Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia.

In the paper

“Second, viral infections can also reduce ciliary beat frequency and the number of ciliated cells, disrupt the coordinated movement of cilia, and impede the repair of respiratory epithelial cells, further leading to reduced mucociliary clearance (126, 127).”

What the sources say

• Not checked yetcites [126] Pittet, 2010, Influenza virus infection decreases tracheal mucociliary velocity and clearance of Streptococcus pneumoniae, Am J Respir Cell Mol Biol source
• Partly supported

  The Discussion reports that RSV caused ciliary dyskinesia and cilia loss, which the authors say are likely to reduce mucociliary clearance. But it explicitly says ciliary beat frequency and the number of motile ciliated cells were not reduced. The paper does not establish that RSV impeded epithelial-cell repair. Page numbers were not supplied in our copy. (LLM, conf=0.90)

  cites [127] Smith, 2014, Ciliary dyskinesia is an early feature of respiratory syncytial virus infection, Eur Respir J sourceExperimental — accuracy not yet measured

In the paper

“Bacterial co-infection was also detected in ~30% of cases in the 2009 H1N1 pandemic, with high mortality rates despite administration of appropriate antibiotics”

What the sources say

• Not checked yetcites [11] Cillóniz, 2012, Bacterial co-infection with H1N1 infection in patients admitted with community acquired pneumonia, J Infect source
• Not checked yetcites [12] Gill, 2010, Pulmonary pathologic findings of fatal 2009 pandemic influenza A/H1N1 viral infections, Arch Pathol Lab Med source
• Not checked yetcites [13] Jain, 2009, Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009, N Engl J Med source
• Not checked yetcites [14] Kumar, 2009, Critically ill patients with 2009 influenza A(H1N1) infection in Canada, JAMA source
• Not checked yetcites [15] Martín-Loeches, 2011, Community-acquired respiratory coinfection in critically ill patients with pandemic 2009 influenza A(H1N1) virus, Chest source
• Not checked yetcites [16] Palacios, 2009, Streptococcus pneumoniae coinfection is correlated with the severity of H1N1 pandemic influenza, PLoS ONE source
• Not checked yetcites [17] Shieh, 2010, 2009 pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States, Am J Pathol source
• Not checked yetcites [18] Domínguez-Cherit, 2009, Critically Ill patients with 2009 influenza A(H1N1) in Mexico, JAMA source

In the paper

“which in turn may alter subsequent immune function against secondary bacterial infection or alter the dynamics of inter-microbial interactions, thereby enhancing the proliferation of potentially pathogenic bacterial species”

In the paper

“the so-called “Spanish Flu” pandemic of H1N1 influenza A virus from 1918 to 1919 resulted in more than 50 million deaths, with many caused by bacterial super-infection leading to secondary pneumonia”

What the sources say

• Not checked yetcites [1] Brundage, 2006, Interactions between influenza and bacterial respiratory pathogens: implications for pandemic preparedness, Lancet Infect Dis source
• Not checked yetcites [2] Chien, 2009, Bacterial pathogens and death during the 1918 influenza pandemic, N Engl J Med source
• Not checked yetcites [3] Johnson, 2002, Updating the accounts: global mortality of the 1918-1920 “Spanish” influenza pandemic, Bull Hist Med source
• Not checked yetcites [4] McCullers, 2006, Insights into the interaction between influenza virus and pneumococcus, Clin Microbiol Rev source
• Not checked yetcites [5] Morens, 2007, The 1918 influenza pandemic: insights for the 21st century, J Infect Dis source
• Not checked yetcites [6] Morens, 2008, Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness, J Infect Dis source
• Not checked yetcites [7] The origin and virulence of the 1918 “Spanish” influenza virus86112 TaubenbergerJK 17526158Proc Am Philos Soc1502006

In the paper

“which often have a more severe clinical course”

In the paper

“unique microbial communities reside on the mucosal surfaces of the gastrointestinal tract and the respiratory tract”

In the paper

“The mechanisms underlying post-viral bacterial infections are complex, and include multifactorial processes mediated by interactions between viruses, bacteria, and the host immune system.”

