Aspects of infant food factors on intestinal inflammation and effects of probiotics in celiac disease autoimmunity

Sammanfattning: Aims: The overall aim of this thesis was to study dietary components with focus on exposure and ability to affect gutpermeability, peripheral immune response and gut microbiota in children at genetic risk of developing CD. Thespecific aims were to study presence of food components that might induce intestinal inflammation, evaluatepossible effects on intestinal permeability by food emulsifiers, investigate if two different strains of Lactobacillaceaeaffect ongoing CD autoimmunity and gut microbiota composition.Methods: Porridges and milk cereal drinks were analysed for presence of endotoxins. The quantity of bacteria wasdetermined using culturing methods and identified with Sanger sequencing. Enterotoxin producing genes wereanalysed through multiplex PCR. Modification of intestinal permeability ex vivo in rat by emulsifiers were determinedwith Ussing diffusion chamber. Changes in immune response after intake of probiotic bacteria or placebo in 78children with CDA were measured using flow cytometry while changes in tissue transglutaminase autoantibodylevels were measured in radioligand binding assays. Effects of probiotic intake on the gut microbiota weredetermined by 16SrRNA sequencing.Results: Endotoxin concentrations ranged from 1400 to 24200 EU/g powder and bacteria were present in allproducts. Polysorbate 80 (P80) was able to increase the permeability in the rat intestine ex vivo to a greater extentcompared with carboxymethyl cellulose and beta-lactoglobulin. The probiotic bacteria seemed to inhibit theperipheral immune response in children with CDA compared with placebo and affected the gut microbiota towardsa composition more similar to healthy controls.Conclusion: Endotoxins are present in powdered infant cereal-based foods and the amount of living bacteria mightbe substantial. P80 appeared to increase the intestinal permeability ex vivo in rat more compared with the otheremulsifiers. Probiotic supplementation decreased the level of NKT-cells in children with CDA and influenced theabundance of specific bacterial amplicon sequence variants in the gut microbiota.