Background and aim: Evidence exists for the pathogenic role of the enteric flora in inflammatory bowel disease. Probiotics contain living microorganisms which exert health effects on the host. We compared the efficacy in maintaining remission of the probiotic preparation Escherichia coli Nissle 1917 and established therapy with mesalazine in patients with ulcerative colitis. Patients and methods: In total, 327 patients were recruited and assigned to a double blind, double dummy trial to receive either the probiotic drug 200 mg once daily (n = 162) or mesalazine 500 mg three times daily (n = 165). The study lasted for 12 months and patients were assessed by clinical and endoscopic activity indices (Rachmilewitz) as well as by histology. The primary aim of the study was to confirm equivalent efficacy of the two drugs in the prevention of relapses. Results: The per protocol analysis revealed relapses in 40/110 (36.4%) patients in the E coli Nissle 1917 group and 38/112 (33.9%) in the mesalazine group (significant equivalence p = 0.003). Subgroup analyses showed no differences between the treatment groups in terms of duration and localisation of disease or pretrial treatment. Safety profile and tolerability were very good for both groups and were not different. Conclusions: The probiotic drug E coli Nissle 1917 shows efficacy and safety in maintaining remission equivalent to the gold standard mesalazine in patients with ulcerative colitis. The effectiveness of probiotic treatment further underlines the pathogenetic significance of the enteric flora.

No abstract

Structural analysis of lipopolysaccharide (LPS) isolated from semirough, serum-sensitiveLipopolysaccharide (LPS) is a key component of the outer membrane of gram-negative bacteria. It is comprised of three distinct regions: lipid A, the oligosaccharide core, and commonly a long-chain polysaccharide O antigen that causes a smooth phenotype. Lipid A is the most conserved part of LPS. It is connected to the core part, which links it to the O repeating units. In Escherichia coli, five different core structures (K-12 and R1 to R4) have been described (2, 18, 43). The O repeating units are highly polymorphic, and more than 190 serologically distinguished forms in E. coli are known today (35).The LPS core-encoding genes are located at a conserved position on the E. coli K-12 chromosomal map (81 to 82 min) (5). The wa‫ء‬ (formerly called rfa) gene clusters contain the genes which code for the enzymes required for the core assembly and consist of three operons (defined by the first genes in the operons; gmhD, waaQ, and waaA). Although the O-unitencoding gene cluster is extremely polymorphic in the E. coli species, it is localized at a conserved position on the E. coli K-12 chromosome between the galF and gnd genes (45.4 min) (5). These determinants consist of several sugar transferase-, epimerase-, and isomerase-encoding genes, the O-antigen flippase gene (wzx), the O-antigen polymerase gene (wzy [formerly called rfc]), as well as the genes coding for enzymes involved in carbohydrate biosynthesis pathways. Until now, several E. coli O-antigen-encoding gene clusters have been studied, e.g., those of serotypes O7, O111, O113, and O157 (32, 38, 54, 55). These gene clusters show no significant nucleotide homology with each other, with the exception of some common genes such as manC and manB. However, they contain a conserved range of predicted enzyme activities. The O6 antigen is widely distributed among pathogenic and nonpathogenic fecal E. coli isolates and is often found in uropathogenic E. coli strains. It is associated with R1-type core LPS and has not been investigated in detail so far.E. coli strain Nissle 1917 (DSM 6601, serotype O6:K5:H1) is a nonpathogenic fecal isolate, which is used as a probiotic agent in medicine (7), mainly for treatment of various gastroenterological indications (23,26,30,33,41). This strain exhibits a serum-sensitive, semirough phenotype. Since colonies of this strain on agar plates show a special smooth-and-rough

BackgroundProbiotics are effective in inflammatory bowel diseases. Clinical effectiveness and dose dependency of E. coli Nissle (EcN) enemas were investigated in ulcerative colitis (UC).MethodsIn a double-blind study, 90 patients with moderate distal activity in UC were randomly assigned to treatment with either 40, 20, or 10 ml enemas (N = 24, 23, 23) containing 10E8 EcN/ml or placebo (N = 20). The study medication was taken once daily for at least 2 weeks. After 2, 4 and/or 8 weeks the clinical DAI was assessed together with tolerance to treatment. Patients who reached clinical DAI ≤ 2 within that time were regarded as responders.ResultsAccording to ITT analysis the number of responders was not significantly higher in the EcN group than in the placebo group (p = 0.4430, 2-sided). However, the Jonckheere-Terpstra rank correlation for dose-dependent efficacy indicated a significant correlation of per-protocol responder rates (p = 0.0446, 2-sided). Time to remission was shortest with EcN 40 ml, followed by EcN 20 ml. The number of adverse events did not differ notably.ConclusionIn contrast to ITT analysis, efficacy of rectal EcN application was significant in PP and points to EcN as a well tolerated treatment alternative in moderate distal UC.Trial registrationGerman Clinical Trials Register DRK00000234.

