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BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic respiratory diseases, and some patients have overlapping disease features, termed asthma-COPD overlap (ACO). Patients characterized with ACO have increased disease severity; however, the mechanisms driving this have not been widely studied. OBJECTIVES: This study sought to characterize the phenotypic and transcriptomic features of experimental ACO in mice induced by chronic house dust mite antigen and cigarette smoke exposure. METHODS: Female BALB/c mice were chronically exposed to house dust mite antigen for 11 weeks to induce experimental asthma, cigarette smoke for 8 weeks to induce experimental COPD, or both concurrently to induce experimental ACO. Lung inflammation, structural changes, and lung function were assessed. RNA-sequencing was performed on separated airway and parenchyma lung tissues to assess transcriptional changes. Validation of a novel upstream driver SPI1 in experimental ACO was assessed using the pharmacological SPI1 inhibitor, DB2313. RESULTS: Experimental ACO recapitulated features of both asthma and COPD, with mixed pulmonary eosinophilic/neutrophilic inflammation, small airway collagen deposition, and increased airway hyperresponsiveness. Transcriptomic analysis identified common and distinct dysregulated gene clusters in airway and parenchyma samples in experimental asthma, COPD, and ACO. Upstream driver analysis revealed increased expression of the transcription factor Spi1. Pharmacological inhibition of SPI1 using DB2313, reduced airway remodeling and airway hyperresponsiveness in experimental ACO. CONCLUSIONS: A new experimental model of ACO featuring chronic dual exposures to house dust mite and cigarette smoke mimics key disease features observed in patients with ACO and revealed novel disease mechanisms, including upregulation of SPI1, that are amenable to therapy.

The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a "poor" diet or protection against disease with a "healthy" diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.

The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one of the most well-characterized inflammasomes, activated by pathogen-associated molecular patterns and damage-associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut–lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut–lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.

Shiga toxigenic Escherichia coli (STEC) O157 and several other serogroups of non-O157 STEC strains present as commensalism bacteria in small ruminants that possess a high potential of attaining pathogenic virulent genetic elements. The pathogenicity of non-O157 strains is emerging progressively in animals as well as in humans especially in the rural areas as they get transmitted through unsanitary practices of living, consumption of uncooked meat and milk, human-livestock close proximity as well as within livestock pathogenic bacterial transmission. The present study was carried out to determine the prevalence of non-O157 E.coli isolates and characterize based on clinical history, antibiotic sensitivity testing, multiplex PCR (mPCR) detection of virulence genes, genotype identification using pulse field gel electrophoresis (PFGE) and polyacrylamide gel electrophoretic separation of antigenic proteins to determine their prevalence, virulence and genetic comparison between host and environment for epidemiological significance. A total of 300 E.coli isolates were recovered from rectal swabs of goats and their surrounding environment over a period of one year (2016–2017) by selective isolation. Among which 50 isolates were confirmed to be from the non-O157 E.coli family. The mPCR analysis of these 50 isolates revealed the presence of two or more virulent genes, viz., hylA (90%), fliC (74%), eaeA (56%), stx1 (48%) and stx2 (22%).Four isolates exhibited multidrug-resistance to amoxiclav, doxycycline, ciprofloxacin and ceftriazone. The PFGE fingerprint profile showed six major clusters at 100% similarity from the 50 isolates. The major antigenic proteins identified from the isolates were stx1A, stx2B and fliC. This study has significant implications for understanding the molecular diversity of emerging pathotypes of non-O157 in young goats in terms of virulence and epidemiological aspects.