Pathogenesis of various pulmonary diseases by tuning immune response: insight from host-microbial crosstalk

Lung microbiota and gut microbiota are closely related to lung cancer. Studies have shown that the dysbiosis, i.e., the significantly altered composition and structure of gut and lung microbiota, usually occurs in patients with lung cancer. With the introduction of "Gut-Lung Axis", an increasing attention has been paid to the close relationship between the lung and gut microbiota in human body. A deeper insight into this relationship would facilitate understanding the mechanisms behind the carcinogenesis and development of lung cancer. This article summarizes the composition of lung and gut microbiota in patients with lung cancer and the possible interaction mechanisms, highlighting the importance of the immune system in the Gut-Lung Axis. The effects of lung and gut microbiota on the clinical treatment of lung cancer were summarized, based on which the authors propose that the lung and gut microbiota can be used as novel targets for early diagnosis and treatment of lung cancer.

BackgroundThe gut microbiome plays a protective role in the host defense against pneumonia. The composition of the lung microbiota has been shown to be predictive of clinical outcome in critically ill patients. However, the dynamics of the lung and gut microbiota composition over time during severe pneumonia remains ill defined. We used a mouse model of pneumonia-derived sepsis caused by Klebsiella pneumoniae in order to follow the pathogen burden as well as the composition of the lung, tongue and fecal microbiota from local infection towards systemic spread.ResultsAlready at 6 h post-inoculation with K. pneumoniae, marked changes in the lung microbiota were seen. The alpha diversity of the lung microbiota did not change throughout the infection, whereas the beta diversity did. A shift between the prominent lung microbiota members of Streptococcus and Klebsiella was seen from 12 h onwards and was most pronounced at 18 h post-inoculation (PI) which was also reflected in the release of pro-inflammatory cytokines indicating severe pulmonary inflammation. Around 18 h PI, K. pneumoniae bacteremia was observed together with a systemic inflammatory response. The composition of the tongue microbiota was not affected during infection, even at 18–30 h PI when K. pneumoniae had become the dominant bacterium in the lung. Moreover, we observed differences in the gut microbiota during pulmonary infection. The gut microbiota contributed to the lung microbiota at 12 h PI, however, this decreased at a later stage of the infection.ConclusionsAt 18 h PI, K. pneumoniae was the dominant member in the lung microbiota. The lung microbiota profiles were significantly explained by the lung K. pneumoniae bacterial counts and Klebsiella and Streptococcus were correlating with the measured cytokine levels in the lung and/or blood. The oral microbiota in mice, however, was not influenced by the severity of murine pneumonia, whereas the gut microbiota was affected. This study is of significance for future studies investigating the role of the lung microbiota during pneumonia and sepsis.

The Role of Gut Microbiata in Multiple Sclerosis

The effect of long-term macrolide treatment on respiratory microbiota composition in non-cystic fibrosis bronchiectasis: an analysis from the randomised, double-blind, placebo-controlled BLESS trial

BackgroundAutism spectrum disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis, changes in microbiota composition as well as in the fecal, serum, and urine levels of microbial metabolites. Yet a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolite p-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice.ResultsMice exposed to p-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced by p-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further, p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred from p-Cresol-treated mice to control mice by fecal microbiota transplantation (FMT). We also showed that mice transplanted with the microbiota of p-Cresol-treated mice exhibited increased fecal p-Cresol excretion, compared to mice transplanted with the microbiota of control mice. In addition, we identified possible p-Cresol bacterial producers. Lastly, the microbiota of control mice rescued social interactions, dopamine neurons excitability, and fecal p-Cresol levels when transplanted to p-Cresol-treated mice.ConclusionsThe microbial metabolite p-Cresol induces selectively ASD core behavioral symptoms in mice. Social behavior deficits induced by p-Cresol are dependant on changes in microbiota composition. Our study paves the way for therapeutic interventions targeting the microbiota and p-Cresol production to treat patients with ASD.23y8Eg2qi-yqeo7gGCFq9cVideo abstract

