Treatment of experimental colitis by modulating microbiota and eicosanoids : Effects of probiotics, prebiotics and leukotriene antagonist
Year: 2002
Type: dissertation
Abstract: The aim of the present study was to investigate the effects of treating experimental colitis by modulating colonic microbiota and eicosanoids, more specifically, the effects of Lactobacillus rhamnosus GG, Lactobacillus reuteri R2LC, two galactooligosaccharide mixtures and the cys-LT-1 receptor antagonist montelukast in chemically induced colitis in rats.L. rhamnosus GG increased the number of caecal and colonic crypt cells as well as the rate of mitoses in the caecal crypts, and decreased the depth of the crypts, when given orally to healthy germ-free rats for 3 or 21 days.In spite of these potentially beneficial effects on intestinal inflammation, L. rhamnosus GG, as well as L. reuteri R2LC, when given orally beginning seven days before colitis induction, were ineffective in the attenuation of acetic acid-induced colitis, as was the reference drug sulphasalazine.The oral administration of galacto-oligosaccharides, starting 10 days before the induction of colitis, stimulated the growth of bifidobacteria, but neither they nor the reference drug dexamethasone affected acute colitis induced by trinitrobenzene sulphonic acid (TNBS).Animals with acute colitis induced by TNBS, when treated with the cys-LT-1 receptor antagonist montelukast (5-20 mg kg -1 day -1 , intracolonically, starting 12 hours before colitis induction), had an increased colonic in vitro production of prostaglandin E 2 , an eicosanoid beneficial in the treatment of colonic inflammation in a TNBS model and a number of other models.However, montelukast, as well as the reference drug zileuton, a 5-lipoxygenase inhibitor, did not ameliorate macroscopic and histological inflammation in the colon in this acute severe model.On the other hand, in a milder colitis model, the dextran sulphate sodium (DSS) model, animals treated with montelukast (10 mg kg -1 day -1 , p.o., starting concurrently with DSS) had less occult blood in the faeces/ gross bleeding and normal body weight gain.They also tended to have a lower ratio of leukotriene B 4 / prostaglandin E 2 production in the colon in vitro.No increase in the production of cysteinyl leukotrienes in vitro was detected in either of the colitis models.The models used in the present study for investigating the effects of modulating microbiota appear severe because the reference drugs were ineffective.Neither the beneficial effects of L. rhamnosus GG seen in this study, both on the rate of mitoses and on the morphology of the mucosa, nor the hypothesised mechanisms (i.e. the production of antimicrobial products, the decrease in intestinal permeability, the promotion of gut immunoglobulin A response, and the increase in short-chain fatty acid concentration in the case of galacto-oligosaccharides) seem to be sufficient to deal with the acute phase of these severe colitis models.The cys-LT-1 receptor antagonist montelukast slightly ameliorated the mild colitis induced with DSS, but not the severe acute TNBS-induced colitis.The fact that the former was not associated with increased cysteinyl leukotriene production suggests that some other mechanism than cys-LT-1 receptor blockade is responsible for the colitis-attenuating effect.Theoretically, L. rhamnosus GG, L. reuteri R2LC, galacto-oligosaccharides and montelukast all have the potential to attenuate colonic inflammation.They are not, however, efficient in reducing the damage in acute severe models such as those used in the present study.
Source: Työväentutkimus Vuosikirja
Author: Reetta Holma
Language: English
Topic: Inflammatory Bowel Disease
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1539363105