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Biomedical subjects

Francisco Guarner

Publications and source records attributed to Francisco Guarner.

At least 19 recordsLinked to original sources
PubMed2007

Fecal excretion of deoxyribonucleic acid in long-term follow-up of patients with inactive ulcerative colitis.

BACKGROUND: We have developed a technique for measuring fecal excretion of human DNA by assuming that luminal desquamation of epithelial and inflammatory cells increases in damaged colonic mucosa. However, the clinical usefulness of this technique in the follow-up of patients with ulcerative colitis has not been established. The aim of this study was to determine the stability of fecal DNA in inactive ulcerative colitis and its potential value as an indicator of relapse. METHODS: The 54 patients with clinically quiescent ulcerative colitis in this prospective study were followed for 12 months or until clinical relapse (clinical activity index > 7). Fecal calprotectin concentration was determined by ELISA, and fecal DNA concentration was determined by quantitative PCR. RESULTS: During the year of follow-up, 23 of the 54 patients relapsed, with a median increase in the colitis activity index from 1.0 to 8.0 (P < 0.01). Median fecal DNA remained unchanged in patients with stable, inactive colitis, ranging from 6.8 copies/microg at inclusion to 1.7 copies/microg at the end of follow-up. Fecal calprotectin level also was unchanged, ranging from 414.0 microg/g at inclusion to 128.9 microg/g at the end of follow-up. In contrast, fecal DNA concentration increased significantly in patients who relapsed (259.0 versus 3.9 copies/microg at entry; P < 0.01). Similar increases in relapsing patients were also observed with fecal calprotectin. ROC curve analysis to assess the accuracy of fecal DNA and calprotectin in detecting relapses during follow-up yielded similar results. CONCLUSIONS: Fecal DNA concentration remained stable in patients with inactive ulcerative colitis but increased significantly with relapses. Determining fecal DNA concentration may be a new objective instrument to use in the follow-up of patients.

Adult↗
PubMed2006

Modulatory effect of nitric oxide on mast cells during induction of dextran sulfate sodium colitis.

Nitric oxide (NO) is implicated in the pathophysiology of intestinal inflammation. Intestinal mast cells may amplify inflammatory response and mucosal injury in inflammatory bowel disease. Our aim was to examine the role of NO and intestinal mast cells by investigating the effects of NO synthase (NOS) inhibitors and a mast cell stabilizer during induction of dextran sulfate sodium (DSS) colitis. Colitis was induced by 4% DSS in drinking water, in rats pretreated with L-NAME or aminoguanidine. In another set of experiments, we investigated the effect of ketotifen in this setting. Inhibition of NO by L-NAME worsened DSS-induced inflammation, however, aminoguanidine had no effect. On the other hand, ketotifen abolished the deleterious effects of L-NAME on colonic inflammation, suggesting that hyperactivation of mast cells by NOS inhibition amplifies mucosal injury induced by DSS. Our results suggest that constitutive isoforms of NOS prevent mast cell activation.

Animals↗
PubMed2006

Polyethylene glycol enhances colonic barrier function and ameliorates experimental colitis in rats.

OBJECTIVE: Polyethylene glycol (PEG) has been suggested to protect against pathogen colonization by improving colonic barrier function. We aimed to establish whether PEG 4000 affects colonic barrier function and the development of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. MATERIALS AND METHODS: PEG was included in the drinking water for a period of 48 h before intracolonic administration of TNBS. RESULTS AND DISCUSSION: PEG increased colonic surface hydrophobicity and diminished luminal bacterial load. Moreover, PEG markedly reduced mucosal damage and inflammation induced by TNBS. This protection effect appeared to be independent of its laxative properties since the laxatives mannitol or senna extracts had no effect on TNBS colitis. Using everted colonic sacs, pretreatment with PEG produced a lasting reduction in epithelial permeability to mannitol and dextran-70 K that correlated with decreased surface hydrophobicity. CONCLUSION: Our results suggest that the protective effect of PEG on TNBS colitis is associated with reinforcement of the epithelial barrier.

Animals↗
PubMed2006

Lactobacillus casei prevents the upregulation of ICAM-1 expression and leukocyte recruitment in experimental colitis.

