Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity

doi:10.1128/mSystems.00123-18

CORC > 武汉植物园 > 中国科学院武汉植物园

	Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity
	Patterson, Andrew D.3; Smith, Philip B.1; Zhang, Jingtao 3; Tian, Yuan 2,3; Zhang, Limin 2,3; Kalikow, Zachary A.3; Koo, Imhoi 3; Nichols, Robert G.3; Cai, Jingwei 3
刊名	MSYSTEMS
	2018-11-01
卷号	3 期号:6 页码:14
关键词	metabolomics NMR mass spectrometry metabolism toxicology xenobiotic
ISSN号	2379-5077
DOI	10.1128/mSystems.00123-18
英文摘要	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 'H 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 oli-gosaccharides. 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.
资助项目	NIH[ES022186] ; NIH[ES028288] ; NIH[026684] ; Huck Institutes of the Life Sciences (Penn State University) ; Pennsylvania Department of Health Tobacco CURE funds
WOS研究方向	Microbiology
语种	英语
出版者	AMER SOC MICROBIOLOGY
WOS记录号	WOS:000455120400004
内容类型	期刊论文
源URL	[http://202.127.146.157/handle/2RYDP1HH/6252]
专题	中国科学院武汉植物园
通讯作者	Patterson, Andrew D.
作者单位	1.Penn State Univ, Metabol Facil, Huck Inst Life Sci, University Pk, PA 16802 USA 2.Chinese Acad Sci, CAS Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Natl Ctr Magnet Resonance Wuhan,Wuhan Inst Phys &, Wuhan, Hubei, Peoples R China 3.Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA
推荐引用方式 GB/T 7714	Patterson, Andrew D.,Smith, Philip B.,Zhang, Jingtao,et al. Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity[J]. MSYSTEMS,2018,3(6):14.
APA	Patterson, Andrew D..,Smith, Philip B..,Zhang, Jingtao.,Tian, Yuan.,Zhang, Limin.,...&Cai, Jingwei.(2018).Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity.MSYSTEMS,3(6),14.
MLA	Patterson, Andrew D.,et al."Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity".MSYSTEMS 3.6(2018):14.