Microbiome Of Upper Respiratory Tract Research Articles

Meta-analysis of the human upper respiratory tract microbiome reveals robust taxonomic associations with health and disease

BackgroundThe human upper respiratory tract (URT) microbiome, like the gut microbiome, varies across individuals and between health and disease states. However, study-to-study heterogeneity in reported case–control results has made the identification of consistent and generalizable URT-disease associations difficult.ResultsIn order to address this issue, we assembled 26 independent 16S rRNA gene amplicon sequencing data sets from case–control URT studies, with approximately 2–3 studies per respiratory condition and ten distinct conditions covering common chronic and acute respiratory diseases. We leveraged the healthy control data across studies to investigate URT associations with age, sex, and geographic location, in order to isolate these associations from health and disease states.ConclusionsWe found several robust genus-level associations, across multiple independent studies, with either health or disease status. We identified disease associations specific to a particular respiratory condition and associations general to all conditions. Ultimately, we reveal robust associations between the URT microbiome, health, and disease, which hold across multiple studies and can help guide follow-up work on potential URT microbiome diagnostics and therapeutics.

General dynamics of the URT microbiome and microbial signs of recovery in COVID-19 patients.

COVID-19 is caused by an airborne virus, SARS-CoV-2. The upper respiratory tract (URT) is, therefore, the first system to endure the attack. Inhabited by an assemblage of microbial communities, a healthy URT wards off the invasion. However, once invaded, it becomes destabilised, which could be crucial to the establishment and progression of the infection. We examined 696 URT samples collected from 285 COVID-19 patients at three time-points throughout their hospital stay and 100 URT samples from 100 healthy controls. We used 16S ribosomal RNA sequencing to evaluate the abundance of various bacterial taxa, α-diversity, and β-diversity of the URT microbiome. Ordinary least squares regression was used to establish associations between the variables, with age, sex, and antibiotics as covariates. The URT microbiome in the COVID-19 patients was distinctively different from that of healthy controls. In COVID-19 patients, the abundance of 16 genera was significantly reduced. A total of 47 genera were specific to patients, whereas only 2 were unique to controls. The URT samples collected at admission differed more from the control than from the samples collected at later stages of treatment. The following four genera originally depleted in the patients grew significantly by the end of treatment: Fusobacterium, Haemophilus, Neisseria, and Stenotrophomonas. Our findings strongly suggest that SARS-CoV-2 caused significant changes in the URT microbiome, including the emergence of numerous atypical taxa. These findings may indicate increased instability of the URT microbiome in COVID-19 patients. In the course of the treatment, the microbial composition of the URT of COVID-19 patients tended toward that of controls. These microbial changes may be interpreted as markers of recovery.

Antimicrobial Resistance in the Upper Respiratory Tract of Children Compared with Adults

