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.

Saccharomyces boulardii alleviates allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.

BACKGROUND: Allergic asthma is a heterogeneous disease and new strategies are needed to prevent or treat this disease. Studies have shown that probiotic interventions are effective in preventing asthma. Here, we investigated the impact of Saccharomyces boulardii (S. boulardii) on ovalbumin (OVA)-induced allergic asthma in mice, as well as the underlying mechanisms. METHODS: First, we constructed a mouse asthma model using OVA and given S. boulardii intervention. Next, we measured N6-methyladenosine (m6A) levels in lung injury tissues. 16 s rRNA was employed to identify different gut microbiota in fecal samples. The analysis of differential metabolites in feces was performed by non-targeted metabolomics. Pearson correlation coefficient was utilized to analyze correlation between gut microbiota, metabolites and methyltransferase-like 3 (METTL3). Finally, we collected mouse feces treated by OVA and S. boulardii intervention for fecal microbiota transplantation (FMT) and interfered with METTL3. RESULTS: S. boulardii improved inflammation and oxidative stress and alleviated lung damage in asthmatic mice. In addition, S. boulardii regulated m6A modification levels in asthmatic mice. 16 s rRNA sequencing showed that S. boulardii remodeled gut microbiota homeostasis in asthmatic mice. Non-targeted metabolomics analysis showed S. boulardii restored metabolic homeostasis in asthmatic mice. There was a correlation between gut microbiota, differential metabolites, and METTL3 analyzed by Pearson correlation. Additionally, through FMT and interference of METTL3, we found that gut microbiota mediated the up-regulation of METTL3 by S. boulardii improved inflammation and oxidative stress in asthmatic mice, and alleviated lung injury. CONCLUSIONS: S. boulardii alleviated allergic asthma by restoring gut microbiota and metabolic homeostasis via up-regulation of METTL3 in an m6A-dependent manner.

Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation.

BACKGROUND: Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma. METHODS: Whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs). RESULTS: α-diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α-diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack-years of smoking. α- and ß-diversities were stable at one year. CONCLUSIONS: Haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL-13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation.

Current situation of fungal diseases in Eritrea.

The epidemiology of fungal infections in Eritrea is unknown. Most cases are under-reported due to a lack of diagnostics. This study estimates the burden of serious fungal infections and highlights treatment and diagnostic gaps in the country. All publications related to fungal infections were identified by searches using PubMed/Medline and Google Scholar. Where no data were available, data from neighbouring countries, then sub-Saharan African countries, then other parts of the world were considered for deriving estimates. The Eritrea population was 3,546,427 in 2020. In 2020, HIV/AIDS patients numbered 1400 and TB incidence were 2875. The five-year adult prevalence of asthma (2016-2020) was 41,390, and the total prevalence estimate of chronic obstructive pulmonary disease (COPD) was 308,328. The annual incidence of cryptococcal meningitis and Pneumocystis jirovecii pneumonia in AIDS patients was estimated at 96 and 205 cases. Oesophageal candidiasis incidence is 715 HIV-infected patients. Chronic pulmonary aspergillosis prevalence, including post-tuberculosis cases, was estimated at 1399 (39/100,000). Fungal asthma has a prevalence of 1035 and 1366 in adults. The estimated prevalence of recurrent vulvovaginal candidiasis and tinea capitis is 59,391 and 342,585, respectively. There are no data on candidaemia, but it is estimated at 5/100,000 (177 cases annually). Invasive aspergillosis in leukaemia, lung cancer, COPD and HIV is estimated at 540 cases and fungal keratitis in 514 cases annually. Serious fungal infections are prevalent in Eritrea with approximately 408,164 people (11.5%) affected annually. Studies on fungal diseases to improve diagnosis and treatment are required with the implementation of a national surveillance program.

Therapeutic ketosis decreases methacholine hyperresponsiveness in mouse models of inherent obese asthma.