In the paper

“microbial metabolites are integral for promoting immune responses in the gut against pathogens, including inducing secretion of IL-18 (36) and defensins (37, 38)”

What the sources say

• Not checked yetcites [36] Kalina, 2002, Enhanced production of IL-18 in butyrate-treated intestinal epithelium by stimulation of the proximal promoter region, Eur J Immunol source
• Not checked yetcites [37] Schauber, 2003, Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways, Gut source
• Not checked yetcites [38] Schauber, 2004, Histone-deacetylase inhibitors induce the cathelicidin LL-37 in gastrointestinal cells, Mol Immunol source

In the paper

“SCFAs promote the development of naive CD4+ T cells into regulatory T cells (31, 32), induce “tolerogenic” dendritic cells in the intestinal mucosa (33), and limit autoimmity (34, 35).”

What the sources say

• Not checked yetcites [31] Smith, 2013, The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis, Science source
• Not checked yetcites [32] Arpaia, 2013, Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation, Nature source
• Not checked yetcites [33] Goverse, 2017, Diet-derived short chain fatty acids stimulate intestinal epithelial cells to induce mucosal tolerogenic dendritic cells, J Immunol source
• Not checked yetcites [34] Mariño, 2017, Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes, Nat Immunol source
• Not checked yetcites [35] Haase, 2018, Impacts of microbiome metabolites on immune regulation and autoimmunity, Immunology source

In the paper

“potential mechanisms by which these changes might modulate susceptibility to secondary bacterial infections include alterations in the nature and magnitude of the immune response in the host (microbiome on host effects) and facilitating growth of pathogens in the absence of normal commensals (inter-microbial effects)”

In the paper

“Germ-free (GF) mice (which lack microbiota) have markedly underdeveloped gut-associated lymphoid tissues, decreased number and smaller-sized Peyer's patches and mesenteric lymph nodes, and defects in antibody production, compared to specific pathogen free (SPF) mice.”

In the paper

“Wild-living mice exhibit more diverse microbiomes, with significant abundance of Proteobacteria as well as Firmicutes and Bacteroidetes”

What the sources say

• Not checked yetcites [21] Rosshart, 2017, Wild mouse gut microbiota promotes host fitness and improves disease resistance, Cell source

In the paper

“While the effects of these alterations on risk of secondary bacterial pneumonia have not been studied”

In the paper

“germ-free animals exhibit increased susceptibility to multiple types of infections, including viruses, bacteria, and parasites”

What the sources say

• Not checked yetcites (22,–27)

In the paper

“short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate are fermentation products of dietary fiber and carbohydrates by large intestinal bacteria”

What the sources say

• Not checked yetcites [30] Cummings, 1983, Fermentation in the human large intestine: evidence and implications for health, Lancet source

In the paper

“This raises the possibility that disruptions in the normal microbial communities by an acute viral infection might contribute to the development of post-viral bacterial pneumonia.”

In the paper

“During health, the human gut bacterial community is diverse, with each individual harboring over 100 trillion bacteria, comprised of over 150 different species.”

In the paper

“The gastrointestinal microbiota is dominated by Firmicutes (e.g., Lactobacillus, Bacillus, and Clostridium) and Bacteroidetes (e.g., Bacteroides), with lower abundances of Proteobacteria (e.g., Escherichia) and Actinobacteria (e.g., Bifidobacterium)”

What the sources say

• Not checked yetcites [19] Honda, 2012, The microbiome in infectious disease and inflammation, Annu Rev Immunol source
• Not checked yetcites [20] Human, 2012, Structure, function and diversity of the healthy human microbiome, Nature source

In the paper

“segmented filamentous bacteria are critical promoters of intestinal mucosal IgA production (39, 40)and Th17 cell induction (41, 42)”

What the sources say

• Not checked yetcites [39] Klaasen, 1993, Apathogenic, intestinal, segmented, filamentous bacteria stimulate the mucosal immune system of mice, Infect Immun source
• Not checked yetcites [40] Talham, 1999, Segmented filamentous bacteria are potent stimuli of a physiologically normal state of the murine gut mucosal immune system, Infect Immun source
• Not checked yetcites [41] Ivanov, 2009, Induction of intestinal Th17 cells by segmented filamentous bacteria, Cell source
• Not checked yetcites [42] Gaboriau-Routhiau, 2009, The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses, Immunity source

In the paper

“The gut microbiome, in particular, has been shown to play an integral role in shaping the immune system starting early in life, with continued influence on priming the nature and robustness of immune responses throughout one's lifetime.”

