Gut Dysbiosis and Its Associations with Gut Microbiota-Derived Metabolites in Dogs with Myxomatous Mitral Valve Disease

ABSTRACT Gut dysbiosis and gut microbiota-derived metabolites, including bile acid (BA), short-chain fatty acid, and trimethylamine N-oxide (TMAO), are associated with cardiovascular disease. Canine myxomatous mitral valve disease (MMVD) is a model for human MMVD. The aim of the study is to evaluate...

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Autores principales:	Qinghong Li, Éva Larouche-Lebel, Kerry A. Loughran, Terry P. Huh, Jan S. Suchodolski, Mark A. Oyama
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	microbiota trimethylamine N-oxide mitral valve disease canine dysbiosis bile acid Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4420997eaf8f4c7e92984b96b8bc2b00
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spelling	oai:doaj.org-article:4420997eaf8f4c7e92984b96b8bc2b002021-12-02T18:21:19ZGut Dysbiosis and Its Associations with Gut Microbiota-Derived Metabolites in Dogs with Myxomatous Mitral Valve Disease10.1128/mSystems.00111-212379-5077https://doaj.org/article/4420997eaf8f4c7e92984b96b8bc2b002021-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00111-21https://doaj.org/toc/2379-5077ABSTRACT Gut dysbiosis and gut microbiota-derived metabolites, including bile acid (BA), short-chain fatty acid, and trimethylamine N-oxide (TMAO), are associated with cardiovascular disease. Canine myxomatous mitral valve disease (MMVD) is a model for human MMVD. The aim of the study is to evaluate gut microbial dysbiosis and its relationship with gut-produced metabolites in dogs with MMVD. Fecal samples from 92 privately owned dogs, including 17 healthy, 23 and 27 asymptomatic MMVD dogs without (stage B1) and with (stage B2) secondary cardiac enlargement, respectively, and 25 MMVD dogs with history of congestive heart failure (stage C or D), were analyzed by 16S rRNA sequencing. Alpha and beta diversities were different between healthy and MMVD dogs (adjusted P < 0.05). The average dysbiosis indexes were −1.48, −0.6, 0.01, and 1.47 for healthy, B1, B2, and C/D dogs, respectively (P = 0.07). Dysbiosis index was negatively correlated with Clostridium hiranonis (P < 0.0001, r = −0.79). Escherichia coli, capable of trimethylamine production in the gut, had an increased abundance (adjusted P < 0.05) and may be responsible for the increased circulating TMAO levels in stage B2 and C/D MMVD dogs. Primary and secondary BAs showed opposite associations with C. hiranonis, a key BA converter (P < 0.0001 for both, r = −0.94 and 0.95, respectively). Secondary BAs appeared to promote the growth of Fusobacterium and Faecalibacterium but inhibit that of E. coli. Multivariate analysis revealed significant but weak associations between gut microbiota and several circulating metabolites, including short-chain acylcarnitines and TMAO. IMPORTANCE Our study expands the current “gut hypothesis” to include gut dysbiosis at the preclinical stage, prior to the onset of heart failure. Gut dysbiosis index increases in proportion to the severity of myxomatous mitral valve disease (MMVD) and is inversely associated with Clostridium hiranonis, a key bile acid (BA) converter in the gut. Secondary BAs appear to promote the growth of beneficial bacteria but inhibit that of harmful ones. An intricate interplay between gut microbiota, gut microbiota-produced metabolites, and MMVD pathophysiological progression is implicated.Qinghong LiÉva Larouche-LebelKerry A. LoughranTerry P. HuhJan S. SuchodolskiMark A. OyamaAmerican Society for Microbiologyarticlemicrobiotatrimethylamine N-oxidemitral valve diseasecaninedysbiosisbile acidMicrobiologyQR1-502ENmSystems, Vol 6, Iss 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microbiota trimethylamine N-oxide mitral valve disease canine dysbiosis bile acid Microbiology QR1-502
