S1835 Gut Bacteria Phenotyping Using Dynamic Breath Analysis

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Introduction: Gut microbiota dysbiosis results in the overproduction of metabolites that exacerbate certain chronic diseases. For example, ethanol and 2-3-butanediol, produced by carbohydrate fermentation, were found associated with non-alcoholic steatohepatitis (NASH). Similarly, trimethylamine, produced from choline, is further metabolized in the liver to trimethylamine-N-oxide, a metabolite found associated with NASH severity and that exacerbates cardiovascular diseases. We explored the feasibility of a novel approach to measure gut bacteria metabolites, which can be applied to assess the extent of gut bacteria metabolism in disease populations. Methods: A total of 8 healthy subjects were recruited with age ≥ 18 years and body weight ≥ 50 Kg. Subjects were instructed to fast overnight and to not drink alcoholic beverages the day before the experiments. Breath samples were collected before, and up to 90 minutes after ingestion of 75g of glucose with a time resolution of 5 minutes. Compounds of interest were measured using SIFT-MS with direct sampling. Results were expressed as part per billion (PPB v/v) as a function of time post-glucose ingestion. Results: Ambient measurements showed that all the investigated compounds were absent before and after conducting the experiment. Median (M) and interquartile range (IQR) baselines levels (before glucose administration) of ethanol, propanoic acid, and acetoin (an intermediate of the 2-3-butanediol fermentation), were respectively 99.4 [71.6-182.4], 13.3 [10-16.2], 3.2 [2.7, 4.2] PPB (Figure 1A). Post glucose ingestion we observed spikes of these compounds in breath of up to respectively 8629, 153, and 20 PPB (Figure 1B). Additional diseases associated compounds, unrelated to glucose ingestion, were also detected, such as trimethylamine (M: 42.3, IQR: 33.6-54.3 PPB) (Figure 1C), methanol (M: 443, IQR: 199-531.4 PPB) (Figure 1D), and methane (M: 26988, IQR: 10100-76213 PPB) (Figure 1E). Conclusion: Dynamic breath analysis can be used for the clinical characterization of gut bacteria metabolism in healthy and disease populations to establish correlations between metabolites and disease severity and progression, as well as the 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.Figure 1.: Dynamic breath analysis.

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