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000268848 041__ $$aEnglish
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000268848 1001_ $$00000-0002-7435-275X$$aBudden, Kurtis F$$b0
000268848 245__ $$aFaecal microbial transfer and complex carbohydrates mediate protection against COPD.
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000268848 520__ $$aChronic 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.Using an in vivo mouse 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.FMT 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 of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family 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.The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.
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000268848 650_7 $$2Other$$aBASIC SCIENCES
000268848 650_7 $$2Other$$aCOLONIC MICROFLORA
000268848 650_7 $$2Other$$aDIETARY FIBRE
000268848 650_7 $$2Other$$aIMMUNOLOGY
000268848 650_7 $$2Other$$aINFLAMMATORY DISEASES
000268848 650_7 $$2NLM Chemicals$$aCarbohydrates
000268848 650_2 $$2MeSH$$aHumans
000268848 650_2 $$2MeSH$$aMice
000268848 650_2 $$2MeSH$$aAnimals
000268848 650_2 $$2MeSH$$aPulmonary Disease, Chronic Obstructive: etiology
000268848 650_2 $$2MeSH$$aLung: metabolism
000268848 650_2 $$2MeSH$$aLung: pathology
000268848 650_2 $$2MeSH$$aPneumonia: etiology
000268848 650_2 $$2MeSH$$aInflammation: metabolism
000268848 650_2 $$2MeSH$$aCarbohydrates: pharmacology
000268848 693__ $$0EXP:(DE-2719)PRECISE-20190321$$5EXP:(DE-2719)PRECISE-20190321$$ePlatform for Single Cell Genomics and Epigenomics at DZNE  University of Bonn$$x0
000268848 7001_ $$00000-0002-5796-0171$$aShukla, Shakti D$$b1
000268848 7001_ $$00000-0003-2339-114X$$aBowerman, Kate L$$b2
000268848 7001_ $$00000-0001-5890-7877$$aVaughan, Annalicia$$b3
000268848 7001_ $$00000-0002-7361-2337$$aGellatly, Shaan L$$b4
000268848 7001_ $$00000-0002-1001-2019$$aWood, David L A$$b5
000268848 7001_ $$aLachner, Nancy$$b6
000268848 7001_ $$00000-0001-8512-7593$$aIdrees, Sobia$$b7
000268848 7001_ $$00000-0001-6269-355X$$aRehman, Saima Firdous$$b8
000268848 7001_ $$00000-0003-1740-3538$$aFaiz, Alen$$b9
000268848 7001_ $$aPatel, Vyoma K$$b10
000268848 7001_ $$00000-0003-4558-329X$$aDonovan, Chantal$$b11
000268848 7001_ $$aAlemao, Charlotte A$$b12
000268848 7001_ $$00000-0002-1004-1936$$aShen, Sj$$b13
000268848 7001_ $$00000-0002-3619-7410$$aAmorim, Nadia$$b14
000268848 7001_ $$00000-0002-7244-6058$$aMajumder, Rajib$$b15
000268848 7001_ $$00000-0003-3641-2499$$aVanka, Kanth S$$b16
000268848 7001_ $$aMason, Jazz$$b17
000268848 7001_ $$00000-0003-2315-7089$$aHaw, Tatt Jhong$$b18
000268848 7001_ $$00000-0002-0159-6649$$aTillet, Bree$$b19
000268848 7001_ $$00000-0002-8587-1774$$aFricker, Michael$$b20
000268848 7001_ $$00000-0002-1248-9590$$aKeely, Simon$$b21
000268848 7001_ $$00000-0002-2371-7990$$aHansbro, Nicole$$b22
000268848 7001_ $$00000-0002-9660-9587$$aBelz, Gabrielle T$$b23
000268848 7001_ $$00000-0002-8526-0631$$aHorvat, Jay$$b24
000268848 7001_ $$00000-0001-7269-7773$$aAshhurst, Thomas$$b25
000268848 7001_ $$00000-0003-4151-3470$$avan Vreden, Caryn$$b26
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000268848 7001_ $$00000-0001-6817-9690$$aFazekas de St Groth, Barbara$$b28
000268848 7001_ $$00000-0002-3877-9772$$aKing, Nicholas J C$$b29
000268848 7001_ $$00000-0001-5366-4554$$aCrossett, Ben$$b30
000268848 7001_ $$00000-0002-0995-0171$$aCordwell, Stuart J$$b31
000268848 7001_ $$0P:(DE-2719)9001512$$aBonaguro, Lorenzo$$b32$$udzne
000268848 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b33
000268848 7001_ $$00000-0003-4892-3691$$aHamilton-Williams, Emma E$$b34
000268848 7001_ $$aMann, Elizabeth$$b35
000268848 7001_ $$00000-0003-4144-2537$$aForster, Samuel C$$b36
000268848 7001_ $$00000-0003-4144-2537$$aCooper, Matthew A$$b37
000268848 7001_ $$00000-0003-3559-9431$$aSegal, Leopoldo N$$b38
000268848 7001_ $$aChotirmall, Sanjay H$$b39
000268848 7001_ $$00000-0002-5273-8213$$aCollins, Peter$$b40
000268848 7001_ $$aBowman, Rayleen$$b41
000268848 7001_ $$00000-0002-6507-1403$$aFong, Kwun M$$b42
000268848 7001_ $$00000-0001-8338-1993$$aYang, Ian A$$b43
000268848 7001_ $$00000-0001-5676-6126$$aWark, Peter A B$$b44
000268848 7001_ $$00000-0002-4895-3105$$aDennis, Paul G$$b45
000268848 7001_ $$00000-0001-5386-7925$$aHugenholtz, Philip$$b46
000268848 7001_ $$00000-0002-4741-3035$$aHansbro, Philip M$$b47
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