Lactobacillus casei has been shown to attenuate the severity of experimental colitis. The objective of the present study was to determine whether the effects of L. casei on colitis are related to modulation of leukocyte recruitment into the inflamed intestine. Rats with a colonic segment excluded from fecal transit were surgically prepared. The segment was decontaminated with antibiotics and recolonized with normal flora isolated from the inflamed rat colon, associated or not to L. casei. Control and colitic [2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced] animals were studied. Leukocyte-endothelial cell interactions were characterized in the colonic microcirculation by intravital microscopy, and ICAM-1 and VCAM-1 expression was measured by the radiolabeled antibody technique. Compared with the noninflamed colonic segment, induction of colitis by TNBS provoked a marked increase in the number of leukocytes firmly adherent to the venular wall (0.5 +/- 0.1 vs. 2.1 +/- 0.6 leukocytes/100 mum, P < 0.01). Colonization with L. casei significantly reduced the number of adherent leukocytes (1.3 +/- 0.4 leukocytes/100 mum; P < 0.05) but did not affect the increased rolling interactions associated with the induction of colitis. Compared with the noncolitic group, induction of colitis was associated with a marked increase in ICAM-1 expression (117 +/- 4 vs. 180 +/- 3 ng antibody/g tissue) that was abrogated when the colitic segment was colonized by L. casei (117 +/- 3 ng antibody/g tissue, P < 0.05). However, L. casei administration did not modify VCAM-1 upregulation in colitic animals. L. casei attenuates leukocyte recruitment observed in experimental colitis induced by TNBS. This effect is possibly related to abrogation of ICAM-1 upregulation.

Animals↗
PubMed2006

Enteric flora in health and disease.

The human gut is the natural habitat for a large and dynamic bacterial community. Recently developed molecular biology tools suggest that a substantial part of these bacterial populations are still to be described. However, the relevance and impact of resident bacteria on host's physiology and pathology is well documented. Major functions of the gut microflora include metabolic activities that result in salvage of energy and absorbable nutrients, protection of the colonized host against invasion by alien microbes, and important trophic effects on intestinal epithelia and on immune structure and function. Gut bacteria play an essential role in the development and homeostasis of the immune system. It is important to underscore that the specialised lymphoid follicles of the gut mucosa are the major sites for induction and regulation of the immune system. On the other hand, there is evidence implicating the gut flora in certain pathological conditions, including multisystem organ failure, colon cancer and inflammatory bowel diseases.

Animals↗
PubMed2006

Mechanisms of disease: the hygiene hypothesis revisited.

In industrialized countries the incidence of diseases caused by immune dysregulation has risen. Epidemiologic studies initially suggested this was connected to a reduction in the incidence of infectious diseases; however, an association with defects in immunoregulation is now being recognized. Effector T(H)1 and T(H)2 cells are controlled by specialized subsets of regulatory T cells. Some pathogens can induce regulatory cells to evade immune elimination, but regulatory pathways are homeostatic and mainly triggered by harmless microorganisms. Helminths, saprophytic mycobacteria, bifidobacteria and lactobacilli, which induce immunoregulatory mechanisms in the host, ameliorate aberrant immune responses in the setting of allergy and inflammatory bowel disease. These organisms cause little, if any, harm, and have been part of human microecology for millennia; however, they are now less frequent or even absent in the human environment of westernized societies. Deficient exposure to these 'old friends' might explain the increase in immunodysregulatory disorders. The use of probiotics, prebiotics, helminths or microbe-derived immunoregulatory vaccines might, therefore, become a valuable approach to disease prevention.

Adjuvants, Immunologic↗
PubMed2006

Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn's disease.

Apoptosis of active T lymphocytes constitutes a major control mechanism of immune homeostasis and tolerance. In Crohn's disease, abnormal activation of mucosal T lymphocytes against enteric bacteria is the key event triggering intestinal inflammation. Resistance of lymphocytes to apoptosis has been proposed as the pathogenetic defect. We examined the influence of bacteria-mucosa interactions on apoptosis of mucosal T lymphocytes. Ileal specimens were obtained at surgery from 12 patients with Crohn's disease. Mucosal explants from each specimen were cultured with nonpathogenic Escherichia coli ATCC 35345, Lactobacillus casei DN-114 001, or no bacteria. Cytokine release was measured in supernatant, and mononuclear cells were isolated for phenotypic characterization and Bcl-2 family protein expression. Coculture of inflamed tissue with L. casei significantly reduced the release of interleukin (IL)-6 and tumor necrosis factor alpha (P < 0.05). In addition, coculture with L. casei significantly reduced the number of T cells displaying the IL-2 receptor in the lamina propria. Expression of the antiapoptotic protein Bcl-2 in lamina propria lymphocytes was also reduced after coculture with L. casei, and the percentage of deoxyuridine triphosphate nick-end labeling positive lymphocytes increased. The nonpathogenic E. coli strain had no significant effect. In conclusion, L. casei reduces the number of activated T lymphocytes in the lamina propria of Crohn's disease mucosa. A balanced, local microecology may restore immune homeostasis.

