Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity

ABSTRACT The gut microbiota is susceptible to modulation by environmental stimuli and therefore can serve as a biological sensor. Recent evidence suggests that xenobiotics can disrupt the interaction between the microbiota and host. Here, we describe an approach that combines in vitro microbial incu...

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Autores principales:	Jingwei Cai, Robert G. Nichols, Imhoi Koo, Zachary A. Kalikow, Limin Zhang, Yuan Tian, Jingtao Zhang, Philip B. Smith, Andrew D. Patterson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	metabolomics NMR mass spectrometry metabolism toxicology xenobiotic Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/436a48a829634c6897b733884bbee6f0
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spelling	oai:doaj.org-article:436a48a829634c6897b733884bbee6f02021-12-02T18:15:43ZMultiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity10.1128/mSystems.00123-182379-5077https://doaj.org/article/436a48a829634c6897b733884bbee6f02018-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00123-18https://doaj.org/toc/2379-5077ABSTRACT The gut microbiota is susceptible to modulation by environmental stimuli and therefore can serve as a biological sensor. Recent evidence suggests that xenobiotics can disrupt the interaction between the microbiota and host. Here, we describe an approach that combines in vitro microbial incubation (isolated cecal contents from mice), flow cytometry, and mass spectrometry- and 1H nuclear magnetic resonance (NMR)-based metabolomics to evaluate xenobiotic-induced microbial toxicity. Tempol, a stabilized free radical scavenger known to remodel the microbial community structure and function in vivo, was studied to assess its direct effect on the gut microbiota. The microbiota was isolated from mouse cecum and was exposed to tempol for 4 h under strict anaerobic conditions. The flow cytometry data suggested that short-term tempol exposure to the microbiota is associated with disrupted membrane physiology as well as compromised metabolic activity. Mass spectrometry and NMR metabolomics revealed that tempol exposure significantly disrupted microbial metabolic activity, specifically indicated by changes in short-chain fatty acids, branched-chain amino acids, amino acids, nucleotides, glucose, and oligosaccharides. In addition, a mouse study with tempol (5 days gavage) showed similar microbial physiologic and metabolic changes, indicating that the in vitro approach reflected in vivo conditions. Our results, through evaluation of microbial viability, physiology, and metabolism and a comparison of in vitro and in vivo exposures with tempol, suggest that physiologic and metabolic phenotyping can provide unique insight into gut microbiota toxicity. IMPORTANCE The gut microbiota is modulated physiologically, compositionally, and metabolically by xenobiotics, potentially causing metabolic consequences to the host. We recently reported that tempol, a stabilized free radical nitroxide, can exert beneficial effects on the host through modulation of the microbiome community structure and function. Here, we investigated a multiplatform phenotyping approach that combines high-throughput global metabolomics with flow cytometry to evaluate the direct effect of tempol on the microbiota. This approach may be useful in deciphering how other xenobiotics directly influence the microbiota.Jingwei CaiRobert G. NicholsImhoi KooZachary A. KalikowLimin ZhangYuan TianJingtao ZhangPhilip B. SmithAndrew D. PattersonAmerican Society for MicrobiologyarticlemetabolomicsNMRmass spectrometrymetabolismtoxicologyxenobioticMicrobiologyQR1-502ENmSystems, Vol 3, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	metabolomics NMR mass spectrometry metabolism toxicology xenobiotic Microbiology QR1-502
spellingShingle	metabolomics NMR mass spectrometry metabolism toxicology xenobiotic Microbiology QR1-502 Jingwei Cai Robert G. Nichols Imhoi Koo Zachary A. Kalikow Limin Zhang Yuan Tian Jingtao Zhang Philip B. Smith Andrew D. Patterson Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity
description	ABSTRACT The gut microbiota is susceptible to modulation by environmental stimuli and therefore can serve as a biological sensor. Recent evidence suggests that xenobiotics can disrupt the interaction between the microbiota and host. Here, we describe an approach that combines in vitro microbial incubation (isolated cecal contents from mice), flow cytometry, and mass spectrometry- and 1H nuclear magnetic resonance (NMR)-based metabolomics to evaluate xenobiotic-induced microbial toxicity. Tempol, a stabilized free radical scavenger known to remodel the microbial community structure and function in vivo, was studied to assess its direct effect on the gut microbiota. The microbiota was isolated from mouse cecum and was exposed to tempol for 4 h under strict anaerobic conditions. The flow cytometry data suggested that short-term tempol exposure to the microbiota is associated with disrupted membrane physiology as well as compromised metabolic activity. Mass spectrometry and NMR metabolomics revealed that tempol exposure significantly disrupted microbial metabolic activity, specifically indicated by changes in short-chain fatty acids, branched-chain amino acids, amino acids, nucleotides, glucose, and oligosaccharides. In addition, a mouse study with tempol (5 days gavage) showed similar microbial physiologic and metabolic changes, indicating that the in vitro approach reflected in vivo conditions. Our results, through evaluation of microbial viability, physiology, and metabolism and a comparison of in vitro and in vivo exposures with tempol, suggest that physiologic and metabolic phenotyping can provide unique insight into gut microbiota toxicity. IMPORTANCE The gut microbiota is modulated physiologically, compositionally, and metabolically by xenobiotics, potentially causing metabolic consequences to the host. We recently reported that tempol, a stabilized free radical nitroxide, can exert beneficial effects on the host through modulation of the microbiome community structure and function. Here, we investigated a multiplatform phenotyping approach that combines high-throughput global metabolomics with flow cytometry to evaluate the direct effect of tempol on the microbiota. This approach may be useful in deciphering how other xenobiotics directly influence the microbiota.
format	article
author	Jingwei Cai Robert G. Nichols Imhoi Koo Zachary A. Kalikow Limin Zhang Yuan Tian Jingtao Zhang Philip B. Smith Andrew D. Patterson
author_facet	Jingwei Cai Robert G. Nichols Imhoi Koo Zachary A. Kalikow Limin Zhang Yuan Tian Jingtao Zhang Philip B. Smith Andrew D. Patterson
author_sort	Jingwei Cai
title	Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity
title_short	Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity
title_full	Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity
title_fullStr	Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity
title_full_unstemmed	Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity
title_sort	multiplatform physiologic and metabolic phenotyping reveals microbial toxicity
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/436a48a829634c6897b733884bbee6f0
work_keys_str_mv	AT jingweicai multiplatformphysiologicandmetabolicphenotypingrevealsmicrobialtoxicity AT robertgnichols multiplatformphysiologicandmetabolicphenotypingrevealsmicrobialtoxicity AT imhoikoo multiplatformphysiologicandmetabolicphenotypingrevealsmicrobialtoxicity AT zacharyakalikow multiplatformphysiologicandmetabolicphenotypingrevealsmicrobialtoxicity AT liminzhang multiplatformphysiologicandmetabolicphenotypingrevealsmicrobialtoxicity AT yuantian multiplatformphysiologicandmetabolicphenotypingrevealsmicrobialtoxicity AT jingtaozhang multiplatformphysiologicandmetabolicphenotypingrevealsmicrobialtoxicity AT philipbsmith multiplatformphysiologicandmetabolicphenotypingrevealsmicrobialtoxicity AT andrewdpatterson multiplatformphysiologicandmetabolicphenotypingrevealsmicrobialtoxicity
_version_	1718378329594134528

Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity

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