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.

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.

Effects on weight gain and gut microbiota in rats given bacterial supplements and a high-energy-dense diet from fetal life through to 6 months of age.

The aim of the present study was to assess the long-term effects of a high-energy-dense diet, supplemented with Lactobacillus plantarum (Lp) or Escherichia coli (Ec), on weight gain, fattening and the gut microbiota in rats. Since the mother's dietary habits can influence offspring physiology, dietary regimens started with the dams at pregnancy and throughout lactation and continued with the offspring for 6 months. The weight gain of group Lp was lower than that of groups C (control) and Ec (P = 0·086). More retroperitoneal adipose tissue (P = 0·030) and higher plasma leptin (P = 0·035) were observed in group Ec compared with group Lp. The viable count of Enterobacteriaceae was higher in group Ec than in group Lp (P = 0·019), and when all animals were compared, Enterobacteriaceae correlated positively with body weight (r 0·428, P = 0·029). Bacterial diversity was lower in group Ec than in groups C (P ≤ 0·05) and Lp (P ≤ 0·05). Firmicutes, Bacteroidetes and Verrucomicrobia dominated in all groups, but Bacteroidetes were more prevalent in group C than in groups Lp (P = 0·036) and Ec (P = 0·056). The same five bacterial families dominated the microbiota of groups Ec and C, and four of these were also present in group Lp. The other five families dominating in group Lp were not found in any of the other groups. Multivariate data analysis pointed in the same directions as the univariate statistics. The present results suggest that supplementation of L. plantarum or E. coli can have long-term effects on the composition of the intestinal microbiota, as well as on weight gain and fattening.

Effect of lactobacilli on paracellular permeability in the gut.

Paracellular permeability is determined by the complex structures of junctions that are located between the epithelial cells. Already in 1996, it was shown that the human probiotic strain Lactobacillus plantarum 299v and the rat-originating strain Lactobacillus reuteri R2LC could reduce this permeability in a methotrexate-induced colitis model in the rat. Subsequently, many animal models and cell culture systems have shown indications that lactobacilli are able to counteract increased paracellular permeability evoked by cytokines, chemicals, infections, or stress. There have been few human studies focusing on the effect of lactobacilli on intestinal paracellular permeability but recently it has been shown that they could influence the tight junctions. More precisely, short-term administration of L. plantarum WCSF1 to healthy volunteers increased the relocation of occludin and ZO-1 into the tight junction area between duodenal epithelial cells.

Lactobacillus plantarum 299v enhances the concentrations of fecal short-chain fatty acids in patients with recurrent clostridium difficile-associated diarrhea.

Our objective was to document how intake of Lactobacillus plantarum 299v affects the concentrations of fecal organic acids during and after metronidazole treatment in 19 patients with recurrent Clostridium difficile-associated diarrhea. Fecal samples were analyzed by gas-liquid chromatography. After intake of metronidazole a significant decrease in total short-chain fatty acids was seen in the placebo group (from 77.1 to 45.5 micromol/g; P=0.028) but not in the Lactobacillus group (79.8-60.4 micromol/g). In addition, a statistically significant difference between treatment groups was noted for butyrate (5.6-1.2 micromol/g in the placebo group vs. 7.6-5.6 micromol/g in the Lactobacillus group; P=0.047). At the end of the study and after cessation of placebo or Lactobacillus, the total short-chain fatty acids rose to the same levels as before antibiotic treatment in the placebo group. Both treatment groups showed a significant decrease in concentrations of succinate at the end of the study in comparison to the time when metronidazole intake was stopped (6.3-1.5 micromol/g in the placebo group versus 9.3-0.9 micromol/g in the Lactobacillus group; P=0.028). The present study of fecal samples from a clinical trial is the first to demonstrate that administration of Lactobacillus plantarum 299v reduces the negative effects of an antibiotic on colonic fermentation. The intake of this probiotic strain may thereby provide an additional benefit for patients with recurrent Clostridium difficile-associated diarrhea.

Lactobacillus plantarum 299v for the treatment of recurrent Clostridium difficile-associated diarrhoea: a double-blind, placebo-controlled trial.

A double-blind, placebo-controlled trial was performed to analyse the ability of Lactobacillus plantarum 299v to prevent further recurrent episodes of Clostridium difficile-associated diarrhoea (RCDAD). Recurrence of clinical symptoms (main outcome) was seen in 4 of 11 patients who received metronidazole in combination with L. plantarum 299v and in 6 of 9 treated with metronidazole in combination with placebo. The lactobacilli treatment had no side-effects. Although the small sample size does not allow any conclusion to be drawn concerning the efficacy of L. plantarum in patients with RCDAD, these results may contribute to the ongoing discussion about the benefits of probiotics in patients with RCDAD and encourage the performance of larger multicentre studies.