Adult↗
PubMed2005

Inulin and oligofructose: impact on intestinal diseases and disorders.

A large and diverse variety of bacteria have evolved and adapted to live in the human intestinal habitat in a symbiotic arrangement that influences both physiology and pathology in the host. Symbiosis between host and flora can be optimised by prebiotics. Inulin-type fructans have been shown to improve the metabolic functions of the commensal flora. Clinical and experimental data suggest that they also improve the gut mucosal barrier. Furthermore, modulation of the trophic functions of the flora by these prebiotics could help in the prevention of inflammatory bowel diseases. The anti-inflammatory effects of inulin or oligofructose have been assessed in the rat model of distal colitis induced by dextran sodium sulphate, which histologically resembles human ulcerative colitis, and in the trinitrobenzene sulphonic acid model that resembles human Crohn's disease. Both inulin and oligofructose stimulate colonic production of SCFA and favour the growth of indigenous lactobacilli and/or bifidobacteria. These effects are associated with reduced mucosal inflammation and decreased mucosal lesion scores. Inulin has also been tested in a placebo-controlled clinical trial in patients with relapsing pouchitis. Treatment reduced endoscopic and histological parameters of inflammation of the pouch mucosa. Inulin and oligofructose may offer an opportunity to prevent chronic inflammatory intestinal disorders, and this potential should be tested in further clinical studies.

Animals↗
PubMed2005

Should yoghurt cultures be considered probiotic?

Probiotics are live micro-organisms that when administered in adequate amounts confer a health benefit on the host. Consumption of yoghurt has been shown to induce measurable health benefits linked to the presence of live bacteria. A number of human studies have clearly demonstrated that yoghurt containing viable bacteria (Streptococcus thermophilus and Lactobacillus delbrueckii sp. bulgaricus) improves lactose digestion and eliminates symptoms of lactose intolerance. Thus, these cultures clearly fulfil the current concept of probiotics.

Dietary Supplements↗
PubMed2005

Induction of colonic transmural inflammation by Bacteroides fragilis: implication of matrix metalloproteinases.

BACKGROUND: Commensal bacteria are implicated in the pathophysiology of intestinal inflammation, but the precise pathogenetic mechanisms are not known. We hypothesized that Bacteroides fragilis-produced metalloproteinases (MMPs) are responsible for bacterial migration through the intestinal wall and transmural inflammation. AIM: To investigate the role of bacterial-MMP activity in an experimental model of colitis induced by the intramural injection of bacteria. METHODS: Suspensions of viable B. fragilis or Escherichia coli were injected into the colonic wall, and the effect of the MMP inhibitor (phenantroline) on histologic lesion scores was tested. MMP activity in bacterial suspensions was measured by azocoll assay. RESULTS: The inoculation with B. fragilis induced chronic inflammatory lesions that were preferentially located in the subserosa, whereas inoculation with E. coli induced acute-type inflammatory reactions, evenly distributed in both the submucosa and subserosa. Treatment with phenantroline significantly decreased subserosal lesion scores in rats inoculated with B. fragilis, but not in rats inoculated with E. coli. Bacterial suspensions of B. fragilis showed MMP activity, but E. coli suspensions did not. Sonication of B. fragilis reduced MMP activity and virulence to induce serosal lesions. CONCLUSION: Our data suggest that bacterial MMPs may be implicated in the serosal migration of B. fragilis and in the induction of transmural inflammation.

Animals↗
PubMed2005

The intestinal flora in inflammatory bowel disease: normal or abnormal?