Abstract Background Antimicrobial resistance (AMR) is a growing global public health threat. In 2019, resistant bacterial infections and respiratory tract infections were a leading cause of death in children worldwide. While the gut is a known reservoir of AMR genes, there is little data on the AMR burden in the respiratory tract. We used metagenomic RNA next-generation sequencing (mNGS) to describe bacterial AMR genes detected in the upper respiratory tract of children and compare with adults. Methods We leveraged two established cohort studies of children and adults diagnosed with acute respiratory illnesses in the inpatient and outpatient setting in California and Colorado. Nasopharyngeal (NP) swabs were collected between March to September 2020. Specimens underwent RNA extraction and paired-end Illumina sequencing. AMR genes were detected using the ARG-ANNOT database and the CZID pipeline. Children ≤18 years of age and adults≥ 40 years of age were eligible for inclusion in the analysis. We described and compared AMR genes and AMR gene classes detected in children and adults. P-values were calculated using the Wilcoxon rank-sum test. A multiple logistic regression model was fitted to evaluate the association of age cohort (children vs adults) with presence of AMR genes, while accounting for possible confounding from sex and encounter setting. 95% confidence intervals (CI) were calculated using the Wald CI. Results NP swab mNGS data from 236 patients (82 children, 154 adults) were analyzed. Children were a median age of 4 years (range: 0-17 years), and adults were a median age of 62 years (range: 40-89 years). Both cohorts were 50% male. AMR genes were detected in 44 (54%) children and 109 (71%) adults. Genes conferring resistance to beta-lactams (n=112, 47%), macrolides (n=89, 38%), and tetracyclines (n=72, 31%) were the most frequently detected. Among children, children ages 0 to 2 years had a higher number of AMR genes than children of other age groups, particularly when compared with children ages 3 to 10 years (p-value: 0.031) (Figure 1A). When comparing children with adults, children had fewer AMR genes (p-value: 0.014) as well as fewer AMR gene classes (p-value: 0.031) (Figure 1B). In the multiple logistic regression model, children still had lower odds of any AMR genes detected compared with adults (odds ratio: 0.39, 95% CI: 0.21-0.71). Figure 1. Box plots of (A) the number of antimicrobial resistance (AMR) genes detected in children stratified by age, and (B) the number of AMR genes and AMR gene classes detected in children (n=82) and adults (n=154). The size of the individual data points within the box plots correlates with the number of patients at each data point. Conclusion Children had fewer AMR genes and gene classes than adults in their upper respiratory tract microbiome. Despite this, over half of the children had detectable resistance genes, and children 2 years and younger had more AMR genes than other children. Almost half of the children had resistance genes to beta-lactams, the most frequently prescribed antibiotics to children. These findings suggest that presence of AMR organisms in the airway is common even in children, and that continued efforts to reduce AMR burden in this population are essential.

Bacterial Biomarkers of the Oropharyngeal and Oral Cavity during SARS-CoV-2 Infection.

(1) Background: Individuals with COVID-19 display different forms of disease severity and the upper respiratory tract microbiome has been suggested to play a crucial role in the development of its symptoms. (2) Methods: The present study analyzed the microbial profiles of the oral cavity and oropharynx of 182 COVID-19 patients compared to 75 unaffected individuals. The samples were obtained from gargle screening samples. 16S rRNA amplicon sequencing was applied to analyze the samples. (3) Results: The present study shows that SARS-CoV-2 infection induced significant differences in bacterial community assemblages, with Prevotella and Veillonella as biomarkers for positive-tested people and Streptococcus and Actinomyces for negative-tested people. It also suggests a state of dysbiosis on the part of the infected individuals due to significant differences in the bacterial community in favor of a microbiome richer in opportunistic pathogens. (4) Conclusions: SARS-CoV-2 infection induces dysbiosis in the upper respiratory tract. The identification of these opportunistic pathogenic biomarkers could be a new screening and prevention tool for people with prior dysbiosis.

Upper respiratory tract microbiome profiles in SARS-CoV-2 Delta and Omicron infected patients exhibit variant specific patterns and robust prediction of disease groups.

The pandemic caused by the SARS-CoV-2 virus is the reason for many deaths globally. It is hypothesized that the upper respiratory tract (URT) microbiome shares similarities with lung microbiota and can modulate host immune responses to the virus. During the pandemic, several SARS-CoV-2 variants have emerged with different clinical outcomes and immune dysfunction, yet their association with changes in the URT microbiome has not been identified, which may provide an assessment of lung health in the presence of those variants with differential disease outcomes. In this study, we sequenced V3-V4 region of the 16S rRNA gene from the URT microbiome of healthy controls (HC), Delta- and Omicron-infected patients from Eastern India, which showed higher inter-individual diversity (β) and lower intra-individual diversity (α) in COVID-19 patients compared to healthy controls. Healthy control microbiome showed enrichment of commensals like Streptococcus symci, Prevotella melaninogenica, Neisseria perflava, Veillonella tobetsuensis, Veillonella nakazawae, Haemophilus parainfluenzae, Fusobacterium pseudoperiodonticum, and Bifidobacterium longum compared to COVID-19 samples. Ct value of patients significantly positively correlated with Streptococcus symci and Streptococcus toyakuensis indicating a possible inverse relation with viral load. We also observed few bacterial taxa like Staphylococcus caprae, Pseudomonas aeruginosa, Vibrio tritonious, and Rothia mucilaginosa are discriminating Omicron from Delta which is, in turn, enriched mostly with Enterobacter mori, Acinetobacter baumannii, and Klebsiella pneumoniae. Further investigation showed nine control-associated bacteria had higher to lower trends among three groups viz., Control > Omicron > Delta. These bacteria also contributed to the successful prediction of disease groups with high accuracy (90% ± 0.5%) by random forest analysis. IMPORTANCE The role of the upper respiratory tract (URT) microbiome in predicting lung health has been documented in several studies. The dysbiosis in COVID patients has been associated with disease outcomes by modulating the host immune system. However, although it has been known that different SARS-CoV-2 variants manifest distinct transmissibility and mortality rates in human populations, their effect on the composition and diversity of the URT microbiome has not been studied to date. Unlike the older variant (Delta), the newer variant (Omicron) have become more transmissible with lesser mortality and the symptoms have also changed significantly. Hence, in the present study, we have investigated the change in the URT microbiome associated with Delta and Omicron variants and identified variant-specific signatures that will be useful in the assessment of lung health and can be utilized for nasal probiotic therapy in the future.

