P162 Changing the gastro-intestinal transit time in healthy volunteers affects gut homeostasis through changes in the microbiome and bile acid pool

Introduction The time it takes for food to travel from the oral cavity until it is expelled in stool is known as the whole-gut transit-time (WGTT). The composition of the gut microbiome and its metabolites are major contributors in gut health. Indeed, alterations in the gut microbiome, bile acid levels, and WGTT were reported in various gastrointestinal disorders including irritable bowel syndrome, Parkinson’s disease, bile acid diarrhoea and colorectal cancer. However, the impact of the WGTT on the microbiome and bile acid metabolism has yet to be established. Methods Healthy volunteers were administered Loperamide and Senna. Each for a total of 6 days, in random order, separated by an interval of at least 4 weeks. The microbiome and the bile acid composition were analysed in stool samples, and markers of bile acid synthesis were analysed in blood samples. Results Administration of Senna and Loperamide resulted in the desired outcomes: a decrease and increase of the WGTT respectively, as well as alteration to the stool form, the frequency of bowel movements, and the stool weight. The Senna treatment group had a significant increase of both primary (p=0.003) and secondary (p=0.008) bile acids in the stool, while the blood concentration of the ileal hormone fibroblast growth factor 19, which regulates bile acid synthesis, was significantly reduced compared to the Loperamide treatment group. Slowing WGTT by administration of Loperamide increased levels of bacterial bile acid transforming genes namely, bile salt hydrolase genes (p=0.02), as well as bacterial species richness (p=0.04). More specifically, an over 20-fold increase of the probiotic specie Bifidobacterium dentium as well as Bifidobacterium angulatum. By contrast, administration of Senna resulted in a 6-fold elevation of species specifically associated with dysbiosis and bile acid metabolism such as Ruminococcus gnavus, while B. dentium decreased 23-fold. WGTT was negatively correlated with total primary and secondary bile acids (specifically chenodeoxycholic acid, ursodeoxycholic acid and glycochenodeoxycholic acid), the presence of Gemella sanguinis and R. gnavus, while species richness significantly decreased. Thus, changes in WGTT impacted both the composition of the microbiome and bile acid metabolism, however both reverted back to their original condition within 21 days of finishing treatments. Conclusion Our study provides strong evidence that changes in WGTT are a contributing factor to dysbiosis and bile acid imbalance. Our findings suggest that gut transit time should be considered a crucial factor in future microbiome research, as they show changes in gut transit time can have a major effect on microbiome composition and function, independent from gastro-intestinal disease.