PURPOSE OF REVIEW: The human gut is the natural habitat for a large and dynamic bacterial community. There is a substantial body of evidence implicating the resident flora in the pathogenesis of chronic intestinal inflammation. This review discusses the possible role of a microbial imbalance in the pathophysiology of inflammatory bowel disease. RECENT FINDINGS: Recently developed molecular biologic tools suggest that a sizeable part of the microbial populations of the human gut remains to be defined. Conversely, the relevance of gut bacteria in the host's physiology is well documented. The specialised lymphoid follicles of the gut mucosa are the major sites for induction of effector and regulatory mechanisms of the intestinal immune system, and it is now becoming clear that resident and in-transit microorganisms play an essential role in the homeostasis of local and systemic immunity. An infectious origin of inflammatory bowel disease is not supported by our current knowledge. Several studies, however, have disclosed substantial differences in the intestinal flora between patients with inflammatory bowel disease and healthy subjects, in regard to both composition and mucosal colonisation. Aggressive species are abundant on the inflammatory bowel disease mucosal surface whereas protective genera are underrepresented, but the biologic relevance of these changes needs further investigation. SUMMARY: A balanced microbial environment would likely help in both prevention and control of inflammatory bowel disease. Research is needed to identify microorganisms able to mediate immunoregulation in the gut mucosa.

Bacteria, Aerobic↗
PubMed2005

Selected topics in probiotics and prebiotics: meeting report for the 2004 international scientific association for probiotics and prebiotics.

On August 29-31, 2004, 84 academic and industry scientists from 16 countries gathered in Copper Mountain, Colorado USA to discuss certain issues at the forefront of the science of probiotics and prebiotics. The format for this invitation only meeting included six featured lectures: engineering human vaginal lactobacilli to express HIV-inhibitory molecules (Peter Lee, Stanford University), programming the gut for health (Thaddeus Stappenbeck, Washington University School of Medicine), immune modulation by intestinal helminthes (Joel Weinstock, University of Iowa Hospitals and Clinics), hygiene as a cause of autoimmune disorders (G. A. Rook, University College London), prebiotics and bone health (Connie Weaver, Purdue University) and prebiotics and colorectal cancer risk (Ian Rowland, Northern Ireland Centre for Food and Health). In addition, all participants were included in one of eight discussion groups on the topics of engineered probiotics, host-commensal bacteria communication, 'omics' technologies, hygiene and immune regulation, biomarkers for healthy people, prebiotic and probiotic applications to companion animals, development of a probiotic dossier, and physiological relevance of prebiotic activity. Brief conclusions from these discussion groups are summarized in this paper.

Animals↗
PubMed2004

PASSCLAIM--gut health and immunity.

BACKGROUND: The gut and immune system form a complex integrated structure that has evolved to provide effective digestion and defence against ingested toxins and pathogenic bacteria. However, great variation exists in what is considered normal healthy gut and immune function. Thus, whilst it is possible to measure many aspects of digestion and immunity, it is more difficult to interpret the benefits to individuals of variation within what is considered to be a normal range. Nevertheless, it is important to set standards for optimal function for use both by the consumer, industry and those concerned with the public health. The digestive tract is most frequently the object of functional and health claims and a large market already exists for gut-functional foods worldwide. AIM: To define normal function of the gut and immune system and describe available methods of measuring it. RESULTS: We have defined normal bowel habit and transit time, identified their role as risk factors for disease and how they may be measured. Similarly, we have tried to define what is a healthy gut flora in terms of the dominant genera and their metabolism and listed the many, varied and novel methods for determining these parameters. It has proved less easy to provide boundaries for what constitutes optimal or improved gastric emptying, gut motility, nutrient and water absorption and the function of organs such as the liver, gallbladder and pancreas. The many tests of these functions are described. We have discussed gastrointestinal well being. Sensations arising from the gut can be both pleasant and unpleasant. However, the characteristics of well being are ill defined and merge imperceptibly from acceptable to unacceptable, a state that is subjective. Nevertheless, we feel this is an important area for future work and method development. The immune system is even more difficult to make quantitative judgements about. When it is defective, then clinical problems ensure, but this is an uncommon state. The innate and adaptive immune systems work synergistically together and comprise many cellular and humoral factors. The adaptive system is extremely sophisticated and between the two arms of immunity there is great redundancy, which provides robust defences. New aspects of immune function are discovered regularly. It is not clear whether immune function can be "improved". Measuring aspects of immune function is possible but there is no one test that will define either the status or functional capacity of the immune system. Human studies are often limited by the ability to sample only blood or secretions such as saliva but it should be remembered that only 2% of lymphocytes circulate at any given time, which limits interpretation of data. We recommend assessing the functional capacity of the immune system by: measuring specific cell functions ex vivo. measuring in vivo responses to challenge, e. g. change in antibody in blood or response to antigens. determining the incidence and severity of infection in target populations during naturally occurring episodes or in response to attenuated pathogens.

