Sa2050 Increased Gut Permeability in Patients With Metabolic Syndrome

Sa2050 Increased Gut Permeability in Patients With Metabolic Syndrome

Sa2050 crypt damage score respectively. In TG(15), MPO activity was significantly lower compared to TG(0).(0.028 vs 0.043, p < 0.05). DNA microarray ...

75KB Sizes 0 Downloads 54 Views

Sa2050

crypt damage score respectively. In TG(15), MPO activity was significantly lower compared to TG(0).(0.028 vs 0.043, p < 0.05). DNA microarray analysis showed down-regulation of IL17 signaling pathway, T cell receptor signaling pathway, and toll-like receptor (TLR) signaling pathway, and showed up-regulation of tight junction signaling by TG. Bacteroides, especially Bacteroides fragilis, was increased by TG administration. Conclusions: Oligosaccharide synthesize enzyme, transglucosidase, ameliorated the disease activity of DSS colitis via regulation of immune system. TG might be helpful to national health care by prophylaxis of metabolic syndrome and inflammatory bowel disease.

AGA Abstracts

Increased Gut Permeability in Patients With Metabolic Syndrome Vanessa Stadlbauer, Bettina Leber, Norbert J. Tripolt, Daniela Blattl, Michaela Eder, Thomas R. Pieber, Thomas C. Wascher, Rudolf Stauber, Karl Oettl, Harald Sourij Introduction: Obesity and metabolic disorders are linked to inflammation via gut flora and/ or gut permeability. Gut derived endotoxin triggers inflammation leading to metabolic syndrome (MetS) and contributing to oxidative stress. Aim: To investigate the effect of Lactobacillus casei Shirota on gut permeability, presence of endotoxin and neutrophil function in MetS. Patients and Methods: Patients with MetS were randomized to receive 3 x 6.5x109 CFU Lactobacillus casei Shirota (probiotic group) or not for 3 months. Gut permeability was assessed by a differential sugar absorption method, endotoxin by an adapted limulus amoebocyte lysate assay, neutrophil function and toll-like receptor (TLR) expression by flow cytometry and ELISA was used to detect lipopolysaccharide binding protein (LBP) and sCD14 levels. Results: Twenty-eight patients and 10 healthy controls were included. Gut permeability was significantly increased in MetS compared to controls but did not differ between patient groups. None of the patients were positive for endotoxin. LBP and sCD14 levels were not significantly different from healthy controls. C-reactive protein and LBP levels slightly but significantly increased after 3 months within the probiotics group. Neutrophil function and TLR expression did not differ from healthy controls or within the patient groups. Discussion: Gut permeability of MetS patients was increased before markers of low grade inflammation were measurable, most likely because only a minority of patients had morbid obesity normally leading to inflammation. Lactobacillus casei Shirota did not have any influence on any parameter tested possibly due to too short study duration or underdosing of Lactobacillus casei Shirota.

Sa2053 Bacillus Coagulans Bc30 Limits the Recurrence of Clostridium difficile-Induced Colitis Following Vancomycin Withdrawal in Mice Leo R. Fitzpatrick, Jeffrey S. Small, Wallace Greene, Kelly Karpa, David Keller Recently, we found that the probiotic strain BC30 (Bacillus coagulans GBI-30) improved indices of Clostridium difficile (CD)-induced colitis in mice (Fitzpatrick et al., Gut Microbes, 2011). Aim: Our goal was to determine if BC30 could prevent the recurrence of CD-induced colitis in mice, following initial treatment with vancomycin (Vanco). Methods: On study days 0 through 3, female C57BL/6 mice received an antibiotic mixture of kanamycin, gentamicin, colistin, metronidazole and Vanco in the drinking water, followed by clindamycin (10 mg/kg, i.p., on day 5). On day 6, the CD strain VPI 10463 was given by oro-gastric gavage at ≈ 5x104 CFU to induce colitis. Mice were treated on study days 6 to 10 with Vanco (50 mg/kg) or vehicle (saline) by gavage. On days 10 to 16, mice were dosed by gavage with vehicle (n=29) or BC30 (2 x 109 CFU per day, n=28). One negative control group of mice (n=6) was dosed with vehicle, but did not receive CD, while a positive control group (n=8) received CD but not Vanco. Mice were monitored for mortality, weight loss and diarrhea. On study days 14, 16 and 17, stools and colons were collected for further analyses. The presence of CD and toxins in the stools (commercial antibody-based kit), stool consistency (0-4 scale), colon weights, colonic histology (0-9 scale), and colonic KC chemokine content (by ELISA) were measured as key indices of CD-induced disease. Results: Infection (89 to 100%) was found in all the CD treatment groups. One mouse in the no Vanco/CD group died (mortality rate = 12.5%), while no mice died in the other groups. The mean stool consistency score in Vanco/Vehicle mice increased from 0.4 (day 10) to a range of 1.1 to 1.4 (days 14 to 17), indicating the recurrence of colitis. On days 13 through 17, the stool consistency scores for the Vanco/BC30 group were significantly lower (p < 0.05) than for the Vanco/Vehicle cohort of mice. On days 14 to 17, significant differences (p < 0.05) in the percentages of mice with normal stools were found in the Vanco/BC30 group, as compared to the Vanco/Vehicle group. On day 17, 88.9% of mice treated with BC30 had normal stools, while this value was 0% with vehicle treatment (p value = 0.0004). The colonic weight was increased in Vanco/Vehicle treated mice. Crypt damage, submucosal edema and leukocyte influx were evident in these animals. These indices were improved in BC30 treated animals. Colonic MPO (Units/2 cm colon) was significantly (p < 0.05) reduced from 4.3 ± 0.7 (Vanco/Vehicle) to 2.6 ± 0.2 (Vanco/BC30). The colonic KC level was also lower in BC30 treated mice. Summary: In Vanco/BC30-treated mice, there was evidence of better stool consistency, as well as improved biochemical and histological indices of colitis, following initial treatment of animals with Vanco. Conclusion: BC30 limited the recurrence of CD-induced colitis, following Vanco withdrawal in mice.