In the paper

“compared to free-living mice or laboratory animals exposed to gut flora from wild mice, SPF animals have a more limited microbial community and are also more susceptible to inflammatory diseases, with a reduced immune repertoire including deficits in memory responses”

What the sources say

• Not checked yetcites [21] Rosshart, 2017, Wild mouse gut microbiota promotes host fitness and improves disease resistance, Cell source
• Not checked yetcites [28] Reese, 2016, Sequential infection with common pathogens promotes human-like immune gene expression and altered vaccine response, Cell Host Microbe source
• Not checked yetcites [29] Beura, 2016, Normalizing the environment recapitulates adult human immune traits in laboratory mice, Nature source

In the paper

“emerging evidence suggests that our microbial communities residing on our mucosal surfaces likely shape the rigor of our immune responses and shape the ecological relationships between host and pathogens”

In the paper

“bacterial metabolites generated by gut commensals contribute to the maintenance of intact epithelial integrity, regulatory T-cell development, and a relatively anti-inflammatory immune state”

In the paper

“The pathogenesis of super-infection has been attributed to direct mucosal/epithelial damage by influenza virus, increased bacterial colonization of the upper and lower respiratory tracts (URT and LRT, respectively), and dysregulation of immune responses, which all lead to increased susceptibility to secondary bacterial infections.”

In the paper

“the effects of viral infection on the respiratory microbiome appear to be relatively modest, but detectable”

In the paper

“The respiratory tract also harbors distinct communities of microbes, with multiple discrete ecological niches (e.g., nasal cavity, oropharynx, upper airways) that vary in terms of temperature, pH, oxygen tension, mucus production, and other factors.”

In the paper

“The gut microbiome, in addition to its metabolic functions in the host, plays an integral role in the development, instruction, and priming of the immune system.”

In the paper

“The increase in Proteobacteria appears to be mediated by type I interferons (IFNs) (18), which not only depleted anaerobic bacteria but also increased susceptibility to secondary Salmonella colitis.”

What the sources say

• Not checked yetcites [18] Domínguez-Cherit, 2009, Critically Ill patients with 2009 influenza A(H1N1) in Mexico, JAMA source

In the paper

“antibiotic treatment prior to influenza infection ameliorated the degree of intestinal injury, but not lung injury, suggesting that gut dysbiosis contributed to local but not systemic inflammation”

What the sources say

• Not checked yetcites [43] Wang, 2014, Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation, J Exp Med source

In the paper

“Dysbiosis, or an imbalance in the normal composition of the microbiome, is associated with a variety of chronic diseases, many of which are characterized by chronic inflammation or abnormal metabolism, including inflammatory bowel disease, cardiovascular disease, and diabetes.”

In the paper

“caloric restriction also results in increased relative abundance of Proteobacteria and increased Bacteroidetes to Firmicutes ratio, raising the possibility that decreased oral intake during influenza may contribute to changes in the microbiome”

What the sources say

• Not checked yetcites [45] Bartley, 2017, Impact of age, caloric restriction, and influenza infection on mouse gut microbiome: an exploratory study of the role of age-related microbiome changes on influenza responses, Front Immunol source
• Not checked yetcites [47] Groves, 2018, Respiratory disease following viral lung infection alters the murine gut microbiota, Front Immunol source
• Not checked yetcites [49] Ley, 2006, Microbial ecology: human gut microbes associated with obesity, Nature source
• Not checked yetcites [50] Ruiz, 2017, One-year calorie restriction impacts gut microbial composition but not its metabolic performance in obese adolescents, Environ Microbiol source

In the paper

“Macrophages from animals treated with antibiotics exhibited defective responses to type I and II IFNs and impaired capacity to limit viral replication, suggesting that intestinal microbiota provide immune stimulation that establishes an “activation threshold” for innate antiviral immune responses”

What the sources say

• Not checked yetcites [52] Abt, 2012, Commensal bacteria calibrate the activation threshold of innate antiviral immunity, Immunity source

In the paper

“Mice given a 4 week oral course of broad-spectrum antibiotics before respiratory viral infection mounted an attenuated anti-PR8 antibody response, were incapable of inducing CD4+ T cell-mediated IFN-γ response to PR8 antigen, and had fewer influenza-specific CD8+T cells”

What the sources say

• Not checked yetcites [51] Ichinohe, 2011, Microbiota regulates immune defense against respiratory tract influenza A virus infection, Proc Natl Acad Sci USA source
• Not checked yetcites [52] Abt, 2012, Commensal bacteria calibrate the activation threshold of innate antiviral immunity, Immunity source

In the paper

“In a murine model of influenza infection, the investigators found that although the total numbers of bacteria in the gut did not decrease, there was a reduction in the quantities of segmented filamentous bacteria (SFB) and Lactobacillus/Lactococcus, accompanied by increases in Enterobacteriaceae.”

