Increased gastrointestinal ethanol production in obese mice: Implications for fatty liver disease pathogenesis

Background & Aims: Similarities in the hepatic responses to obesity and eth anol exposure suggest that these conditions evoke common pathogenic mechani sms. Thus, it is possible that ethanol exposure is increased in obesity. Gi ven that intestinal bacteria can produce ethanol, the aim of this study was to determine if the intestinal production of ethanol is increased in obesi ty. Methods: Breath was collected from genetically obese, ob/ob male C57BL/ 6 mice and lean male littermates at different ages (14, 20, and 24 weeks) a nd times of the day (9 AM, 3 PM, and 9 PM). Obese mice (24 weeks old) were then treated with neomycin (1 mg/mL) for 5 days, and sampling was repeated. Results: Breath collected in the morning from 24-week-old obese mice had a higher ethanol content than breath from their lean littermates (271 vs. 78 pmol/mL CO2; P < 0.0001). Subsequent studies in 14- and 20-week-old mice s howed that exhaled ethanol increased with age in obese (from 26 to 107 pmol /ml CO2; P < 0.002) but not lean (29 and 12 pmol/ml CO2) mice and was great er in older obese mice than in older lean mice (P < 0.0006). Obese mice sho wed a diurnal increase in breath ethanol in the morning that decreased thro ugh the afternoon and evening (107 to 33 to 13 pmol/mL CO2). Neomycin treat ment decreased morning breath ethanol levels by 50% (from 220 to 110 pmol/m l CO2; P < 0.0003), Conclusions: Even in the absence of ethanol ingestion, ethanol can be detected in exhaled breath, In obesity, an age-related incre ase in breath ethanol content reflects increased production of ethanol by t he intestinal microflora. Hence, intestinal production of ethanol may contr ibute to the genesis of obesity-related fatty liver.