In most cases, acute diarrhoea will become selflimiting during the first few days after onset. For young children, however, health risks may develop when the disease lasts longer than 3 days. The purpose of the present trial was to determine whether the stool frequency of infants and toddlers suffering from acute diarrhoea could be normalised more quickly by administering the probiotic Escherichia coli Nissle 1917 (EcN) solution than by administering a placebo. The safety of EcN were also assessed. A total of 113 children (aged 2-47 months) with acute diarrhoea (> three watery or loose stools in 24 h) were randomised to either a group receiving the probiotic EcN suspension (n =55) or a group receiving the placebo suspension (n=58) in a confirmative, double-blind clinical trial. Depending on the age of patients, 1-3 ml per day of verum suspension (10 8 viable EcN cells per millilitre) or placebo were administered orally. The causes of the diarrhoea were viral rather than bacterial, but they were mainly unspecific infections. The median onset of treatment response (reduction of daily stool frequency to ≤ three watery or loose stools over at least 2 consecutive days) occurred more rapidly in the children receiving the EcN solution (2.5 days) than in those receiving the placebo (4.8 days), a significant difference (2.3 days; p=0.0007). The number of patients showing a response was clearly higher (p<0.0001) in the EcN group (52/55; 94.5%) than in the placebo group (39/58; 67.2%). EcN was found to be safe and well-tolerated, and it showed a significant superiority compared to the placebo in the treatment of acute diarrhoea in infants and toddlers.

No abstract

The six clones pTB112, pTB324, pTBs12, pCd122, pCd14 and pCd13 cover the tox locus of Clostridium difficile VPI 10463. This region of 19 kb of chromosomal DNA contains four open reading frames including the complete toxB and toxA genes. The two toxins show 63% amino acid (aa) homology, a relatedness that had been predicted by the cross-reactivity of some monoclonal antibodies (mAb) but that is in contrast to the toxin specificity of polyclonal antisera. A special feature of ToxA and ToxB is their repetitive C-termini. We define herein 19 individual CROPs (combined repetitive oligopeptides of 20-50 aa length) in the ToxB C-terminus, which are separable into five homologous groups. Comparison of the aa sequences of the N-terminal two-thirds of ToxA and ToxB revealed three marked structures, a cluster of 172 hydrophobic, highly conserved aa in the centre of both toxins, a sequence of 120 residues with an accumulation of highly conserved arginine, cysteine, histidine, methionine, and tryptophan residues, and a stretch of 248 less conserved aa. The probable function of these domains is discussed. Structural and functional homologies of ToxA and ToxB indicate that both genes have a common ancestor and may have evolved by gene duplication, with subsequent recombination and mutation, as has been reported for streptococcal glucosyltransferases (Gtf).

The aim of this study was to analyze the influence of oral administration of E. coli Nissle 1917 on the systemic humoral and cellular immunity in premature infants. Thirty-four premature infants were colonized with E. coli Nissle 1917 in a randomized, placebo-controlled blinded clinical trial. Stool samples of infants were analyzed repeatedly for the presence of the administered strain. The proliferative response to bacterial antigens of E. coli origin was measured in whole blood of 34 colonized infants and 27 noncolonized controls. E. coli colonization induced a significant increase in the proliferation of blood cells cultivated with bacterial components of E. coli Nissle 1917 and another E. coli strain in colonized infants as compared with noncolonized controls. Significantly higher amounts of specific anti-E. coli Nissle 1917 antibodies (Ab) of immunoglobulin (Ig)A isotype and nonspecific polyclonal IgM were found in the blood of colonized infants compared to noncolonized placebo controls. We concluded that the oral application of E. coli Nissle 1917 after birth significantly stimulates specific humoral and cellular responses and simultaneously induces nonspecific natural immunity.