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      Treatment of irritable bowel syndrome with probiotics: An etiopathogenic approach at last? Translated title: Tratamiento con probióticos del síndrome de intestino irritable: ¿Por fin un enfoque etiopatogénico?

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          Abstract

          Irritable bowel syndrome (IBS) is the most common functional digestive disorder, and may affect 11-20% of the adult population in industrialized countries. In accordance with Rome III criteria (2006) IBS involves abdominal pain and bowel habit disturbance, which are not explained by structural or biochemical abnormalities. Several hypotheses attempt to account for the pathophysiology of IBS, but the etiology still remains uncertain or obscure, perhaps multifactorial. Abnormalities in colonic microflora have recently been suggested in such patients, as has abnormal small-intestine bacterial overgrowth (SIBO), or in particular a significant reduction in the amount of intraluminal Bifidobacteria or Lactobacilli, with consequences like the production of colonic gas, and motility or sensitivity disturbances of the intestinal tract. The disorder is difficult to treat, and the wide spectrum of non-drug and drug treatments shows our ignorance about the cause of the condition. Newer drugs, both pro- and anti-serotonin, have failed to show long-term efficacy or have been withdrawn due to concerns about harmful effects. Recent research has provided increasing support for the idea that disturbances of intestinal microbiota occur in patients with IBS, and that such abnormalities may contribute to IBS symptoms. Studies in Scandinavian countries in the last ten years emphasize the role of probiotics in the modulation of intestinal microbiota, and as a consequence in the regulation of the motility and hypersensitivity of the digestive tract. Although results between studies are difficult to compare because of differences in study design, probiotic dose, strain, and duration of therapy, some studies show symptom improvement. Lactobacilli are found among the normal bacterial flora of the gastrointestinal tract, and Lactobacillus plantarum (Lp) is one of the species frequently isolated from the human mucosa, which is capable of surviving the low pH of the stomach and duodenum, resisting the effect of bile acids in the upper small intestine when ingested, and temporarily colonizing the gastrointestinal tract by binding to the intestinal and colonic mucosa. Concurrent with colonization by Lp there is a decrease in bacterial groups with gas-producing ability, such as Veillonella spp. and Clostridia spp. Evidence has now accumulated to suggest the efficacy of certain probiotics like Lp299v, which may be capable of bringing about a significant reduction in pain, abdominal distension and flatulence, while increasing health-related quality of life in IBS.

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          Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome.

          Probiotic bacteria exhibit a variety of properties, including immunomodulatory activity, which are unique to a particular strain. Thus, not all species will necessarily have the same therapeutic potential in a particular condition. We have preliminary evidence that Bifidobacterium infantis 35624 may have utility in irritable bowel syndrome (IBS). This study was designed to confirm the efficacy of the probiotic bacteria B. infantis 35624 in a large-scale, multicenter, clinical trial of women with IBS. A second objective of the study was to determine the optimal dosage of probiotic for administration in an encapsulated formulation. After a 2-wk baseline, 362 primary care IBS patients, with any bowel habit subtype, were randomized to either placebo or freeze-dried, encapsulated B. infantis at a dose of 1 x 10(6), 1 x 10(8), or 1 x 10(10), cfu/mL for 4 wk. IBS symptoms were monitored daily and scored on to a 6-point Likert scale with the primary outcome variable being abdominal pain or discomfort. A composite symptom score, the subject's global assessment of IBS symptom relief, and measures of quality of life (using the IBS-QOL instrument) were also recorded. B. infantis 35624 at a dose of 1 x 10(8) cfu was significantly superior to placebo and all other bifidobacterium doses for the primary efficacy variable of abdominal pain as well as the composite score and scores for bloating, bowel dysfunction, incomplete evacuation, straining, and the passage of gas at the end of the 4-wk study. The improvement in global symptom assessment exceeded placebo by more than 20% (p < 0.02). Two other doses of probiotic (1 x 10(6) and 1 x 10(10)) were not significantly different from placebo; of these, the 1 x 10(10) dose was associated with significant formulation problems. No significant adverse events were recorded. B. infantis 35624 is a probiotic that specifically relieves many of the symptoms of IBS. At a dosage level of 1 x 10(8) cfu, it can be delivered by a capsule making it stable, convenient to administer, and amenable to widespread use. The lack of benefits observed with the other dosage levels of the probiotic highlight the need for clinical data in the final dosage form and dose of probiotic before these products should be used in practice.
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            Immune activation in patients with irritable bowel syndrome.

