The capacity of short-chain fructo-oligosaccharides to stimulate faecal bifidobacteria: a dose-response relationship study in healthy humans

BACKGROUND: Short-chain fructo-oligosaccharides (scFOS) are well-known for their bifidogenicity. In a large study comprising 200 healthy volunteers, we determined the bifidogenic properties of 7 non-digestible carbohydrates administered at a dose of 10 g/d in the diet; we analysed dose-response relationships of the bifidogenic substrates at doses ranging from 2.5 to 10 g/d in comparison with a placebo. The aim of this presentation is to give more details about the dose-response effects of short-chain fructo-oligosaccharides (scFOS). METHODS: Forty healthy volunteers (18 males, 22 females) eating their usual diets were randomly divided into 5 groups of 8 subjects and received scFOS at a dose of 2.5, 5.0, 7.5 and 10 g/d or a placebo for 7 d. Stools were collected before (day (d) 8) and at the end (day (d) 15) of sugar consumption, and tolerance was evaluated using a daily chart. RESULTS (M ± SEM): Bifidobacteria counts increase was higher in scFOS than in placebo group for all doses tested [2.5 g/d (from 9.15 ± 0.59 to 9.39 ± 0.70; P = 0.02); 5 g/d (from 10.21 ± 0.21 to 10.67 ± 0.22; P = 0.03); 7.5 g/d (from 9.28 ± 0.49 to 9.85 ± 0.35;P = 0.01); 10 g/d (from 9.00 ± 0.81 to 10.18 ± 0.60; P = 0.003)]. A significant correlation between the ingested dose of scFOS and faecal bifidobacteria counts was observed at d15 (r(2 )= 0.307, P < 0.001). Total anaerobes increased at the dose of 10 g/d. No significant differences were found for Bacteroides, Lactobacillus, enterobacteria or pH in any group. The frequency of digestive symptoms was not different between scFOS at any of the doses tested and placebo. Bloating was significantly more intense during scFOS ingestion at doses of 2.5 and 5 g/d, but not at doses of 7.5 and 10 g/d. Excess flatus, borborygmi and abdominal pain did not differ from the placebo at any of the doses tested. CONCLUSION: This study showed that scFOS is bifidogenic and well tolerated at doses ranging from 2.5 to 10 g/d, and that there is a dose-response relationship in healthy volunteers

Four-week short chain fructo-oligosaccharides ingestion leads to increasing fecal bifidobacteria and cholesterol excretion in healthy elderly volunteers

<p>Abstract</p> <p>Background</p> <p>Short-chain fructo-oligosaccharides (scFOS) are increasingly used in human diet for their prebiotic properties. We aimed at investigating the effects of scFOS ingestion on the colonic microflora and oro-fecal transit time in elderly healthy humans.</p> <p>Methods</p> <p>Stools composition, oro-fecal transit time, and clinical tolerance were evaluated in 12 healthy volunteers, aged 69 ± 2 yrs, in three consecutive periods: basal period (2 weeks), scFOS (Actilight^®) ingestion period (8 g/d for 4 weeks) and follow-up period (4 weeks). Two-way ANOVA, with time and treatment as factors, was used to compare the main outcome measures between the three periods.</p> <p>Results</p> <p>Fecal bifidobacteria counts were significantly increased during the scFOS period (9.17 ± 0.17 log cfu/g vs 8.52 ± 0.26 log cfu/g during the basal period) and returned to their initial values at the end of follow-up (8.37 ± 0.21 log cfu/g; P < 0.05). Fecal cholesterol concentration increased during the scFOS period (8.18 ± 2.37 mg/g dry matter vs 2.81 ± 0.94 mg/g dry matter during the basal period) and returned to the baseline value at the end of follow-up (2.87 ± 0.44 mg/g dry matter; P < 0.05). Fecal pH tended to decrease during scFOS ingestion and follow-up periods compared to the basal period (P = 0.06). Fecal bile acids, stool weight, water percentage, and oro-fecal transit time did not change throughout the study. Excess flatus and bloating were significantly more frequent during scFOS ingestion when compared to the basal period (P < 0.05), but the intensity of these symptoms was very mild.</p> <p>Conclusion</p> <p>Four-week 8 g/d scFOS ingestion is well tolerated and leads to a significant increase in fecal bifidobacteria in healthy elderly subjects. Whether the change in cholesterol metabolism found in our study could exert a beneficial action warrants further studies.</p

