[Probiotics and inflammatory bowel disease].
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
F Guarner
Publications and source records attributed to F Guarner.
Increased mucosal tumour necrosis factor alpha production in Crohn's disease can be downregulated ex vivo by probiotic bacteria.
BACKGROUND AND AIMS: Tumour necrosis factor alpha (TNF-alpha) plays a key role in the pathogenesis of intestinal inflammation in Crohn's disease. The effect of bacteria on TNF-alpha release by intestinal mucosa was investigated. METHODS: Ileal specimens were obtained at surgery from 10 patients with Crohn's disease (ileal stricture) and five disease controls undergoing right hemicolectomy (caecal cancer). Mucosal explants from each specimen were cultured for 24 hours with either non-pathogenic Escherichia coli, Lactobacillus casei DN-114001, L bulgaricus LB10, or L crispatus (each study contained blank wells with no bacteria). Tissue and bacterial viability was confirmed by lactate dehydrogenase (LDH) release and culture. Concentrations of TNF-alpha were measured in supernatants and the phenotype of the intestinal lymphocytes was analysed by flow cytometry. RESULTS: Coculture of mucosa with bacteria did not modify LDH release. Release of TNF-alpha by inflamed Crohn's disease mucosa was significantly reduced by coculture with L casei or L bulgaricus; changes induced by L crispatus or E coli were not significant. The effect of L casei and L bulgaricus was not prevented by protease inhibitors. Coculture with L casei and L bulgaricus reduced the number of CD4 cells as well as TNF-alpha expression among intraepithelial lymphocytes from Crohn's disease mucosa. None of the bacteria induced changes in non-inflamed mucosa. CONCLUSIONS: Probiotics interact with immunocompetent cells using the mucosal interface and modulate locally the production of proinflammatory cytokines.
Adult↗
[The colon as an organ: habitat of bacterial flora].
The intestinal flora constitutes a complex ecosystem comprising several hundred species of micro-organism, most of them in the genus bacteria. This ecosystem includes some micro-organism considered to be pathogenes for their capacity to invade the host, but they also contain numerous species capable of promoting beneficial effects on health. Bacterial flora begins to be acquired inmmediately after birth. By the age of two years, the flora etablished is practically definitive. There are transiet modifications derived from the use of antibiotics or in connection with changes in diet, but these are normally reversible so that every individual tends to have a relatively stable flora. The composition of bacterial flora varies from one individual to another but it is metabolic functions show less diversity. The flora in the human colon is like an organ with intense metabolic activity due to the action of bacterial enzymes on the substrates present in the intestine. Many authors have considered it more relevant to identify the enzymatic activity of the bacterial flora than the variety of species contained. The main function of the flora are: 1) fermentation of dietary waste and endogenous mucins; 2) energy recovery through the generation of short-chain fatty acids; 3) protection against colonization and invasion by pathogens (barrier effect), and 4) development, stimulation and modulation of the immune system. Special attention has been paid in recent years to the recognition of certain bacterial species that can have such salutary effects on the host. Probiotics are living microorganism that are consumed in order to obtain a beneficial effect regardless of their intrinsic nutritional value. Considerable experimental evidence has been gathered to suggest that probiotics are useful in many health-related spheres. There is good documentation to the effect that the consumption of yoghurt reduces the signs and symptoms of intestinal lactase deficiency. Some probiotics have been shown to be useful in the prevention and treatment of acute diarrhoea due to rotavirus in children and adolescents. The consumption of certain probiotics has also been seen to reinforce certain functions in the human immune system.
Bacterial Physiological Phenomena↗
Therapeutic effect of phenantroline in two rat models of inflammatory bowel disease.
BACKGROUND: Phenantroline is a zinc-chelator that inhibits biological activities of matrix metalloproteinases (MMPs). Over-expression of MMPs can accelerate tissue destruction and disrupt subsequent tissue repair. The effects of phenantroline in two rat models of inflammatory bowel disease (IBD) are evaluated: transmural colitis induced by trinitrobenzensulphonic acid (TNBS) and distal colitis caused by dextran sulphate sodium (DSS). METHODS: Transmural colitis was induced by TNBS in two groups of 15 rats each, and distal colitis was induced by DSS in two other groups of 15 rats each. Phenantroline was administered by oral gavage at 20 mg kg(-1) day(-1) to the test groups, whereas matched control groups received oral vehicle. On the last day of dosing, rats were subjected to intracolonic dialysis under anaesthesia for assessment of luminal eicosanoid release (PGE2, TXB2 and LTB4) and euthanized. Colons were removed and lesions were blindly scored according to macroscopic and histological scales. Myeloperoxidase (MPO) activity was measured in homogenates of colonic tissue. RESULTS: In the TNBS model, phenantroline treatment significantly reduced colonic strictures; in the DSS model, phenantroline significantly decreased scores of epithelial injury. In both models, the levels of PGE2, TXB2 and LTB4 and tissue MPO were not significantly altered. CONCLUSIONS: Although phenantroline did not modify the activity of inflammatory mediators, this compound substantially reduced intestinal injury associated with tissue remodelling.