What the sources say

• Not checked yetcites [43] Wang, 2014, Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation, J Exp Med source

In the paper

“Short-term perturbations in the gut microenvironment caused by illness, antibiotic usage, or dietary changes (e.g., starvation) can alter the gut microbiome and subsequently lead to transient alterations in immune responses.”

In the paper

“Germ-free mice and antibiotic-treated mice also exhibit impaired antibody responses to seasonal influenza vaccination, which was restored by oral administration of flagellated E. coli, demonstrating a dependence on TLR5-mediated sensing of the host microbiota”

What the sources say

• Not checked yetcites [53] Oh, 2014, TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination, Immunity source

In the paper

“The respiratory tract is the main site of continuous contact with exogenous microbes.”

In the paper

“Skin and oral cavity lineages are represented in the nasopharynx—e.g., Streptococcus, Staphylococcus, Corynebacterium, and Prevotella”

What the sources say

• Not checked yetcites [70] Charlson, 2011, Topographical continuity of bacterial populations in the healthy human respiratory tract, Am J Respir Crit Care Med source
• Not checked yetcites [72] Ling, 2013, Pyrosequencing analysis of the human microbiota of healthy Chinese undergraduates, BMC Genomics source
• Not checked yetcites [73] Allen, 2014, Characterization of the nasopharyngeal microbiota in health and during rhinovirus challenge, Microbiome source

In the paper

“Oral administration of a probiotic cocktail containing Lactobacillus restored the immune response and enhanced the activation of signaling pathways associated with recognition of single-stranded RNA virus”

What the sources say

• Not checked yetcites [62] Wu, 2013, Microbiota regulates the TLR7 signaling pathway against respiratory tract influenza A virus infection, Curr Microbiol source

In the paper

“clinical studies have shown that although probiotics do not influence the incidence of respiratory tract infection, they do reduce the severity of symptoms and duration of the illness”

What the sources say

• Not checked yetcites [57] de, 2006, Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial, Vaccine source
• Not checked yetcites [58] Vouloumanou, 2009, Probiotics for the prevention of respiratory tract infections: a systematic review, Int J Antimicrob Agents source

In the paper

“Antibiotic-pretreated animals displayed altered cytokine profiles in the lung compared to untreated controls following S. pneumoniae infection, including significantly decreased TNF-α levels at 6 and 24 h after infection.”

What the sources say

• Not checked yetcites [55] Schuijt, 2016, The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia, Gut source

In the paper

“animals fed a high fiber diet had increased generation of SCFAs, leading to enhanced antiviral CD8+ T cell immune responses and attenuated neutrophil-mediated lung injury during influenza infection, resulting in improved survival”

What the sources say

• Not checked yetcites [63] Trompette, 2018, Dietary fiber confers protection against flu by shaping Ly6c- patrolling monocyte hematopoiesis and CD8+ T cell metabolism, Immunity source

In the paper

“The oropharynx contains members of Firmicutes, Proteobacteria, and Bacteroidetes, including Streptococcus, Neisseria, Haemophilus, and Lachnospira spp.”

What the sources say

• Not checked yetcites [68] Lemon, 2010, Comparative analyses of the bacterial microbiota of the human nostril and oropharynx, MBio source
• Not checked yetcites [70] Charlson, 2011, Topographical continuity of bacterial populations in the healthy human respiratory tract, Am J Respir Crit Care Med source
• Not checked yetcites [71] Yi, 2014, Profiling bacterial community in upper respiratory tracts, BMC Infect Dis source

In the paper

“In healthy adults, bacteria present in the nasal cavity are typically those associated with skin, predominantly members of the Actinobacteria (e.g., Corynebacterium spp., Propionibacterium spp.), followed by Firmicutes (e.g., Staphylococcus spp.), and Proteobacteria”

What the sources say

• Not checked yetcites [67] Frank, 2010, The human nasal microbiota and Staphylococcus aureus carriage, PLoS ONE source
• Not checked yetcites [68] Lemon, 2010, Comparative analyses of the bacterial microbiota of the human nostril and oropharynx, MBio source
• Not checked yetcites [69] Bassis, 2014, The nasal cavity microbiota of healthy adults, Microbiome source

