Projectomschrijving

This project was part of a Joint programming Initiative on Healthy Diet for a Healthy Life, involving 3 partner organisations (1). Dr Harry Sokol at Sokol from the French National Institute for Agricultural Research (INRA) and the French Medical Research Institute (INSERM), (2) Dr Elena Verdu, Famcombe Family Digestive Health Research Institute at McMaster University, Canada and (3) Prof Jerry Wells, Wageningen University and Research, The Netherlands.

The intestinal metabolism of tryptophan, an essential amino acid and important component of our diet is perturbed in intestinal diseases (such as inflammatory bowel disease and irritable bowel syndrome), but also in some non-intestinal diseases. In the gut, tryptophan can be transformed by certain intestinal bacteria into several molecules some of which promote a healthy intestine and immune system through interaction with a host receptor called the arylhydrocarbon receptor (AhR).

In this project we obtained further evidence that a harmless Lactobacilus bacterium with a strong and natural ability to produce beneficial metabolites of tryptophan or the metabolites themselves, can have beneficial effects in certain diseases where the gut bacteria have a reduced capacity to produce tryptophan metabolites interacting with AhR.

Results of AryImune

AhR signalling orchestrates immune responses at barrier sites such as the gut mucosa, promoting tolerance, intra-epithelial lymphocytes (IEL), organogenesis of intestinal lymphoid follicles, T cells and innate lymphoid cells (ILCs) group 3, that produce IL-17 and IL-22,16 all of which could have an impact on gut barrier function and intestinal inflammatory diseases where the microbiota has a reduced capacity to produce AhR ligands. The aims of the project were to identify AhR-activating microorganisms, or their tryptophan metabolites and assess their health effects including a clinical trial in human subjects performed in Canada.

Lactobacillus species (commonly used as probiotics) vary in their capacity to produce AhR activating ligands in vitro and L. reuteri strains were among the highest producers. The selected Lactobacillus strains had no significant effect on the severity of colitis or C. rodentium infection in vivo. However, administration of indoles (found in cruciform vegetables) in the diet increased AhR activation activity in faecal extracts and reduced disease activity. Results of the human trial are still being analysed but indicate that high-tryptophan diets increase AhR activating metabolites in some subjects.

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