Obese asthmatics tend to have severe, poorly controlled disease and exhibit methacholine hyperresponsiveness manifesting in proximal airway narrowing and distal lung tissue collapsibility. Substantial weight loss in obese asthmatics or in mouse models of the condition decreases methacholine hyperresponsiveness. Ketone bodies are rapidly elevated during weight loss, coinciding with or preceding relief from asthma-related comorbidities. As ketone bodies may exert numerous potentially therapeutic effects, augmenting their systemic concentrations is being targeted for the treatment of several conditions. Circulating ketone body levels can be increased by feeding a ketogenic diet or by providing a ketone ester dietary supplement, which we hypothesized would exert protective effects in mouse models of inherent obese asthma. Weight loss induced by feeding a low-fat diet to mice previously fed a high-fat diet was preceded by increased urine and blood levels of the ketone body ß-hydroxybutyrate (BHB). Feeding a ketogenic diet for 3 wk to high-fat diet-fed obese mice or genetically obese db/db mice increased BHB concentrations and decreased methacholine hyperresponsiveness without substantially decreasing body weight. Acute ketone ester administration decreased methacholine responsiveness of normal mice, and dietary ketone ester supplementation of high-fat diet-fed mice decreased methacholine hyperresponsiveness. Ketone ester supplementation also transiently induced an "antiobesogenic" gut microbiome with a decreased Fermicutes/Bacteroidetes ratio. Dietary interventions to increase systemic BHB concentrations could provide symptom relief for obese asthmatics without the need for the substantial weight loss required of patients to elicit benefits to their asthma through bariatric surgery or other diet or lifestyle alterations.

mBodyMap: a curated database for microbes across human body and their associations with health and diseases.

mBodyMap is a curated database for microbes across the human body and their associations with health and diseases. Its primary aim is to promote the reusability of human-associated metagenomic data and assist with the identification of disease-associated microbes by consistently annotating the microbial contents of collected samples using state-of-the-art toolsets and manually curating the meta-data of corresponding human hosts. mBodyMap organizes collected samples based on their association with human diseases and body sites to enable cross-dataset integration and comparison. To help users find microbes of interest and visualize and compare their distributions and abundances/prevalence within different body sites and various diseases, the mBodyMap database is equipped with an intuitive interface and extensive graphical representations of the collected data. So far, it contains a total of 63 148 runs, including 14 401 metagenomes and 48 747 amplicons related to health and 56 human diseases, from within 22 human body sites across 136 projects. Also available in the database are pre-computed abundances and prevalence of 6247 species (belonging to 1645 genera) stratified by body sites and diseases. mBodyMap can be accessed at: https://mbodymap.microbiome.cloud.

Meta-analysis of sputum microbiome studies identifies airway disease-specific taxonomic and functional signatures.

Introduction. Studying taxonomic and functional signatures of respiratory microbiomes provide a better understanding of airway diseases.Gap Statement. Several human airway metagenomics studies have identified taxonomic and functional features restricted to a single disease condition and the findings are not comparable across airway diseases due to use of different samples, NGS platforms, and bioinformatics databases and tools.Aim. To study the microbial taxonomic and functional components of sputum microbiome across airway diseases and healthy smokers.Methodology. Here, 57 whole metagenome shotgun sequencing (WMSS) runs coming from the sputum of five airway diseases: asthma, bronchiectasis, chronic obstructive pulmonary diseases (COPD), cystic fibrosis (CF), tuberculosis (TB), and healthy smokers as the control were reanalysed using a common WMSS analysis pipeline.Results. Shannon's index (alpha diversity) of the healthy smoker group was the highest among all. The beta diversity showed that the sputum microbiome is distinct in major airway diseases such as asthma, COPD and cystic fibrosis. The microbial composition based on differential analysis showed that there are specific markers for each airway disease like Acinetobacter bereziniae as a marker for COPD and Achromobacter xylosoxidans as a marker of cystic fibrosis. Pathways and metabolites identified from the sputum microbiome of these five diseases and healthy smokers also show specific markers. 'ppGpp biosynthesis' and 'purine ribonucleosides degradation' pathways were identified as differential markers for bronchiectasis and COPD. In this meta-analysis, besides bacteria kingdom, Aspergillus fumigatus was detected in asthma and COPD, and Roseolovirus human betaherpesvirus 7 was detected in COPD. Our analysis showed that the majority of the gene families specific to the drug-resistant associated genes were detected from opportunistic pathogens across all the groups.Conclusion. In summary, the specific species in the sputum of airway diseases along with the microbial features like specific gene families, pathways, and metabolites were identified which can be explored for better diagnosis and therapy.

