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PubMed2002

Effect of probiotic strains on interleukin 8 production by HT29/19A cells.

OBJECTIVES: Promising results from clinical studies on the effect of probiotics as maintenance therapy in inflammatory bowel disease and in the prevention of onset of pouchitis ask for studies to unravel the still poorly understood mechanism of action of probiotics. METHODS: To evaluate whether the probiotic bacteria that were used in the clinical studies (VSL#3, Escherichia coli Nissle 1917, and Lactobacillus GG) are able to induce chemokine production in epithelial cells, HT29/19A monolayers were incubated with cell debris and cell extract fractions of single strains of the probiotic bacteria in doses ranging from 10(3) to 10(9) colony-forming units/ml for 32 h. Supernatants were measured for interleukin 8 by ELISA. RESULTS: Lactobacilli and bifidobacteria strains from VSL#3 and Lactobacillus GG did not induce interleukin 8, whereas both cell debris and cell extracts from E. coli Nissle 1917 induced interleukin 8 production in a dose-dependent way. Cell extracts from streptococcal strains induced interleukin 8 when applied at high concentrations. CONCLUSIONS: Probiotic Gram-positive bacteria did not induce interleukin 8, whereas the nonpathogenic, Gram-negative E. coli Nissle 1917 strain induced interleukin 8 in a dose-dependent way in this culture model. These results suggest that probiotic Gram-positive bacteria and E. coli Nissle 1917 may exert their beneficial effects on the host by a different mechanism of action.

Bacterial Physiological Phenomena↗
PubMed2005

Technetium-99m-HMPAO labeled leukocyte single photon emission computerized tomography (SPECT) for assessing Crohn's disease extent and intestinal infiltration.

OBJECTIVES: Scintigraphy using radiolabeled leukocytes is a useful technique for assessing intestinal infiltration in Crohn's disease (CD). However, limits of planar images include overlapping activity in other organs and low specificity. To investigate the usefulness of (99m)Tc-HMPAO (hexametyl propylene amine oxime) labeled leukocyte single photon emission computerized tomography (SPECT) for assessing CD lesions, in comparison with planar images. METHODS: Twenty-two inflammatory bowel disease patients (19 CD; 2 ulcerative colitis, UC; 1 ileal pouch) assessed by conventional endoscopy or radiology were enrolled. Leukocytes were labeled with (99m)Tc-HMPAO. SPECT images were acquired at 2 h and planar images at 30 min and 2 h. Bowel uptake was quantitated in nine regions (score 0-3). RESULTS: Both SPECT and planar images detected a negative scintigraphy (score 0) in the UC patient with no pouchitis and a positive scintigraphy (score 1-3) in the 21 patients showing active inflammation by conventional techniques. SPECT showed a higher global score than planar images (0.71 +/- 0.09 vs 0.30 +/- 0.05; p < 0.001), and in particular in the right iliac fossa (p= 0.003), right and left flank (p < 0.001; p= 0.02), hypogastrium (p= 0.002), and mesogastrium (p < 0.001). SPECT provided a better visualization and a higher uptake than planar images in patients with ileal and ileocolonic CD (6.45 +/- 0.82 vs 2.8 +/- 0.55, p < 0.001; 5.5 +/- 1.6 vs 2.6 +/- 0.7, p= 0.03), and with perianal CD (6.6 +/- 1.6 vs 3.4 +/- 1.2; p= 0.03). CONCLUSIONS: (99m)Tc-HMPAO labeled leukocyte SPECT provides a more detailed visualization of CD lesions than planar images. This technique may better discriminate between intestinal and bone marrow uptake, thus being useful for assessing CD lesions within the pelvis, including perianal disease.

Colitis, Ulcerative↗
PubMed2002

Distribution of genes encoding the trypsin-dependent lantibiotic ruminococcin A among bacteria isolated from human fecal microbiota.