Studies on populations at different ages have shown that after birth, the gastrointestinal (GI) microbiota composition keeps evolving, and this seems to occur especially in old age. Significant changes in GI microbiota composition in older subjects have been reported in relation to diet, drug use and the settings where the older subjects are living, that is, in community nursing homes or in a hospital. Moreover, changes in microbiota composition in the old age have been related to immunosenescence and inflammatory processes that are pathophysiological mechanisms involved in the pathways of frailty. Frailty is an age-related condition of increased vulnerability to stresses due to the impairment in multiple inter-related physiologic systems that are associated with an increased risk of adverse outcomes, such as falls, delirium, institutionalization, hospitalization and death. Preliminary data suggest that changes in microbiota composition may contribute to the variations in the biological, clinical, functional and psycho-social domains that occur in the frail older subjects. Multidimensional evaluation tools based on a Comprehensive Geriatric Assessment (CGA) have demonstrated to be useful in identifying and measuring the severity of frailty in older subjects. Thus, a CGA approach should be used more widely in clinical practice to evaluate the multidimensional effects potentially related to GI microbiota composition of the older subjects. Probiotics have been shown to be effective in restoring the microbiota changes of older subjects, promoting different aspects of health in elderly people as improving immune function and reducing inflammation. Whether modulation of GI microbiota composition, with multi-targeted interventions, could have an effect on the prevention of frailty remains to be further investigated in the perspective of improving the health status of frail ‘high risk' older individuals.

Background:Recently, it has been shown that changes in microbiota composition play a role in the etiology and pathogenesis of chronic diseases. Changes in oral and intestinal microbiota diversity and composition are suggested in Behcet disease (BD), however there are no study available about the potential gut microbiota changes among different clinical forms of BD.Objectives:The aim of this study was to evaluate the intestinal microbiota composition of patient with BD and healthy controls, and also compare BD patients regarding to their eye, mucocutaneous and vascular involvement.Methods:In this prospective cohort study,27 patients diagnosed with BD and 10 aged and sex matched healthy controls were included. Patients with a body mass index> 35, who have used antibiotics or probiotics in the last 4 weeks, patients with chronic gastrointestinal or other systemic diseases, and those with acute / severe gastrointestinal symptoms requiring medical treatment were excluded from the study. For the intestinal microbiota analysis, gene amplification, library formation, sequence analysis and bioinformatic evaluation of the results were performed with 16SrRNA next generation sequencing methods with Illumina MiSeq.Results:There was no difference between the BD group and the control group in terms of alpha (Chao-1 and Shannon) and beta (Bray-Curtis) microbiota diversity indices (p> 0.05).Actinomyces, Libanicoccus, Collinsella, Eggerthella, Enetrohabdus, Catenibacterium and Enterobacterwere significantly higher in BD group compared to the control group. In addition,Bacteriodes, Cricetibacter, Alistipes, Lachnospira, Dielma, Akkermansia, Sutterella, Anaerofilum, Ruminococcease-UCG007, Acetanaerobacterium; and Copropaacterwere lower than the control group. There was no difference between the uveitis, mucocutaneous and vascular involvement groups in terms of alpha (Chao-1 and Shannon) and beta (Bray-Curtis) microbiota diversity and wealth indices (p> 0.05) while we obtained a significant p value of the beta diversity between three groups in weighted UniFrac PCoA (p<0.05). When we compared 3 three different system involvement (Eye, Mucocutaneous and Vascular), The LEfSe provides us with cladograms of six-level (from kingdom to genus). We found difference for the generaLachnospiraceae NK4A136in uveitis group,Dialister, İntestinomonas and Marvinbryantiain mucocutaneous group andGemellain vascular involvement group.Conclusion:There was a significant difference in the composition of intestinal microbiota in Behçet’s disease compared to healthy adults. We found also found the different clinical forms of Behcet’s disease have some different gut microbiota composition. Especially in Behçet’s disease, it will be useful to evaluateCatenibacterium, Collinsella and Eggerthellaincrease,Bacteroides and Akkermansiadecrease in larger series. In addition, due to the increase in theEggerthella lentastrain observed both in the FMF and Behcet patient group, it is useful to make more detailed metagenomic analyzes regarding the role of this agent in the etiopathogenesis and course of rheumatic diseases.Disclosure of Interests:None declared