Animals↗
Dietary inulin improves distal colitis induced by dextran sodium sulfate in the rat.
OBJECTIVES: Inulin stimulates intracolonic generation of butyrate and growth of lactic acid bacteria. This study investigated whether inulin protects against colitis. METHODS: Rats with dextran sodium sulfate colitis received inulin either orally (1% in drinking water, or 400 mg/day) or by enema. Matched groups received vehicle. In addition, fecal water obtained from inulin-fed rats was administered by enema to rats with colitis and compared with fecal water from control rats. Finally, rats with colitis received daily enemas of either butyrate (at 40 or 80 mmol/L) or vehicle. Inflammation was assessed by eicosanoid asssay in rectal dialysates and MPO activity in colonic tissue. Mucosal lesions were blindly scored by microscopic examination. Luminal pH was measured from cecum to rectum by a surface microelectrode. RESULTS: Oral inulin prevented inflammation, as evidenced by lower lesion scores (p < 0.05), decreased release of mediators (p < 0.05), and lower tissue MPO (p < 0.05) as compared with controls. Inulin induced acidic environment (pH <7.0) from cecum to left colon and increased counts of lactobacilli. Fecal water from inulin-fed rats also reduced scores (p < 0.05) and inflammation (p < 0.05). However, inulin or butyrate enemas had no effect. CONCLUSIONS: Oral inulin reduces the severity of dextran sodium sulfate colitis. The effect seems to be mediated by modification of the intracolonic milieu.
Animals↗
Modulation of colonic barrier function by the composition of the commensal flora in the rat.
BACKGROUND AND AIMS: Altered intestinal permeability is a key pathogenetic factor of idiopathic bowel inflammation. We investigated in the rat if changes in the composition of the bowel flora can alter colonic permeability. METHODS: A colonic segment was surgically excluded from faecal transit and brought out as a loop to the abdominal wall through two colostomies. The loop was used for colonisation with specific bacterial strains after eradication of the native flora with antibiotics. Lumen to blood clearance of dextran (molecular weight 70 000) and mannitol (molecular weight 182) was measured in rats recolonised with a single bacterial strain from rat colonic origin, and in control rats whose colonic loop was kept free of bacteria by antibiotics. Actual colonisation was confirmed by culture of segment effluents. RESULTS: Colonisation with Escherichia coli, Klebsiella pneumoniae, and Streptococcus viridans significantly increased lumen to blood clearance of mannitol. Colonisation with Lactobacillus brevis had the opposite effect and reduced permeability to mannitol. Bacteroides fragilis did not induce significant changes. Permeability to dextran was not altered by any of the strains tested. CONCLUSIONS: Certain commensal bacteria can modify colonic wall permeability to luminal substances.
Analysis of Variance↗
Epidermal growth factor increases surface hydrophobicity and resistance to acid in the rat duodenum.
Epidermal growth factor (EGF) is produced in Brunner's glands and plays a role in healing and repair of duodenal ulcers. We examined the participation of zwitterionic phospholipids of mucus in the effects of EGF. Under anesthesia, groups of rats received an intraduodenal bolus of either saline or EGF. Some rats received subcutaneous indomethacin followed by EGF or EGF followed by a detergent (5% Brij 35, a nonionic detergent that solubilizes luminal phospholipids). Thirty minutes after treatment, mucosal surface hydrophobicity and phospholipid concentration in the mucus layer were measured. Matched groups of rats were challenged with 0.5 M HCl, instilled intraduodenally 30 min after treatment, and mucosal damage was assessed 1 h after acid challenge. Exogenous EGF significantly increased surface hydrophobicity and phosphatidylcholine concentration in the mucus layer. EGF treatment also reduced mucosal damage induced by acid. However, indomethacin pretreatment or detergent administration after EGF abolished both protection against acid and changes in the mucus layer. These data suggest that EGF increases duodenal resistance to luminal acid via stimulation of mucosal zwitterionic phospholipids.
Animals↗
Surface hydrophobicity of the rat colonic mucosa is a defensive barrier against macromolecules and toxins.