Fourteen bacterial strains capable of producing a trypsin-dependent antimicrobial substance active against Clostridium perfringens were isolated from human fecal samples of various origins (from healthy adults and children, as well as from adults with chronic pouchitis). Identification of these strains showed that they belonged to Ruminococcus gnavus, Clostridium nexile, and Ruminococcus hansenii species or to new operational taxonomic units, all from the Clostridium coccoides phylogenetic group. In hybridization experiments with a probe specific for the structural gene encoding the trypsin-dependent lantibiotic ruminococcin A (RumA) produced by R. gnavus, seven strains gave a positive response. All of them harbored three highly conserved copies of rumA-like genes. The deduced peptide sequence was identical to or showed one amino acid difference from the hypothetical precursor of RumA. Our results indicate that the rumA-like genes have been disseminated among R. gnavus and phylogenetically related strains that can make up a significant part of the human fecal microbiota.

Bacteria↗
PubMed1993

Outcome of restorative proctocolectomy when the diagnosis is suggestive of Crohn's disease.

Twenty of 81 patients treated by restorative proctocolectomy for presumed ulcerative colitis had some features of Crohn's disease: 10 were classified as definite Crohn's disease and 10 as indeterminate colitis. These pathological features were first apparent during synchronous colectomy and pouch construction in 10 of 11 cases. In the remainder, histological features of possible Crohn's disease were first identified during rectal excision (n = 6), preliminary subtotal colectomy (n = 2), and after pouch excision (= 2). Complications were marginally more common in patients with features of possible Crohn's disease: pelvic sepsis 30% (Crohn's disease 30%, indeterminate colitis 30%) v 20%, fistulas 45% (Crohn's disease 30%, indeterminate colitis 60%) v 16%; ileal stenosis 40% (Crohn's disease 40%, indeterminate colitis 40%) v 21%, pouchitis 50% (Crohn's disease 50%, indeterminate colitis 50%) v 26%, and small bowel obstruction 25% (Crohn's disease 30%, indeterminate colitis 30%) v 13%. Pouch excision or a persistent proximal stoma has been necessary in six patients with possible Crohn's disease (30%) (Crohn's disease 3 cases 30%, indeterminate colitis 3 cases 30%) compared with nine (15%) of the remainder. Median hospital stay, however, was the same and stool frequency in those with a functioning pouch were comparable. These results show that there is a higher complication rate if there are features of Crohn's disease but that the medium term functional results are acceptable if the pouch can be retained.

Adolescent↗
PubMed1993

Ileal and colonic epithelial metabolism in quiescent ulcerative colitis: increased glutamine metabolism in distal colon but no defect in butyrate metabolism.

Previous studies have shown that butyrate is an important energy source for the distal colon, and that its metabolism may be defective in ulcerative colitis (UC). A similar metabolic defect in the ileum might account for the occurrence of 'pouchitis' in UC patients after colectomy. A method has been developed that allows the measurement of metabolism in ileocolonoscopic biopsy specimens, and this has been used to assess butyrate and glutamine metabolism in quiescent UC and controls. Preliminary experiments showed optimal metabolism of butyrate at 1 mmol/l. In controls glutamine metabolism was greater in the ascending (mean (SD)) (4.9 (3.2) nmol/h/micrograms protein) than in the descending colon (1.4 0.7)) (p < 0.05, Mann-Whitney U test), but butyrate metabolism was similar in the two regions (ascending 62.6 (44.2), descending 51.5 (32.0)). Consequently ratios of butyrate/glutamine metabolism were higher in the descending colon (20.6 (14.3)) than in the ascending colon (14.3 (9.6)) (p < 0.05). In UC, rates of butyrate metabolism were similar in the ascending (92.5 (58.3) nmol/h/micrograms protein) and descending (93.3 (115)) colon, and these were not significantly different from controls. In UC, glutamine metabolism was similar in the ascending (6.2 (7.7) nmol/h/micrograms protein) and descending colon (7.8 (7.9)); the metabolism in the descending colon was significantly greater than in controls (p < 0.01). Butyrate (135 (56) nmol/h/microgram protein) and glutamine (24.1 (16.2)) metabolism in the ileum in UC, were not significantly different from control values (butyrate 111 (57), glutamine 15.5 (15.6)). These results confirm that there is regional variation of nutrient utilisation throughout the colon, but they do not support the hypothesis that UC is caused by a deficiency of butyrate metabolism.

