The gut microbiome as a potential source of non-invasive biomarkers of chronic obstructive pulmonary disease

Li, Naijian; Yi, Xinzhu; C, Chen; Dai, Zhouli; Deng, Zhishan; Pu, Jinding; Zhou, Yumin; Li, Bing; Wang, Zhang; Ran, Pixin

doi:10.3389/fmicb.2023.1173614

Cited by 6 publications

(4 citation statements)

References 44 publications

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“…8 Chinese mild COPD cohorts had higher abundance of Prevotellaceae while patients with severe disease had lower abundance of Bacteroidaceae and Fusobacteriaceae, 43 and identified that Bacteroides sp CAG875, Christensenella minuta and Clostridium sp Marseille-P2538 were the most abundant species in faeces differentiating healthy donors from patients with COPD. 44 In a Korean cohort, patients with COPD were differentiated from asymptomatic smokers by 17 bacterial groups including lower Prevotella copri, Dialister succinatiphilus and Catenibacterium mitsuokai and increased Bacteroides fragilis and Bifidobacterium longum, 45 highlighting the challenges of identifying a consistent microbial marker of disease especially given the demographic differences between cohorts. Some studies in mice have identified that CS-exposure increased Lachnospiraceae abundance, 11 while others report decreases.…”

Section: Discussionmentioning

confidence: 99%

Faecal microbial transfer and complex carbohydrates mediate protection against COPD

Budden,

Shukla,

Bowerman

et al. 2024

Gut

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ObjectiveChronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear.DesignUsing anin vivomouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation.ResultsFMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance ofMuribaculaceae, DesulfovibrionaceaeandLachnospiraceaefamily members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes.ConclusionThe gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

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Section: Discussionmentioning

confidence: 99%

Faecal microbial transfer and complex carbohydrates mediate protection against COPD

Budden,

Shukla,

Bowerman

et al. 2024

Gut

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“…As a whole, we report new data supporting important NLRP6 functions in basal and pathological lung settings that could be translated to a clinical setting following preclinical validations. Gut microbiota-derived metabolites or components might represent biomarkers present in the blood of COPD patients ( 43 , 71 ). In addition, this study uncovers NLRP6 as a new target for the development of potential therapeutic strategies against COPD by specific inhibition of NLRP6.…”

Section: Discussionmentioning

confidence: 99%

NLRP6 controls pulmonary inflammation from cigarette smoke in a gut microbiota-dependent manner

Nascimento,

Huot-Marchand,

Fanny

et al. 2023

Front. Immunol.

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Chronic obstructive pulmonary disease (COPD) is a major health issue primarily caused by cigarette smoke (CS) and characterized by breathlessness and repeated airway inflammation. NLRP6 is a cytosolic innate receptor controlling intestinal inflammation and orchestrating the colonic host–microbial interface. However, its roles in the lungs remain largely unexplored. Using CS exposure models, our data show that airway inflammation is strongly impaired in Nlrp6-deficient mice with drastically fewer recruited neutrophils, a key cell subset in inflammation and COPD. We found that NLRP6 expression in lung epithelial cells is important to control airway and lung tissue inflammation in an inflammasome-dependent manner. Since gut-derived metabolites regulate NLRP6 inflammasome activation in intestinal epithelial cells, we investigated the link between NLRP6, CS-driven lung inflammation, and gut microbiota composition. We report that acute CS exposure alters gut microbiota in both wild-type (WT) and Nlrp6-deficient mice and that antibiotic treatment decreases CS-induced lung inflammation. In addition, gut microbiota transfer from dysbiotic Nlrp6-deficient mice to WT mice decreased airway lung inflammation in WT mice, highlighting an NLRP6-dependent gut-to-lung axis controlling pulmonary inflammation.

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“…Thus, integrating the oral–lung axis as a single niche with inter‐connected microenvironments may take multi‐omics microbiome studies into a next level, towards establishing more robust clinically meaningful interactions between exposure, microbial dysbiosis and disease outcomes. Going further, functional associations between oral–lung dysbiosis and respiratory dysfunction could be expanded towards a more comprehensive view by integrating links between gut microbiota dysbiosis and airway disease into the equation, as gut dysbiosis is another well‐known microbiome contributor of COPD development (Li et al., 2021 ; Li, Wang, et al., 2023 ; Li, Yi, et al., 2023 ; Wang et al., 2023 ) (Figure 1 , lower left panels).…”

Section: Challenges and Opportunities Of The Oral–lung Axis Microbiom...mentioning

confidence: 99%

Environmental exposures, the oral–lung axis and respiratory health: The airway microbiome goes on stage for the personalized management of human lung function

Garmendia,

Cebollero‐Rivas

2024

Microbial Biotechnology

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The human respiratory system is constantly exposed to environmental stimuli, sometimes including toxicants, which can trigger dysregulated lung immune responses that lead to respiratory symptoms, impaired lung function and airway diseases. Evidence supports that the microbiome in the lungs has an indispensable role in respiratory health and disease, acting as a local gatekeeper that mediates the interaction between the environmental cues and respiratory health. Moreover, the microbiome in the lungs is intimately intertwined with the oral microbiome through the oral–lung axis. Here, we discuss the intricate three‐way relationship between (i) cigarette smoking, which has strong effects on the microbial community structure of the lung; (ii) microbiome dysbiosis and disease in the oral cavity; and (iii) microbiome dysbiosis in the lung and its causal role in patients suffering chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality worldwide. We highlight exciting outcomes arising from recently established interactions in the airway between environmental exposures, microbiome, metabolites–functional attributes and the host, as well as how these associations have the potential to predict the respiratory health status of the host through an airway microbiome health index. For completion, we argue that incorporating (synthetic) microbial community ecology in our contemporary understanding of lung disease presents challenges and also rises novel opportunities to exploit the oral–lung axis and its microbiome towards innovative airway disease diagnostics, prognostics, patient stratification and microbiota‐targeted clinical interventions in the context of current therapies.

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The gut microbiome as a potential source of non-invasive biomarkers of chronic obstructive pulmonary disease

Cited by 6 publications

References 44 publications

Faecal microbial transfer and complex carbohydrates mediate protection against COPD

Faecal microbial transfer and complex carbohydrates mediate protection against COPD

NLRP6 controls pulmonary inflammation from cigarette smoke in a gut microbiota-dependent manner

Environmental exposures, the oral–lung axis and respiratory health: The airway microbiome goes on stage for the personalized management of human lung function

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