Lactulose increases small bowel but not colonic water content; questioning the osmotic laxative dogma

Introduction Lactulose is widely perceived as an osmotic laxative which increases small bowel water content but its impact on large bowel water content is unclear. Ondansetron has been shown to slow left sided colonic transit but whether this is due to reduced secretions, enhanced absorption or solely altered motility is unknown. Our aim was to test the effect of therapeutic doses of lactulose and whether ondansetron altered its laxative effect. Methods This was a double-blind, randomised, two-treatment crossover study in 16 healthy volunteers who attended for 2 study periods. Participants received the study drug (either 8 mg ondansetron or placebo) and had MRI scans fasted then every 2 hours for 6 hours after a rice pudding meal. They then received lactulose (20 ml [39 mmol]) twice daily and the study drug three times daily for 36 hours. On day 3 they had lactulose and the study drug, and further MRI scans every 2 hours for 4 hours. Measurements included small bowel water content (SBWC), magnetic resonance T1 relaxometry to assess water content in the ascending colon (AC) (T1 has previously shown to be directly proportion to stool% water) and gut transit from the weighted average position of transit markers ingested on Day 2. Results In the placebo arm, lactulose increased small bowel water content maximally at 120 minutes (figure 1), with an increase of 89 ml (95% CI 32 ml to 145 ml) compared to the test meal without lactulose. Lactulose significantly increased AUC SBWC from 0-240 minutes (43.3 [25.0] l. hour versus 30.0 [17.0] l.hour with no lactulose, p=0.0078) but had no effect on T1AC even after 36 hours treatment (0.74 [0.4]s versus 0.64 [0.28]s, p=0.72). Ondansetron did not significantly alter SBWC or T1AC, either after a meal alone or when combined with repeated doses of lactulose. Gut transit (median [IQR]), was unchanged by ondansetron compared to placebo (1.7 [0.5-5.8] versus 1.4 [0.5-6], p=0.63). Conclusions Although lactulose increases SBWC by an amount close to that predicted by its osmotic load (130 ml) this did not significantly alter colonic water content. This may be due to its known rapid metabolism and suggests its laxative effect may be due to the stimulatory effects of products of fermentation. Ondansetron did not alter postprandial intestinal water nor reduce the effect of lactulose suggesting that its anti-diarrhoeal effect may be primarily due to altered colonic motility. (Table Presented).