The fodder legume Chamaecytisus albidus establishes functional symbiosis with different Bradyrhizobial symbiovars in Morocco

In this work, we analyzed the symbiotic performance and diversity of rhizobial strains isolated from the endemic shrubby legume Chamaecytisus albidus grown in soils of three different agroforestry ecosystems representing arid and semi-arid forest areas in Morocco. The analysis of the rrs gene sequences from twenty-four representative strains selected after REP-PCR fingerprinting showed that all the strains belong to the genus Bradyrhizobium. Following multi-locus sequence analysis (MLSA) using the rrs, gyrB, recA, glnII, and rpoB housekeeping genes, five representative strains, CA20, CA61, CJ2, CB10, and CB61 were selected for further molecular studies. Phylogenetic analysis of the concatenated glnII, gyrB, recA, and rpoB genes showed that the strain CJ2 isolated from Sahel Doukkala soil is close to Bradyrhizobium canariense BTA-1 (96.95%); that strains CA20 and CA61 isolated from the Amhach site are more related to Bradyrhizobium valentinum LmjM3, with 96.40 and 94.57% similarity values; and that the strains CB10 and CB60 isolated from soil in the Bounaga site are more related to Bradyrhizobium murdochi CNPSo 4020 and Bradyrhizobium. retamae Ro19, with which they showed 95.45 and 97.34% similarity values, respectively. The phylogenetic analysis of the symbiotic genes showed that the strains belong to symbiovars lupini, genistearum, and retamae. All the five strains are able to nodulate Lupinus luteus, Retama monosperma, and Cytisus monspessilanus, but they do not nodulate Glycine max and Phaseolus vulgaris. The inoculation tests showed that the strains isolated from the 3 regions improve significantly the plant yield as compared to uninoculated plants. However, the strains of Bradyrhizobium sp. sv. retamae isolated from the site of Amhach were the most performing. The phenotypic analysis showed that the strains are able to use a wide range of carbohydrates and amino acids as sole carbon and nitrogen source. The strains isolated from the arid areas of Bounaga and Amhach were more tolerant to salinity and drought stress than strains isolated in the semi-arid area of Sahel Doukkala.Financial support was obtained from Académie Hassan II des Sciences et Techniques (in Morocco). Mr Omar Bouhnik received a grant from the Hassan II Academy of Science and Technolog

OP12 Blood proteins related to immunoregulation or cellular junctions reveal distinct biological profiles associated with the risk of short-term versus mid/long-term relapse in Crohn’s Disease patients stopping infliximab

peer reviewe

Effect of oral lactulose on clinical and immunohistochemical parameters in patients with inflammatory bowel disease: a pilot study

<p>Abstract</p> <p>Background</p> <p>The prebiotic potential of lactulose is well established and preclinical studies demonstrated a protective effect of lactulose in murine models of colitis. The aim of the present study was to investigate the clinical and histological efficacy of lactulose in patients with inflammatory bowel disease (IBD), for which probiotic therapy yielded promising results.</p> <p>Methods</p> <p>Patients were treated with standard medication alone or combined with 10 g lactulose daily as adjuvant therapy for 4 months. Clinical efficacy of treatment was assessed using clinical activity indices, a quality of life index (IBDQ), endoscopic scores, defecation frequency and monitoring corticosteroid medication. Orsomucoid, alpha1-antitrypsin and other laboratory parameters were determined. In addition, in some participants colonic biopsies were analyzed with haematoxylin-eosin staining or with antibodies against HLA-DR, CD68, IgA and CD3, and evaluated systematically. All measurements were performed both at enrolment and at the end of the trial.</p> <p>Results</p> <p>14 patients presenting ulcerative colitis (UC) and 17 patients presenting Crohn's disease (CD), most of them in a clinically active state, were enrolled in this pilot study. After 4 month no significant improvement of clinical activity index, endoscopic score or immunohistochemical parameters was observed in CD or UC patients receiving lactulose in comparison to the control group. However, significant improvement of quality of life was observed in UC patients receiving lactulose compared to the control group (p = 0.04).</p> <p>Conclusion</p> <p>The findings of the present pilot study indicate that oral lactulose has no beneficial effects in IBD patients in particular with regard to clinical activity, endoscopic score or immunohistochemical parameters. The importance of the beneficial effect of lactulose in UC patients regarding the quality of life needs further evaluation in larger controlled clinical trials.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN92101486</p