The Role of Respiratory Flora in the Pathogenesis of Chronic Respiratory Diseases.

Large quantities of bacteria, including Firmicutes, Actinobacteria, and Bacteroidetes, colonize the surface of the respiratory mucosa of healthy people. They interact and coexist with the local mucosal immune system of the human airway, maintaining the immune stability and balance of the respiratory system. While suffering from chronic respiratory diseases, the microbial population in the airway changes and the proportion of Proteobacteria is increased in patients with asthma. The abundance of the microbial population in patients with chronic obstructive pulmonary disease (COPD) is decreased, and conversely, the proportion of Firmicutes and Proteobacteria increased. The diversity of airway microorganisms in cystic fibrosis (CF) patients is decreased, while pathogenic bacteria and conditional pathogenic bacteria are proliferated in large numbers. The proportion of Firmicutes and Proteobacteria is increased in patients with upper airway cough syndrome (UACS), which replaces the dominance of Streptococcus and Neisseria in the pharynx of a normal population. Therefore, a clear understanding of the immune process of the airway flora and the immune dysfunction of the flora on the pathogenesis of chronic respiratory diseases can provide new ideas for the prevention and treatment of human respiratory diseases.

Microbiota: A Missing Link in The Pathogenesis of Chronic Lung Inflammatory Diseases.

Chronic respiratory diseases account for high morbidity and mortality, with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) being the most prevalent globally. Even though the diseases increase in prevalence, the exact underlying mechanisms have still not been fully understood. Despite their differences in nature, pathophysiologies, and clinical phenotypes, a growing body of evidence indicates that the presence of lung microbiota can shape the pathogenic processes underlying chronic inflammation, typically observed in the course of the diseases. Therefore, the characterization of the lung microbiota may shed new light on the pathogenesis of these diseases. Specifically, in chronic respiratory tract diseases, the human microbiota may contribute to the disease's development and severity. The present review explores the role of the microbiota in the area of chronic pulmonary diseases, especially COPD, asthma, and CF.

Household mold exposure interacts with inflammation-related genetic variants on childhood asthma: a case-control study.

BACKGROUND: A number of studies have examined the association between mold exposure and childhood asthma. However, the conclusions were inconsistent, which might be partly attributable to the lack of consideration of gene function, especially the key genes affecting the pathogenesis of childhood asthma. Research on the interactions between genes and mold exposure on childhood asthma is still very limited. We therefore examined whether there is an interaction between inflammation-related genes and mold exposure on childhood asthma. METHODS: A case-control study with 645 asthmatic children and 910 non-asthmatic children aged 3-12 years old was conducted. Eight single nucleotide polymorphisms (SNPs) in inflammation-related genes were genotyped using MassARRAY assay. Mold exposure was defined as self-reported visible mold on the walls. Associations between visible mold exposure, SNPs and childhood asthma were evaluated using logistic regression models. In addition, crossover analyses were used to estimate the gene-environment interactions on childhood asthma on an additive scale. RESULTS: After excluding children without information on visible mold exposure or SNPs, 608 asthmatic and 839 non-asthmatic children were included in the analyses. Visible mold exposure was reported in 151 asthmatic (24.8%) and 119 non-asthmatic children (14.2%) (aOR 2.19, 95% CI 1.62-2.97). The rs7216389 SNP in gasdermin B gene (GSDMB) increased the risk of childhood asthma with each C to T substitution in a dose-dependent pattern (additive model, aOR 1.32, 95% CI 1.11-1.57). Children carrying the rs7216389 T allele and exposed to visible mold dramatically increased the risk of childhood asthma (aOR 3.21; 95% CI 1.77-5.99). The attributable proportion due to the interaction (AP: 0.47, 95% CI 0.03-0.90) and the relative excess risk due to the interaction (RERI: 1.49, 95% CI 0-2.99) were statistically significant. CONCLUSIONS: In the present study, there was a significant additive interaction between visible mold exposure and rs7216389 SNP on childhood asthma. Future studies need to consider the gene-environment interactions when exploring the risk factors of childhood asthma.

