RESUMEN
The constituents of the gut microbiome are determined by the local habitat, which itself is shaped by immunological pressures, such as mucosal IgA. Using a mouse model of restricted antibody repertoire, we identified a role for antibody-microbe interactions in shaping a community of bacteria with an enhanced capacity to metabolize L-tyrosine. This model led to increased concentrations of p-cresol sulfate (PCS), which protected the host against allergic airway inflammation. PCS selectively reduced CCL20 production by airway epithelial cells due to an uncoupling of epidermal growth factor receptor (EGFR) and Toll-like receptor 4 (TLR4) signaling. Together, these data reveal a gut microbe-derived metabolite pathway that acts distally on the airway epithelium to reduce allergic airway responses, such as those underpinning asthma.
Asunto(s)
Anticuerpos/metabolismo , Bacterias/metabolismo , Cresoles/metabolismo , Microbioma Gastrointestinal , Intestinos/microbiología , Pulmón/metabolismo , Neumonía/prevención & control , Hipersensibilidad Respiratoria/prevención & control , Ésteres del Ácido Sulfúrico/metabolismo , Tirosina/metabolismo , Administración Oral , Alérgenos , Animales , Anticuerpos/inmunología , Diversidad de Anticuerpos , Bacterias/inmunología , Células Cultivadas , Quimiocina CCL20/metabolismo , Técnicas de Cocultivo , Cresoles/administración & dosificación , Modelos Animales de Enfermedad , Receptores ErbB/metabolismo , Femenino , Interacciones Huésped-Patógeno , Inyecciones Intravenosas , Pulmón/inmunología , Pulmón/patología , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Neumonía/inmunología , Neumonía/metabolismo , Neumonía/microbiología , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/metabolismo , Hipersensibilidad Respiratoria/microbiología , Transducción de Señal , Ésteres del Ácido Sulfúrico/administración & dosificación , Receptor Toll-Like 4/metabolismo , Tirosina/administración & dosificaciónRESUMEN
Antibiotic use in early life disrupts microbial colonization and increases the risk of developing allergies and asthma. We report that mice given antibiotics in early life (EL-Abx), but not in adulthood, were more susceptible to house dust mite (HDM)-induced allergic airway inflammation. This susceptibility was maintained even after normalization of the gut microbiome. EL-Abx decreased systemic levels of indole-3-propionic acid (IPA), which induced long-term changes to cellular stress, metabolism, and mitochondrial respiration in the lung epithelium. IPA reduced mitochondrial respiration and superoxide production and altered chemokine and cytokine production. Consequently, early-life IPA supplementation protected EL-Abx mice against exacerbated HDM-induced allergic airway inflammation in adulthood. These results reveal a mechanism through which EL-Abx can predispose the lung to allergic airway inflammation and highlight a possible preventative approach to mitigate the detrimental consequences of EL-Abx.
Asunto(s)
Antibacterianos , Asma , Disbiosis , Microbioma Gastrointestinal , Indoles , Pyroglyphidae , Animales , Ratones , Disbiosis/inmunología , Indoles/farmacología , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/inmunología , Asma/inmunología , Pyroglyphidae/inmunología , Pulmón/inmunología , Pulmón/patología , Ratones Endogámicos C57BL , Femenino , Inflamación/inmunología , Modelos Animales de Enfermedad , Mitocondrias/metabolismo , Citocinas/metabolismo , Hipersensibilidad/inmunología , PropionatosRESUMEN
The revolution in microbiota research over the past decade has provided invaluable knowledge about the function of the microbial species that inhabit the human body. It has become widely accepted that these microorganisms, collectively called 'the microbiota', engage in networks of interactions with each other and with the host that aim to benefit both the microbial members and the mammalian members of this unique ecosystem. The lungs, previously thought to be sterile, are now known to harbor a unique microbiota and, additionally, to be influenced by microbial signals from distal body sites, such as the intestine. Here we review the role of the lung and gut microbiotas in respiratory health and disease and highlight the main pathways of communication that underlie the gut-lung axis.
Asunto(s)
Microbioma Gastrointestinal , Enfermedades Pulmonares/microbiología , Pulmón/microbiología , Microbiota , Probióticos/uso terapéutico , Acinetobacter , Animales , Bifidobacterium , Suplementos Dietéticos , Femenino , Interacciones Huésped-Patógeno , Humanos , Lactobacillus , Pulmón/inmunología , Enfermedades Pulmonares/dietoterapia , Enfermedades Pulmonares/inmunología , Exposición Materna , EmbarazoRESUMEN
The human body and its resident microbiota form a complex ecosystem, shaped by both inherited and environmental factors. The use of antibiotics represents an extreme example of environmental pressure and can broadly disrupt the microbial landscape. The benefits that antibiotics have brought to modern medicine are unquestionable; however, their overuse comes with consequences, including the potential for secondary infections by opportunistic pathogens and the spread of antibiotic resistance. Here, we discuss the implications of microbial dysbiosis driven by antibiotics, with a focus on potential links with allergy and asthma. We review epidemiological data on humans, as well as mechanistic studies performed in animal models, and highlight gaps in current knowledge, which if addressed, could drive the design of novel therapeutic strategies and improved clinical care.
