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Rationale: Progressive lung function loss is recognized in chronic obstructive pulmonary disease (COPD); however, no study concurrently evaluates how accelerated lung function decline relates to mucus properties and the microbiome in COPD. Objectives: Longitudinal assessment of mucus and microbiome changes accompanying accelerated lung function decline in patients COPD. Methods: This was a prospective, longitudinal assessment of the London COPD cohort exhibiting the greatest FEV1 decline (n = 30; accelerated decline; 156 ml/yr FEV1 loss) and with no FEV1 decline (n = 28; nondecline; 49 ml/yr FEV1 gain) over time. Lung microbiomes from paired sputum (total 116 specimens) were assessed by shotgun metagenomics and corresponding mucus profiles evaluated for biochemical and biophysical properties. Measurements and Main Results: Biochemical and biophysical mucus properties are significantly altered in the accelerated decline group. Unsupervised principal component analysis showed clear separation, with mucus biochemistry associated with accelerated decline, whereas biophysical mucus characteristics contributed to interindividual variability. When mucus and microbes are considered together, an accelerated decline mucus-microbiome association emerges, characterized by increased mucin (MUC5AC [mucin 5AC] and MUC5B [mucin 5B]) concentration and the presence of Achromobacter and Klebsiella. As COPD progresses, mucus-microbiome shifts occur, initially characterized by low mucin concentration and transition from viscous to elastic dominance accompanied by the commensals Veillonella, Gemella, Rothia, and Prevotella (Global Initiative for Chronic Obstructive Lung Disease [GOLD] A and B) before transition to increased mucus viscosity, mucins, and DNA concentration together with the emergence of pathogenic microorganisms including Haemophilus, Moraxella, and Pseudomonas (GOLD E). Conclusions: Mucus-microbiome associations evolve over time with accelerated lung function decline, symptom progression, and exacerbations affording fresh therapeutic opportunities for early intervention.
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Microbiota , Moco , Enfermedad Pulmonar Obstructiva Crónica , Esputo , Humanos , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Esputo/microbiología , Moco/microbiología , Estudios Longitudinales , Progresión de la Enfermedad , Mucina 5B/metabolismo , Volumen Espiratorio Forzado , Mucina 5AC/metabolismo , LondresRESUMEN
Dietary fiber-rich foods have been associated with numerous health benefits, including a reduced risk of cardiovascular and metabolic diseases. Harnessing the potential to deliver positive health outcomes rests on our understanding of the underlying mechanisms that drive these associations. This review addresses data and concepts concerning plant-based food functionality by dissecting the cascade of physical and chemical digestive processes and interactions that underpin these physiological benefits. Functional transformations of dietary fiber along the gastrointestinal tract from the stages of oral processing and gastric emptying to intestinal digestion and colonic fermentation influence its capacity to modulate digestion, transit, and commensal microbiome. This analysis highlights the significance, limitations, and challenges in decoding the complex web of interactions to establish a coherent framework connecting specific fiber components' molecular and macroscale interactions across multiple length scales within the gastrointestinal tract. One critical area that requires closer examination is the interaction between fiber, mucus barrier, and the commensal microbiome when considering food structure design and personalized nutritional strategies for beneficial physiologic effects. Understanding the response of specific fibers, particularly concerning an individual's physiology, will offer the opportunity to exploit these functional characteristics to elicit specific, symptom-targeting effects or use fiber types as adjunctive therapies.
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Microbiomics have significantly advanced over the last decade, driven by the widespread availability of next-generation sequencing (NGS) and multi-omic technologies. Integration of NGS and multi-omic datasets allow for a holistic assessment of endophenotypes across a range of chronic respiratory disease states, including chronic obstructive pulmonary disease (COPD). Valuable insight has been attained into the nature, function, and significance of microbial communities in disease onset, progression, prognosis, and response to treatment in COPD. Moving beyond single-biome assessment, there now exists a growing literature on functional assessment and host-microbe interaction and, in particular, their contribution to disease progression, severity, and outcome. Identifying specific microbes and/or metabolic signatures associated with COPD can open novel avenues for therapeutic intervention and prognosis-related biomarkers. Despite the promise and potential of these approaches, the large amount of data generated by such technologies can be challenging to analyze and interpret, and currently, there remains a lack of standardized methods to address this. This review outlines the current use and proposes future avenues for the application of NGS and multi-omic technologies in the endophenotyping, prognostication, and treatment of COPD.