Saliva microbiome in relation to SARS-CoV-2 infection in a prospective cohort of healthy US adults.

The clinical outcomes of SARS-CoV-2 infection vary in severity, potentially influenced by the resident human microbiota. There is limited consensus on conserved microbiome changes in response to SARS-CoV-2 infection, with many studies focusing on severely ill individuals. This study aimed to assess the variation in the upper respiratory tract microbiome using saliva specimens in a cohort of individuals with primarily mild to moderate disease. In early 2020, a cohort of 831 adults without known SARS-CoV-2 infection was followed over a six-month period to assess the occurrence and natural history of SARS-CoV-2 infection. From this cohort, 81 participants with a SARS-CoV-2 infection, along with 57 unexposed counterparts were selected with a total of 748 serial saliva samples were collected for analysis. Total bacterial abundance, composition, population structure, and gene function of the salivary microbiome were measured using 16S rRNA gene and shotgun metagenomic sequencing. The salivary microbiome remained stable in unexposed individuals over the six-month study period, as evidenced by all measured metrics. Similarly, participants with mild to moderate SARS-CoV-2 infection showed microbiome stability throughout and after their infection. However, there were significant reductions in microbiome diversity among SARS-CoV-2-positive participants with severe symptoms early after infection. Over time, the microbiome diversity in these participants showed signs of recovery. These findings demonstrate the resilience of the salivary microbiome in relation to SARS-CoV-2 infection. Mild to moderate infections did not significantly disrupt the stability of the salivary microbiome, suggesting its ability to maintain its composition and function. However, severe SARS-CoV-2 infection was associated with temporary reductions in microbiome diversity, indicating the limits of microbiome resilience in the face of severe infection. This project was supported in part by Danone North America and grants from the National Institutes of Health, United States.

Characterization of upper airway microbiome across severity of COVID-19 during hospitalization and treatment.

Longitudinal studies on upper respiratory tract microbiome in coronavirus disease 2019 (COVID-19) without potential confounders such as antimicrobial therapy are limited. The objective of this study is to assess for longitudinal changes in the upper respiratory microbiome, its association with disease severity, and potential confounders in adult hospitalized patients with COVID-19. Serial nasopharyngeal and throat swabs (NPSTSs) were taken for 16S rRNA gene amplicon sequencing from adults hospitalized for COVID-19. Alpha and beta diversity was assessed between different groups. Principal coordinate analysis was used to assess beta diversity between groups. Linear discriminant analysis was used to identify discriminative bacterial taxa in NPSTS taken early during hospitalization on need for intensive care unit (ICU) admission. A total of 314 NPSTS samples from 197 subjects (asymptomatic = 14, mild/moderate = 106, and severe/critical = 51 patients with COVID-19; non-COVID-19 mechanically ventilated ICU patients = 11; and healthy volunteers = 15) were sequenced. Among all covariates, antibiotic treatment had the largest effect on upper airway microbiota. When samples taken after antibiotics were excluded, alpha diversity (Shannon, Simpson, richness, and evenness) was similar across severity of COVID-19, whereas beta diversity (weighted GUniFrac and Bray-Curtis distance) remained different. Thirteen bacterial genera from NPSTS taken within the first week of hospitalization were associated with a need for ICU admission (area under the receiver operating characteristic curve, 0.96; 95% CI, 0.91-0.99). Longitudinal analysis showed that the upper respiratory microbiota alpha and beta diversity was unchanged during hospitalization in the absence of antimicrobial therapy.

