The gut-airway microbiome axis in health and respiratory diseases.

Communication between the gut and remote organs, such as the brain or the cardiovascular system, has been well established and recent studies provide evidence for a potential bidirectional gut-airway axis. Observations from animal and human studies indicate that respiratory insults influence the activity of the gut microbiome and that microbial ligands and metabolic products generated by the gut microbiome shape respiratory immunity. Information exchange between these two large mucosal surface areas regulates microorganism-immune interactions, with significant implications for the clinical and treatment outcomes of a range of respiratory conditions, including asthma, chronic obstructive pulmonary disease and lung cancer. In this Review, we summarize the most recent data in this field, offering insights into mechanisms of gut-airway crosstalk across spatial and temporal gradients and their relevance for respiratory health.

Exploring the role of the ocular surface in the lung-eye axis: Insights into respiratory disease pathogenesis.

Chronic respiratory diseases (CRDs) represent a significant proportion of global health burden, with a wide spectrum of varying, heterogenic conditions largely affecting the pulmonary system. Recent advances in immunology and respiratory biology have highlighted the systemic impact of these diseases, notably through the elucidation of the lung-eye axis. The current review focusses on understanding the pivotal role of the lung-eye axis in the pathogenesis and progression of chronic respiratory infections and diseases. Existing literature published on the immunological crosstalk between the eye and the lung has been reviewed. The various roles of the ocular microbiome in lung health are also explored, examining the eye as a gateway for respiratory virus transmission, and assessing the impact of environmental irritants on both ocular and respiratory systems. This novel concept emphasizes a bidirectional relationship between respiratory and ocular health, suggesting that respiratory diseases may influence ocular conditions and vice versa, whereby this conception provides a comprehensive framework for understanding the intricate axis connecting both respiratory and ocular health. These aspects underscore the need for an integrative approach in the management of chronic respiratory diseases. Future research should further elucidate the in-depth molecular mechanisms affecting this axis which would pave the path for novel diagnostics and effective therapeutic strategies.

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

BACKGROUND: The 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. RESULTS: In 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. CONCLUSIONS: We 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.

Human nasal microbiota shifts in healthy and chronic respiratory disease conditions.

BACKGROUND: An increasing number of studies investigate various human microbiotas and their roles in the development of diseases, maintenance of health states, and balanced signaling towards the brain. Current data demonstrate that the nasal microbiota contains a unique and highly variable array of commensal bacteria and opportunistic pathogens. However, we need to understand how to harness current knowledge, enrich nasal microbiota with beneficial microorganisms, and prevent pathogenic developments. RESULTS: In this study, we have obtained nasal, nasopharyngeal, and bronchoalveolar lavage fluid samples from healthy volunteers and patients suffering from chronic respiratory tract diseases for full-length 16 S rRNA sequencing analysis using Oxford Nanopore Technologies. Demographic and clinical data were collected simultaneously. The microbiome analysis of 97 people from Lithuania suffering from chronic inflammatory respiratory tract disease and healthy volunteers revealed that the human nasal microbiome represents the microbiome of the upper airways well. CONCLUSIONS: The nasal microbiota of patients was enriched with opportunistic pathogens, which could be used as indicators of respiratory tract conditions. In addition, we observed that a healthy human nasal microbiome contained several plant- and bee-associated species, suggesting the possibility of enriching human nasal microbiota via such exposures when needed. These candidate probiotics should be investigated for their modulating effects on airway and lung epithelia, immunogenic properties, neurotransmitter content, and roles in maintaining respiratory health and nose-brain interrelationships.

Association of clinical respiratory disease signs and lower respiratory tract bacterial pathogens with systemic inflammatory response in preweaning dairy calves.