Adolescent↗
PubMed1994

Relationship of small bowel motility to ileoanal reservoir function.

Some patients with an ileoanal reservoir have a high defecation frequency, despite a good anatomical result and the absence of pouchitis. This study aimed to determine whether variation in function is related to a difference in small bowel motility proximal to the reservoir and if small bowel motility is propagated into the reservoir. Ambulatory small bowel and reservoir motility was studied for 24 hours in five patients with good function (median bowel frequency 4 per day, range 3-6) and seven subjects with poor function (median bowel frequency 12 per day, range 10-20). Five solid state pressure sensors were positioned in the small bowel and one in the reservoir. During the fasting nocturnal period (2300-0800 h), patients with poor function had a median of 10 (range 5-13) migrating motor complexes (MMC), significantly greater (p = 0.03) than the corresponding median number of 3 (range 2-7) in patients with good function. A total of 120 MMCs were observed in the whole series of 12 patients. Of these only two were propagated from the small bowel into the reservoir. Discrete clustered contractions were not propagated into the reservoir, although prolonged propagated contractions did pass into the reservoir in one patient. Patients with poor function had similar 24 hour stool output and radiological reservoir size to those with good function, but the median maximum tolerated volume on reservoir distension was 290 ml (range 160-450) for patients with poor function compared with 475 ml (range 460-550) for patients with good function (p = 0.005). Small bowel motility proximal to the reservoir bears an important relationship to pouch function and defecation frequency. Propagation of coordinated proximal small intestinal motility into the reservoir is rare.

Adult↗
PubMed1995

Restorative proctocolectomy and pouch anal anastomosis for ulcerative colitis following orthotopic liver transplantation.

This study reports on the outcome of four patients having ileal pouch anal anastomosis after orthotopic liver transplantation for sclerosing cholangitis complicating ulcerative colitis. There were no deaths on follow up. Early postoperative bleeding was a complication of colectomy or rectal excision in three, one of whom developed hepatic artery thrombosis and the overall complication rate was high. All patients are continent but one has chronic pouchitis (while receiving longterm metronidazole) and one patient has recurrent sclerosing cholangitis in the transplant.

Adult↗
PubMed2003

Lactobacillus GG prevents recurrence of colitis in HLA-B27 transgenic rats after antibiotic treatment.

BACKGROUND AND AIMS: Bacteroides vulgatus induces colitis in gnotobiotic HLA-B27 transgenic (TG) rats while broad spectrum antibiotics prevent and treat colitis in specific pathogen free (SPF) TG rats although disease recurs after treatment ends. Lactobacilli treat human pouchitis and experimental colitis. We investigated if Lactobacillus rhamnosus GG (L GG) can prevent colitis in TG rats monoassociated with B vulgatus and if L GG or Lactobacillus plantarum 299v (LP 299v) can treat established colitis in SPF TG rats and prevent recurrent disease after antibiotics were stopped. METHODS: Germfree B27 TG rats were monoassociated with B vulgatus for four weeks following two weeks of colonisation with L GG or no bacteria. SPF B27 TG rats received oral vancomycin and imipenem for two weeks, or water alone, followed by four weeks of treatment with oral L GG, LP 299v, or water only. Disease activity was quantified by blinded gross and histological scores, caecal myeloperoxidase (MPO) activity, and levels of interleukin (IL)-1 beta, tumour necrosis factor (TNF), transforming growth factor beta, and IL-10. RESULTS: L GG did not prevent colitis in B vulgatus co-associated TG rats or treat established disease in SPF rats. However, L GG but not LP 299v prevented colitis relapse in antibiotic treated rats with reduced gross and histological scores, caecal MPO, IL-1 beta, and TNF whereas caecal IL-10 was increased. CONCLUSIONS: L GG does not prevent colitis in gnotobiotic TG rats or treat established disease in SPF rats, but is superior to LP 299v in the prevention of recurrent colitis. These studies suggest that antibiotics and probiotic agents provide synergistic therapeutic effects, perhaps mediated by altered immunomodulation with selective activity of different lactobacillus species.