The Upper Respiratory Tract Microbiome Network Impacted by SARS-CoV-2.

The microbiome of upper respiratory tract (URT) acts as a gatekeeper to respiratory health of the host. However, little is still known about the impacts of SARS-CoV-2 infection on the microbial species composition and co-occurrence correlations of the URT microbiome, especially the relationships between SARS-CoV-2 and other microbes. Here, we characterized the URT microbiome based on RNA metagenomic-sequencing datasets from 1737 nasopharyngeal samples collected from COVID-19 patients. The URT-microbiome network consisting of bacteria, archaea, and RNA viruses was built and analyzed from aspects of core/periphery species, cluster composition, and balance between positive and negative interactions. It is discovered that the URT microbiome in the COVID-19 patients is enriched with Enterobacteriaceae, a gut associated family containing many pathogens. These pathogens formed a dense cooperative guild that seemed to suppress beneficial microbes collectively. Besides bacteria and archaea, 72 eukaryotic RNA viruses were identified in the URT microbiome of COVID-19 patients. Only five of these viruses were present in more than 10% of all samples, including SARS-CoV-2 and a bat coronavirus (i.e., BatCoV BM48-31) not detected in humans by routine means. SARS-CoV-2 was inhibited by a cooperative alliance of 89 species, but seems to cooperate with BatCoV BM48-31 given their statistically significant, positive correlations. The presence of cooperative bat-coronavirus partner of SARS-CoV-2 (BatCoV BM48-31), which was previously discovered in bat but not in humans to the best of our knowledge, is puzzling and deserves further investigation given their obvious implications. Possible microbial translocation mechanism from gut to URT also deserves future studies.

The upper respiratory tract microbiome and its role in human health: barrier function

The human respiratory tract is a complex system characterized by a series of niches colonized with specific microbial communities. Until recently, researchers were mostly interested in lung microbiomes associated with acute and chronic infections. The upper respiratory tract microbiota has gained attention during COVID-19 (COronaVIrus Disease 2019) pandemic because it was suspected to influence the course and the outcome of viral infections. Aim. In this two-part review (see part 1, Pul’monolog;iya. 2022; 32 (5): 745-754), we summarize current knowledge of the microbial communities at each upper respiratory tract location, considering the proposed barrier function of the respiratory microbiome. Conclusion. Based on the evidence presented in this review, we can see how the respiratory microbiome is involved in the pathogenesis of viral respiratory infections, including SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2).

The upper respiratory tract microbiome and its role in human health: biotopes and variability

Human respiratory tract is a complex system with a specific microbiological profile. Until recently, researchers were mostly interested in lung microbial communities associated with acute and chronic infections. The upper respiratory tract microbiota has gained attention during COVID-19 pandemic as it was proposed to be one of the factors affecting the course and the outcome of viral infections. The aim. In this review, we summarized the current knowledge about microbial communities in each section of the upper respiratory tract, considering the proposed barrier function of the respiratory microbiome. Conclusion. The facts provided in the first part of this review give a modern perspective on the structure of microbial communities of each part of the upper respiratory tract and factors that affect their variability.

Characterization of the Upper Respiratory Bacterial Microbiome in Critically Ill COVID-19 Patients.

The upper respiratory tract (URT) microbiome can contribute to the acquisition and severity of respiratory viral infections. The described associations between URT microbiota and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited at microbiota genus level and by the lack of functional interpretation. Our study, therefore, characterized the URT bacterial microbiome at species level and their encoded pathways in patients with COVID-19 and correlated these to clinical outcomes. Whole metagenome sequencing was performed on nasopharyngeal samples from hospitalized patients with critical COVID-19 (n = 37) and SARS-CoV-2-negative individuals (n = 20). Decreased bacterial diversity, a reduction in commensal bacteria, and high abundance of pathogenic bacteria were observed in patients compared to negative controls. Several bacterial species and metabolic pathways were associated with better respiratory status and lower inflammation. Strong correlations were found between species biomarkers and metabolic pathways associated with better clinical outcome, especially Moraxella lincolnii and pathways of vitamin K2 biosynthesis. Our study demonstrates correlations between the URT microbiome and COVID-19 patient outcomes; further studies are warranted to validate these findings and to explore the causal roles of the identified microbiome biomarkers in COVID-19 pathogenesis.

