Colorectal Oncogenesis and Inflammation in a Rat Model Based on Chronic Inflammation due to Cycling DSS Treatments

Inflammation is known to be linked with development of colorectal cancer, and the aim was to assess the malignant potential and degree of inflammation in a dextran-sulphate-sodium-(DSS-) induced cyclic colonic tumour model (CTM) in rats and to compare it with the azoxymethane-(AOM-) induced CTM model. Tumours developed in both groups, although, in the DSS group, the colonic mucosa appeared edematous and the number of haemorrhagic erosions and quantity of dysplastic lesions were higher as well as the mucosal concentration of myeloperoxidase and faecal viable count of Enterobacteriaceae. The livers were affected as evaluated by steatosis, parenchymal loss, haemorrhage, and inflammatory infiltrations, and higher proportions of acetate and lower proportions of butyrate in colonic content were found. The DSS model seems to mimic the clinical situation and may be valuable for investigation of inflammation-related dysplasia and colon cancer, as well as for altered liver function by endogenous inflammatory mediators

Blueberry Husks and Probiotics Attenuate Colorectal Inflammation and Oncogenesis, and Liver Injuries in Rats Exposed to Cycling DSS-Treatment.

Long-term colonic inflammation promotes carcinogenesis and histological abnormalities of the liver, and colorectal tumours frequently arise in a background of dysplasia, a precursor of adenomas. Altered colonic microbiota with an increased proportion of bacteria with pro-inflammatory characteristics, have been implicated in neoplastic progression. The composition of the microbiota can be modified by dietary components such as probiotics, polyphenols and dietary fibres. In the present study, the influence of probiotics in combination with blueberry husks on colorectal carcinogenesis and subsequent liver damage was evaluated.Colorectal tumours were induced in rats by cyclic treatment with dextran sulphate sodium (DSS). Blueberry husks and a mixture of three probiotic strains (Bifidobacterium infantis DSM 15159, Lactobacillus gasseri, DSM 16737 and Lactobacillus plantarum DSM 15313) supplemented a basic diet fortified with oats. The condition of the rats was monitored using a disease activity index (DAI). A qualitative and quantitative histological judgement was performed on segments of distal colon and rectum and the caudate lobe of the liver. The formation of short-chain fatty acids, bacterial translocation, the inflammatory reaction and viable count of lactobacilli and Enterobaceriaceae were addressed.Blueberry husks with or without probiotics significantly decreased DAI, and significantly reduced the number of colonic ulcers and dysplastic lesions. With a decreased proportion of blueberry husk in the diet, the probiotic supplement was needed to achieve a significant decrease in numbers of dysplastic lesions. Probiotics decreased faecal viable count of Enterobacteriaceae and increased that of lactobacilli. Blueberry husks with or without probiotics lowered the proportion of butyric acid in distal colon, and decreased the haptoglobin levels. Probiotics mitigated hepatic injuries by decreasing parenchymal infiltration and the incidence of stasis and translocation. The results demonstrate a dietary option for use of blueberry husks and probiotics to delay colonic carcinogenesis and hepatic injuries in the rat model

Bifidobacterium infantis strains with and without a combination of Oligofructose and Inulin (OFI) attenuate inflammation in DSS-induced colitis in rats