Asunto(s)
Antibacterianos/efectos adversos , Asma/etiología , Disbiosis , Hipersensibilidad/etiología , Microbiota/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Asma/epidemiología , Modelos Animales de Enfermedad , Farmacorresistencia Bacteriana , Disbiosis/tratamiento farmacológico , Disbiosis/microbiología , Humanos , Hipersensibilidad/epidemiología , Sistema Inmunológico/citología , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismoAsunto(s)
Microbioma Gastrointestinal , Microbiota , Femenino , Humanos , Lactancia Materna , AnticuerposRESUMEN
BACKGROUND: Allergic diseases, including respiratory and food allergies, as well as allergic skin conditions have surged in prevalence in recent decades. In allergic diseases, the gut microbiome is dysbiotic, with reduced diversity of beneficial bacteria and increased abundance of potential pathogens. Research findings suggest that the microbiome, which is highly influenced by environmental and dietary factors, plays a central role in the development, progression, and severity of allergic diseases. The microbiome generates metabolites, which can regulate many of the host's cellular metabolic processes and host immune responses. AIMS AND METHODS: Our goal is to provide a narrative and comprehensive literature review of the mechanisms through which microbial metabolites regulate host immune function and immune metabolism both in homeostasis and in the context of allergic diseases. RESULTS AND DISCUSSION: We describe key microbial metabolites such as short-chain fatty acids, amino acids, bile acids and polyamines, elucidating their mechanisms of action, cellular targets and their roles in regulating metabolism within innate and adaptive immune cells. Furthermore, we characterize the role of bacterial metabolites in the pathogenesis of allergic diseases including allergic asthma, atopic dermatitis and food allergy. CONCLUSION: Future research efforts should focus on investigating the physiological functions of microbiota-derived metabolites to help develop new diagnostic and therapeutic interventions for allergic diseases.
RESUMEN
This study showed that a polylactide (PLA)-based composite filled with nanostructured hydroxyapatite (HAp) and a natural extract from the rhizome of Curcuma longa L. could provide an alternative to commonly used fossil-based plasticsfor food packaging. The incorporation of HAp into the PLA matrix had a positive effect on improving selected properties of the composites; the beneficial effect could be enhanced by introducing a green modifier in the form of an extract. Prior to the fabrication of the composite, the filler was characterized in terms of morphology and composition, and the composite was then fully characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), Raman and Fourier transform infrared spectroscopy (FT-IR), and the mechanical, thermal, thermomechanical, and optical properties were investigated. The proposed material exhibits antioxidant properties against DPPH radicals and antibacterial performance against Escherichia coli (E. coli). The results showed that the nanocomposite has the highest antioxidant and antibacterial properties for 10 wt% HAp with an average diameter of rod-shaped structures below 100 nm. In addition, the introduction of turmeric extract had a positive effect on the tensile strength of the nanocomposites containing 1 and 5% HAp. As the resulting material adsorbs light in a specific wavelength range, it can be used in the medical sector, food-packaging, or coatings.
RESUMEN
The gut microbiome engages in constant interactions with the immune system, laying down the fundamentals of what we perceive as health or disease. The gut microbiota acts locally in the intestines and distally in other organs, such as the lungs. This influence (termed "the gut-lung axis") constitutes the basis for harnessing the microbiome to prevent or treat chronic respiratory diseases. Within this context, two approaches gained the most attention: the diet interventions (which shape the microbiome) and the probiotics (which exert beneficial effects directly on the host). Microbial products, which constitute a means of communication along the gut-lung axis, are only now emerging as a new class of potential therapeutics. Here, we provide a comprehensive overview of microbial products active in the airways, describe the immunological mechanisms they trigger, and discuss their clinical advantages and pitfalls.
RESUMEN
Host-microbiota interactions are bidirectional. On one hand, ecological pressures exerted by the host shape the composition and function of the microbiota. On the other, resident microbes trigger multiple pathways that influence the immunity of the host. Bile acids participate in both parts of this interplay. As host-derived compounds, they display bacteriostatic properties and affect the survival and growth of the members of the microbial community. As microbiota-modified metabolites, they further influence the microbiota composition and, in parallel, modulate the immunity of the host. Here, we provide a comprehensive overview of the mechanisms behind this unique dialogue and discuss how we can harness bile acids to treat intestinal inflammation.
