Chronic obstructive pulmonary disease (COPD) is the third commonest cause of death globally, and manifests as a progressive inflammatory lung disease with no curative treatment. The lung microbiome ...contributes to COPD progression, but the function of the gut microbiome remains unclear. Here we examine the faecal microbiome and metabolome of COPD patients and healthy controls, finding 146 bacterial species differing between the two groups. Several species, including Streptococcus sp000187445, Streptococcus vestibularis and multiple members of the family Lachnospiraceae, also correlate with reduced lung function. Untargeted metabolomics identifies a COPD signature comprising 46% lipid, 20% xenobiotic and 20% amino acid related metabolites. Furthermore, we describe a disease-associated network connecting Streptococcus parasanguinis_B with COPD-associated metabolites, including N-acetylglutamate and its analogue N-carbamoylglutamate. While correlative, our results suggest that the faecal microbiome and metabolome of COPD patients are distinct from those of healthy individuals, and may thus aid in the search for biomarkers for COPD.
Chronic obstructive pulmonary disease (COPD) primarily affects the lungs but due to the accompanying chronic systematic inflammation and the symptoms associated with the disease there are many ...extrapulmonary effects which include complex physical and metabolic adaptations. These changes have been associated with reduced exercise capacity, increased nutritional requirements, altered metabolic processes and compromised nutritional intake. As a result, nutritional depletion in COPD is multi-faceted and can involve imbalances of energy (weight loss), protein (sarcopenia), and periods of markedly increased inflammation (pulmonary cachexia) which can increase nutritional losses. As a result, depletion of both fat-mass (FM) and fat-free mass (FFM) can occur. There is good evidence that nutritional support, in the form of oral nutritional supplements (ONS), can overcome energy and protein imbalances resulting in improved nutritional status and functional capacity. However, in order to treat the aetiology of sarcopenia, frailty and cachexia, it is likely that targeted multi-modal interventions are required to address energy and protein imbalance, specific nutrient deficiencies, reduced androgens and targeted exercise training. Furthermore, interventions taking a disease-course approach, are likely to hold the key to effectively managing the common and costly problem of nutritional depletion in COPD.
are prominent gut commensals that produce the short-chain fatty acid (SCFA) acetate, and they are often used as probiotics. Connections between the gut and the lung, termed the gut-lung axis, are ...regulated by the microbiome. The gut-lung axis is increasingly implicated in cigarette smoke-induced diseases, and cigarette smoke exposure has been associated with depletion of
species. In this study, we assessed the impact of acetate-producing
subsp.
(WT) and a mutant strain with an impaired acetate production capacity (MUT) on cigarette smoke-induced inflammation. The mice were treated with WT or MUT
subsp.
and exposed to cigarette smoke for 8 weeks before assessments of lung inflammation, lung tissue gene expression and cecal SCFAs were performed. Both strains of
subsp.
reduced lung inflammation, inflammatory cytokine expression and adhesion factor expression and alleviated cigarette smoke-induced depletion in caecum butyrate. Thus, the probiotic administration of
subsp.
irrespective of its acetate-producing capacity, alleviated cigarette smoke-induced inflammation and the depletion of cecal butyrate levels.
Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung fibrosis, and lung cancer, pose a huge socio-economic burden on society and are one of the leading causes of ...death worldwide. In the past, culture-dependent techniques could not detect bacteria in the lungs, therefore the lungs were considered a sterile environment. However, the development of culture-independent techniques, particularly 16S rRNA sequencing, allowed for the detection of commensal microbes in the lung and with further investigation, their roles in disease have since emerged. In healthy individuals, the predominant commensal microbes are of phylum Firmicutes and Bacteroidetes, including those of the genera
Veillonella
and
Prevotella
. In contrast, pathogenic microbes (
Haemophilus, Streptococcus, Klebsiella, Pseudomonas
) are often associated with lung diseases. There is growing evidence that microbial metabolites, structural components, and toxins from pathogenic and opportunistic bacteria have the capacity to stimulate both innate and adaptive immune responses, and therefore can contribute to the pathogenesis of lung diseases. Here we review the multiple mechanisms that are altered by pathogenic microbiomes in asthma, COPD, lung cancer, and lung fibrosis. Furthermore, we focus on the recent exciting advancements in therapies that can be used to restore altered microbiomes in the lungs.