In the paper

“oral administration of Lactobacillus plantarum enhanced the type I IFN response and lowered viral titers in the lungs in a murine model of influenza infection”

What the sources say

• Not checked yetcites [60] Maeda, 2009, Oral administration of heat-killed Lactobacillus plantarum L-137 enhances protection against influenza virus infection by stimulation of type I interferon production in mice, Int Immunopharmacol source

In the paper

“Antibiotic-treated mice exhibited markedly decreased fecal and serum DAT levels, which was associated with attenuated type I IFN responses to influenza infection and increased mortality”

What the sources say

• Not checked yetcites [59] Steed, 2017, The microbial metabolite desaminotyrosine protects from influenza through type I interferon, Science source

In the paper

“microbiome depletion led to decreased survival, increased lung bacterial burden, and increased systemic dissemination of bacteria”

What the sources say

• Not checked yetcites [55] Schuijt, 2016, The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia, Gut source

In the paper

“Several factors are known to influence airway microbiome composition including infection history, age, genetics, and structural lung disease.”

In the paper

“SFB-deficient animals have increased lung bacterial burdens and more severe pneumonia when challenged with methicillin-resistant Staphylococcus aureus (MRSA) (54), which was associated with decreased IL-17-mediated responses in the lung.”

What the sources say

• Not checked yetcites [54] Gauguet, 2015, Intestinal Microbiota of Mice Influences Resistance to Staphylococcus aureus Pneumonia, Infect Immun source

In the paper

“in the microbiota-depleted group, alveolar macrophages and blood neutrophils exhibited decreased phagocytic activity, and decreased inflammatory cytokine production following ex vivo stimulation by Toll-like receptor (TLR) ligands such as lipoteichoic acid (LTA)”

What the sources say

• Not checked yetcites [55] Schuijt, 2016, The gut microbiota plays a protective role in the host defence against pneumococcal pneumonia, Gut source

In the paper

“The URT and LRT have similar microbial community compositions, although microbe densities are much higher in the former in healthy hosts.”

In the paper

“Individuals with chronic airway diseases (e.g., cystic fibrosis, COPD) have increased bacterial populations in the lungs (77) and differences in the relative abundance of certain species”

What the sources say

• Not checked yetcites [77] Venkataraman, 2015, Application of a neutral community model to assess structuring of the human lung microbiome, MBio source
• Not checked yetcites [81] Rogers, 2015, Respiratory microbiota: addressing clinical questions, informing clinical practice, Thorax source

In the paper

“The major phyla in healthy lungs are Bacteroidetes and Firmicutes, which mainly include Prevotella, Veillonella, and Streptococcus”

What the sources say

• Not checked yetcites [78] Morris, 2013, Comparison of the respiratory microbiome in healthy nonsmokers and smokers, Am J Respir Crit Care Med source
• Not checked yetcites [79] Segal, 2013, Enrichment of lung microbiome with supraglottic taxa is associated with increased pulmonary inflammation, Microbiome source
• Not checked yetcites [80] Dickson, 2015, Spatial variation in the healthy human lung microbiome and the adapted island model of lung biogeography, Ann Am Thorac Soc source

In the paper

“Contrary to dogma that normal healthy lungs are a sterile environment, a distinct, and somewhat dynamic lung microbiome can be identified using sequencing technology, with microaspiration serving as the primary route of microbial immigration from the URT to the LRT”

What the sources say

• Not checked yetcites [76] Bassis, 2015, Analysis of the upper respiratory tract microbiotas as the source of the lung and gastric microbiotas in healthy individuals, MBio source
• Not checked yetcites [77] Venkataraman, 2015, Application of a neutral community model to assess structuring of the human lung microbiome, MBio source

In the paper

“A limited number of pathogens including Streptococcus pneumoniae, Neisseria meningitides, and Haemophilus influenzae are commensal bacteria of the URT.”

In the paper

“Both studies included subjects ranging from infants to adults >80 years of age, limiting conclusions about age-related effects.”