            We set out to test the hypothesis that irritable bowel syndrome (IBS) is characterized by an augmented cellular immune response with enhanced production of proinflammatory cytokines. We further aimed to explore whether symptoms and psychiatric comorbidity in IBS are linked to the release of proinflammatory cytokines. We characterized basal and Escherichia coli lipopolysaccharide (LPS)-induced cytokine production in peripheral blood mononuclear cells (PBMCs) from 55 IBS patients (18 mixed-, 17 constipation-, 20 diarrhea-predominant) and 36 healthy controls (HCs). PBMCs were isolated by density gradient centrifugation and cultured for 24 hours with or without (1 ng/mL) LPS. Cytokine production (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, and IL-6) was measured by enzyme-linked immunosorbent assay. Abdominal symptoms and psychiatric comorbidities were assessed by using the validated Bowel Disease Questionnaire and the Hospital Anxiety and Depression Scale. IBS patients showed significantly (P < .017) higher baseline TNF-alpha, IL-1beta, IL-6, and LPS-induced IL-6 levels compared with HCs. Analyzing IBS subgroups, all cytokine levels were significantly (P < .05) higher in diarrhea-predominant IBS (D-IBS) patients, whereas constipation-predominant IBS patients showed increased LPS-induced IL-1beta levels compared with HCs. Baseline TNF-alpha and LPS-induced TNF-alpha and IL-6 levels were significantly higher in patients reporting more than 3 bowel movements per day, urgency, watery stools, and pain associated with diarrhea compared with patients without these symptoms (all P < .05). LPS-induced TNF-alpha production was associated significantly (r = 0.59, P < .001) with anxiety in patients with IBS. Patients with D-IBS display enhanced proinflammatory cytokine release, and this may be associated with symptoms and anxiety.
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              Screening of probiotic activities of forty-seven strains of Lactobacillus spp. by in vitro techniques and evaluation of the colonization ability of five selected strains in humans.

              The probiotic potential of 47 selected strains of Lactobacillus spp. was investigated. The strains were examined for resistance to pH 2.5 and 0.3% oxgall, adhesion to Caco-2 cells, and antimicrobial activities against enteric pathogenic bacteria in model systems. From the results obtained in vitro, five strains, Lactobacillus rhamnosus 19070-2, L. reuteri DSM 12246, L. rhamnosus LGG, L. delbrueckii subsp. lactis CHCC 2329, and L. casei subsp. alactus CHCC 3137, were selected for in vivo studies. The daily consumption by 12 healthy volunteers of two doses of 10(10) freeze-dried bacteria of the selected strains for 18 days was followed by a washout period of 17 days. Fecal samples were taken at days 0 and 18 and during the washout period at days 5 and 11. Lactobacillus isolates were initially identified by API 50CHL and internal transcribed spacer PCR, and their identities were confirmed by restriction enzyme analysis in combination with pulsed-field gel electrophoresis. Among the tested strains, L. rhamnosus 19070-2, L. reuteri DSM 12246, and L. rhamnosus LGG were identified most frequently in fecal samples; they were found in 10, 8, and 7 of the 12 samples tested during the intervention period, respectively, whereas reisolations were less frequent in the washout period. The bacteria were reisolated in concentrations from 10(5) to 10(8) cells/g of feces. Survival and reisolation of the bacteria in vivo appeared to be linked to pH tolerance, adhesion, and antimicrobial properties in vitro.
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                Author and article information

                Contributors
                Role: ND
                Journal
                diges
                Revista Española de Enfermedades Digestivas
                Rev. esp. enferm. dig.
                Sociedad Española de Patología Digestiva (Madrid, Madrid, Spain )
                1130-0108
                August 2009
                : 101
                : 8
                : 553-564
                Affiliations
                [01] Valencia orgnameUniversity of Valencia orgdiv1School of Medicine (Gastroenterology Teaching Unit) orgdiv2Department of Medicine Spain
                [02] Valencia orgnameHospital Arnau de Vilanova orgdiv1Department of Digestive Medicine Spain
                Article
                S1130-01082009000800006
                10.4321/s1130-01082009000800006
                4faf6cd7-2184-4f8f-b298-362c4db8253b

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 23 February 2009
                : 27 February 2009
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 76, Pages: 12
                Product

                SciELO Spain


                Functional digestive disorders,Irritable bowel syndrome (IBS),Intestinal microflora,Mucosal associated microbiota (MAM)

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