Effect of the consumption of a fermented dairy product containing Bifidobacterium lactis DN-173 010 on constipation in childhood: a multicentre randomised controlled trial (NTRTC: 1571)

<p>Abstract</p> <p>Background</p> <p>Constipation is a frustrating symptom affecting 3% of children worldwide. Randomised controlled trials show that both polyethylene glycol and lactulose are effective in increasing defecation frequency in children with constipation. However, in 30–50%, these children reported abdominal pain, bloating, flatulence, diarrhoea, nausea and bad taste of the medication. Two recent studies have shown that the fermented dairy product containing <it>Bifidobacterium lactis </it>strain DN-173 010 is effective in increasing stool frequency in constipation-predominant irritable bowel syndrome patients with a defecation frequency < 3/week and in constipated women with a defecation frequency < 3/week. Goal of this study is to determine whether this fermented dairy product is effective in the treatment of constipated children with a defecation frequency < 3/week.</p> <p>Methods/design</p> <p>It is a two nation (The Netherlands and Poland) double-blind, placebo-controlled randomised multicentre trial in which 160 constipated children (age 3–16 years) with a defecation frequency <3/week will be randomly allocated to consume a fermented dairy product containing <it>Bifidobacterium lactis </it>DN-173 010 or a control product, twice a day, for 3 weeks. During the study all children are instructed to try to defecate on the toilet for 5–10 minutes after each meal (3 times a day) and daily complete a standardized bowel diary. Primary endpoint is stool frequency. Secondary endpoints are stool consistency, faecal incontinence frequency, pain during defecation, digestive symptoms (abdominal pain, flatulence), adverse effects (nausea, diarrhoea, bad taste) and intake of rescue medication (Bisacodyl). Rate of success and rate of responders are also evaluated, with success defined as ≥ 3 bowel movements per week and ≤1 faecal incontinence episode over the last 2 weeks of product consumption and responder defined as a subject reporting a stool frequency ≥ 3 on the last week of product consumption. To demonstrate that the success percentage in the intervention group will be 35% and the success percentage in the control group (acidified milk without ferments, toilet training, bowel diary) will be 15%, with alpha 0.05 and power 80%, a total sample size of 160 patients was calculated.</p> <p>Conclusion</p> <p>This study is aimed to show that the fermented dairy product containing <it>Bifidobacterium lactis </it>strain DN-173 010 is effective in increasing stool frequency after 3 weeks of product consumption in children with functional constipation and a defecation frequency < 3/week.</p

T cell lymphoproliferative disorders associated with anti-tumor necrosis factor alpha antibody therapy for ulcerative colitis: literature summary

