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Ozone-induced changes in the serum metabolome: Role of the microbiome.
PLoS One 2019; 14(8):e0221633Plos

Abstract

Ozone is an asthma trigger. In mice, the gut microbiome contributes to ozone-induced airway hyperresponsiveness, a defining feature of asthma, but the mechanistic basis for the role of the gut microbiome has not been established. Gut bacteria can affect the function of distal organs by generating metabolites that enter the blood and circulate systemically. We hypothesized that global metabolomic profiling of serum collected from ozone exposed mice could be used to identify metabolites contributing to the role of the microbiome in ozone-induced airway hyperresponsiveness. Mice were treated for two weeks with a cocktail of antibiotics (ampicillin, neomycin, metronidazole, and vancomycin) in the drinking water or with control water and then exposed to air or ozone (2 ppm for 3 hours). Twenty four hours later, blood was harvested and serum analyzed via liquid-chromatography or gas-chromatography coupled to mass spectrometry. Antibiotic treatment significantly affected 228 of the 562 biochemicals identified, including reductions in the known bacterially-derived metabolites, equol, indole propionate, 3-indoxyl sulfate, and 3-(4-hydroxyphenyl)propionate, confirming the efficacy of the antibiotic treatment. Ozone exposure caused significant changes in 334 metabolites. Importantly, ozone-induced changes in many of these metabolites were different in control and antibiotic-treated mice. For example, most medium and long chain fatty acids declined by 20-50% with ozone exposure in antibiotic-treated but not control mice. Most taurine-conjugated bile acids increased with ozone exposure in antibiotic-treated but not control mice. Ozone also caused marked (9-fold and 5-fold) increases in the polyamines, spermine and spermidine, respectively, in control but not antibiotic-treated mice. Each of these metabolites has the capacity to alter airway responsiveness and may account for the role of the microbiome in pulmonary responses to ozone.

Authors+Show Affiliations

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.Metabolon Inc., Durham, North Carolina, United States of America.Metabolon Inc., Durham, North Carolina, United States of America.Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31454377

Citation

Cho, Youngji, et al. "Ozone-induced Changes in the Serum Metabolome: Role of the Microbiome." PloS One, vol. 14, no. 8, 2019, pp. e0221633.
Cho Y, Osgood RS, Bell LN, et al. Ozone-induced changes in the serum metabolome: Role of the microbiome. PLoS ONE. 2019;14(8):e0221633.
Cho, Y., Osgood, R. S., Bell, L. N., Karoly, E. D., & Shore, S. A. (2019). Ozone-induced changes in the serum metabolome: Role of the microbiome. PloS One, 14(8), pp. e0221633. doi:10.1371/journal.pone.0221633.
Cho Y, et al. Ozone-induced Changes in the Serum Metabolome: Role of the Microbiome. PLoS ONE. 2019;14(8):e0221633. PubMed PMID: 31454377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ozone-induced changes in the serum metabolome: Role of the microbiome. AU - Cho,Youngji, AU - Osgood,Ross S, AU - Bell,Lauren N, AU - Karoly,Edward D, AU - Shore,Stephanie A, Y1 - 2019/08/27/ PY - 2019/05/07/received PY - 2019/08/12/accepted PY - 2019/8/28/entrez PY - 2019/8/28/pubmed PY - 2019/8/28/medline SP - e0221633 EP - e0221633 JF - PloS one JO - PLoS ONE VL - 14 IS - 8 N2 - Ozone is an asthma trigger. In mice, the gut microbiome contributes to ozone-induced airway hyperresponsiveness, a defining feature of asthma, but the mechanistic basis for the role of the gut microbiome has not been established. Gut bacteria can affect the function of distal organs by generating metabolites that enter the blood and circulate systemically. We hypothesized that global metabolomic profiling of serum collected from ozone exposed mice could be used to identify metabolites contributing to the role of the microbiome in ozone-induced airway hyperresponsiveness. Mice were treated for two weeks with a cocktail of antibiotics (ampicillin, neomycin, metronidazole, and vancomycin) in the drinking water or with control water and then exposed to air or ozone (2 ppm for 3 hours). Twenty four hours later, blood was harvested and serum analyzed via liquid-chromatography or gas-chromatography coupled to mass spectrometry. Antibiotic treatment significantly affected 228 of the 562 biochemicals identified, including reductions in the known bacterially-derived metabolites, equol, indole propionate, 3-indoxyl sulfate, and 3-(4-hydroxyphenyl)propionate, confirming the efficacy of the antibiotic treatment. Ozone exposure caused significant changes in 334 metabolites. Importantly, ozone-induced changes in many of these metabolites were different in control and antibiotic-treated mice. For example, most medium and long chain fatty acids declined by 20-50% with ozone exposure in antibiotic-treated but not control mice. Most taurine-conjugated bile acids increased with ozone exposure in antibiotic-treated but not control mice. Ozone also caused marked (9-fold and 5-fold) increases in the polyamines, spermine and spermidine, respectively, in control but not antibiotic-treated mice. Each of these metabolites has the capacity to alter airway responsiveness and may account for the role of the microbiome in pulmonary responses to ozone. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/31454377/Ozone_induced_changes_in_the_serum_metabolome:_Role_of_the_microbiome_ L2 - http://dx.plos.org/10.1371/journal.pone.0221633 DB - PRIME DP - Unbound Medicine ER -