Constipation↗
PubMed2004

Fecal excretion of human deoxyribonucleic acid as an index of inflammatory activity in ulcerative colitis.

BACKGROUND & AIMS: Several indices evaluate disease activity in ulcerative colitis, but most have drawbacks to their application (invasiveness, complexity, or lack of specificity), and discrepancies between them are frequent. Assuming that desquamation of epithelial and inflammatory cells increases in damaged colonic mucosa, we hypothesized that fecal excretion of human DNA is an index of mucosal inflammation and damage. The aim of our study was to determine whether excretion of human DNA is useful in the evaluation of disease activity in ulcerative colitis. METHODS: Thirty-one controls and 36 ulcerative colitis patients were included. Ulcerative colitis patients and controls underwent colonoscopic examination after preparation by gut lavage with polyethylene-glycol electrolyte solution. In patients, disease activity was established using the clinical index of Rachmilewitz and an endoscopic score. Feces and gut lavage fluid were obtained and DNA levels were measured by quantitative polymerase chain reaction of the human beta-globin gene. RESULTS: Fecal DNA excretion correlated with the clinical index (r = 0.59, P < 0.05) and the endoscopic score (r = 0.76, P < 0.01). Gut lavage fluid DNA levels also correlated with clinical and endoscopic activity scores (r = 0.41 and 0.51, respectively, P < 0.05). Fecal DNA excretion was significantly higher in patients with endoscopically or clinically active disease than in controls or patients in remission. Fecal DNA excretion discriminates between endoscopically active disease and remission (sensitivity 0.67, specificity 1.00, P < 0.01). CONCLUSIONS: Excretion of human DNA in feces, as an expression of cellular desquamation, is a novel noninvasive technique to objectively assess disease activity in ulcerative colitis.

Adult↗
PubMed2003

Gut flora in health and disease.

The human gut is the natural habitat for a large and dynamic bacterial community, but a substantial part of these bacterial populations are still to be described. However, the relevance and effect of resident bacteria on a host's physiology and pathology has been well documented. Major functions of the gut microflora include metabolic activities that result in salvage of energy and absorbable nutrients, important trophic effects on intestinal epithelia and on immune structure and function, and protection of the colonised host against invasion by alien microbes. Gut flora might also be an essential factor in certain pathological disorders, including multisystem organ failure, colon cancer, and inflammatory bowel diseases. Nevertheless, bacteria are also useful in promotion of human health. Probiotics and prebiotics are known to have a role in prevention or treatment of some diseases.

Bacteria, Aerobic↗
PubMed2003

Role of bacteria in experimental colitis.

Epidemiology suggests some relationship between the establishment of the gut flora and the risk of developing inflammatory bowel disease. Unrestrained activation of the immune system against commensal bacteria appears to be responsible for the chronicity of these diseases. In animal models, broad-spectrum antibiotics reduce the bacterial load and militate against intestinal inflammation. Several bacterial species found in of the common microflora, including anaerobes, are able to invade the colonic wall when there is dysfunction of the colonic mucosal barrier. Most aerobes provoke focal areas of acute inflammation, but some anaerobes in the predominant flora induce diffuse a fibrogenic transmural response. Current research aims to identify the probiotics that might act against these bacteria. Colonization with specific probiotic strains, including a bacterium genetically engineered to secrete interleukin-10, prevents spontaneous colitis in susceptible mice. Certain lactobacilli exhibit anti-inflammatory properties naturally, i.e. without previous genetic manipulation. Prebiotics may increase colonization by lactobacilli and can prevent mucosal inflammation. Modulation of the gut flora with probiotics may prove useful in the prevention and control of inflammatory bowel diseases.

Animals↗