On Lactobacillus plantarum 299v, bacterial translocation and intestinal permeability.

The gastrointestinal tract harbours a huge load of bacteria which exerts important biological functions to maintain health. In certain conditions the relation between commensal bacteria and pathogens may be set off balance, with an increase in number of pathogens and risk of bacterial translocation (BT). Disease and trauma may also render the intestinal barrier dysfunctional, inducing BT and increased permeability. Probiotic bacteria, i.e. living bacteria which, when ingested, exerts beneficial effects on the host, have been found to stabilize the intestinal mucosa and affect the intestinal microflora. The aim of this thesis was to study the effects of Lactobacillus plantarum 299v in relation to intestinal permeability and BT. In study I L. plantarum 299v normalized E. coli-induced permeability in distal ileum of rats. This effect was achieved with a more continuous supply of L. plantarum 299v, rather than intermittent or acute pretreatment. Study II showed that pretreatment with L. plantarum 299v prevented BT in rats rendered septic with LPS. The protective effect seemed to be dependent on the ability of L. plantarum 299v to adhere to intestinal mucosa, indicating competitive inhibition as a possible mechanism behind prevention of translocation. Moreover, treatment with prebiotics, without a probioticum, did not prevent translocation. In study III LPS-induced intestinal barrier dysfunction on rats was found to be regulated by P-selectin-dependent leukocyte recruitment. With anti-P-selectin antibody intestinal permeability was attenuated, as well as leukocyte rolling and adhesion. This indicates anti-P-selectin treatment as a mean of ameliorating barrier dysfunction in sepsis. Finally, in study IV, it was found that high doses of L. plantarum 299v given to patients undergoing colon surgery were not able to reduce translocation of selected enteric bacteria but seemed to have a stimulatory effect on bacterial load in the colon. Further, L. plantarum 299v could be give