Bovine respiratory microbiota of feedlot cattle and its association with disease

Bovine respiratory disease (BRD), as one of the most common and costly diseases in the beef cattle industry, has significant adverse impacts on global food security and the economic stability of the industry. The bovine respiratory microbiome is strongly associated with health and disease and may provide insights for alternative therapy when treating BRD. The niche-specific microbiome communities that colonize the inter-surface of the upper and the lower respiratory tract consist of a dynamic and complex ecological system. The correlation between the disequilibrium in the respiratory ecosystem and BRD has become a hot research topic. Hence, we summarize the pathogenesis and clinical signs of BRD and the alteration of the respiratory microbiota. Current research techniques and the biogeography of the microbiome in the healthy respiratory tract are also reviewed. We discuss the process of resident microbiota and pathogen colonization as well as the host immune response. Although associations between the microbiota and BRD have been revealed to some extent, interpreting the development of BRD in relation to respiratory microbial dysbiosis will likely be the direction for upcoming studies, which will allow us to better understand the importance of the airway microbiome and its contributions to animal health and performance.

A Single Intranasal Dose of Bacterial Therapeutics to Calves Confers Longitudinal Modulation of the Nasopharyngeal Microbiota

To address the emergence of antimicrobial-resistant pathogens in livestock, microbiome-based strategies are increasingly being sought to reduce antimicrobial use. Here, we describe the intranasal application of bacterial therapeutics (BTs) for mitigating bovine respiratory disease (BRD) and used structural equation modeling to investigate the causal networks after BT application. Beef cattle received i) an intranasal cocktail of previously characterized BT strains, ii) an injection of metaphylactic antibiotic tulathromycin or iii) intranasal saline. Despite being transient colonizers, inoculated BT strains induced longitudinal modulation of the nasopharyngeal bacterial microbiota while showing no adverse effect on animal health. The BT-mediated changes in bacteria included reduced diversity and richness and strengthened cooperative and competitive interactions. In contrast, tulathromycin increased bacterial diversity and antibiotic resistance, and disrupted bacterial interactions. Overall, a single intranasal dose of BTs can modulate the bovine respiratory microbiota, highlighting that microbiome-based strategies have the potential in being utilized to mitigate BRD in feedlot cattle.

Bacterial Signatures of Paediatric Respiratory Disease: An Individual Participant Data Meta-Analysis

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies.Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (<18 years) microbiota in acute and chronic respiratory conditions, with >10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses.Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus. Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively.Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis.

JMM Profile: Streptococcus pneumoniae: sugar-coated captain of the men of death

Streptococcus pneumoniae is a highly adept human pathogen. A frequent asymptomatic member of the respiratory microbiota, the pneumococcus has a remarkable capacity to cause mucosal (pneumonia and otitis media) and invasive diseases (bacteremia, meningitis). In addition, the organism utilizes a vast battery of virulence factors for tissue and immune evasion. Though recognized as a significant cause of pneumonia for over a century, efforts to develop more effective vaccines remain ongoing. The pathogen’s inherent capacity to exchange genetic material is critical to the pneumococcus’ success. This feature historically facilitated essential discoveries in genetics and is vital for disseminating antibiotic resistance and vaccine evasion.

Metataxonomic investigation of the microbial community in the trachea and oropharynx of healthy controls and diabetic patients using endotracheal tubes

Background Although the study of respiratory microbiota has been an active field of research, obtaining the appropriate respiratory samples for healthy controls remains to be a challenge. As such, this study aims to evaluate the use of endotracheal tube washing as a viable control for sputum samples. Methods A total of 14 subjects, including 8 healthy respiratory controls and 6 diabetic patients without any respiratory disease, were enrolled in this study, during which the endotracheal tubes used in their scheduled routine surgery were collected. Pre-operative oral gargles were also collected from non-diabetic subjects. Results 16S amplicon sequencing revealed similar taxa composition in endotracheal tube washings and oral gargles in the healthy control subjects, although the relative abundance of 11 genus level operational taxonomic units was significantly different between the two sample sources. The diabetic subjects showed relatively lower diversity than those of non-diabetic subjects. The proportion range of the most abundant taxa detected in each endotracheal tube washings were 10.1–33.2%. Conclusion Endotracheal tube washing fluid may provide healthy control samples for upper respiratory investigations without incurring any additional risk to the subject.

