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Attenuation of Oxidative Stress, Inflammation and Colorectal Oncogenesis by Food Constituents: Ischaemia/Reperfusion Injury and Induced Colitis in Rodents

by Håkansson, Åsa, PhD

Abstract (Summary)
The enteric microbiota is increasingly implicated as a central factor in the development of intestinal inflammation in humans and experimental animals, and the intestinal environment is considered important in both colorectal cancer development and modulation of mucosal immunity. Diet-induced changes in the different populations of the intestinal microbiota can be achieved by use of probiotic bacteria, dietary fibre and berries rich in phenolic compounds. The present thesis aims to find relevant animal models with clinical similarities and use these models to evaluate the anti-inflammatory effects of feed supplements. Supplementation of L. plantarum and rose hip in combination decreases lipidperoxidation in caecum independently of the vitamin C content and inhibits the growth of Enterobacteriaceae, in response to ischaemia/reperfusion injury. An attempt was made to understand how the immune system is regulated and responds to variations in the composition of the intestinal microflora during DSS-induced acute colitis. An increased immunological response against LPS, increased populations of regulatory T-cells and higher levels of IL-6, IL-17 and KC were found. The amount of lactobacilli decreased, while that of Akkermansia, the total amount of bacteria and the incidence of Enterobacteriaceae increased. As revealed by T-RFLP patterns, the composition of the bacterial flora changed during induction of colitis and there was a complex close relationship in comparison to multiple immune parameters. Supplementation of probiotics and blueberry husks decreased disease activity, Enterobacteriaceae load, bacterial translocation and inflammation, and increased lactobacilli count and affected bacterial fermentation in the gut. Long-term colonic inflammation promotes carcinogenesis and histological abnormalities of the liver. Two different ways of inducing chronic inflammation and colorectal tumours were investigated and cyclic DSS administration showed similar clinical and histopathological features of both colon and liver. Dysplastic lesions and a continuous mucosal inflammation were observed along with increased Enterobacteriaceae load and liver dysfunction. Also, the SCFAs patterns coincide with clinical findings. Supplementation of probiotics and blueberry husks during cyclic DSS administration delayed carcinogenic development as evaluated by lower numbers of dysplastic lesions. The mucosa was less affected after feed supplementation which may be favourable for SCFA absorption. Enterobacteriaceae load was decreased, especially by the addition of probiotics, and lactobacilli count was increased. Judged by histopathological evaluation, bacterial translocation and the concentration of propionic acid in blood, supplementation of probiotics seemed to moderate the negative liver effects and protect against injury, i.e. the findings indicated the potential of probotics and blueberry husks in prevention of colonic inflammation and tumour development.
Bibliographical Information:

Advisor:

School:Lunds universitet

School Location:Sweden

Source Type:Doctoral Dissertation

Keywords:MEDICINE; Ischaemia/Reperfusion; Colorectal cancer; Rose hips; Colitis; Probiotics; Inflammation; Blueberry

ISBN:978-91-628-8044-6

Date of Publication:01/01/2010

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