Insights into gut microbiome and its functional pathways in asthma patients through high-throughput sequencing.

Aim: To describe gut microbiome and functional genes of asthma. Patients & methods: Fecal microbiome in controls, asthma patients with and without inhaled corticosteroid (ICS) treatment was determined. Results: Patients with ICS had lower abundance of Alloprevotella, unclassified_f_Lachnospiraceae and Lachnospiraceae_NC2004_group, higher abundance of Sutterella and Sphingomonas than patients without ICS. In all the asthma patients, there are microbial differences in aging distribution, different gender and different asthmatic phenotypes. Asthma patients without ICS treatment had more microbial genes related to geraniol degradation, ethylbenzene degradation and bladder cancer than controls; 15 pathways showed significant difference between asthma patients with and without ICS treatment. Conclusion: We found gut dysbiosis in asthma and different functional pathways associated with both asthma and ICS.

Merged Affinity Network Association Clustering: Joint multi-omic/clinical clustering to identify disease endotypes.

Although clinical and laboratory data have long been used to guide medical practice, this information is rarely integrated with multi-omic data to identify endotypes. We present Merged Affinity Network Association Clustering (MANAclust), a coding-free, automated pipeline enabling integration of categorical and numeric data spanning clinical and multi-omic profiles for unsupervised clustering to identify disease subsets. Using simulations and real-world data from The Cancer Genome Atlas, we demonstrate that MANAclust's feature selection algorithms are accurate and outperform competitors. We also apply MANAclust to a clinically and multi-omically phenotyped asthma cohort. MANAclust identifies clinically and molecularly distinct clusters, including heterogeneous groups of "healthy controls" and viral and allergy-driven subsets of asthmatic subjects. We also find that subjects with similar clinical presentations have disparate molecular profiles, highlighting the need for additional testing to uncover asthma endotypes. This work facilitates data-driven personalized medicine through integration of clinical parameters with multi-omics. MANAclust is freely available at https://bitbucket.org/scottyler892/manaclust/src/master/.

Lignosus rhinocerotis Cooke Ryvarden ameliorates airway inflammation, mucus hypersecretion and airway hyperresponsiveness in a murine model of asthma.

Lignosus rhinocerotis Cooke. (L. rhinocerotis) is a medicinal mushroom traditionally used in the treatment of asthma and several other diseases by the indigenous communities in Malaysia. In this study, the effects of L. rhinocerotis on allergic airway inflammation and hyperresponsiveness were investigated. L. rhinocerotis extract (LRE) was prepared by hot water extraction using soxhlet. Airway hyperresponsiveness (AHR) study was performed in house dust mite (HDM)-induced asthma in Balb/c mice while airway inflammation study was performed in ovalbumin (OVA)-induced asthma in Sprague-Dawley rats. Treatment with different doses of LRE (125, 250 and 500 mg/kg) significantly inhibited AHR in HDM-induced mice. Treatment with LRE also significantly decreased the elevated IgE in serum, Th2 cytokines in bronchoalveolar lavage fluid and ameliorated OVA-induced histological changes in rats by attenuating leukocyte infiltration, mucus hypersecretion and goblet cell hyperplasia in the lungs. LRE also significantly reduced the number of eosinophils and neutrophils in BALF. Interestingly, a significant reduction of the FOXP3+ regulatory T lymphocytes was observed following OVA induction, but the cells were significantly elevated with LRE treatment. Subsequent analyses on gene expression revealed regulation of several important genes i.e. IL17A, ADAM33, CCL5, IL4, CCR3, CCR8, PMCH, CCL22, IFNG, CCL17, CCR4, PRG2, FCER1A, CLCA1, CHIA and Cma1 which were up-regulated following OVA induction but down-regulated following treatment with LRE. In conclusion, LRE alleviates allergy airway inflammation and hyperresponsiveness, thus suggesting its therapeutic potential as a new armamentarium against allergic asthma.