Dysbiosis and structural disruption of the respiratory microbiota in COVID-19 patients with severe and fatal outcomes

The COVID-19 outbreak has caused over three million deaths worldwide. Understanding the pathology of the disease and the factors that drive severe and fatal clinical outcomes is of special relevance. Studying the role of the respiratory microbiota in COVID-19 is especially important as the respiratory microbiota is known to interact with the host immune system, contributing to clinical outcomes in chronic and acute respiratory diseases. Here, we characterized the microbiota in the respiratory tract of patients with mild, severe, or fatal COVID-19, and compared it to healthy controls and patients with non-COVID-19-pneumonia. We comparatively studied the microbial composition, diversity, and microbiota structure between the study groups and correlated the results with clinical data. We found differences in the microbial composition for COVID-19 patients, healthy controls, and non-COVID-19 pneumonia controls. In particular, we detected a high number of potentially opportunistic pathogens associated with severe and fatal levels of the disease. Also, we found higher levels of dysbiosis in the respiratory microbiota of patients with COVID-19 compared to the healthy controls. In addition, we detected differences in diversity structure between the microbiota of patients with mild, severe, and fatal COVID-19, as well as the presence of specific bacteria that correlated with clinical variables associated with increased risk of mortality. In summary, our results demonstrate that increased dysbiosis of the respiratory tract microbiota in patients with COVID-19 along with a continuous loss of microbial complexity structure found in mild to fatal COVID-19 cases may potentially alter clinical outcomes in patients. Taken together, our findings identify the respiratory microbiota as a factor potentially associated with the severity of COVID-19.

Analysis of the upper respiratory tract microbiota in mild and severe COVID-19 patients

The microbiota of the respiratory tract remains a relatively poorly studied subject. At the same time, like the intestinal microbiota, it is involved in modulating the immune response to infectious agents in the host organism. A causal relationship between the composition of the respiratory microbiota and the likelihood of development and the severity of COVID-19 may be hypothesized. We analyze biomaterial from nasopharyngeal smears from 336 patients with a confirmed diagnosis of COVID-19, selected during the first and second waves of the epidemic in Russia. Sequences from a similar study conducted in Spain were also included in the analysis. We investigated associations between disease severity and microbiota at the level of microbial community (community types) and individual microbes (differentially represented species). To search for associations, we performed multivariate analysis, taking into account comorbidities, type of community and lineage of the virus. We found that two out of six community types are associated with a more severe course of the disease, and one of the community types is characterized by high stability (very similar microbiota profiles in different patients) and low level of lung damage. Differential abundance analysis with respect to comorbidities and community type suggested association of Rothia and Streptococcus genera representatives with more severe lung damage, and Leptotrichia, unclassified Lachnospiraceae and Prevotella with milder forms of the disease.

Respiratory Microbiota Profiles Associated With the Progression From Airway Inflammation to Remodeling in Mice With OVA-Induced Asthma

BackgroundThe dysbiosis of respiratory microbiota plays an important role in asthma development. However, there is limited information on the changes in the respiratory microbiota and how these affect the host during the progression from acute allergic inflammation to airway remodeling in asthma.ObjectiveAn ovalbumin (OVA)-induced mouse model of chronic asthma was established to explore the dynamic changes in the respiratory microbiota in the different stages of asthma and their association with chronic asthma progression.MethodsHematoxylin and eosin (H&E), periodic acid-schiff (PAS), and Masson staining were performed to observe the pathological changes in the lung tissues of asthmatic mice. The respiratory microbiota was analyzed using 16S rRNA gene sequencing followed by taxonomical analysis. The cytokine levels in bronchoalveolar lavage fluid (BALF) specimens were measured. The matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF-A) expression levels in lung tissues were measured to detect airway remodeling in OVA-challenged mice.ResultsAcute allergic inflammation was the major manifestation at weeks 1 and 2 after OVA atomization stimulation, whereas at week 6 after the stimulation, airway remodeling was the most prominent observation. In the acute inflammatory stage, Pseudomonas was more abundant, whereas Staphylococcus and Cupriavidus were more abundant at the airway remodeling stage. The microbial compositions of the upper and lower respiratory tracts were similar. However, the dominant respiratory microbiota in the acute inflammatory and airway remodeling phases were different. Metagenomic functional prediction showed that the pathways significantly upregulated in the acute inflammatory phase and airway remodeling phase were different. The cytokine levels in BALF and the expression patterns of proteins associated with airway remodeling in the lung tissue were consistent with the metagenomic function results.ConclusionThe dynamic changes in respiratory microbiota are closely associated with the progression of chronic asthma. Metagenomic functional prediction indicated the changes associated with acute allergic inflammation and airway remodeling.

Manipulation of the Upper Respiratory Microbiota to Reduce Incidence and Severity of Upper Respiratory Viral Infections: A Literature Review

There is a high incidence of upper respiratory viral infections in the human population, with infection severity being unique to each individual. Upper respiratory viruses have been associated previously with secondary bacterial infection, however, several cross-sectional studies analyzed in the literature indicate that an inverse relationship can also occur. Pathobiont abundance and/or bacterial dysbiosis can impair epithelial integrity and predispose an individual to viral infection. In this review we describe common commensal microorganisms that have the capacity to reduce the abundance of pathobionts and maintain bacterial symbiosis in the upper respiratory tract and discuss the potential and limitations of localized probiotic formulations of commensal bacteria to reduce the incidence and severity of viral infections.