Characterization of bacterial populations in infectious respiratory diseases will provide improved understanding of the relationship between the lung microbiota, disease pathogenesis, and treatment outcomes. To comprehensively define lung microbiota composition during stable disease and exacerbation in patients with bronchiectasis. Sputum was collected from patients when clinically stable and before and after completion of antibiotic treatment of exacerbations. Bacterial abundance and community composition were analyzed using anaerobic culture and 16S rDNA pyrosequencing. In clinically stable patients, aerobic and anaerobic bacteria were detected in 40 of 40 (100%) and 33 of 40 (83%) sputum samples, respectively. The dominant organisms cultured were Pseudomonas aeruginosa (n = 10 patients), Haemophilus influenzae (n = 12), Prevotella (n = 18), and Veillonella (n = 13). Pyrosequencing generated more than 150,000 sequences, representing 113 distinct microbial taxa; the majority of observed community richness resulted from taxa present in low abundance with similar patterns of phyla distribution in clinically stable patients and patients at the onset of exacerbation. After treatment of exacerbation, there was no change in total (P = 0.925), aerobic (P = 0.917), or anaerobic (P = 0.683) load and only a limited shift in community composition. Agreement for detection of bacteria by culture and pyrosequencing was good for aerobic bacteria such as P. aeruginosa (κ = 0.84) but poorer for other genera including anaerobes. Lack of agreement was largely due to bacteria being detected by pyrosequencing but not by culture. A complex microbiota is present in the lungs of patients with bronchiectasis and remains stable through treatment of exacerbations, suggesting that changes in microbiota composition do not account for exacerbations.

The comorbidity due to pulmonary tuberculosis (TB) and diabetes mellitus (DM) is a global health problem, but its mechanism remains unclear. It is suspected that hyperglycemic alteration of the immune response to TB and the composition of the lung microbiota play an important role. This scoping review aimed to contribute to the understanding of the mechanisms by mapping evidence on the effect of hyperglycemia on physical health indicators, immune cell counts, cytokine levels, and the composition of lung microbiota in patients with the DM-TB comorbidity. A systematic search for research articles about the relationship between hyperglycemia and physical health, immune cells, and cytokine levels in humans was conducted in MEDLINE, Scopus, and CINAHL Plus. Then, articles on the interactions between the immune cells, cytokines, and lung microbiota were identified through Google Scholar and Google search engines. Characteristics of the studies focusing on effects of hyperglycemia, the findings of the articles relevant to the research objectives, and strengths and weaknesses of the selected articles were charted in a data extraction tool. Twenty-one articles on the effects of hyperglycemia on immune mediators and health outcomes of patients with DM-TB were included. The evidence showed hyperglycemia to be associated with unfavorable treatment outcomes; altered counts and functioning of dendritic cells, monocytes, and CD4+ T cells; and changes in cytokine levels (mainly INF-γ, IL-17, IL-1β, IL-2, IL-6, IL-10, and TNF-α) in patients with DM-TB. The composition of the lung microbiota changed in correlation with changes in physical health outcomes, counts of immune cells, and cytokine levels. Thus, hyperglycemia, immune responses, and dysbiosis of the lung microbiota are integral in the pathogenesis of DM-TB and TB treatment outcomes. A prospective cohort study, especially in individuals with newly diagnosed DM versus known DM and concomitant latent TB versus active TB, is recommended to define causal relationships.