Sputum microbiome profiles identify severe asthma phenotypes of relative stability at 12 to 18 months.

BACKGROUND: Asthma is a heterogeneous disease characterized by distinct phenotypes with associated microbial dysbiosis. OBJECTIVES: Our aim was to identify severe asthma phenotypes based on sputum microbiome profiles and assess their stability after 12 to 18 months. A further aim was to evaluate clusters' robustness after inclusion of an independent cohort of patients with mild-to-moderate asthma. METHODS: In this longitudinal multicenter cohort study, sputum samples were collected for microbiome profiling from a subset of the Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes adult patient cohort at baseline and after 12 to 18 months of follow-up. Unsupervised hierarchical clustering was performed by using the Bray-Curtis ß-diversity measure of microbial profiles. For internal validation, partitioning around medoids, consensus cluster distribution, bootstrapping, and topological data analysis were applied. Follow-up samples were studied to evaluate within-patient clustering stability in patients with severe asthma. Cluster robustness was evaluated by using an independent cohort of patients with mild-to-moderate asthma. RESULTS: Data were available for 100 subjects with severe asthma (median age 55 years; 42% males). Two microbiome-driven clusters were identified; they were characterized by differences in asthma onset, smoking status, residential locations, percentage of blood and/or sputum neutrophils and macrophages, lung spirometry results, and concurrent asthma medications (all P values < .05). The cluster 2 patients displayed a commensal-deficient bacterial profile that was associated with worse asthma outcomes than those of the cluster 1 patients. Longitudinal clusters revealed high relative stability after 12 to 18 months in those with severe asthma. Further inclusion of an independent cohort of 24 patients with mild-to-moderate asthma was consistent with the clustering assignments. CONCLUSION: Unbiased microbiome-driven clustering revealed 2 distinct robust phenotypes of severe asthma that exhibited relative overtime stability. This suggests that the sputum microbiome may serve as a biomarker for better characterizing asthma phenotypes.

DMFMDA: Prediction of Microbe-Disease Associations Based on Deep Matrix Factorization Using Bayesian Personalized Ranking.

Identifying the microbe-disease associations is conducive to understanding the pathogenesis of disease from the perspective of microbe. In this paper, we propose a deep matrix factorization prediction model (DMFMDA) based on deep neural network. First, the disease one-hot encoding is fed into neural network, which is transformed into a low-dimensional dense vector in implicit semantic space via embedding layer, and so is microbe. Then, matrix factorization is realized by neural network with embedding layer. Furthermore, our model synthesizes the non-linear modeling advantages of multi-layer perceptron based on the linear modeling advantages of matrix factorization. Finally, different from other methods using square error loss function, Bayesian Personalized Ranking optimizes the model from a ranking perspective to obtain the optimal model parameters, which makes full use of the unobserved data. Experiments show that DMFMDA reaches average AUCs of 0.9091 and 0.9103 in the framework of 5-fold cross validation and Leave-one-out cross validation, which is superior to three the-state-of-art methods. In case studies, 10, 9 and 9 out of top-10 candidate microbes are verified by recently published literature for asthma, inflammatory bowel disease and colon cancer, respectively. In conclusion, DMFMDA is successful application of deep learning in the prediction of microbe-disease association.

Specialized Proresolving Mediators Overcome Immune Suppression Induced by Exposure to Secondhand Smoke.

