REFLEX CONTROL OF INTESTINAL GAS DYNAMICS AND TOLERANCE IN HUMANS Running title: reflex control of intestinal gas dynamics

Intestinal transit of gas is normally adapted to the luminal gas load, but in some patients impaired transit may lead to gas retention and symptoms. We hypothesized that intestinal gas transit is regulated by reflex mechanisms released by segmental distension at various gut levels. In 24 healthy subjects we measured gas evacuation and perception of jejunal gas infusion (12 ml/min) during simultaneous infusion of duodenal lipids mimicking the postprandial caloric load (Intralipid, 1 Kcal/min). We evaluated the effects of proximal (duodenal) distension (n=8), distal (rectal) distension (n=8) and sham distension, as control (n=8). Duodenal lipid infusion produced gas retention (366±106 ml) with low abdominal perception (1.5±0.8 score). Distension of either the duodenum or rectum during lipid infusion expedited gas transit and prevented retention (-120±164 ml and -124±162 ml retention, respectively; p<0.05 vs control). However, the tolerance to the intestinal gas load differed markedly depending on the site of distension: perception remained low during rectal distension (2.6±0.7 score; N.S. vs control), but increased during duodenal distension (4.4±0.7 score; p<0.05 vs control). We conclude that focal gut distension, either at proximal or distal sites, accelerates gas transit, but the symptomatic response depends on the site of stimulation.