This study investigated the potential associations between 3 acute phase proteins (APP)-haptoglobin, serum amyloid A-and fibrinogen, clinical signs of respiratory disease, and the presence of bacterial pathogens in the lower respiratory tract (LRT) of preweaning dairy calves. This cross-sectional study included 150 preweaning calves (2-86 d old) from 15 large dairy herds in Estonia. Tracheobronchial lavage, blood, and fecal samples were collected from 5 calves showing clinical signs indicative of LRT disease, and samples from 5 calves without clinical signs of LRT disease per herd. All samples collected from these calves were analyzed for concentrations of systemic APP, LRT bacteria, and intestinal pathogens. Heifer blood and bulk tank milk samples were collected for the detection of disease-specific antibodies against bovine herpesvirus 1, bovine viral diarrhea virus, bovine respiratory syncytial virus, and Mycoplasma bovis. Mixed-effects linear regression models were used to analyze the associations of clinical respiratory disease signs and LRT bacteria with APP. Increased plasma fibrinogen concentrations in calves were associated with higher rectal temperature (>39.5°C), increased respiratory rate (>50 breaths/min), and coughing. Increased serum amyloid A concentrations were associated with higher rectal temperature (>39.5°C) and respiratory rate between 40 and 50 breaths/min. Calves with the presence of fecal Cryptosporidium spp. and rectal temperature of 39°C and above had increased serum haptoglobin concentrations. Increased fibrinogen concentrations were associated with the presence of Pasteurella multocida in the calf LRT, whereas increased concentrations of fibrinogen and serum amyloid A were associated with the presence of Trueperella pyogenes. In conclusion, APP showed variable associations with clinical signs of respiratory disease and LRT bacteria. Plasma fibrinogen concentration could be used as a complementary calf-side test to assess systemic inflammation caused by LRT bacteria such as Pasteurella multocida and Trueperella pyogenes in preweaning dairy calves.

Epidemiology and pathogenicity of M. equirhinis in equine respiratory disorders.

Mycoplasmas are pathogens involved in respiratory disorders of various animal hosts. In horses, Mycoplasma (M.) equirhinis is the species most frequently detected in clinical respiratory specimens, with a prevalence of 12-16%, but its clinical implication in equine respiratory disorders remains unclear. Here we screened 1948 clinical specimens for the presence of M. equirhinis. The samples were both tracheal washes (TW) and bronchoalveolar lavages (BAL) collected by veterinarians in France in day-to-day work between 2020 and 2022. The samples were associated with a standardized form that served to collect key general and clinical information, such as horse age, breed, and living environment. M. equirhinis was detected using a combination of culture and post-enrichment PCR. Other diagnostic data included virology and bacteriology as well as neutrophil counts, when available. Prevalence of M. equirhinis was examined as a function of a clinical score based on four significant clinical signs (nasal discharge, cough, dyspnoea, and hyperthermia). Multivariate logistic regression analysis was run to identify risk factors for the presence of M. equirhinis, and comparative prevalence analysis was used to test for association with other bacteria and viruses. TW and BAL were analysed independently, as we found that TW samples were associated with a higher prevalence of M. equirhinis. As prevalence remained steady whatever the clinical score, M. equirhinis cannot be considered a primary pathogen. M. equirhinis was more frequently isolated in thoroughbreds and trotters and in horses living exclusively stabled compared to other horses or other living environments. M. equirhinis was never detected in BAL specimens with a 'normal' neutrophil count, i.e. 5%, suggesting it could be associated with an inflammatory response, similar to that observed in equine asthma. Prevalence of M. equirhinis was shown to increase in the presence of other bacteria such as Streptococcus equi subsp. zooepidemicus (S. zoo) or viruses, and S. zoo load was higher in M. equirhinis-positive samples, suggesting a potential increase of clinical signs in the event of co-infection.

Prevalence of respiratory bacterial pathogens and associated management factors in dairy calves in Taiwan.

This study aimed to investigate the prevalence at both farm-level and calf-level and to identify the risk factors of respiratory bacterial pathogens in dairy calves in Taiwan. The status of bovine respiratory disease (BRD) was evaluated by using the Wisconsin scoring system from a total of 400 pre-weaned calves from 32 different farms in Taiwan, then the nasopharyngeal swabs were collected. The prevalence of respiratory pathogens was 84.37% at farm-level and 45.50% at calf-level, and Pasteurella multocida (P. multocida) was the most prevalent pathogen. The presence of Mycoplasma bovis (M. bovis), P. multocida, Mannheimia haemolytica (M. haemolytica) and Histophilus somni (H. somni) were all higher in BRD positive calves than BRD negative calves, but only in H. somni was significant (P<0.001). Then nine farm management risk factors were analyzed by using multivariate logistic regression models to determine the risk factors of respiratory bacterial pathogens (farm and calf-level). In the result at farm-level, only unheated colostrum was significantly associated with pathogen positive farms (Odds Ratio (OR)=11.43). At calf-level, the predominant risk factor for each pathogen, M. bovis, P. multocida, M. haemolytica and H. somni, was late first colostrum feeding (OR=272.82), unheated colostrum (OR=3.41), waste milk feeding (OR=6.59) and high pneumonia treatment cost (OR=2.52), respectively. For effective preventive measures, farmer education on milk and colostrum feeding are urgently warranted.