Severe COVID-19 Is Associated With an Altered Upper Respiratory Tract Microbiome.

BackgroundThe upper respiratory tract (URT) is the portal of entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and SARS-CoV-2 likely interacts with the URT microbiome. However, understanding of the associations between the URT microbiome and the severity of coronavirus disease 2019 (COVID-19) is still limited.ObjectiveOur primary objective was to identify URT microbiome signature/s that consistently changed over a spectrum of COVID-19 severity.MethodsUsing data from 103 adult participants from two cities in the United States, we compared the bacterial load and the URT microbiome between five groups: 20 asymptomatic SARS-CoV-2-negative participants, 27 participants with mild COVID-19, 28 participants with moderate COVID-19, 15 hospitalized patients with severe COVID-19, and 13 hospitalized patients in the ICU with very severe COVID-19.ResultsURT bacterial load, bacterial richness, and within-group microbiome composition dissimilarity consistently increased as COVID-19 severity increased, while the relative abundance of an amplicon sequence variant (ASV), Corynebacterium_unclassified.ASV0002, consistently decreased as COVID-19 severity increased.ConclusionsWe observed that the URT microbiome composition significantly changed as COVID-19 severity increased. The URT microbiome could potentially predict which patients may be more likely to progress to severe disease or be modified to decrease severity. However, further research in additional longitudinal cohorts is needed to better understand how the microbiome affects COVID-19 severity.

Clinical practices underlie COVID-19 patient respiratory microbiome composition and its interactions with the host

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

Effect of maternal separation and transportation stress on the bovine upper respiratory tract microbiome and the immune response to resident opportunistic pathogens

BackgroundThe bovine upper respiratory tract (URT) microbiome includes opportunistic pathogens that cause respiratory disease and stress associated with maternal separation and transportation contributes to the severity of this respiratory disease. Stress is known to alter the gut microbiome but little is known regarding the effect of stress on the URT microbiota. This study used six-month old suckling beef calves to investigate whether maternal separation (weaned), by itself or combined with transportation (weaned + transport), altered the URT microbiome and host immune responses to resident opportunistic pathogens.ResultsTaxonomic and functional composition of the URT microbiome in suckling and weaned beef calves did not change significantly when serially sampled over a one-month period. Subtle temporal changes in the URT microbiome composition were observed in weaned + transport calves. Total bacterial density was lower (p < 0.05) on day 4 post-weaning in both the weaned and weaned + transport groups when compared to suckling calves. In addition, significant (p < 0.05) temporal changes in the density of the opportunistic pathogens, M. haemolytica and P. multocida, were observed independent of treatment but these changes did not correlate with significantly increased (p < 0.05) serum antibody responses to both of these bacteria in the weaned and weaned + transport groups. Serum antibody responses to My. bovis, another opportunistic pathogen, remained unchanged in all treatment groups. Weaning, by itself and in combination with transportation, also had significant (p < 0.05) short- (2 to 8 days post-weaning) and long-term (28 days post-weaning) effects on the expression of adrenergic receptor genes in blood leukocytes when compared to age-matched suckling beef calves.ConclusionsMaternal separation (weaning) and transportation has minor effects on the taxonomic and functional composition of the URT microbiome and temporal changes in the density of opportunistic pathogen residing in the URT did not correlate with significant changes in immune responses to these bacteria. Significant changes in adrenergic receptor expression in blood leukocytes following weaning, with or without transportation, suggests altered neuroimmune regulation should be further investigated as a mechanism by which stress can alter host-microbiome interactions for some opportunistic respiratory pathogens that reside in the URT.

