Summary
There is emerging focus on the gut microbiota’s (GM) effects on health. GM is suggested to be a contributing factor to the rapid development of obesity and its related diseases like type 2 diabetes and cardiovascular disease. The omposition of the GM has been associated with weight, insulin resistance and blood lipid profile among others. Probiotics which are health promoting bacteria can potentially be used to affect the GM and thereby change metabolic outcomes of the host. Animal studies have shown associations between intake of probiotics and appetite regulation, but currently no human studies have investigated this effect. Supplementation with different probiotic strains have been shown to have an effect on blood lipid profiles in both animals and humans and the mechanisms behind have been studied in vitro and in rodents.

The aim of the present thesis was to examine in an ex vivo intestine, in an animal study and in two human studies the effect of the probiotic bacteria Lactobacillus paracasei subsp. paracasei L. casei W8 (W8) on appetite regulation, blood lipids and blood fatty acids. In addition, it was investigated if W8 had an effect on the fecal microbiota of the human participants and if changes in GM could be associated with blood lipid profile.

The effect of W8 on release of glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2) and peptide YY (PYY) was investigated by perfusion of W8 into an isolated porcine intestine. The expression of mRNA for the glucagon (GCG) gene encoding GLP-1 and GLP-2 and expression of the gene SCD1 encoding stearoyl-CoA desaturase-1 (SCD1); which is involved in the formation of triacylglycerol (TAG); was studied in piglets supplemented with W8 for two weeks. To study the acute effect of W8 on appetite regulation, glycemic response and energy intake in humans a randomized, double-blinded, three-armed cross over study was done on normal to over-weight, young participants with a low dose W8 (109 colony forming units (CFU)), a high dose W8 (1010 CFU) and a placebo capsule. Hereafter a randomized, double-blinded, two-armed parallel four weeks intervention study with W8 (1010 CFU) or placebo capsules was performed on young, normal to overweight participants. In the four weeks intervention study the effects of W8 on appetite, blood lipids, SCD1 activity and fecal microbiota were also investigated. Finally, associations between changes in GM composition and blood lipids were investigated.

The results presented in this thesis, demonstrate that W8 was able to increase the release of GLP-1, GLP-2 and PYY in the isolated porcine intestine. In the piglet study it was observed that W8 upregulated the mRNA expression of GCG and decreased the expression of SCD1. However, no difference in the GLP-1 levels of the human participants in both the acute and four weeks intervention study could be detected. In the acute study a decreased energy intake was observed four hours after the high dose W8 capsule was consumed in comparison to placebo. In the four weeks intervention study with high dose W8 a decrease in TAG levels was observed. In addition it was observed that the activity of SCD1 tended to decrease, which indicate that W8 has an effect on the formation of TAG. Finally, W8 had an increasing effect on the L. casei group counts in the feces of the participants supplemented with W8 for four weeks. But no associations between the L. casei group in fecal samples and the blood lipids were observed.

In conclusion the present thesis shows that the probiotic bacteria W8 may be able to lower energy intake possibly through an effect on GLP-1, which was however not possible to detect in the human studies. Moreover, W8 has a lowering effect on TAG probably caused by reducing the activity of SCD1. In addition, it was possible to increase the L. casei group in the fecal samples from participants supplemented with W8 for four weeks