BACKGROUND: Pathogenesis of inflammatory bowel disease is thought to be through different factors and there is a relationship between the gut flora and the risk of its development. Probiotics can manipulate the microflora in chronic inflammation and may be effective in treating inflammation. Bifidobacterium are saccharolytic and their growth in the gut can be promoted by non-absorbable carbohydrates and its increase in the colon appears to be of benefit. METHODS: Oligofructose and inulin (OFI) alone and the two B. infantis DSM 15158 and DSM 15159 with and without OFI, were fed to Sprague-Dawley rats for 7 days prior to colitis induction and administrations continued for another 7 days with the DSS. Colitis severity assessed using a Disease Activity Index. Samples were collected 7 days after colitis induction, for intestinal bacterial flora, bacterial translocation, short chain fatty acids (SCFAs), myeloperoxidase (MPO), cytokines (IL-1β, TNF-α, IL-10 and TGF-β) and malondialdehyde (MDA). RESULTS: OFI alone or the B. infantis strains with and without OFI improved significantly the DAI and decreased colonic MPO activity. Colonic tissue IL-1β decreased significantly in all treated groups except B. infantis DSM 15158. MDA decreased significantly in B. infantis DSM 15159 with and without OFI compared to colitis control. Succinic acid increased significantly in OFI group with and without DSM 15159 compared to all groups. Sum values of propionic, succinic acid and butyric acid increased significantly in all groups compare to the colitis control. Bacterial translocation to mesenteric lymph nodes decreased significantly in all groups compared to colitis control. Translocation to the liver decreased significantly in all groups compare to the colitis control and OFI + B. infantis DSM 15158 groups. CONCLUSION: Administrations of OFI and Bifidobacterium improve DSS-induced acute colitis and have an anti-inflammatory effect. Major differences in effect were observed between the two B. infantis strains as indicated in MDA and succinic acid concentration as well as bacterial translocation rate in synbiotic combinations

Acute Liver Injury and the Gut. Role of Nitric Oxide, and the Effect of Arginine and Probiotic Administration

Infectious complications with enteric bacteria are common in liver diseases and liver surgery. An increased bacterial translocation from the gut has been proposed as one underlying mechanism. In order to elucidate pathogenetic mechanisms and find possible preventive measures, we manipulated the enteric content and therefore we investigated the role of nitric oxide and the effect of arginine and probiotic administration on bacterial translocation, extent of liver injury and the associated intestinal mucosal changes in a D-galactosamine acute liver injury model. We showed that bacterial translocation could be one of the mechanisms potentiating the liver injury in this model of hepatotoxicity. Nitric oxide protects the liver from the acute injury. It reduces the liver injury and decreases bacterial translocation to the extraintestinal sites. Arginine has beneficial effects on the liver and reduces bacterial translocation. Nitric oxide production plays a role in the effects of arginine, but arginine can have effects on both liver and gut besides nitric oxide production. Modulation of the intestinal microflora by the administration of lactobacilli, reduces the potentially pathogenic Enterobacteriaceae count, bacterial translocation to extraintestinal sites and liver injury. The reduction of bacterial translocation and liver injury could be mediated via nitric oxide production. We have shown the importance of the gut and luminal factors in modulating the extent of the liver injury. It seems possible to alter the microecology of the gut by administration of probiotics and the addition of substrates, such as arginine, may locally influence the production of biological mediators. This can act as nutrition for the mucosa and host, but simultaneously give rise to pharmacologic actions both locally and at distant sites

Safety of the probiotic strain Lactobacillus plantarum DSM 9843 (strain 299v) in an endocarditis animal model

Objective: Lactobacilli are often considered to be beneficial or non-pathogenic to man, with small numbers of human infections being reported, including septicemia and infective endocarditis. To verify the safety of Lactobacillus plantarum DSM 9843 (=strain 299v) administration, we used a well-known endocarditis animal model. Design: Experimental study using Sprague-Dawley rats. Setting: University Hospital, Sweden. Interventions: A catheter was passed down the right common carotid artery into the lumen of the left ventricle. The catheter was tied in place and the neck incision was closed. After 48 h, 0.5 ml of a bacterial suspension was injected through the tail vein. In the endocarditis control we inoculated Staphylococcus lugdunesis CCUG 25349T (T = type strain) and L. plantarum 299v was injected in the blood in L. plantarum group. Main outcome measures: Rats were sacrificed 96 h later and samples were taken from the heart, blood and catheter for bacterial culture and Randomly Amplified Polymorphic DNA (RAPD) evaluation. Results: L. plantarum 299v was injected in the blood but no lactobacilli were found in the heart, blood or catheter after 96 h. RAPD evaluation showed that S. lugdunesis CCUG 25349T was isolated from both blood and heart. Conclusion: The results showed that L. plantarum 299v has no role in the tested endocarditis animal model, which indicates the safety of L. plantarum 299v