Asunto(s)
Microbioma Gastrointestinal , Microbiota , Ácidos y Sales BiliaresRESUMEN
The airway epithelium protects us from environmental insults, which we encounter with every breath. Not only does it passively filter large particles, it also senses potential danger and alerts other cells, including immune and nervous cells. Together, these tissues orchestrate the most appropriate response, balancing the need to eliminate the danger with the risk of damage to the host. Each cell subset within the airway epithelium plays its part, and when impaired, may contribute to the development of respiratory disease. Here we highlight recent advances regarding the cellular and functional heterogeneity along the airway epithelium and discuss how we can use this knowledge to design more effective, targeted therapeutics.
Asunto(s)
Variación Biológica Poblacional , Homeostasis , Mucosa Respiratoria/citología , Mucosa Respiratoria/fisiología , Animales , Biomarcadores , Susceptibilidad a Enfermedades , Desarrollo de Medicamentos , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Mucosa , Terapia Molecular Dirigida , Transducción de SeñalRESUMEN
The mechanisms maintaining adult lymphatic vascular specialization throughout life and their role in coordinating inter-organ communication to sustain homeostasis remain elusive. We report that inactivation of the mechanosensitive transcription factor Foxc2 in adult lymphatic endothelium leads to a stepwise intestine-to-lung systemic failure. Foxc2 loss compromised the gut epithelial barrier, promoted dysbiosis and bacterial translocation to peripheral lymph nodes, and increased circulating levels of purine metabolites and angiopoietin-2. Commensal microbiota depletion dampened systemic pro-inflammatory cytokine levels, corrected intestinal lymphatic dysfunction, and improved survival. Foxc2 loss skewed the specialization of lymphatic endothelial subsets, leading to populations with mixed, pro-fibrotic identities and to emergence of lymph node-like endothelial cells. Our study uncovers a cross-talk between lymphatic vascular function and commensal microbiota, provides single-cell atlas of lymphatic endothelial subtypes, and reveals organ-specific and systemic effects of dysfunctional lymphatics. These effects potentially contribute to the pathogenesis of diseases, such as inflammatory bowel disease, cancer, or lymphedema.
Asunto(s)
Vasos Linfáticos , Linfedema , Células Endoteliales/metabolismo , Endotelio Linfático/metabolismo , Endotelio Linfático/patología , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Humanos , Vasos Linfáticos/metabolismo , Linfedema/metabolismo , Linfedema/patologíaRESUMEN
From an evolutionary standpoint, allergy has only recently emerged as a significant health problem. Various hypotheses were proposed to explain this, but they all indicated the importance of rapid lifestyle changes, which occurred in industrialized countries in the last few decades. In this review, we discuss evidence from epidemiological and experimental studies that indicate changes in dietary habits may have played an important role in this phenomenon. Based on the example of dietary fiber, we discuss molecular mechanisms behind this and point towards the importance of diet-induced changes in the microbiota. Finally, we reason that future studies unraveling mechanisms governing these changes, along with the development of better tools to manipulate microbiota composition in individuals will be crucial for the design of novel strategies to combat numerous inflammatory disorders, including atopic diseases.
Asunto(s)
Dieta , Microbioma Gastrointestinal , Hipersensibilidad/epidemiología , Estilo de Vida , Hipersensibilidad a la Leche/epidemiología , Animales , Grasas de la Dieta/administración & dosificación , Fibras de la Dieta/administración & dosificación , Modelos Animales de Enfermedad , Ácidos Grasos Volátiles/administración & dosificación , Humanos , Hipersensibilidad/microbiología , Pulmón/metabolismo , Pulmón/microbiología , Leche/química , Leche/inmunología , Hipersensibilidad a la Leche/microbiología , Leche Humana/química , Leche Humana/inmunología , Estudios Observacionales como AsuntoRESUMEN
The Western world has witnessed a tremendous increase in the occurrence of allergy and autoimmunity in the second half of the 20th century. Extensive efforts have been made to explain this phenomenon and various hypotheses have been formulated. Among them, two concepts have attracted the most attention: the "hygiene hypothesis," identifying the reduced exposure to environmental microorganisms as a driving force behind the observed epidemiological trends; and the "diet hypotheses," pointing to the importance of changes in our dietary habits. In this review, we discuss the interplay between the Western diet, microbiota, and inflammatory conditions, with particular emphasis on respiratory diseases. This is followed by an in-depth overview of the immunomodulatory potential of different dietary fatty acids. We conclude by identifying the outstanding questions, which, if answered, could shed further light on the impact of dietary habits on immunity and interconnect it with postulates proposed by the hygiene hypothesis. Linking these two concepts will be an important step towards understanding how Western lifestyle shapes disease susceptibility.