BACKGROUND & AIMS: Short chain fatty acids (SCFAs; acetate, propionate and butyrate) are important energy sources for colonocytes and are assumed to play a key role in gut health. Local effects of SCFAs have been investigated, but less is known about whole body metabolism of these SCFAs. The aim of the present study was to quantify the role of the gut and liver in interorgan exchange of SCFAs in humans in vivo. METHODS: Twenty-two patients undergoing major upper abdominal surgery were studied. Blood was sampled from a radial artery, the portal and a hepatic vein. Portal, splanchnic and arterial blood flow was measured using intra-operative Duplex ultrasonography. SCFAs were measured on a liquid chromatography system combined with mass spectrometry. RESULTS: SCFAs were released by the gut, 34.9 (9.1)mumolkg bodyweight(-1)h(-1). SCFAs uptake by the liver was significant for propionate and butyrate; -5.6 (1.3) and -3.8 (1.6)mumolkg bodyweight(-1)h(-1) (p=0.0002 and p=0.03) respectively and counterbalanced gut release. Liver uptake of acetate was not significant, -5.2 (6.6)mumolkg bodyweight(-1)h(-1) (p=0.434). Splanchnic (i.e., gut+liver) SCFAs release was significant for acetate and propionate, 17.3 (7.3) and 1.2 (0.4)mumolkg bodyweight(-1)h(-1) (p=0.027 and p=0.0038), respectively. Splanchnic release of butyrate was not significantly different from zero (1.9 (1.2)mumolkg bodyweight(-1)h(-1), p=0.129). BMI and previous colonic resection did not affect gut release of SCFAs. CONCLUSION: This is the first in vivo study on the role of the gut and liver in SCFAs exchange in humans in vivo. It is shown that intestinal SCFAs release by the gut is equalled by hepatic uptake.