use genetically modified mouse strains and drug interventions has shown the mouse model to be an invaluable research tool defining causal relationships between host immunity and disease and supporting development of new treatments. Used in combination the insights achieved from human and animal experimental infection models provide complementary insights into RV biology and yield novel therapeutic options to reduce the burden of RV-induced disease.
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