Upper respiratory tract bacterial-immune interactions during respiratory syncytial virus infection in infancy

The risk factors determining short- and long-term morbidity following acute respiratory infection (ARI) due to respiratory syncytial virus (RSV) in infancy remain poorly understood. Our aim was to examine the associations of the upper respiratory tract (URT) microbiome during RSV ARI in infancy with the acute local immune response and short- and long-term clinical outcomes. We characterized the URT microbiome by 16S ribosomal RNA sequencing and assessed the acute local immune response by measuring 53 immune mediators with high-throughput immunoassays in 357 RSV-infected infants. Our short- and long-term clinical outcomes included several markers of disease severity and the number of wheezing episodes in the fourth year of life, respectively. We found several specific URT bacterial-immune mediator associations. In addition, the Shannon ⍺-diversity index of the URT microbiome was associated with a higher respiratory severity score (β=.50 [95% CI= 0.13-0.86]), greater odds of a lower ARI (odds ratio= 1.63 [95% CI= 1.10-2.43]), and higher number of wheezing episodes in the fourth year of life (β= 0.89 [95% CI= 0.37-1.40]). The Jaccard β-diversity index of the URT microbiome differed by level of care required (P= .04). Furthermore, we found an interaction between the Shannon ⍺-diversity index of the URT microbiome and the first principal component of the acute local immune response on the respiratory severity score (P= .048). The URT microbiome during RSV ARI in infancy is associated with the acute local immune response, disease severity, and number of wheezing episodes in the fourth year of life. Our results also suggest complex URT bacterial-immune interactions that can affect the severity of the RSV ARI.

SARS-CoV-2 infection and viral load are associated with the upper respiratory tract microbiome

BackgroundLittle is known about the relationships between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the respiratory virus responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, and the upper respiratory tract (URT) microbiome.ObjectiveWe sought to compare the URT microbiome between SARS-CoV-2–infected and –uninfected adults and to examine the association of SARS-CoV-2 viral load with the URT microbiome during COVID-19.MethodsWe characterized the URT microbiome using 16S ribosomal RNA sequencing in 59 adults (38 with confirmed, symptomatic, mild to moderate COVID-19 and 21 asymptomatic, uninfected controls). In those with COVID-19, we measured SARS-CoV-2 viral load using quantitative reverse transcription PCR. We then examined the association of SARS-CoV-2 infection status and its viral load with the ⍺-diversity, β-diversity, and abundance of bacterial taxa of the URT microbiome. Our main models were all adjusted for age and sex.ResultsThe observed species index was significantly higher in SARS-CoV-2–infected than in –uninfected adults (β linear regression coefficient = 7.53; 95% CI, 0.17-14.89; P = .045). In differential abundance testing, 9 amplicon sequence variants were significantly different in both of our comparisons, with Peptoniphilus lacrimalis, Campylobacter hominis, Prevotella 9 copri, and an Anaerococcus unclassified amplicon sequence variant being more abundant in those with SARS-CoV-2 infection and in those with high viral load during COVID-19, whereas Corynebacterium unclassified, Staphylococcus haemolyticus, Prevotella disiens, and 2 Corynebacterium_1 unclassified amplicon sequence variants were more abundant in those without SARS-CoV-2 infection and in those with low viral load during COVID-19.ConclusionsOur findings suggest complex associations between SARS-CoV-2 and the URT microbiome in adults. Future studies are needed to examine how these viral-bacterial interactions can impact the clinical progression, severity, and recovery of COVID-19.

Regulation divergences of Lactobacillus fermentum PCC and Lactobacillus paracasei 431 on penicillin-induced upper respiratory tract microbial dysbiosis in BALB/c mice.