Animals↗
PubMed2004

Probiotics and human health: a clinical perspective.

There is unequivocal evidence that administration of probiotics could be effective in the treatment of acute infectious diarrhoea in children and the prevention of antibiotic associated diarrhoea and nosocomial/community acquired diarrhoea. Encouraging evidence is also emerging for the effectiveness of probiotics in the prevention and management of pouchitis and paediatric atopic diseases, and the prevention of postoperative infections. There is also strong evidence that certain probiotic strains are able to enhance immune function, especially in subjects with less than adequate immune function such as the elderly. Efficacy of probiotics in the prevention of traveller's diarrhoea, sepsis associated with severe acute pancreatitis, and cancers, the management of ulcerative colitis, and lowering of blood cholesterol remains unproven. In addition to firm evidence of efficacy (for a range of conditions), major gaps exist in our knowledge regarding the mechanisms by which probiotics modulate various physiological functions and the optimum dose, frequency, and duration of treatment for different probiotic strains.

Bacterial Infections↗
PubMedDate not supplied

Radiology of ileal pouch-anal anastomosis: normal findings, examination pitfalls, and complications.

Ileal pouch-anal anastomosis (IPAA) is a procedure in which an ileal reservoir is constructed after total colectomy and anastomosed to the anus. IPAA is a well-established option for patients who require surgery for chronic ulcerative colitis or familial adenomatous polyposis. Although excellent functional results can be achieved with IPAA, the procedure is associated with an appreciable number of complications, including small bowel obstruction, pouch fistula, anastomotic separation, anastomotic leakage, pelvic infection and abscess, stricture, and pouchitis. However, most of these complications do not require surgical intervention and can be managed with aggressive medical treatment and delay of ileostomy closure. Radiography of the IPAA pouch is routinely performed before closure of the diverting ileostomy to evaluate the integrity of the pouch and anastomosis. Such radiography can demonstrate many of the complications of IPAA, thus allowing identification of patients who may require intervention or delay before closure of the ileostomy.

Adolescent↗
PubMed2000

Inflammatory bowel diseases in Indo-Canadians with and without antineutrophil cytoplasmic autoantibodies.

A sequentially evaluated cohort of Indo-Canadians with either ulcerative colitis or Crohn's disease were prospectively examined for antineutrophil cytoplasmic autoantibodies (ANCA). Of 84 patients, 62 had ulcerative colitis and 22 had Crohn's disease. About one-third were born in Canada, and two-thirds were migrants from India or other countries, particularly East African nations. There was a disease-based and geographically based male predominance. The mean age of Canadian-born patients was significantly less than that of those born in other countries. Moreover, for migrants, the mean duration of residence in Canada before developing disease was 8.9 years for Crohn's disease patients and 13.5 years for ulcerative colitis patients. Moderate to severe disease was present; virtually all those with Crohn's disease had colonic involvement, and most of those with ulcerative colitis had extensive colonic disease. Overall, 40 of 84 (48%) were seropositive for ANCA, including a majority of those with ulcerative colitis but not Crohn's disease. In addition, eight had cytoplasmic ANCA, a reported seromarker for extensive colitis. Seropositive and seronegative patients were similar in age, sex, birth or duration of residence in Canada, site and severity of disease, familial history and complications, including pouchitis. This study supports the view that these diseases arise in individuals with a genetic predisposition following exposure to some, as yet unknown, environmental factor.

