Redoxpotentiaal en residente darmflora van de muis

In dit proefschrift wordt, in hoofdstuk I, een overzicht gegeven van de milieukenmerken die de samenstelling van de residente darmflora bepalen, Vanuit ecologisch standpunt gezien is de redoxpotentiaal één van de belangrijkste van deze factoren. De lage redoxpotentiaal in het coecum van conventionele dieren is ervoor verantwoordelijk dat de residente flora uit facultatief anaerobe en strikt anaerobe micro-organismen bestaat. De darmflora zelf houdt de redoxpotentiaal op een laag niveau, hetgeen blijkt uit het feit dat de potentiaal in het coecum van kiemvrije muizen ongeveer 200 mV hoger is dan in het coecum van conventionele dieren. In hoeverre de hoge redoxpotentiaal in het coecum van kiemvrije muizen bepalend is voor het al dan niet koloniseren van strikt anaerobe darmbacteriën en hoe de redoxpotentiaal verandert onder invloed van de nesteling van deze micro-organismen wordt in dit onderzoek bestudeer

Structural and mechanistic insights into a Bacteroides vulgatus retaining N-acetyl-β-galactosaminidase that uses neighbouring group participation

Bacteroides vulgatus is a member of the human microbiota whose abundance is increased in patients with Crohn's disease. We show that a B. vulgatus glycoside hydrolase from the carbohydrate active enzyme family GH123, BvGH123, is an N-acetyl-β-galactosaminidase that acts with retention of stereochemistry, and, through a 3-D structure in complex with Gal-thiazoline, provide evidence in support of a neighbouring group participation mechanism

Gut Microbiota Dysbiosis Is Associated with Inflammation and Bacterial Translocation in Mice with CCl4-Induced Fibrosis

BACKGROUND: Gut is the major source of endogenous bacteria causing infections in advanced cirrhosis. Intestinal barrier dysfunction has been described in cirrhosis and account for an increased bacterial translocation rate. HYPOTHESIS AND AIMS: We hypothesize that microbiota composition may be affected and change along with the induction of experimental cirrhosis, affecting the inflammatory response. ANIMALS AND METHODS: Progressive liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at weeks 6, 10, 13 and 16 in a subgroup of treated mice (n = 6/week) and control animals (n = 4/week). Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected at laparotomies. Fibrosis grade, pro-fibrogenic genes expression, gut bacterial composition, bacterial translocation, host's specific butyrate-receptor GPR-43 and serum cytokine levels were measured. RESULTS: Expression of pro-fibrogenic markers was significantly increased compared with control animals and correlated with the accumulated dose of carbon tetrachloride. Bacterial translocation episodes were less frequent in control mice than in treated animals. Gram-positive anaerobic Clostridia spp count was decreased in treated mice compared with control animals and with other gut common bacterial species, altering the aerobic/anaerobic ratio. This fact was associated with a decreased gene expression of GPR43 in neutrophils of treated mice and inversely correlated with TNF-alpha and IL-6 up-regulation in serum of treated mice along the study protocol. This pro-inflammatory scenario favoured blood bacterial translocation in treated animals, showing the highest bacterial translocation rate and aerobic/anaerobic ratio at the same weeks. CONCLUSIONS: Gut microbiota alterations are associated with the development of an inflammatory environment, fibrosis progression and bacterial translocation in carbon tetrachloride-treated mice