The enhanced risk of development of lymphoproliferative disorders in patients with inflammatory bowel disease has been attributed to immunosuppressive/immunomodulatory therapies. Infliximab is a chimeric monoclonal immunoglobulin G1 antibody directed against tumor necrosis factor alpha (TNF-α) that was approved by the Food and Drug Administration (FDA) in 1998 as an effective therapeutic agent against inflammatory bowel disease. Malignant lymphomas of both B and T cell lineage have been described in patients undergoing therapy involving TNF-α blockade. To date, eight cases of Epstein–Barr virus (EBV)-negative hepatosplenic T cell lymphoma associated with infliximab have been reported to the FDA’s Adverse Event Reporting System, as well as several other T cell lymphoproliferative disorders with aggressive clinical outcomes. We present the histologic, immunophenotypic, and molecular features of a T cell lymphoproliferative disorder involving the axillary lymph node of a 33-year-old male following infliximab treatment for ulcerative colitis. These EBV-negative lymphomas suggest that lymphoproliferative disorders following infliximab treatment for inflammatory bowel disease may involve EBV-independent immune dysregulation. The spectrum of lymphoproliferative disorders associated with infliximab and the potential mechanisms by which they occur are discussed

Combined NADPH Oxidase 1 and Interleukin 10 Deficiency Induces Chronic Endoplasmic Reticulum Stress and Causes Ulcerative Colitis-Like Disease in Mice

Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the rectum which progressively extents. Its etiology remains unknown and the number of treatments available is limited. Studies of UC patients have identified an unbalanced endoplasmic reticulum (ER) stress in the non-inflamed colonic mucosa. Animal models with impaired ER stress are sensitive to intestinal inflammation, suggesting that an unbalanced ER stress could cause inflammation. However, there are no ER stress-regulating strategies proposed in the management of UC partly because of the lack of relevant preclinical model mimicking the disease. Here we generated the IL10/Nox1(dKO) mouse model which combines immune dysfunction (IL-10 deficiency) and abnormal epithelium (NADPH oxidase 1 (Nox1) deficiency) and spontaneously develops a UC-like phenotype with similar complications (colorectal cancer) than UC. Our data identified an unanticipated combined role of IL10 and Nox1 in the fine-tuning of ER stress responses in goblet cells. As in humans, the ER stress was unbalanced in mice with decreased eIF2 alpha phosphorylation preceding inflammation. In IL10/Nox1(dKO) mice, salubrinal preserved eIF2 alpha phosphorylation through inhibition of the regulatory subunit of the protein phosphatase 1 PP1R15A/GADD34 and prevented colitis. Thus, this new experimental model highlighted the central role of epithelial ER stress abnormalities in the development of colitis and defined the defective eIF2 alpha pathway as a key pathophysiological target for UC. Therefore, specific regulators able to restore the defective eIF2 alpha pathway could lead to the molecular remission needed to treat UC

Spectrum and antibiotic sensitivity of bacteria contaminating the upper gut in patients with malabsorption syndrome from the tropics

BACKGROUND: Various causes of malabsorption syndrome (MAS) are associated with intestinal stasis that may cause small intestinal bacterial overgrowth (SIBO). Frequency, nature and antibiotic sensitivity of SIBO in patients with MAS are not well understood. METHODS: Jejunal aspirates of 50 consecutive patients with MAS were cultured for bacteria and colony counts and antibiotic sensitivity were performed. Twelve patients with irritable bowel syndrome were studied as controls. RESULTS: Culture revealed growth of bacteria in 34/50 (68%) patients with MAS and 3/12 controls (p < 0.05). Colony counts ranged from 3 × 10(2 )to 10(15 )(median 10(5)) in MAS and 100 to 1000 (median 700) CFU/ml in controls (p 0.003). 21/50 (42%) patients had counts ≥10(5 )CFU/ml in MAS and none of controls (p < 0.05). Aerobes were isolated in 34/34 and anaerobe in 1/34. Commonest Gram positive and negative bacteria were Streptococcus species and Escherichia coli respectively. The isolated bacteria were more often sensitive to quinolones than to tetracycline (ciprofloxacin: 39/47 and norfloxacin: 34/47 vs. tetracycline 19/47, <0.01), ampicillin, erythromycin and co-trimoxazole (21/44, 14/22 and 24/47 respectively vs. tetracycline, p = ns). CONCLUSIONS: SIBO is common in patients with MAS due to various causes and quinolones may be the preferred treatment. This needs to be proved further by a randomized controlled trial