What the sources say

• Not checked yetcites [71] Yi, 2014, Profiling bacterial community in upper respiratory tracts, BMC Infect Dis source
• Not checked yetcites [100] Edouard, 2018, The nasopharyngeal microbiota in patients with viral respiratory tract infections is enriched in bacterial pathogens, Eur J Clin Microbiol Infect Dis source

In the paper

“Thus, unlike other diseases where decreased diversity is considered deleterious to the host, the effects of viral infections on diversity per se are variable and not presently considered a good indicator of risk for complications, including secondary bacterial pneumonias.”

In the paper

“Children with severe influenza showed decreased relative abundance of S. aureus and increased abundance of Prevotella, Streptobacillus, Porphyromonas, Granulicatella, Veillonella, Fusobacterium, and Haemophilus.”

What the sources say

• Not checked yetcites [105] Langevin, 2017, Early nasopharyngeal microbial signature associated with severe influenza in children: a retrospective pilot study, J Gen Virol source

In the paper

“RSV-infected mice who underwent antibiotic-mediated depletion of Streptococcus viridans in the nasopharynx exhibited increases in number of inflammatory lymphocytes and airway hyperresponsiveness, and decreases in regulatory T cell number and transforming growth factor-β production”

What the sources say

• Not checked yetcites [103] Ni, 2012, Pharyngeal microflora disruption by antibiotics promotes airway hyperresponsiveness after respiratory syncytial virus infection, PLoS ONE source

In the paper

“In a study of mice colonized with S. pneumoniae and then infected with influenza A virus 3 days after, S. pneumoniae transmission occurred only when all mice were infected with influenza and was blocked by an influenza-neutralizing antibody”

What the sources say

• Not checked yetcites [95] Diavatopoulos, 2010, Influenza A virus facilitates Streptococcus pneumoniae transmission and disease, FASEB J source

In the paper

“In healthy children, the major phyla among nasopharyngeal microbiotas are Proteobacteria, Firmicutes, Bacteroidetes, Actinobacteria, and Fusobacteria, with Moraxella, Haemophilus, Streptococcus, Flavobacteria, Dolosigranulum, Corynebacterium, and Neisseria as predominant genera.”

What the sources say

• Not checked yetcites [114] Bogaert, 2011, Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis, PLoS ONE source

In the paper

“Another complicating factor particularly in cross-sectional studies examining the microbiome during viral infections is that the groups are not well-controlled and the sample numbers are relatively small considering the number of variables that could affect the respiratory tract microbiome–such as age, gender, oral hygiene and nose-picking habits, healthcare-based employment status, smoking status”

In the paper

“although mean relative abundances of Haemophilus, Moraxella, Staphylococcus, and Corynebacterium varied significantly between summer and fall samples and between age groups.”

What the sources say

• Not checked yetcites [115] Pérez-Losada, 2017, Nasopharyngeal microbiome diversity changes over time in children with asthma, PLoS ONE source

In the paper

“The underlying type of viral infection, sampling timepoint after onset of infection, severity of infection, and concomittant antimicrobial usage are other confounding factors.”

In the paper

“However, these studies demonstrated that there was considerable inter-subject variability, highlighting the need for longitudinal studies to decipher changes following viral infection.”

What the sources say

• Not checked yetcites [108] Leung, 2013, Modulation of potential respiratory pathogens by pH1N1 viral infection, Clin Microbiol Infect source
• Not checked yetcites [109] Chaban, 2013, Characterization of the upper respiratory tract microbiomes of patients with pandemic H1N1 influenza, PLoS ONE source
• Not checked yetcites [110] Greninger, 2010, A metagenomic analysis of pandemic influenza A (2009 H1N1) infection in patients from North America, PLoS ONE source

In the paper

“An investigation of the frequency and seasonal variation in bacterial and viral load in asymptomatic healthcare professionals during the winter and summer months showed that of the 100 subjects tested during the winter, 34 were colonized with at least one bacterial species and 11 tested positive for at least one virus.”

What the sources say

• Not checked yetcites [116] Hassoun, 2015, Seasonal variation of respiratory pathogen colonization in asymptomatic health care professionals: A single-center, cross-sectional, 2-season observational study, Am J Infect Control source

In the paper

“In the nasopharyngeal compartment of Aboriginal and non-Aboriginal children in Australia, positive associations were detected between hRV and S. pneumoniae, H. influenza, and Moraxella catarrhalis carriage as well as between adenovirus and M. catarrhalis (111).”