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Microbiota , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Multiómica , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/terapia , Microbiota/genética , Interacciones Microbiota-Huesped , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Bacterial cellulose (BC) is a promising material for use as an artificial skin in wound healing application, however, its applications are limited due to its poor malleability. Incorporating non-cellulosic polysaccharides such as dextran and xyloglucan (XG) may enhance its respective wound healing and malleability. This study presents a novel in situ biopreparation method to produce BC-based hybrid hydrogels containing dextran (BC-D) and xyloglucan-dextran (BC-XG-D) with unique mechanical and rheological properties. Structural analysis revealed that dextran of different sizes (10 k, 70 k and 2 M of Mw) form micron-sized particles by loosely binding to cellulosic fibres. The addition of xyloglucan resulted acts as a lubricant in mechanical testing. The BC-XG-D hybrid hydrogels showed a reduced Young's modulus of 4 MPa and a higher maximum tensile strain of 53 % compared to native BC. Moreover, they displayed less plastic but more viscous behaviour under large shear strain deformation. The wound healing animal model experiments demonstrated that the BC-XG-D hybrid hydrogels promoted wound healing process and skin maturation. Overall, these findings contribute to the development of functional BC-based medical materials with desired mechanical and rheological properties that have the potential to accelerate wound healing.
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Celulosa , Dextranos , Animales , Celulosa/farmacología , Dextranos/farmacología , Hidrogeles/farmacología , Cicatrización de HeridasRESUMEN
The European Respiratory Society International Congress took place both in person, in Barcelona, Spain, and online in 2022. The congress welcomed over 19 000 attendees on this hybrid platform, bringing together exciting updates in respiratory science and medicine from around the world. In this article, Early Career Members of the Respiratory Infections Assembly (Assembly 10) summarise a selection of sessions across a broad range of topics, including presentations on bronchiectasis, nontuberculous mycobacteria, tuberculosis, cystic fibrosis and coronavirus disease 2019.
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The extracellular matrix of bacterial biofilms consists of diverse components including polysaccharides, proteins and DNA. Extracellular RNA (eRNA) can also be present, contributing to the structural integrity of biofilms. However, technical difficulties related to the low stability of RNA make it difficult to understand the precise roles of eRNA in biofilms. Here, we show that eRNA associates with extracellular DNA (eDNA) to form matrix fibres in Pseudomonas aeruginosa biofilms, and the eRNA is enriched in certain bacterial RNA transcripts. Degradation of eRNA associated with eDNA led to a loss of eDNA fibres and biofilm viscoelasticity. Compared with planktonic and biofilm cells, the biofilm matrix was enriched in specific mRNA transcripts, including lasB (encoding elastase). The mRNA transcripts colocalised with eDNA fibres in the biofilm matrix, as shown by single molecule inexpensive FISH microscopy (smiFISH). The lasB mRNA was also observed in eDNA fibres in a clinical sputum sample positive for P. aeruginosa. Thus, our results indicate that the interaction of specific mRNAs with eDNA facilitates the formation of viscoelastic networks in the matrix of Pseudomonas aeruginosa biofilms.
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Pseudomonas aeruginosa , ARN , Pseudomonas aeruginosa/metabolismo , ARN/metabolismo , Biopelículas , ADN/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ADN Bacteriano/genética , ADN Bacteriano/metabolismoRESUMEN
The European Respiratory Society International Congress 2021 took place virtually for the second year running due to the coronavirus pandemic. The Congress programme featured more than 400 sessions and 3000 abstract presentations, covering the entire field of respiratory science and medicine. In this article, early career members of the Respiratory Infections Assembly summarise a selection of sessions across a broad range of topics, including presentations on bronchiectasis, non-tuberculosis mycobacteria, tuberculosis, cystic fibrosis and COVID-19.
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The respiratory tract harbors a stable and diverse microbial population within an extracellular mucus layer. Mucus provides a formidable defense against infection and maintaining healthy mucus is essential to normal pulmonary physiology, promoting immune tolerance and facilitating a healthy, commensal lung microbiome that can be altered in association with chronic respiratory disease. How one maintains a specialized (healthy) microbiome that resists significant fluctuation remains unknown, although smoking, diet, antimicrobial therapy, and infection have all been observed to influence microbial lung homeostasis. In this review, we outline the specific role of polymerizing mucin, a key functional component of the mucus layer that changes during pulmonary disease. We discuss strategies by which mucin feed and spatial orientation directly influence microbial behavior and highlight how a compromised mucus layer gives rise to inflammation and microbial dysbiosis. This emerging field of respiratory research provides fresh opportunities to examine mucus, and its function as predictors of infection risk or disease progression and severity across a range of chronic pulmonary disease states and consider new perspectives in the development of mucolytic treatments.