spellingShingle	microbiota trimethylamine N-oxide mitral valve disease canine dysbiosis bile acid Microbiology QR1-502 Qinghong Li Éva Larouche-Lebel Kerry A. Loughran Terry P. Huh Jan S. Suchodolski Mark A. Oyama Gut Dysbiosis and Its Associations with Gut Microbiota-Derived Metabolites in Dogs with Myxomatous Mitral Valve Disease
description	ABSTRACT Gut dysbiosis and gut microbiota-derived metabolites, including bile acid (BA), short-chain fatty acid, and trimethylamine N-oxide (TMAO), are associated with cardiovascular disease. Canine myxomatous mitral valve disease (MMVD) is a model for human MMVD. The aim of the study is to evaluate gut microbial dysbiosis and its relationship with gut-produced metabolites in dogs with MMVD. Fecal samples from 92 privately owned dogs, including 17 healthy, 23 and 27 asymptomatic MMVD dogs without (stage B1) and with (stage B2) secondary cardiac enlargement, respectively, and 25 MMVD dogs with history of congestive heart failure (stage C or D), were analyzed by 16S rRNA sequencing. Alpha and beta diversities were different between healthy and MMVD dogs (adjusted P < 0.05). The average dysbiosis indexes were −1.48, −0.6, 0.01, and 1.47 for healthy, B1, B2, and C/D dogs, respectively (P = 0.07). Dysbiosis index was negatively correlated with Clostridium hiranonis (P < 0.0001, r = −0.79). Escherichia coli, capable of trimethylamine production in the gut, had an increased abundance (adjusted P < 0.05) and may be responsible for the increased circulating TMAO levels in stage B2 and C/D MMVD dogs. Primary and secondary BAs showed opposite associations with C. hiranonis, a key BA converter (P < 0.0001 for both, r = −0.94 and 0.95, respectively). Secondary BAs appeared to promote the growth of Fusobacterium and Faecalibacterium but inhibit that of E. coli. Multivariate analysis revealed significant but weak associations between gut microbiota and several circulating metabolites, including short-chain acylcarnitines and TMAO. IMPORTANCE Our study expands the current “gut hypothesis” to include gut dysbiosis at the preclinical stage, prior to the onset of heart failure. Gut dysbiosis index increases in proportion to the severity of myxomatous mitral valve disease (MMVD) and is inversely associated with Clostridium hiranonis, a key bile acid (BA) converter in the gut. Secondary BAs appear to promote the growth of beneficial bacteria but inhibit that of harmful ones. An intricate interplay between gut microbiota, gut microbiota-produced metabolites, and MMVD pathophysiological progression is implicated.
format	article
author	Qinghong Li Éva Larouche-Lebel Kerry A. Loughran Terry P. Huh Jan S. Suchodolski Mark A. Oyama
author_facet	Qinghong Li Éva Larouche-Lebel Kerry A. Loughran Terry P. Huh Jan S. Suchodolski Mark A. Oyama
author_sort	Qinghong Li
title	Gut Dysbiosis and Its Associations with Gut Microbiota-Derived Metabolites in Dogs with Myxomatous Mitral Valve Disease
title_short	Gut Dysbiosis and Its Associations with Gut Microbiota-Derived Metabolites in Dogs with Myxomatous Mitral Valve Disease
title_full	Gut Dysbiosis and Its Associations with Gut Microbiota-Derived Metabolites in Dogs with Myxomatous Mitral Valve Disease
title_fullStr	Gut Dysbiosis and Its Associations with Gut Microbiota-Derived Metabolites in Dogs with Myxomatous Mitral Valve Disease
title_full_unstemmed	Gut Dysbiosis and Its Associations with Gut Microbiota-Derived Metabolites in Dogs with Myxomatous Mitral Valve Disease
title_sort	gut dysbiosis and its associations with gut microbiota-derived metabolites in dogs with myxomatous mitral valve disease
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/4420997eaf8f4c7e92984b96b8bc2b00
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Gut Dysbiosis and Its Associations with Gut Microbiota-Derived Metabolites in Dogs with Myxomatous Mitral Valve Disease

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