BACKGROUND: Mucosal surface hydrophobicity is a key factor of the gastric acid defence barrier. In the colon, surface hydrophobicity is high but its biological function remains unexplored. AIMS: To investigate the functional changes of the barrier due to removal of the surface active phospholipid layer by a detergent, or to reinforcement of the surface active phospholipid by local application of a suspension of lipids. METHODS: Surface hydrophobicity (contact angle measurement), colonic permeability (lumen to blood clearance of mannitol and dextran), and mucosal resistance against luminal aggression (distal colitis induced by dextran sodium sulphate, DSS) were investigated in three study groups: (a) rats pretreated with a detergent (Brij 35) known to remove surfactant lipids; (b) rats pretreated with a suspension of surface active lipids (tripalmitin and dipalmitoyl-phosphatidylcholine); and (c) control rats pretreated with the corresponding vehicles. RESULTS: In controls, surface hydrophobicity was low on the caecal mucosa and high in colon and rectum. Detergent treatment reduced surface hydrophobicity, and increased colonic permeability to mannitol and dextran. Conversely, treatment with lipids increased surface hydrophobicity, and reduced colonic permeability. Administration of DSS induced a progressive loss of colonic surface hydrophobicity, and an increase in permeability to mannitol and dextran. Detergent treatment increased susceptibility to epithelial damage and mucosal inflammation by DSS. Treatment with lipids reduced susceptibility to DSS colitis. CONCLUSION: Colonic surface hydrophobicity modulates permeability to hydrophilic molecules and protects against toxins.
Animals↗
Stimulation of transforming growth factor beta1 by enteric bacteria in the pathogenesis of rat intestinal fibrosis.
BACKGROUND & AIMS: Bacteria and their products stimulate inflammatory responses. Certain mediators, such as transforming growth factor beta1 (TGF-beta1), induce collagen synthesis. Excess collagen deposition results in bowel strictures. The aim of this study was to investigate the role of bacteria and TGF-beta1 in the pathogenesis of intestinal fibrosis. METHODS: In rats with colitis, the effects of bowel decontamination with antibiotics on TGF-beta1, tumor necrosis factor alpha (TNF-alpha), and collagen content in colonic tissue were studied. In normal rats, bacteria of the predominant flora were inoculated into the colonic wall. The effect of neutralizing antibody to TGF-beta1 on tissue collagen deposition was studied. RESULTS: Rats with chronic colitis showed increased levels of TGF-beta1, TNF-alpha, and collagen in the tissue and a high rate of bowel strictures. Antibiotic treatment significantly prevented the increase in TGF-beta1 and collagen and the formation of strictures. Inoculation of bacterial suspensions into the colonic wall increased tissue TGF-beta1 and collagen content. Neutralizing antibody to TGF-beta1 prevented collagen deposition. Colonic wall inoculations with single anaerobic strains (Clostridium ramosum, Bacteroides fragilis, and Bacteroides uniformis), but not with aerobes, induced collagen deposition. CONCLUSIONS: Certain strains of the common flora stimulate TGF-beta1 and induce deposition of collagen in the colonic wall.
Animals↗
Derangement of mucosal barrier function by bacteria colonizing the rat colonic mucosa.
BACKGROUND: Interaction between gut flora and the intestinal barrier may involve changes in permeability. METHODS: Rats with a colonic segment excluded from faecal transit were surgically prepared. Matched groups were either kept on luminal antibiotics to prevent colonization of the segment or recolonized with mixed rat flora. Permeability to low-dose trinitrobenzenesulphonic acid (TNBS) or trinitrophenol (TNP), and mucosal injury by the compounds at a high dose were tested in antibiotic and recolonized rats (the compounds differ in water solubility but share a common antigenic domain). RESULTS: Lumen to blood clearance of the hydrophilic probe (TNBS) was faster in recolonized than in antibiotic rats. The hydrophobic compound TNP was absorbed at faster rates than TNBS, but there was no difference between antibiotic and recolonized rats. Instillation of TNBS at a high dose induced mucosal release of inflammatory mediators and tissue myeloperoxidase accumulation in recolonized rats but not in antibiotic rats. Large necrotic lesions with submucosal involvement after TNBS were only observed in recolonized rats. In contrast, TNP induced mucosal inflammation and large lesions with submucosal necrosis both in recolonized and in antibiotic rats. CONCLUSION: Colonizing bacteria may increase intestinal permeability to hydrophilic compounds and render the mucosa susceptible to injury.
Animals↗
Antiinflammatory effects of enterically coated amoxicillin-clavulanic acid in active ulcerative colitis.