Current management strategies for chronic obstructive pulmonary disease (COPD) incorporate a step-wise, multidisciplinary approach to effectively manage patient symptoms and prevent disease ...progression. However, there has been limited advancement in therapies to address the underlying cause of COPD pathogenesis. Recent research has established the link between the lungs and the gut—the gut-lung axis -and the gut microbiome is a major component. The gut microbiome is likely perturbed in COPD, contributing to chronic inflammation. Diet is a readily modifiable factor and the diet of COPD patients is often deficient in nutrients such as fibre. The metabolism of dietary fibre by gut microbiomes produces anti-inflammatory short chain fatty acid (SCFAs), which could protect against inflammation in the lungs. By addressing the ‘fibre gap’ in the diet of COPD patients, this targeted dietary intervention may reduce inflammation, both systemically and in the airways, and value-add to the paradigm shift in respiratory medicine, from reactive to personalised and participatory medicine.
The health effects of e-cigarettes in patients with pre-existing lung disease are unknown. The aim of this study was to investigate whether aerosols from a fourth-generation e-cigarette produces ...similar in-vitro cytotoxic, DNA damage and inflammatory effects on bronchial epithelial cells (BECs) from patients with COPD, as cigarette smoke.
BECs from patients with COPD who underwent surgery for lung cancer and comparator (immortalised 16HBE) cells were grown at air liquid interface (ALI). BECs were exposed to aerosols from a JUUL® e-cigarette (Virginia Tobacco and Menthol pods at 5% nicotine strength) or reference 3R4F cigarette for 30 min at ALI. Cell cytotoxicity, DNA damage and inflammation were measured.
In response to the Virginia Tobacco and Menthol flavoured e-cigarette aerosols, COPD BECs showed comparable LDH release (cell cytotoxicity, p = 0.59, p = 0.67 respectively), DNA damage (p = 0.41, p = 0.51) and inflammation (IL-8, p = 0.20, p = 0.89 and IL-6, p = 0.24, p = 0.93), to cigarette smoke. 16HBE cells also showed comparable cellular responses to cigarette smoke.
In airway cells from patients with COPD, aerosols from a fourth-generation e-cigarette were associated with similar toxicity to cigarette smoke. These results have potential implications for the safety of e-cigarette use in patients with lung disease.
•E-cigarette aerosols cause similar adverse effects as cigarette smoke in bronchial epithelial cells from COPD patients .•Heightened cell cytotoxicity, DNA damage and inflammation was observed in in as little as 30 min of aerosol exposure.•E-liquid flavourings and their composition are an important source of toxicity.
Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death world-wide by 2020. Prolonged exposure to particulate matter is associated with COPD progression and mortality. ...Diesel emissions are a major contributor to particulate matter pollution. In this study we test a therapeutic antioxidant, N-acetylcysteine (NAC), for its ability to protect bronchial epithelial cells (pHBECs) from patients with COPD from adverse effects of diesel emission exposure.
pHBECs from patients with or without COPD were cultured at air-liquid interface (ALI). Cells were exposed to diesel emissions for 30 min with or without 3-h post-exposure treatment with 5 mM N-acetylcysteine (NAC). Filtered laboratory air was tested as a negative control. Cell responses (cell viability, inflammation and oxidative stress) and gene expression profiles for intracellular and immune signaling were assessed.
Diesel emissions exposure increased IL-8 secretion and production, antioxidant production, and cytochrome P450 1a1 (CYP1a1) mRNA expression and suppressed superoxide dismutase-1 (SOD1) mRNA expression in bronchial epithelial cells from COPD patients. Treatment with N-acetyl cysteine attenuated the suppression of SOD1. Nanostring gene expression profiling of the filtered air controls showed COPD epithelial cells have increased expression of MHC class II and an interferon signaling profile.
This study indicates that bronchial epithelial cells from COPD patients may be vulnerable to diesel emission exposure due to reduced antioxidant capacity, and elevated CYP1a1 mRNA expression. NAC did not appear to offer protection. Future research will be needed to explore other means of recovering oxidant capacity in COPD airways.
•Diesel emission exposure leads to inflammation and oxidative stress in pHBECs.•COPD pHBECs may have reduced antioxidant and a heightened metabolic responses.•COPD pHBECs may promote a CD4+ Th1 immune response.•N-acetylcysteine had a limited effect on inflammation and oxidative stress.
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