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.

Treatable Traits in Chronic Respiratory Disease: A Comprehensive Review.

Chronic respiratory diseases are major contributors to the global burden of disease. While understanding of these diseases has improved, treatment guidelines have continued to rely on severity and exacerbation-based approaches. A new personalised approach, termed the "treatable traits" approach, has been suggested to address the limitations of the existing treatment strategies. We aim to systematically review the current evidence regarding treatable traits in chronic respiratory diseases and to identify gaps in the current literature. We searched the PubMed and Embase databases and included studies on treatable traits and chronic respiratory diseases. We then extracted information on prevalence, prognostic implications, treatment options and benefits from these studies. A total of 58 papers was included for review. The traits identified were grouped into five broad themes: physiological, biochemical, psychosocial, microbiological, and comorbidity traits. Studies have shown advantages of the treatable traits paradigm in the clinical setting. However, few randomised controlled trials have been conducted. Findings from our review suggest that multidisciplinary management with therapies targeted at treatable traits has the potential to be efficacious when added to the best practices currently implemented. This paradigm has the potential to improve the holistic care of chronic respiratory diseases.

Comparison of 11 respiratory pathogens among hospitalized children before and during the COVID-19 epidemic in Shenzhen, China.

BACKGROUND: The effect of SARS-CoV-2 on existing respiratory pathogens in circulation remains uncertain. This study aimed to assess the impact of SARS-CoV-2 on the prevalence of respiratory pathogens among hospitalized children. METHODS: This study enrolled hospitalized children with acute respiratory infections in Shenzhen Children's Hospital from September to December 2019 (before the COVID-19 epidemic) and those from September to December 2020 (during the COVID-19 epidemic). Nasopharyngeal swabs were collected, and respiratory pathogens were detected using multiplex PCR. The absolute case number and detection rates of 11 pathogens were collected and analyzed. RESULTS: A total of 5696 children with respiratory tract infection received multiplex PCR examination for respiratory pathogens: 2298 from September to December 2019 and 3398 from September to December 2020. At least one pathogen was detected in 1850 (80.5%) patients in 2019, and in 2380 (70.0%) patients in 2020; the detection rate in 2020 was significantly lower than that in 2019.The Influenza A (InfA) detection rate was 5.6% in 2019, but 0% in 2020. The detection rates of Mycoplasma pneumoniae, Human adenovirus, and Human rhinovirus also decreased from 20% (460), 8.9% (206), and 41.8% (961) in 2019 to 1.0% (37), 2.1% (77), and 25.6% (873) in 2020, respectively. In contrast, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased from 6.6% (153), 9.9% (229), and 0.5% (12) in 2019 to 25.6% (873), 15.5% (530), and 7.2% (247) in 2020, respectively (p < 0.0001). CONCLUSIONS: Successful containment of seasonal influenza as a result of COVID-19 control measures will ensure we are better equipped to deal with future outbreaks of both influenza and COVID-19.Caused by virus competition, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased in Shenzhen,that reminds us we need to take further monitoring and preventive measures in the next epidemic season.

Occurrence of major and minor pathogens in calves diagnosed with bovine respiratory disease.