A Meta-Analysis of Probiotic Efficacy for Gastrointestinal Diseases

Background: Meta-analyses on the effects of probiotics on specific gastrointestinal diseases have generally shown positive effects on disease prevention and treatment; however, the relative efficacy of probiotic use for treatment and prevention across different gastrointestinal diseases, with differing etiology and mechanisms of action, has not been addressed. Methods/Principal Findings: We included randomized controlled trials in humans that used a specified probiotic in the treatment or prevention of Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, Antibiotic Associated Diarrhea, Traveler’s Diarrhea, or Necrotizing Enterocolitis. Random effects models were used to evaluate efficacy as pooled relative risks across the eight diseases as well as across probiotic species, single vs. multiple species, patient ages, dosages, and length of treatment. Probiotics had a positive significant effect across all eight gastrointestinal diseases with a relative risk of 0.58 (95 % (CI) 0.51–0.65). Six of the eight diseases: Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, and Antibiotic Associated Diarrhea, showed positive significant effects. Traveler’s Diarrhea and Necrotizing Enterocolitis did not show significant effects of probiotcs. Of the 11 species and species mixtures, all showed positive significant effects except for Lactobacillus acidophilus, Lactobacillus plantarum, and Bifidobacterium infantis. Across all diseases and probiotic species, positive significant effects of probiotics were observed for all age groups, single vs. multiple species, and treatment lengths

Intestinal microbiota in human health and disease: the impact of probiotics

The complex communities of microorganisms that colonise the human gastrointestinal tract play an important role in human health. The development of culture-independent molecular techniques has provided new insights in the composition and diversity of the intestinal microbiota. Here, we summarise the present state of the art on the intestinal microbiota with specific attention for the application of high-throughput functional microbiomic approaches to determine the contribution of the intestinal microbiota to human health. Moreover, we review the association between dysbiosis of the microbiota and both intestinal and extra-intestinal diseases. Finally, we discuss the potential of probiotic microorganism to modulate the intestinal microbiota and thereby contribute to health and well-being. The effects of probiotic consumption on the intestinal microbiota are addressed, as well as the development of tailor-made probiotics designed for specific aberrations that are associated with microbial dysbiosis

Isolation and characterization of the viscous, high-molecular-mass microbial carbohydrate fraction from faeces of healthy subjects and patients with Crohn's disease and the consequences for a therapeutic approach

1. An earlier study by our group revealed that the viscosity of faeces from patients with Crohn's disease is significantly lower than that of healthy subjects. This is due to low concentrations of a high-molecular-mass carbohydrate, probably of bacterial origin. The cause of this phenomenon might be the impaired barrier function of the gut mucosa. Low viscosity may allow close contact of intestinal contents (bacterial products and toxins) with the intestinal wall. This could play a role in the maintenance of the disease. 2. The first aim of this study was to investigate the high-molecular-mass carbohydrate fraction, responsible for viscosity, in detail. We also tried (in a pilot study) to raise the intestinal viscosity of patients with Crohn's disease with the undegradable food additive hydroxypropylcellulose (E463), in an attempt to alleviate clinical symptoms. 3. The high-molecular-mass fraction (> 300 kDa) responsible for faecal viscosity was sensitive to lysozyme and contained high levels of muramic acid. It was concluded that this material consisted mainly of peptidoglycan polysaccharides and was consequently of bacterial origin. The muramic acid in material from patients with Crohn's disease was 7.5 (1.5-13.9)%, which was less than in healthy subjects [11.4 (8.5-24.1)%; P = 0.0004]. Furthermore, viscosity in material from patients with Crohn's disease was found to be half [14.9 (1.0-33.6) cP] of that found in healthy subjects [35.0 (2.7-90.7) cP; P = 0.004]. 4. A daily dose of 1 g of hydroxypropylcellulose caused an increase in faecal viscosity in patients with Crohn's disease (from 1.4 to 2.3 cP) and in healthy subjects (from 4.9 to 7.5 cP). Faecal consistency improved in patients with Crohn's disease (from watery and loose to formed) and the defecation frequency decreased from 3-4 to about 2 times a day. No changes in defecation patterns were found in healthy subjects. 5. These data indicate that the high-molecular-mass fraction that is responsible for faecal viscosity is peptidoglycan. Furthermore, a daily dose of a hydroxypropylcellulose solution to increase the viscosity of the intestinal contents of patients with Crohn's disease might be beneficial. This approach merits further study