What the sources say

• Not checked yetcites [111] Jacoby, 2007, Kalgoorlie Otitis Media Research Project Team. Modelling the co-occurrence of Streptococcus pneumoniae with other bacterial and viral pathogens in the upper respiratory tract, Vaccine source

In the paper

“These profiles, however, were not associated with virus type but were linked to the age of subjects (71).”

What the sources say

• Not checked yetcites [71] Yi, 2014, Profiling bacterial community in upper respiratory tracts, BMC Infect Dis source

In the paper

“Changes in nasopharyngeal microbiome diversity were observed across seasons, with a predominance of Proteobacteria and Fusobacteria in fall-winter and Bacteroidetes and Firmicutes in spring; these differences were independent of recent antibiotics and viral co-infection (114).”

What the sources say

• Not checked yetcites [114] Bogaert, 2011, Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis, PLoS ONE source

In the paper

“In a mouse model, bacterial density in the nasopharynx after LAIV administration was increased as much as 100,000 times compared to influenza-naive hosts, and the duration of carriage of S. pneumoniae or S. aureus was also increased 2 to 5-fold (121).”

What the sources say

• Not checked yetcites [121] Mina, 2014, Live attenuated influenza vaccine enhances colonization of Streptococcus pneumoniae and Staphylococcus aureus in mice, MBio source

In the paper

“In healthy adult volunteers, it was demonstrated that intranasal LAIV administration induced an increase in the diversity of the nasopharyngeal microbiome, as well as relative abundances of Staphylococcus and Bacteroides (107).”

What the sources say

• Not checked yetcites [107] Tarabichi, 2015, The administration of intranasal live attenuated influenza vaccine induces changes in the nasal microbiota and nasal epithelium gene expression profiles, Microbiome source

In the paper

“Nasopharyngeal sampling showed completely opposite results, with decreased relative abundance of Haemophilus and Neisseria spp., but an increase in the normal nasal commensal, Propionibacterium, in subjects following hRV infection (73).”

What the sources say

• Not checked yetcites [73] Allen, 2014, Characterization of the nasopharyngeal microbiota in health and during rhinovirus challenge, Microbiome source

In the paper

“Administration of live attenuated influenza vaccine (LAIV), which is nasally instilled, to healthy children increased the nasal colonization density of S. pneumoniae in subjects who harbored this bacterium at the time of vaccination, and transiently increased rates of colonization by H. influenza (120).”

What the sources say

• Not checked yetcites [120] Thors, 2016, The effects of live attenuated influenza vaccine on nasopharyngeal bacteria in healthy 2 to 4 year olds. a randomized controlled trial, Am J Respir Crit Care Med source

In the paper

“In contrast, of the 100 subjects tested during the summer, 37 harbored at least one bacterium (mainly MRSA and K. pneumoniae) and four tested positive for one virus (116).”

What the sources say

• Not checked yetcites [116] Hassoun, 2015, Seasonal variation of respiratory pathogen colonization in asymptomatic health care professionals: A single-center, cross-sectional, 2-season observational study, Am J Infect Control source

In the paper

“In the oropharyngeal compartment, rhinovirus infection was associated with a strong trend toward transient increases in the relative abundances of H. parainfluenzae, Neisseria subflava and a weak trend toward an increase in S. aureus (119).”

What the sources say

• Not checked yetcites [119] Hofstra, 2015, Changes in microbiota during experimental human Rhinovirus infection, BMC Infect Dis source

In the paper

“Another study of 31 families with small children using longitudinal nasal swab sampling demonstrated that rhinovirus infection was associated with increased acquisition of S. pneumoniae from the community as well as increased transmission of S. pneumoniae within the family (118).”

What the sources say

• Not checked yetcites [118] Karppinen, 2017, Acquisition and transmission of streptococcus pneumoniae are facilitated during rhinovirus infection in families with children, Am J Respir Crit Care Med source

In the paper

“Interestingly, the percentage of colonized children and bacterial density were also higher at asymptomatic visits in which virus was detected than at those in which virus was not detected (117).”

What the sources say

• Not checked yetcites [117] DeMuri, 2018, Dynamics of bacterial colonization with streptococcus pneumoniae, haemophilus influenzae, and moraxella catarrhalis during symptomatic and asymptomatic viral upper respiratory tract infection, Clin Infect Dis source

In the paper

“In subjects with chronic obstructive pulmonary disease (COPD) after hRV infection but not in healthy individuals, there was an increase in bacterial burden and growth of bacteria present at baseline, particularly H. influenzae (124).”

