Dietary Prebiotic Supplementation Normalizes Delayed Colonic Transit in Obese Mice

Introduction Obesity is associated with significant alterations in colonic motility. Such changes do not only affect the quality of life of obese patients, but can also contribute to the development and maintenance of obesity per se . The gut microbiota of obese subjects is typically characterized by a reduced abundance of short‐chain fatty acids (SCFAs)‐producing bacterial species. SCFAs are essential for the maintenance of well‐coordinated colonic transit, in part through the production of serotonin and intestinal regulatory peptides. Prebiotics are non‐digestible dietary fibers which promote the growth of beneficial microbes, including bifidobacteria and other SCFAs‐producers. They have also been demonstrated to affect colonic motility. Clinical evidence supports a positive effect of prebiotics on age‐related constipation in the elderly; however, their effect in the context of obesity‐related colonic dysmotility has not been substantially explored. To this end, we used a mouse model of high fat diet‐induced obesity to investigate whether dietary supplementation of a prebiotic fructooligosaccharides (FOS) and galactooligosaccharides (GOS) mixture can improve impaired colonic transit associated with obesity. Methods Three week old male C57/BL6 mice were fed either a high fat diet (HFD, 45% kcal from fat, 32 mice) or a low fat diet (LFD, 10% kcal from fat, 28 mice) for six weeks, after which half of the animals were supplemented with 6.5% FOS/GOS prebiotic in drinking water for further six weeks. At the 12 week time point, colonic transit time was assessed ex vivo by video analysis of artificial pellet propulsion in the entire colon. Colon tissue was also harvested for the analysis of regulatory pathways involved in orchestrating peristaltic reflexes in the colon. We will analyse serotonin levels (high‐performance liquid chromatography) and gene expression of serotonin receptors, PYY peptide and factors regulating proliferation and differentiation of enteroendocrine cells in the colonic tissues (real‐time PCR), as well as caecum luminal contents of SCFAs (gas‐liquid chromatography). Results HFD intervention did not affect the colon length, but substantially slowed the pellet transit down the colon in obese mice. The time latency to initiate the pellet propagation was increased in the HFD as compared with LFD group (1085 (1650;191) sec vs 257 (272;236) sec, accordingly). Moreover, the pellets were propagated more slowly in HFD (0.6 (2.5;0.2) mm/min) than in LFD (16.8 (19.1;1.1) mm/min) colons. FOS/GOS co‐supplementation significantly improved the propulsive activity of the colon in HFD mice increasing the pellet transit velocity to 7.8 (8.8;7.4) mm/min (p=0.008, U test Mann Whitney), whilst having no effect on the colonic transit in LFD fed animals. Conclusions Dietary enrichment with FOS/GOS can normalize colonic dysmotility associated with the ingestion of high fat diet. On‐going work is aimed at defining the molecular basis of these changes. Together these data suggest that prebiotics maybe a useful dietary adjunct for co‐morbid gastrointestinal symptoms in obesity. Support or Funding Information This work was supported by Science Foundation Ireland (SFI) through the Irish Government's National Development Plan (12/RC/2273).