This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Pritam Sukul
University Medicine Rostock
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5114-1776
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- This study involved human subjects.
- The author confirmed that all appropriate ethical guidelines for the use of human subjects have been followed, any necessary IRB and/or ethics committee review has been obtained, and information about the IRB/ethics committee is included in the manuscript.
- The author has confirmed that all necessary patient/participant consent or assent has been obtained and the appropriate institutional forms have been archived. If the IRB/ethics committee waived the requirement for patient/participant consent or assent, an explanation for the waiver is included in the text.
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
Background: Isoprene (C5H8) is a clinically important breath metabolite. Although, hundreds of studies have reported differential expressions in isoprene exhalation as breath biomarker for diverse diseases, the substance couldn’t enter to clinical practice as diagnostic marker. Moreover, many experimental/basic observations upon breath isoprene remained unrelated to the corresponding pathophysiological effects on its putative metabolic origin (i.e. mevalonate pathway). Here, we investigated the fundamental reason that hindered the rational interpretation and translation of this marker from basic to clinical science.
Methods: Via high-resolution mass-spectrometry based breathomics in 1026 human subjects, we discovered adults with significant deficiency (order of magnitude lower than the normal) and complete absence of breath isoprene. We prospectively applied real-time breathomics, quantitative gene expression analysis of the mevalonate pathway enzymes, lipid-profiling and hemodynamic monitoring on those isoprene deficient subjects and controls. Additionally, the subject with absence of isoprene was followed up throughout different phases of her womanhood.
Results: In contrast to convention, we witnessed that adults can live healthy without exhaling isoprene or with significant deficiency. This rare phenotype represents a recessive inheritance. Despite physio-metabolic changes during menstrual cycle (that is known to profoundly affect isoprene exhalation) and profoundly increased plasma cholesterol during pregnancy and after childbirth, isoprene remained absent. All genes of mevalonate pathway enzymes were normally expressed in all participants, without any down-regulation or compensatory up-regulation.
Conclusions: Absence/deficiency of isoprene despite normal lipid profiles and no mevalonate pathway malfunction disqualifies the long-believed metabolic origin of isoprene from cholesterol biosynthesis. Thus, clinical translation of breath isoprene expressions should not be generally attributed to corresponding pathophysiological effects onto mevalonate/cholesterol pathway. Our finding has refined and optimized the clinical interpretation of isoprene as biomarker in volatile metabolomics and breathomics. Future studies will address the correct metabolic origin of isoprene to imply this important marker to routine practice.
Keywords
Breath isoprene, Disease biomarker, Cholesterol biosynthesis, Mevalonate pathway, PTR-MS, Metabolic disorders, Volatile metabolomics, Breathomics
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementarymaterialSukuletalHeliyon.pdf
Supplementary Information: Transparent Methods, Figure and Tables
Loading...
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Methods Reporting
This manuscript passed our Methods Reporting assessment
Study design is completely described
Adequate information is present regarding materials and organisms
Data collection and analysis are thoroughly described
Methods Reporting
History
CURRENT STATUS: Posted
View the published article at Heliyon.
No community comments so far
Version 1
Posted 05 Jan, 2021
Community comments: 12
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Learn more about our company.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Pritam Sukul
University Medicine Rostock
Corresponding Author
ORCiD: https://orcid.org/0000-0001-5114-1776
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Methods Reporting
This manuscript passed our Methods Reporting assessment
Study design is completely described
Adequate information is present regarding materials and organisms
Data collection and analysis are thoroughly described
Methods Reporting
History
CURRENT STATUS: Posted
View the published article at Heliyon.
No community comments so far
Version 1
Posted 05 Jan, 2021
Community comments: 12
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Declarations:
Declarations
- This study involved human subjects.
- The author confirmed that all appropriate ethical guidelines for the use of human subjects have been followed, any necessary IRB and/or ethics committee review has been obtained, and information about the IRB/ethics committee is included in the manuscript.
- The author has confirmed that all necessary patient/participant consent or assent has been obtained and the appropriate institutional forms have been archived. If the IRB/ethics committee waived the requirement for patient/participant consent or assent, an explanation for the waiver is included in the text.
- The author has confirmed that a statement listing potential conflicts of interest or lack thereof is included in the text.
View the published article at Heliyon.
Background: Isoprene (C5H8) is a clinically important breath metabolite. Although, hundreds of studies have reported differential expressions in isoprene exhalation as breath biomarker for diverse diseases, the substance couldn’t enter to clinical practice as diagnostic marker. Moreover, many experimental/basic observations upon breath isoprene remained unrelated to the corresponding pathophysiological effects on its putative metabolic origin (i.e. mevalonate pathway). Here, we investigated the fundamental reason that hindered the rational interpretation and translation of this marker from basic to clinical science.
Methods: Via high-resolution mass-spectrometry based breathomics in 1026 human subjects, we discovered adults with significant deficiency (order of magnitude lower than the normal) and complete absence of breath isoprene. We prospectively applied real-time breathomics, quantitative gene expression analysis of the mevalonate pathway enzymes, lipid-profiling and hemodynamic monitoring on those isoprene deficient subjects and controls. Additionally, the subject with absence of isoprene was followed up throughout different phases of her womanhood.
Results: In contrast to convention, we witnessed that adults can live healthy without exhaling isoprene or with significant deficiency. This rare phenotype represents a recessive inheritance. Despite physio-metabolic changes during menstrual cycle (that is known to profoundly affect isoprene exhalation) and profoundly increased plasma cholesterol during pregnancy and after childbirth, isoprene remained absent. All genes of mevalonate pathway enzymes were normally expressed in all participants, without any down-regulation or compensatory up-regulation.
Conclusions: Absence/deficiency of isoprene despite normal lipid profiles and no mevalonate pathway malfunction disqualifies the long-believed metabolic origin of isoprene from cholesterol biosynthesis. Thus, clinical translation of breath isoprene expressions should not be generally attributed to corresponding pathophysiological effects onto mevalonate/cholesterol pathway. Our finding has refined and optimized the clinical interpretation of isoprene as biomarker in volatile metabolomics and breathomics. Future studies will address the correct metabolic origin of isoprene to imply this important marker to routine practice.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementarymaterialSukuletalHeliyon.pdf
Supplementary Information: Transparent Methods, Figure and Tables
Loading...