Bovine respiratory disease (BRD) is caused by a mixture of viruses and opportunistic bacteria belonging to Pasteurellaceae and Mycoplasma bovis. However, these organisms are also commonly isolated from healthy calves. This study aimed to determine whether the organisms are present in higher numbers in calves sick with acute BRD than in clinically healthy calves, and further to genetically characterize bacteria of the family Pasteurellaceae to understand whether particular types are associated with disease. Forty-six clinically healthy and 46 calves with BRD were sampled by broncheoalveolar lavage (BAL) method in 11 herds geographically spread over Denmark to determine presence and quantity of microorganisms by culture and quantitative real time qPCR. Isolates of Pasteurellaceae were tested for antibiotic resistance and were whole genome sequenced to determine genotypes. Histophilus somni was in particular positively associated with BRD, suggesting particular importance of this organism as likely aetiology of BRD. In addition, quantification of bacteria revealed that higher counts of H. somni as well as of M. haemolytica was also a good indicator of the disease. Pasteurellaceae isolates were susceptible to the commonly used antibiotics in treatment of BRD, and genotypes were shared between isolates from clinically healthy and sick calves.

Association of Diverse Staphylococcus aureus Populations with Pseudomonas aeruginosa Coinfection and Inflammation in Cystic Fibrosis Airway Infection.

Staphylococcus aureus is one of the most common pathogens isolated from the airways of cystic fibrosis (CF) patients and often persists for extended periods. There is limited knowledge about the diversity of S. aureus in CF. We hypothesized that increased diversity of S. aureus would impact CF lung disease. Therefore, we conducted a 1-year observational prospective study with 14 patients with long-term S. aureus infection. From every sputum, 40 S. aureus isolates were chosen and characterized in terms of phenotypic appearance (size, hemolysis, mucoidy, and pigmentation), important virulence traits such as nuclease activity, biofilm formation, and molecular typing by spa sequence typing. Data about coinfection with Pseudomonas aeruginosa and clinical parameters such as lung function, exacerbation, and inflammatory markers in blood (C-reactive protein [CRP], interleukin 6 [IL-6], and S100A8/9 [calprotectin]) were collected. From 58 visits of 14 patients, 2,319 S. aureus isolates were distinguished into 32 phenotypes (PTs) and 50 spa types. The Simpson diversity index (SDI) was used to calculate the phenotypic and genotypic diversity, revealing a high diversity of PTs ranging from 0.19 to 0.87 among patients, while the diversity of spa types of isolates was less pronounced. The SDI of PTs was positively associated with P. aeruginosa coinfection and inflammatory parameters, with IL-6 being the most sensitive parameter. Also, coinfection with P. aeruginosa was associated with mucoid S. aureus and S. aureus with high nuclease activity. Our analyses showed that in CF patients with long-term S. aureus airway infection, a highly diverse and dynamic S. aureus population was present and associated with P. aeruginosa coinfection and inflammation. IMPORTANCE Staphylococcus aureus can persist for extended periods in the airways of people with cystic fibrosis (CF) in spite of antibiotic therapy and high numbers of neutrophils, which fail to eradicate this pathogen. Therefore, S. aureus needs to adapt to this hostile niche. There is only limited knowledge about the diversity of S. aureus in respiratory specimens. We conducted a 1-year prospective study with 14 patients with long-term S. aureus infection and investigated 40 S. aureus isolates from every sputum in terms of phenotypic appearance, nuclease activity, biofilm formation, and molecular typing. Data about coinfection with Pseudomonas aeruginosa and clinical parameters such as lung function, exacerbation, and inflammatory markers in blood were collected. Thirty-two phenotypes (PTs) and 50 spa types were distinguished. Our analyses revealed that in CF patients with long-term S. aureus airway infection, a highly diverse and dynamic S. aureus population was associated with P. aeruginosa coinfection and inflammation.

Exposure to traffic-related air pollution and bacterial diversity in the lower respiratory tract of children.

BACKGROUND: Exposure to particulate matter has been shown to increase the adhesion of bacteria to human airway epithelial cells. However, the impact of traffic-related air pollution (TRAP) on the respiratory microbiome is unknown. METHODS: Forty children were recruited through the Cincinnati Childhood Allergy and Air Pollution Study, a longitudinal cohort followed from birth through early adolescence. Saliva and induced sputum were collected at age 14 years. Exposure to TRAP was characterized from birth through the time of sample collection using a previously validated land-use regression model. Sequencing of the bacterial 16S and ITS fungal rRNA genes was performed on sputum and saliva samples. The relative abundance of bacterial taxa and diversity indices were compared in children with exposure to high and low TRAP. We also used multiple linear regression to assess the effect of TRAP exposure, gender, asthma status, and socioeconomic status on the alpha diversity of bacteria in sputum. RESULTS: We observed higher bacterial alpha diversity indices in sputum than in saliva. The diversity indices for bacteria were greater in the high TRAP exposure group than the low exposure group. These differences remained after adjusting for asthma status, gender, and mother's education. No differences were observed in the fungal microbiome between TRAP exposure groups. CONCLUSION: Our findings indicate that exposure to TRAP in early childhood and adolescence may be associated with greater bacterial diversity in the lower respiratory tract. Asthma status does not appear to confound the observed differences in diversity. These results demonstrate that there may be a TRAP-exposure related change in the lower respiratory microbiota that is independent of asthma status.