Bacterial translocation: Impact of probiotics

There is a considerable amount of data in humans showing that patients who cannot take in nutrients enterally have more organ failure in the intensive care unit, a less favourable prognosis, and a higher frequency of septicaemia, in particular involving bacterial species from the intestinal tract. However, there is little evidence that this is connected with translocation of bacterial species in humans. Animal data more uniformly imply the existence of such a connection. The main focus of this review is to describe different ways to alter the luminal milieu to decrease bacterial translocation. It is possible to reduce absorption of endotoxin by administration of bile salts in obstructive jaundice. Increasing the oral intake of glutamine will reduce bacterial translocation in rats with radiation-induced gut injury. The bacterial microflora plays a very important role in maintaining the normal intestinal ecological environment and supplying preferred fuels to the intestinal wall, consequently supporting the intestinal barrier. Disruption of the balance of intestinal bacterial microflora may increase the incidence of bacterial translocation by modifying intestinal barrier function. Bacterial species such as enteric Gram-negatives and Gram-positive cocci are more prone to translocation, whereas lactobacilli seem to have a protective effect. Administration of live lactobacilli either orally or by enema will reduce translocation. The mechanisms underlying the decreased translocation are not obvious. One effect may be mediated via an action on the intestinal wall and its permeability. Recently, the results of three randomized studies on the use of L. plantarum in patients with pancreatitis, undergoing liver transplantation or upper gastrointestinal surgery have been published, which all indicate a potential role for lactobacilli in translocation. In conclusion, by altering the luminal content of bacteria it seems possible to reduce the incidence of secondary infections. The influence of the luminal milieu on bacterial translocation is not fully understood. There is convincing evidence from experimental studies, but only circumstantial evidence from clinical studies

Inhibition of matrix metalloproteinases enhances breaking strength of colonic anastomoses in an experimental model

BACKGROUND: The breaking strength of colonic anastomoses declines after operation to a minimum at days 3-4, with a subsequent risk of anastomotic dehiscence. The mechanism is thought to be collagen degradation by matrix metalloproteinases (MMPs). This study examined the pathogenic role of MMPs on the mechanical strength of colonic anastomoses by giving the synthetic broad-spectrum MMP inhibitor BB-1101 systemically. METHODS: Forty-eight male Sprague-Dawley rats were treated daily for 7 days with BB-1101 30 mg/kg or vehicle alone (control) starting 2 days before operation. The breaking strength of standardized left-sided colonic anastomoses was measured on postoperative days 1, 3 and 7. RESULTS: Serum BB-1101 levels were increased at 100 nmol/l in BB-1101-treated rats. The anastomotic breaking strength was 48 per cent higher (P = 0.02) in BB-1101-treated animals compared with controls on postoperative day 3. Neither collagen accumulation nor infiltration of neutrophils in the anastomotic area was influenced by BB-1101 treatment. Net deposition of new collagen in subcutaneous sponges was unaffected by the BB-1101. CONCLUSION: The enhanced breaking strength of colonic anastomoses during the critical early postoperative phase found after administration of a broad-spectrum MMP inhibitor implies that MMPs might increase the risk of anastomotic dehiscence. Presented in part to the third joint meeting of the European Tissue Repair Society and the Wound Healing Society in Bordeaux, France, 24-28 August 1999, and published in abstract form in Wound Repair Regen 1999; 7: A32

Probiotics and Blueberry Attenuate the Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis.

We studied the anti-inflammatory properties of probiotic strains and blueberry in a colitis model. The disease activity index (DAI) was significantly lower on days 9 and 10 in all groups compared to the colitis control. Myeloperoxidase (MPO) and bacterial translocation to the liver and to the mesenteric lymph nodes (MLN) decreased significantly in all groups compared to colitis control. Cecal Enterobacteriaceae count decreased significantly in blueberry with and without probiotics compared to the other groups. Lactobacillus plantarum reisolated from the cecal content in the presence of blueberry, contrary to Lactobacillus fermentum. Colonic MDA decreased significantly in all groups, except the L. fermentum group, compared to the colitis control. The cecal concentration of acetic, propionic, and butyricbutyric acid was significantly higher in the L. plantarum group, while the L. fermentum group yielded the highest concentration of lactic acid compared with all other groups. Lactobacillus plantarum DSM 15313, Lactobacillus fermentum 35D, and blueberry alone and in combination improve the DAI, reduce bacterial translocation, and reduce inflammation