Metabolic phenotyping of the gut microbiome using dynamic breath analysis
Objective
Gut microbiota dysbiosis results in overproduction of metabolites that may exacerbate chronic diseases such as non-alcoholic steatohepatitis and cardiovascular disease. We explored the feasibility of breath analysis to measure gut microbiome metabolites, which can be applied to assess the extent of gut microbiota metabolism in diseases populations.
Method
Ethical approval was obtained, and 10 healthy subjects (aged ≥ 18 years, weight ≥ 50 kg) were instructed to fast overnight. Breath samples were collected before, and up to 90 minutes after ingestion of glucose (75 g). Compounds of interest were measured using SIFT-MS with direct sampling. Results were expressed as part per billion (PPB v/v) as function of time post substrate ingestion.
Results
Median (M) and interquartile range (IQR) baselines levels (before glucose administration) of ethanol, and acetoin (an intermediate of the 2-3-butanediol fermentation), were respectively 96.2 [69.0-105.2], and 3.4 [2.8, 3.6] PPB. Post glucose ingestion we observed spikes of these compounds in breath of up to respectively, 1515, and 17.3 PPB. Additional diseases associated compounds, unrelated to glucose ingestion, were also detected, such as trimethylamine (M: 42.3, IQR: 33.6-54.3 PPB), methanol (M: 443, IQR: 199-531.4 PPB), and methane (M: 26988, IQR: 10100-76213 PPB).
Conclusions
Dynamic breath analysis is suitable for metabolic characterization of gut microbiome in healthy and disease populations to establish correlations between metabolites and disease severity and progression, as well as interaction of gut microbiota with response to therapeutic interventions. This non-invasive method can replace the current need for blood collection allowing scaling to large cohort populations.
Declarations
This study was approved by the Reading Independent Ethics Committee (RIEC) 93 Reading Road Woodley Reading RG5 3AE. Number: OWL-003, date: 2 Feb 2023.