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Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity
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 (i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222046/ https://www.ncbi.nlm.nih.gov/pubmed/30417115 http://dx.doi.org/10.1128/mSystems.00123-18 |
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author | Cai, Jingwei Nichols, Robert G. Koo, Imhoi Kalikow, Zachary A. Zhang, Limin Tian, Yuan Zhang, Jingtao Smith, Philip B. Patterson, Andrew D. |
author_facet | Cai, Jingwei Nichols, Robert G. Koo, Imhoi Kalikow, Zachary A. Zhang, Limin Tian, Yuan Zhang, Jingtao Smith, Philip B. Patterson, Andrew D. |
author_sort | Cai, Jingwei |
collection | PubMed |
description | 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 (1)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 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 | Online Article Text |
id | pubmed-6222046 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62220462018-11-09 Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity Cai, Jingwei Nichols, Robert G. Koo, Imhoi Kalikow, Zachary A. Zhang, Limin Tian, Yuan Zhang, Jingtao Smith, Philip B. Patterson, Andrew D. mSystems Research Article 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 (1)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 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. American Society for Microbiology 2018-11-06 /pmc/articles/PMC6222046/ /pubmed/30417115 http://dx.doi.org/10.1128/mSystems.00123-18 Text en Copyright © 2018 Cai et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Cai, Jingwei Nichols, Robert G. Koo, Imhoi Kalikow, Zachary A. Zhang, Limin Tian, Yuan Zhang, Jingtao Smith, Philip B. Patterson, Andrew D. Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity |
title | 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_short | Multiplatform Physiologic and Metabolic Phenotyping Reveals Microbial Toxicity |
title_sort | multiplatform physiologic and metabolic phenotyping reveals microbial toxicity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222046/ https://www.ncbi.nlm.nih.gov/pubmed/30417115 http://dx.doi.org/10.1128/mSystems.00123-18 |
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