A human respiratory tract-associated bacterium with an extremely small genome.

Recent advances in culture-independent microbiological analyses have greatly expanded our understanding of the diversity of unculturable microbes. However, human pathogenic bacteria differing significantly from known taxa have rarely been discovered. Here, we present the complete genome sequence of an uncultured bacterium detected in human respiratory tract named IOLA, which was determined by developing a protocol to selectively amplify extremely AT-rich genomes. The IOLA genome is 303,838 bp in size with a 20.7% GC content, making it the smallest and most AT-rich genome among known human-associated bacterial genomes to our best knowledge and comparable to those of insect endosymbionts. While IOLA belongs to order Rickettsiales (mostly intracellular parasites), the gene content suggests an epicellular parasitic lifestyle. Surveillance of clinical samples provides evidence that IOLA can be predominantly detected in patients with respiratory bacterial infections and can persist for at least 15 months in the respiratory tract, suggesting that IOLA is a human respiratory tract-associated bacterium.

Staphylococcus aureus Arsenal To Conquer the Lower Respiratory Tract.

Staphylococcus aureus is both a commensal and a pathogenic bacterium for humans. Its ability to induce severe infections is based on a wide range of virulence factors. S. aureus community-acquired pneumonia (SA-CAP) is rare and severe, and the contribution of certain virulence factors in this disease has been recognized over the past 2 decades. First, the factors involved in metabolism adaptation are crucial for S. aureus survival in the lower respiratory tract, and toxins and enzymes are required for it to cross the pulmonary epithelial barrier. S. aureus subsequently faces host defense mechanisms, including the epithelial barrier, but most importantly the immune system. Here, again, S. aureus uses myriad virulence factors to successfully escape from the host's defenses and takes advantage of them. The impact of S. aureus virulence, combined with the collateral damage caused by an overwhelming immune response, leads to severe tissue damage and adverse clinical outcomes. In this review, we summarize step by step all of the S. aureus factors implicated in CAP and described to date, and we provide an outlook for future research.

Respiratory Disorders in Chelonians.

"Respiratory tract disease in chelonians can be difficult to treat and as such proper diagnostics are paramount. Infectious agents that can affect the respiratory tract of chelonians include viral, bacterial, fungal, and parasitic organisms. Noninfectious diseases can also develop. Because chelonians lack a proper diaphragm, changes in size of celomic organs can cause compression of the respiratory system. These conditions result in clinical signs that could be attributed to the respiratory system, such as open-mouth breathing. In this article, anatomy, physiology, and current standards for diagnostics and treatments of major diseases of the respiratory tract in chelonians are discussed."

Diagnostics of Infectious Respiratory Pathogens in Reptiles.

Methods for the detection of pathogens associated with respiratory disease in reptiles, including viruses, bacteria, fungi, and parasites, are constantly evolving as is the understanding of the specific roles played by various pathogens in disease processes. Some are known to be primary pathogens with high prevalence in captive reptiles, for example, serpentoviruses in pythons or mycoplasma in tortoises. Others are very commonly found in reptiles with respiratory disease but are most often considered secondary, for example, gram-negative bacteria. Detection methods as well as specific pathogens associated with upper- and lower-respiratory disease are discussed.

Respiratory Diseases in Guinea Pigs, Chinchillas and Degus.

The diagnosis and treatment of respiratory disease in pet guinea pigs, chinchillas, and degus still face profoundly serious challenges owing to their relatively small size, conspicuous clinical signs, difficulty for sampling, and insufficient scientific evidence to correlate signs and particular pathologies. This article is intended to summarize the available information on the relevant anatomy, physiology, and respiratory pathology in these species.