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The unique mechanical properties of hydrated bacterial cellulose make it suitable for biomedical applications. This study evaluates the effect of concentrated sodium hydroxide treatment on the structural and mechanical properties of bacterial cellulose hydrogels using rheological, tensile, and compression tests combined with mathematical modelling. Bacterial cellulose hydrogels show a concentration-dependent and irreversible reduction in shear moduli, compression, and tensile strength after alkaline treatment. Applying a poroelastic biphasic model to through-thickness compressive stress-relaxation tests showed the alkaline treatment to induce no significant change in axial compression, an effect was observed in the radial direction, potentially due to the escape of water from within the hydrogel. Scanning electron microscopy showed a more porous structure of bacterial cellulose. These results show how concentration-dependent alkaline treatment induces selective weakening of intramolecular interactions between cellulose fibres, allowing the opportunity to precisely tune the mechanical properties for specific biomedical application, e.g., faster-degradable materials.
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Celulosa/química , Hidrogeles/química , Polisacáridos Bacterianos/química , Hidróxido de Sodio/química , Acetobacteraceae/química , Fuerza Compresiva , Permeabilidad , Porosidad , Resistencia a la Tracción , Sustancias Viscoelásticas/químicaRESUMEN
Mucus is characterized by multiple levels of assembly at different length scales which result in a unique set of rheological (flow) and mechanical properties. These physical properties determine its biological function as a highly selective barrier for transport of water and nutrients, while blocking penetration of pathogens and foreign particles. Altered integrity of the mucus layer in the small intestine has been associated with a number of gastrointestinal tract pathologies such as Crohn's disease and cystic fibrosis. In this work, we uncover an intricate hierarchy of intestinal mucin (Muc2) assembly and show how complex rheological properties emerge from synergistic interactions between mucin glycoproteins, non-mucin proteins, and Ca2+. Using a novel method of mucus purification, we demonstrate the mechanism of assembly of Muc2 oligomers into viscoelastic microscale domains formed via hydrogen bonding and Ca2+-mediated links, which require the joint presence of Ca2+ ions and non-mucin proteins. These microscale domains aggregate to form a heterogeneous yield stress gel-like fluid, the macroscopic rheological properties of which are virtually identical to that of native intestinal mucus. Through proteomic analysis, we short-list potential protein candidates implicated in mucin assembly, thus paving the way for identifying the molecules responsible for the physiologically critical biophysical properties of mucus.
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Calcio/metabolismo , Disulfuros , Geles/metabolismo , Enlace de Hidrógeno , Mucinas/metabolismo , Proteínas/química , Proteínas/metabolismo , Fenómenos QuímicosRESUMEN
We demonstrate the enhancement of intestinal mucin (Muc2) binding to plant cell wall structures from fruit (parenchymal apple tissue) and grain (wheat endosperm) mediated by soluble dietary fibers embedded within cellulose networks. Mucin binding occurs through two distinct mechanisms; for pectin polysaccharides characteristic of fruits and vegetables, it is governed by molecular mucoadhesive interactions, while for neutral polysaccharides, arabinoxylan and ß-glucan characteristic of cereal grains, the interaction stems from the properties of their polymer network. Based on microrheological and microscopic measurements, we show that neutral dietary fiber polysaccharides do not adhere to intestinal mucin, but are capable of disrupting the mucin network, which facilitates interpenetration of mucin molecules into the polysaccharide mesh. This effect becomes significant in the context of 'whole foods', where soluble fibers are incorporated within the gel-like matrix of cellulose-reinforced plant cell wall structures. The result of mucoadhesion assay and analysis of microscopy images points to the critical role of entanglements between mucin and polysaccharides as a lock-in mechanism preventing larger mucin from escaping out of plant cell wall structures. These results provide the first indication that non-pectin soluble dietary fiber may influence mucosal interactions, mucus barrier properties, and transmucosal transport of nutrients.