BackgroundA new feature that seems to be decisive in autoimmune pathogenesis is the gut microbiota composition. However, its exact role remains to be determined. In systemic lupus erythematosus (SLE), an...

Influence of azithromycin and allograft rejection on the post–lung transplant microbiota

We report here a study using a model of multiple sclerosis – experimental allergic encephalomyelitis (EAE) – to investigate changes in the qualitative and quantitative composition of the intestinal microbiota in rats with disease symptoms and with a symptom-free course. When clinical symptoms of EAE were apparent, there were changes in the composition of the microbiota of the gastrointestinal tract, with increases in the numbers of Gram-negative opportunistically pathogenic bacteria: Citrobacter spp., Klebsiella spp., and atypical E. coli. Rats without clinical signs of EAE were also found to have increased contents of Faecalibacterium prausnitzii. The significance of complexes changes in the composition of the intestinal microbiota is discussed, as this provides evidence of prolonged persistence of dysbacteriosis in rats on developing EAE.

ObjectivesRecent evidence suggests that the gut microbiota may play a crucial role in the pathogenesis of ankylosing spondylitis (AS). This systematic review aims to examine the existing literature to explore changes in gut microbiota composition between AS patients and healthy controls (HC) to identify microbial signatures associated with AS. Understanding these alterations could enhance our knowledge of the mechanisms underlying AS.MethodsWe queried PubMed, Web of Science, Scopus, Embase, and Cochrane databases through May 2024 to identify studies comparing stool microbiota composition in AS patients and healthy controls (HC). Following PRISMA guidelines, our search yielded 1,163 studies. We included studies comparing microbiota in AS patients and HC. We excluded duplicates, animal studies, case reports, conference abstracts, non-English articles, irrelevant studies, non-full-text manuscripts, and Mendelian randomization studies, as these do not provide direct observational data on microbiota composition and could introduce methodological heterogeneity.ResultsAfter screening 184 studies, 18 manuscripts were included: 14 prospective cohort studies, 2 case-control studies, and 2 cross-sectional studies (Figure 1). These studies covered a total of 900 ankylosing spondylitis (AS) patients and 734 healthy controls (HC). The majority of the participants were male, with 73.8% in the AS group and 66.7% in the HC group, and most participants (73.4%) were of Asian descent. HLA-B27 status was reported in 13 studies, with a 92.3% positive rate among the AS patients. Notably, none of the AS or HC participants, except for 1 study, had received antibiotics in the 3 months prior to enrollment. At the phylum level, 12 studies (66.6%) reported significant changes in microbiota composition (Figure 2). Actinobacteria, Firmicutes, and Proteobacteria were increased in 8, 6, and 5 studies, respectively, while Bacteroidetes, Fusobacteria, and Verrucomicrobia were decreased in 5, 3, and 3 studies, respectively. At the genus level, 16 studies (88.8%) observed changes. Prevotella, Escherichia-Shigella, Streptococcus, and Collinsella were increased in 6, 6, 5, and 4 studies, respectively, while Bacteroides, Lachnospira, and Dialister were decreased in 9, 4, and 4 studies, respectively. Prevotella and Collinsella have been linked to inflammatory diseases in previous studies, suggesting their potential involvement in the inflammatory processes observed in AS patients. On the other hand, a reduction in Lachnospira has been associated with increased inflammation, indicating its potential protective role in inflammatory conditions.Figure 1: Alterations in Microbiota Composition at the Phylum Level in AS Patients Compared to Healthy ControlsFigure 2: Alterations in Microbiota Composition at the Genus Level in AS Patients Compared to Healthy ControlsConclusionOur findings reveal significant differences in gut microbiota composition between AS patients and healthy controls, indicating a role of microbiota in AS pathogenesis. These findings highlight the potential for microbiota-targeted therapies in AS treatment.

Paying the Toll for Inflammation

RNA regulation in immunity.