The inflammatory activity of colonic mucosal lesions may be stimulated by intraluminal bacteria. Our aim was to investigate whether administration of broad-spectrum antibiotics decreases inflammatory activity in ulcerative colitis. To this end, we performed a randomized, 5-day study with either oral enterically coated amoxicillin-clavulanic acid (1 g + 250 mg, t.i.d.); i.v. methylprednisolone (40 mg/day) and oral placebo (t.i.d.); or both i.v. methylprednisolone and oral amoxicillin-clavulanic acid as above, in 30 patients with clinically active ulcerative colitis. Before and after 5 days of treatment, intestinal inflammation was assessed by the quantification of mucosal release of eicosanoids and interleukin-8 by rectal dialysis in each patient. Breath H2 excretion after oral lactulose was determined as an index of metabolic activity of colonic flora. The total release of (IL-8) interleukin-8 and eicosanoids significantly decreased in patients treated with antibiotic or steroids and antibiotic. Antibiotic treatment, but not steroids, markedly inhibited breath H2 excretion. In conclusion, short-term treatment with enteric-coated amoxicillin-clavulanic acid decreases the intraluminal release of IL-8 and other inflammatory mediators.
Adolescent↗
Antitumor necrosis factor therapy in rat chronic granulomatous colitis: critical dose-timing effects on outcome.
Inhibition of tumor necrosis fact (TNFalpha) is of potential benefit in the treatment of chronic inflammatory conditions. However, TNFalpha plays an important role in host defenses against infection, and blocking TNFalpha production may also have adverse effects. We tested the efficacy and safety of anti-TNFalpha therapy in experimental colitis induced by trinitrobenzenesulfonic acid. We cultured colonic wall specimens for bacterial growth and measured native TNFalpha protein synthesis in colonic tissue at days 0, 1, 4, 10 and 18 after induction of colitis. Anti-TNFalpha therapy (monoclonal g1 immunoglobulin, 15 mg/kg i.p., every third day) was started on either day 4 or day 10 after induction of colitis. On day 18, we measured the release of inflammatory mediators and scored colonic lesions. In acute lesions, several species of the common flora were grown, including Streptococcus, Staphylococcus, Bacteroides, clostridia and enterobacteria. In chronic lesions, only enterobacteria, clostridia and lactobacilli were isolated. TNFalpha production by inflamed colonic tissue was increased in both acute and chronic lesions. Anti-TNFalpha therapy induced a significant decrease in the release of inflammatory mediators and histopathological remission when treatment started on day 10. However, anti-TNFalpha therapy increased eicosanoid release and lesion scores when treatment started on day 4. In conclusion, acute colonic lesions showed polymicrobial infection. Anti-TNFalpha therapy induced remission of chronic intestinal inflammation, but early treatment did not prove effective.
Animals↗
Deranged hydrophobic barrier of the rat gastroduodenal mucosa after parenteral nonsteroidal anti-inflammatory drugs.
BACKGROUND & AIMS: Parenteral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastrointestinal mucosal lesions. The aim of this study was to investigate whether parenteral NSAIDs alter surface hydrophobicity of the gastroduodenal mucosa. METHODS: Conscious rats received indomethacin or diclofenac subcutaneously at different doses (0.5-10 mg/kg). Surface hydrophobicity of gastric and duodenal mucosa was determined by contact angle measurement at various time points; mucosal prostaglandin synthesis and mucus phospholipid content were measured. Also, the effects of NSAIDs were studied in bile duct-ligated rats. RESULTS: A single 1-2-mg/kg dose significantly decreased hydrophobicity in the stomach and duodenum. The decrease was associated with a reduction in mucus phosphatidylcholine. In the duodenum, mucosal prostaglandin synthesis was restored 24 hours after NSAID dosing, but hydrophobicity was still decreased. There was no adaptation to long-term treatment. In bile duct-ligated rats, NSAIDs did not decrease gastric or duodenal hydrophobicity. Moreover, oral administration of bile from rats pretreated with parenteral NSAIDs significantly decreased mucosal hydrophobicity in untreated rats. CONCLUSIONS: Low-dose NSAIDs by parenteral route impair the physicochemical barrier against luminal acidity and render the mucosa susceptible to injury. Excretion of NSAIDs in bile seems to play a key role in this effect.
Animals↗
Incrimination of anaerobic bacteria in the induction of experimental colitis.
