Lactulose, but not Macrogol or Bisacodyl, Shows a Prebiotic Effect in a Computer-Controlled In Vitro Model of the Human Large Intestine

Abstract

[12], PEG treatment increased the number of Verrucomicrobia and decreased that of Firmicutes. In mice, Macrogol 3350/PEG decreased the microbial density [13] and relative abundance [14], while Lactulose increased it [13]. Bisacodyl increased the gut microbiota metabolites namely SCFA in rats [15]. Furthermore, a slight increase in bifidobacteria was observed after three months of constipation treatment in humans [1]. Data on direct comparison of the prebiotic effects of the three laxatives Lactulose, Macrogol and Bisacodyl are sparse. In patients with constipation, the efficacy of Lactulose was similar to that of PEG in relieving constipation in a 4 week treatment [16]. The levels of bifidobacteria, but not lactobacilli, were significantly increased in the patients receiving Lactulose, but not in the patients receiving PEG [16]. In contrary, the total amount of bacteria was rather decreased and the colonic fermentation inhibited by treatment with PEG [16]. To our knowledge, no further studies directly comparing at least two of the three laxatives are available, hindering the comparison of Lactulose, Bisacodyl and Macrogol regarding their prebiotic effect. Abstract Background: Patients with chronic constipation often suffer from dysbiosis and may benefit from prebiotic effects of laxatives. Methods: Here we evaluate potential beneficial effects on the gut microbiome of the most commonly used laxatives Macrogol, Bisacodyl, and Lactulose in their usual daily dose for adults using the TIM-2 system, a computer-controlled model of the proximal large intestine with metabolically active, anaerobic microbiota of human origin. Results: Only Lactulose increased the short-chain fatty acid levels and decreased the branched-chain fatty acid levels, pH, and ammonia. Five days of incubation with Lactulose increased the bacterial counts of Bifidobacterium and Lactobacillus which was not observed with Macrogol or Bisacodyl. Conclusion: These data show that Lactulose, in contrast to Macrogol and Bisacodyl, exerts a prebiotic effect when compared in the same in vitro system. In our study, we investigated the prebiotic effect of Lactulose, Macrogol, and Bisacodyl in the TIM-2 model, an in vitro model of the proximal colon. The results of this study demonstrate that Lactulose contrary to Macrogol or Bisacodyl, increased the short-chain fatty acid production as well as the bifidobacterial and lactobacilli count, thereby showing a prebiotic effect.