What the sources say

• Not checked yetcites [124] Molyneaux, 2013, Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease, Am J Respir Crit Care Med source

In the paper

“First, mucus production in the respiratory tract is increased to facilitate viral clearance during infections. However, excessive mucus production can lead to airway obstruction by impeding mucociliary clearance (125).”

What the sources say

• Not checked yetcites [125] Vareille, 2011, The airway epithelium: soldier in the fight against respiratory viruses, Clin Microbiol Rev source

In the paper

“Increased upper respiratory tract persistence of S. aureus as well as increased risk of S. aureus pneumonia was observed in flu-infected wildtype mice compared to mice lacking the type III IFN receptor (123).”

What the sources say

• Not checked yetcites [123] Planet, 2016, Lambda interferon restructures the nasal microbiome and increases susceptibility to staphylococcus aureus superinfection, MBio source

In the paper

“Respiratory viruses not only alter the bacterial community in the URT, but also promote bacterial colonization of the LRT by a variety of mechanisms that impair bacterial clearance.”

In the paper

“Compared to studies of the URT microbiome, studies of the LRT microbiome following viral infections are relatively scarce due to the difficulty of obtaining uncontaminated samples from the lung.”

In the paper

“Samples of convenience, such as sputum, suffer from oral contamination, but bronchoscopic samples are invasive and expensive to obtain on a regular basis.”

In the paper

“Subsequent studies by another group reported that C. pseudodiphtheriticum inhibited S. aureus growth, whereas C. accolens and S. aureus appeared to support each other's growth (139).”

What the sources say

• Not checked yetcites [139] Yan, 2013, Nasal microenvironments and interspecific interactions influence nasal microbiota complexity and S. aureus carriage, Cell Host Microbe source

In the paper

“These data imply that influenza infection perturbs the respiratory microbiome, leading to the production of secondary metabolites including immune-modulating molecules.”

What the sources say

• Not checked yetcites [108] Leung, 2013, Modulation of potential respiratory pathogens by pH1N1 viral infection, Clin Microbiol Infect source

In the paper

“Interestingly, a recent preclinical study using a murine model of RSV and S. pneumoniae superinfection employed nasal priming by a C. pseudodiphtheriticum strain to augment host defense against the viral infection, which enhanced clearance of secondary bacterial challenge and reduced lung injury measures (140).”

What the sources say

• Not checked yetcites [140] Kanmani, 2017, Respiratory commensal bacteria corynebacterium pseudodiphtheriticum improves resistance of infant mice to respiratory syncytial virus and streptococcus pneumoniae superinfection, Front Microbiol source

In the paper

“Conversely, other investigators observed that Corynebacterium spp. were enriched in children who were not nasally colonized with pneumococcus, and demonstrated that C. accolens inhibit S. pneumoniae growth in vitro by expressing a lipase that releases free fatty acids from skin surface triacylglycerols, which inhibit pneumococcal growth.”

In the paper

“The mechanism appeared to be bacteriocin-independent.”

What the sources say

• Not checked yetcites [137] Uehara, 2000, Bacterial interference among nasal inhabitants: eradication of Staphylococcus aureus from nasal cavities by artificial implantation of Corynebacterium sp, J Hosp Infect source

In the paper

“Thus, it is possible that the immune response incited by acute viral infections, changes in the host epithelial surface caused by the virus, or the virus itself might lead to elimination of a host commensal that is responsible for keeping pathobionts in check.”

In the paper

“Viruses have also been found to impair bacterial biofilm formation and disrupt existing biofilm (141–144).”

What the sources say

• Not checked yetcites [141] Reddinger, 2016, Host physiologic changes induced by influenza a virus lead to staphylococcus aureus biofilm dispersion and transition from asymptomatic colonization to invasive disease, MBio source
• Not checked yetcites [142] Pettigrew, 2014, Dynamic changes in the Streptococcus pneumoniae transcriptome during transition from biofilm formation to invasive disease upon influenza A virus infection, Infect Immun source
• Not checked yetcites [143] Marks, 2013, Interkingdom signaling induces Streptococcus pneumoniae biofilm dispersion and transition from asymptomatic colonization to disease, MBio source
• Not checked yetcites [144] Reddinger, 2018, Streptococcus pneumoniae modulates staphylococcus aureus biofilm dispersion and the transition from colonization to invasive disease, MBio source