Adult↗
PubMed2001

The use of probiotics in gastrointestinal disease.

Probiotics are living microorganisms that can affect the host in a beneficial manner. Prebiotics are nondigestible food ingredients that stimulate the growth and activity of probiotic bacteria already established in the colon. Efficacy of probiotic compounds has been shown in a wide range of gastrointestinal diseases. Lactobacillus GG alone, or the combination of Bifidobacterium bifidum and Streptococcus thermophilus, is effective in the treatment of Clostridium difficile, as well as in preventing the frequency and severity of infectious acute diarrhea in children. Prevention of antibiotic-induced diarrhea with the concomitant administration of either Lactobacillus GG or Saccharomyces boulardii has been demonstrated. The most successful studies involve the use of Lactobacillus GG at a dose of 1 x 1010 viable organisms per day and the yeast boulardii at a dose of 1 g/day. A probiotic preparation (VSL#3 - 6 g/day) that uses a combination of three species of Bifidobacterium, four strains of Lactobacillus and one strain of Streptocccus has shown promise in maintaining remission in ulcerative colitis and pouchitis, as well as in preventing the postoperative recurrence of Crohn's disease. The mechanism of action of probiotics may include receptor competition, effects on mucin secretion or probiotic immunomodulation of gut-associated lymphoid tissue. Oral administration of probiotic compounds has been demonstrated to be well tolerated and safe. However, while probiotics have the potential to improve human health and to prevent and treat some diseases, major improvements are needed in labelling and quality assurance procedures for probiotic compounds. In addition, well planned and controlled clinical studies are necessary to delineate fully the potential for probiotic compounds.

Colonic Neoplasms↗
PubMed2000

Poor outcome of a defunctioning stoma after pouch construction for ulcerative colitis.

BACKGROUND: Restorative proctocolectomy for ulcerative colitis can have complications necessitating a later defunctioning ileostomy with uncertain outcome. This analysis was undertaken to assess the outcome in patients needing a later defunctioning ileostomy after pouch construction in patients with ulcerative colitis. METHOD: The notes of our series of 154 patients who underwent restorative proctocolectomy and ileal pouch-anal anastomosis for ulcerative colitis were reviewed and 28 patients identified who needed a later defunctioning ileostomy to deal with complications. RESULTS: A later defunctioning ileostomy was necessary in 28 patients to deal with the following complications: sepsis in 11 patients (5 pouches failed), fistulas in 7 (5 pouches failed), poor function including ileoanal stenosis in 5 (all 5 failed), postoperative intraabdominal bleeding in 2 (both saved), pouchitis in 2 (1 excised) and small bowel obstruction in 1 (saved). 16 pouches were eventually excised or permanently defunctioned (59%). CONCLUSION: Complications necessitating a later defunctioning stoma after pouch construction carry a poor prognosis, especially when used for ileoanal stenosis and fistulae.

Colitis, Ulcerative↗
PubMed2005

Management of inflammatory bowel disease: does rifaximin offer any promise?

An increasing number of both clinical and laboratory-derived observations support the importance of luminal components in driving the inflammatory response in ulcerative colitis and Crohn's disease. Although its role is unclear, antibiotic therapy is commonly used in clinical practice for the treatment of moderately to severely active ulcerative colitis. Metronidazole and/or ciprofloxacin are currently employed in active Crohn's disease, particularly in patients with colonic involvement and with perianal disease. Rifaximin, a rifamycin-derived antibiotic, is characterized by a wide range of antibacterial activity and a very low systemic absorption. Some preliminary data show its efficacy in severe active ulcerative colitis, pouchitis and prevention of postoperative recurrence in Crohn's disease.

Anti-Bacterial Agents↗
PubMed1992

Ultrastructural evidence for piecemeal and anaphylactic degranulation of human gut mucosal mast cells in vivo.

