Breath volatile organic compounds for the gut-fatty liver axis: Promise, peril, and path forward

Table 1 "Fatty liver" volatile organic compounds candidates

Property	Examples
Fermentation activity[29-31]	Alcohols and their aldehydes
Metabolism[32,33]	Acetone and isoprene
Inflammation[34-36]	Dimethylamine, trimethylamine, hydrogen sulfide, ethane, methylsulfide, methylmercaptan

Table 2 Exhaled breath uniquely captures the entire output of the gut liver axis in the context of a person

Gut flora	Lumen factors	Hepatic factors	Host
Bacterial diversity and function	Barrier integrity	Enzyme heterogeneity (e.g., alcohol dehydrogenase)	Diet
Mucosal or lumen associated	Immune defense	Liver disease	Medications
Location	Mucosal disease (e.g., celiac, crohns)	Cirrhosis and porto-systemic shunting	Co-morbid conditions (e.g., diabetes)
(e.g., small bowel, right colon)
	Transit time		Age, gender, body mass index

Table 3 Breath research often failed to meet its potential for multiple reasons

Technical/scientific factors
Monitor/interface/biology	Too many interrelated unknowns
Unique data: uncertain utility	Relevance difficult to establish
	Relevance may not exist
Non-technical factors
Inadequate teams	Engineers, chemists, doctors, statisticians
Inadequate synergy	Single center efforts
Lack of focus	Too many diseases, too little strategy
Lack of common languages	Device development is not drug development
Few models of commercial success	Difficult to envision endgame