Commensal bacteria may participate in the pathogenesis of bowel inflammation. We studied the role of bacteria from the rat colonic flora on transmural inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). First, bacterial translocation to the colonic wall after induction of colitis was assessed by microbiological and histological methods. Second, rats with a colonic segment excluded from fecal transit were prepared for recolonization with preselected bacteria and used to test the effects of different species on inflammation (eicosanoid release, tissue myeloperoxidase) and damage (histology). Six strains (three aerobes and three anaerobes) were identified in colonic tissue 24 h after induction of colitis. Acridine staining showed bacteria in necrotic areas of the mucosa and invading the submucosa. Rats with excluded colon and sterile culture of luminal washings showed mild inflammation and low mucosal damage in response to TNBS. Rats colonized with anaerobes showed significantly higher eicosanoid release than rats colonized with aerobes only. Moreover, submucosal-lesions were mostly observed in rats with anaerobes. Our findings suggest that colonic anaerobes play a key role in transmural inflammation.
Animals↗
Prescribing nonsteroidal anti-inflammatory drugs together with antisecretory agents is safe but may be useless.
Explore the source record for details and available documents.
Anti-Inflammatory Agents, Non-Steroidal↗
Polyunsaturated phosphatidylcholine prevents stricture formation in a rat model of colitis.
BACKGROUND & AIMS: Polyunsaturated phosphatidylcholine stimulates collagen breakdown in experimental models of liver cirrhosis. Bowel strictures are characterized by excess deposition of collagen in the intestinal wall. The aim of this study was to investigate the effect of polyunsaturated phosphatidylcholine in the prevention of bowel strictures. METHODS: Colitis was induced by trinitrobenzenesulfonic acid. On day 21, the presence of strictures was assessed in control rats, rats with colitis, and phosphatidylcholine-fed (100 mg/day) rats with colitis. Furthermore, serum transforming growth factor beta1, collagen deposition, and collagenase activity in colonic tissue were measured in all groups. RESULTS: None of the control rats but 12 of 16 rats with colitis developed colonic strictures. In contrast, only 2 of 15 phosphatidylcholine-fed rats with colitis showed strictures. Collagen content was much higher in rats with colitis than in phosphatidylcholine-fed rats with colitis and control rats. Phosphatidylcholine-fed rats showed significantly higher collagenase activity in colonic tissue than rats with colitis and control rats. In an ancillary study, free linoleic acid-fed rats showed no differences when compared with rats with colitis. Stimulation of transforming growth factor beta1 was similar in all rats with colitis. CONCLUSIONS: Oral supplementation with polyunsaturated phosphatidylcholine prevents the accumulation of collagen in inflamed intestinal tissue and the formation of strictures. This effect is associated with an enhanced collagen catabolism.
Analysis of Variance↗
Induction of chronic pancreatic disease by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts.
Despite being a common disease in humans, little is known about the etiopathogenesis of and effective therapeutic approaches to chronic pancreatitis, due mainly to the fact that few simple animal models suitable to study inflammatory and fibrogenetic processes have been described in the pancreas. Trinitrobenzene sulfonic acid (TNBS) induces chronic colitis and cholangitis in the rat. We hypothesized that TNBS instillation into the pancreatic ducts could also result in the development of a chronic pancreatic disease. The biliopancreatic duct of rats was cannulated and tied close to the liver. TNBS [0.4 ml of 2% TNBS in phosphate-buffered saline (PBS)-10% ethanol, pH 8] was infused into the pancreas under a continuous controlled-pressure system. Control rats underwent the same procedure using vehicle only. Pathology assessment of TNBS-treated rats examined at 48 h was consistent with severe acute necrotizing pancreatitis, having a morality rate of 31% and serum amylase activity of 37.4 +/- 8.8 U/ml at 24 h and 13.3 +/- 1.7 U/ml at 48 h (p < 0.01 for both time points compared to PBS/ethanol-treated rats). Groups of 10 rats each were killed at 3, 4, and 6 week after the surgical procedure. Morphological examination revealed changes mimicking features of chronic pancreatitis in humans in 80% (32 of 40) of TNBS-treated rats, consisting in various degrees of periductal and lobular fibrosis, duct stenosis, patchy acute and chronic inflammatory cell infiltrates, and signs of gland atrophy. Animals developing chronic disease had a weight gain rate significantly lower than that of control rats. Serum amylase, fasting glucose, and a glucose tolerance test were not different in diseased or control rats. In conclusion, we were able to induce chronic fibrogenetic inflammatory disease in the pancreas after a single pulse instillation of TNBS into the pancreatic ducts. This might be a useful animal model to study the pathophysiology of inflammatory, fibrogenetic, and reparative processes in pancreatic tissue.
Amylases↗