One hundred and seventeen coded intestinal biopsies were examined by electron microscopy and evaluated for morphological evidence of mast cell and basophil secretion in situ. Sixty percent of the biopsies had evidence of secretion. Mast cell secretion was evident in control biopsies, many of which were obtained from uninvolved tissues of patients with inflammatory bowel disease. Biopsies of inflamed continent pouches from ulcerative colitis (UC) patients showed more mast cell secretion than noninflamed UC pouch biopsies. This evidence of mast cell secretion supports recent work that documents high constitutive levels of histamine in jejunal fluids of Crohn's disease patients and suggests a proinflammatory role for mast cells in inflammation associated with pouchitis.

Basophils↗
PubMed1997

Effect of anorectal eversion on long-term clinical outcome of restorative proctocolectomy.

Eversion of the rectum during restorative proctocolectomy with stapled ileal pouch-anal anastomosis (IPAA) remains a controversial surgical manoeuvre because of concern that it may impair anal sphincter function and adversely affect outcome. We have reviewed the long-term results in 41 patients whose operation included formation of a 20 cm J-pouch with stapled IPAA by the technique of rectal eversion. At median follow-up of 4 years (range 1-6 years), 4 pouches (10%) had been removed (2 for pelvic sepsis, 1 for rectovaginal fistula and 1 for Crohn's disease). In 34 patients with functioning pouches in situ, median stool frequency was 5 per 24 h (range 2-10). 11 patients (33%) regularly had to evacuate their pouch at night and 4 (12%) used antidiarrhoeal medication. No patients reported major incontinence; 2 (6%) had minor leakage, and in another 2 minor leakage had now ceased. 4 patients had had episodes of pouchitis. These favourable results offer no support for the contention that rectal eversion substantially worsens the long-term results of restorative proctocolectomy.

Adolescent↗
PubMed1999

Antibiotics in inflammatory bowel disease.

The use of antibiotics as primary therapy in inflammatory bowel disease (IBD) has been an issue of great controversy among the experts in the field. Although the utility of certain antimicrobial agents in managing secondary complications, such as abscess formation, toxic megacolon and pouchitis, has been substantiated by clinical trials, clear evidence to support or undermine their use as primary therapeutic agents in IBD is lacking. This may be secondary to the fact that the etiology of IBD remains unknown, and, despite much speculation and research in the area, no infectious agent has been found to cause or contribute to the pathogenesis of these disorders. The dearth of data, in turn, has resulted in widely varying treatment strategies and a lack of a clear standard of care with regard to the use of antibiotics.

Journal Article↗
PubMed2005

Probiotics (VSL#3) in arthralgia in patients with ulcerative colitis and Crohn's disease: a pilot study.

Arthralgia is a common extraintestinal manifestation of inflammatory bowel disease (IBD). Alterations of the immunologic regulation in the gut may contribute to the pathogenesis of arthralgia. Probiotics (VSL#3) have proven effective in the treatment of pouchitis in patients with ileal pouch anal anastomosis after panproctocolectomy for ulcerative colitis both in maintaining remission and in preventing a flare-up without side effects. The aim of this study was to determine the safety and efficacy of VSL#3 in patients with quiescent IBD who suffered from arthralgia for more than two weeks. An open-label trial was conducted using VSL#3. Pre- and post-treatment joint pain intensity were measured on the Ritchie Articular Index and visual analog scale. Disease activity of the bowel was assessed by the Truelove-Witts and the Harvey-Bradshaw scores. Sixteen of 29 patients completed the trial; in 10 of the 16 patients a statistically significant improvement was documented by the Ritchie Articular Index. No one of the patients had a relapse of intestinal disease while on probiotics. These preliminary results suggest that the probiotic mixture VSL#3 may be an alternative treatment for arthralgia in patients with IBD without inducing exacerbation of the disease. Because probiotics may be effective in the treatment of IBD as well, our results suggest that patients with active disease and arthralgia may also derive benefit from this treatment. Proper randomized controlled studies are indicated.

Adult↗