Antibiotic-induced host health imbalance during upper respiratory tract infection (URTI) treatment is an emerging issue. Studies have confirmed that Lactobacillus casei 431 and Lactobacillus fermentum PCC alleviate gut microbiome dysbiosis and improve immune response. However, their effect on the upper respiratory tract (URT) microbial structure and the correlation between the URT microbiota and immunological indicators remain unclear. To evaluate the effects of Lactobacillus strains on restoring penicillin-induced imbalance in the URT microbiome and on immune response, Lactobacillus fermentum PCC and Lactobacillus casei 431 were individually administered to penicillin-pretreated mice, and their effects were assessed. The results revealed that L. casei 431 and L. fermentum PCC could regulate the systemic immune response imbalance, but the regulation direction of L. fermentum PCC was closer to that of the control group. Moreover, the Lactobacillus strains could restore penicillin-induced URT dysbacteriosis in the microbial community structure, but no significant change in alpha diversity was observed. The key bacterial taxa modulated by L. casei 431 were Faecalibaculum, Lactococcus, and Ralstonia. L. fermentum PCC enhanced biofilms and facultatively anaerobic bacteria. Different regulation pathways were observed in the two strains, and RDA revealed that both L. casei 431 and L. fermentum PCC groups were correlated with IL-17 and IL-1α, while the L. casei 431 group was also correlated with IL-6. In conclusion, L. casei 431 and L. fermentum PCC could beneficially and differentially ameliorate penicillin-induced imbalance in the URT microbial composition structure and functional metabolic pathways and modulate immune response, reflecting strain-specific regulation.

Upper Respiratory Tract Microbiome and Otitis Media Intertalk: Lessons from the Literature.

Otitis media (OM) is one of the most common diseases occurring during childhood. Microbiological investigations concerning this topic have been primarily focused on the four classical otopathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes) mainly because most of the studies have been conducted with culture-dependent methods. In recent years, the introduction of culture-independent techniques has allowed high-throughput investigation of entire bacterial communities, leading to a better comprehension of the role of resident flora in health and disease. The upper respiratory tract (URT) is a region of major interest in otitis media pathogenesis, as it could serve as a source of pathogens for the middle ear (ME). Studies conducted with culture-independent methods in the URT and ME have provided novel insights on the pathogenesis of middle ear diseases through the identification of both possible new causative agents and of potential protective bacteria, showing that imbalances in bacterial communities could influence the natural history of otitis media in children. The aim of this review is to examine available evidence in microbiome research and otitis media in the pediatric age, with a focus on its different phenotypes: acute otitis media, otitis media with effusion and chronic suppurative otitis media.

Oropharyngeal microbiome of a college population following a meningococcal disease outbreak

Asymptomatic oropharyngeal carriage of Neisseria meningitidis peaks in adolescence and young adulthood. Following a meningococcal disease outbreak at a U.S. college, we profiled the oropharyngeal microbiomes of 158 students to identify associations between bacterial community composition and meningococcal carriage or risk factors for carriage, including male gender, smoking, and frequent social mixing. Metagenomic shotgun sequencing identified 268 bacterial taxa at the genus or species level, with Streptococcus, Veillonella, and Rothia species being most abundant. Microbiome composition showed weak associations with meningococcal carriage and risk factors for carriage. N. meningitidis abundance was positively correlated with that of Fusobacterium nucleatum, consistent with hypothesized propionic acid cross-feeding. Additional species had positive abundance correlations with N. meningitidis, including Aggregatibacter aphrophilus, Campylobacter rectus, Catonella morbi, Haemophilus haemolyticus, and Parvimonas micra. N. meningitidis abundance was negatively correlated with unidentified Veillonella species. Several of these species are commonly found in dental plaque, while N. meningitidis is primarily found in the pharynx, suggesting that ecological interactions extend throughout the oral cavity. Although risk factors for meningococcal carriage do not strongly impact most bacterial species in the oropharynx, variation in the upper respiratory tract microbiome may create conditions that are more or less favorable for N. meningitidis carriage.

Viral Bacterial Interactions in Children: Impact on Clinical Outcomes

Respiratory viral infections are associated with significant morbidity and mortality in children < 5 years of age worldwide. Among all respiratory viruses, respiratory syncytial virus (RSV) is the world's leading cause of bronchiolitis and pneumonia in young children. There are known populations at risk for severe disease but the majority of children who require hospitalization for RSV infection are previously healthy. Viral and host factors have been associated with the pathogenesis of RSV disease; however, the mechanisms that explain the wide variability in the clinical presentation are not completely understood. Recent studies suggest that the complex interaction between the respiratory microbiome, the host's immune response and the virus may have an impact on the pathogenesis and severity of RSV infection. In this review, we summarize the current evidence regarding the epidemiologic link, the mechanisms of viral-bacterial interactions, and the associations between the upper respiratory tract microbiome and RSV disease severity.