Human Breathomics
NWI-BM086
3 EC
Year 1
Quarter 2
Medical Biology: Human Biology – Master
,Contents
L1 Introduction to Breathomics……………………………………………………………………………….……3
L2 Bacterial volatiles………………………………………………………………………………………..…………8
L3 Breath sampling and confounders………………………………………….………….……………………12
L4 Methods ………………………………………………………………………………………………………….….18
L5 The role of the gut-brain axis in human cognition..……………………………………………………..26
L6 Digging into breathomics data analysis…………..…………..……………………………………………30
L7 Translation into clinical applications………………….……………………………..……………………..34
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,L1 – Introduction to Breathomics
Metabolite: small molecules (<1000 – 2000 Da) that participate in general metabolic reactions
as intermediate or end-product. Building blocks of cellular function; role in enzyme-catalyzed
chemical reactions.
Metabolome = complete set of metabolites in an organism
Metabolomics = study of chemical processes involved metabolites (cells/tissues/organisms).
Identification and quantification of metabolites in a biological system.
Breathomics = non-invasive metabolomics of exhaled air (<300 Da). Identifies & quantifies
volatile (organic) compounds from exhaled breath and/or released by pathogens.
Metabolic profile/breath profile = set of limited number of metabolites selected by their elation
to a specific metabolic pathway/compound class/other shared property. Allows method
development for robust quantification and specificity. Useful for hypothesis-testing &
addressing well-defined biological questions.
Metabolic fingerprint (pattern)/footprint = fingerprint/patterns of many metabolites as possible,
caused by perturbations in metabolism. Relative quantification of peaks between di[erent
samples, no absolute concentrations.
Production of metabolites:
- By human: disease related (urine, blood, exhaled breath, skin emanations)
- Animals: pheromones, individual scent markers
- Bacteria: external chemical cues for proliferation (quorum sensing)
- Fungi: “sick building syndrome” (Cladosporium, Penicillum, Chrysosporium, Alternaria,
Aspergillus)
- Plants: aspirin-like chemicals in stressed walnut trees
Metabolites are not only present during metabolism. Metabolites are perhaps the body’s most
important signaling molecules.
The air we inhale:
- 78.62% N2
- 20.84% O2
- 0.04% CO2
The air we exhale:
- 78.62% N2
- 15% O2
- 4% - 6% CO2
- Aerosols/particles 1% other gases
Exhaled human breath is rich in Volatile Organic Compounds (VOCs).
Exhaled breath is coming from the gastrointestinal tract (parts of the body).
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, The small part of other gases à > 1000 volatiles
These volatiles are from 17 compound classes: alcohols, aldehydes, alkanes/alkenes/alkynes,
amino acids, benzenoids, benzothiazoles, carboxylic acids, esters, fatty acids, furans, indoles,
ketones, sulfur containing compounds, terpenes, inorganic compounds, and “others”
Already in the time of Hippocrates they used exhaled breath already as a technique for
determining health etc.
- Exhaled water vapor in breath detected at a mirror = alive
- Diagnose diseases by exhaled breath
Towards modern medicine:
- 1954: alcohol breath test
- 1971: the Nobel Prize winner Linus Pauling demonstrated that human breath is a
complex gas mixture, containing more than 200 di[erent VOCs
- Sweet fruity nail polish removal à diabetes à associated with metabolite: acetone
- Must fishy reek à liver problems à associated with metabolite: isoprene
- Urine like smell à kidney failure à associated with metabolite: ammonia
Why is breath so attractive?
- Enormous potential, because of:
o Noninvasive to monitor our biology/metabolism
o Clean (no needles, cups of messy urine)
o Its inherent safety/minimum risk
o Practically inexhaustible
o Reflects metabolic processes in the body
o Whole body monitoring
o Acceptable to people
o Fast response (with real-time instruments)
- Everyone can give a breath sample: neonates, very elderly, or ill patients
Breath VOCs reported for a wide range of diseases:
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