Tobacco smoke exposure is associated with multiple diseases including, respiratory diseases like asthma and chronic obstructive pulmonary disease. Tobacco smoke is a potent inflammatory trigger and is immunosuppressive, contributing to increased susceptibility to pulmonary infections in smokers, ex-smokers, and vulnerable populations exposed to secondhand smoke. Tobacco smoke exposure also reduces vaccine efficacy. Therefore, mitigating the immunosuppressive effects of chronic smoke exposure and improving the efficacy of vaccinations in individuals exposed to tobacco smoke, is a critical unmet clinical problem. We hypothesized that specialized proresolving mediators (SPMs), a class of immune regulators promoting resolution of inflammation, without being immunosuppressive, and enhancing B cell Ab responses, could reverse the immunosuppressive effects resulting from tobacco smoke exposure. We exposed mice to secondhand smoke for 8 wk, followed by a period of smoke exposure cessation, and the mice were immunized with the P6 lipoprotein from nontypeable Haemophilus influenzae, using 17-HDHA and aspirin-triggered-resolvin D1 (AT-RvD1) as adjuvants. 17-HDHA and AT-RvD1 used as adjuvants resulted in elevated serum and bronchoalveolar lavage levels of anti-P6-specific IgG and IgA that were protective, with immunized mice exhibiting more rapid bacterial clearance upon challenge, reduced pulmonary immune cell infiltrates, reduced production of proinflammatory cytokines, and less lung-epithelial cell damage. Furthermore, the treatment of mice with AT-RvD1 during a period of smoke-cessation further enhanced the efficacy of SPM-adjuvanted P6 vaccination. Overall, SPMs show promise as novel vaccine adjuvants with the ability to overcome the tobacco smoke-induced immunosuppressive effects.

Go With Your Gut: The Shaping of T-Cell Response by Gut Microbiota in Allergic Asthma.

Novel methods in immunological research and microbiome evaluation have dramatically changed several paradigms associated with the pathogenesis of allergic asthma (AAS). Ovalbumin and house dust mite-induced AAS in germ-free or specific pathogen-free mice are the two leading experimental platforms that significantly contribute to elucidate the relationship between AAS and gut microbiota. Beyond the exacerbation of T helper (Th) 2 responses, a complex network of immunological interaction driven by gut microbiota could modulate the final effector phase. Regulatory T cells are abundant in gastrointestinal mucosa and have been shown to be pivotal in AAS. The gut microbiota could also influence the activity of other T cell subsets such as Th9, Th17, and populations of effector/memory T lymphocytes. Furthermore, gut microbiota metabolites drive the hematopoietic pattern of dendritic cells and ameliorate lung Th2 immunity in AAS models. The administration of probiotics has shown conflicting results in AAS, and limited evidence is available on the immunological pathways beyond their activity. Moreover, the impact of early-life gut dysbiosis on AAS is well-known both experimentally and clinically, but discrepancies are observed between preclinical and clinical settings. Herein, our aim is to elucidate the most relevant preclinical and clinical scenarios to enlighten the potential role of the gut microbiota in modulating T lymphocytes activity in AAS.

Human Microbe-Disease Association Prediction by a Novel Double-Ended Random Walk with Restart.

Microorganisms in the human body play a vital role in metabolism, immune defense, nutrient absorption, cancer control, and prevention of pathogen colonization. More and more biological and clinical studies have shown that the imbalance of microbial communities is closely related to the occurrence and development of various complex human diseases. Finding potential microbial-disease associations is critical for understanding the pathology of a few diseases and thus further improving disease diagnosis and prognosis. In this study, we proposed a novel computational model to predict disease-associated microbes. Specifically, we first constructed a heterogeneous interconnection network based on known microbe-disease associations deposited in a few databases, the similarity between diseases, and the similarity between microorganisms. We then predicted novel microbe-disease associations by a new method called the double-ended restart random walk model (DRWHMDA) implemented on the interconnection network. In addition, we performed case studies of colon cancer and asthma for further evaluation. The results indicate that 10 and 9 of the top 10 microorganisms predicted to be associated with colorectal cancer and asthma were validated by relevant literatures, respectively. Our method is expected to be effective in identifying disease-related microorganisms and will help to reveal the relationship between microorganisms and complex human diseases.

Gut microbiome a promising target for management of respiratory diseases.

The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut-lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut-lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.