Sa2051 Safety and Tolerability of a 2-Month Course of Lactobacillus Reuteri and Effect on Circulating and Fecal Biomarkers in Healthy Adults Nisha Mangalat, Yuying Liu, Nicole Y. Fatheree, Melissa R. Van Arsdall, Michael J. Ferris, Zhongxue Chen, Mohammad H. Rahbar, Dat Q. Tran, Jon M. Rhoads BACKGROUND: There has been increasing clinical evidence indicating beneficial effects of probiotics in the prevention and/or treatment of gastrointestinal diseases. Surprisingly, there is a paucity of carefully-designed studies investigating the safety of individual probiotics. OBJECTIVES: The primary aim of this prospective, double-blind placebo-controlled trial was to investigate whether daily treatment of adults with Lactobacillus reuteri DSM 17938 (LR) for 2 months is safe and well-tolerated, with an ultimate goal to demonstrate that LR is a safe and effective therapy for infantile colic. Our secondary aim was to determine if LR treatment had immune effects as determined by regulatory T cell (Treg) percentages, expression of toll-like receptors (TLR)-2 and -4 on circulating peripheral blood mononuclear cells (PMBCs), cytokine expression by stimulated PBMC, and intestinal inflammation as measured by fecal calprotectin. METHODS: The study was conducted between October 2009 and July 2011. Forty healthy subjects were randomized by block allocation to a daily dose of 5 X 108 CFUs of LR (n=30) or placebo (n=10) for two months. Subjects completed daily diary cards of symptoms, and had 7 clinic visits during treatment and observation. RESULTS: There were no significant severe adverse events and there was no significant difference in reported adverse events in the probiotic versus in the placebo group (p=0.46). There were no significant differences noted in PBMCs, TLR or cytokine expression after treatment. There was a trend toward lower IL-1β production by PBMCs in the LR group (p=0.09). Fecal calprotectin level was significantly higher in the treated group versus the placebo group: 50.3 μg/g (IQR 23.8-126.6) vs. 17.3 μg/g (IQR 11.1-26.2) (p=0.03), though values remained in the normal clinical range. LR vials retained > 108 CFUs of viable organisms/ml throughout the study period but only small numbers of LR were detected in stool by PCR. CONCLUSIONS: In summary, LR is safe and well tolerated without significant changes to most of the immunologic parameters investigated. There was a small but significant increase in fecal calprotectin within the normal range, indicating that there may be some element of immune recognition at the intestinal level that may be related to its purported beneficial effects in diarrheal and other diseases.

Sa2054 Oligosaccharides: A Promising New Approach for Minimizing the Pathological Effects of Deoxynivalenol on the Intestinal Tract Saskia Braber, Peyman Akbari, Aletta D. Kraneveld, Gert Folkerts, Johan Garssen, Johanna Fink-Gremmels Mycotoxins are secondary metabolites formed by fungi growing on agricultural commodities in the field or during storage. One of the most prevalent mycotoxins in European cereals and cereal products intended for human consumption is deoxynivalenol (DON). In humans, dietary exposure to DON causes gastro-intestinal illness with specific lesions observed at the intestinal level including induction and promotion of inflammatory reactions and an increased susceptibility to intestinal infections. Oligosaccharides have demonstrated to not only exert beneficial effects on the composition and activity of the intestinal microflora in the gastrointestinal tract, but these compounds have also been associated with immunemodulating effects in the intestine. One of the most prominent sources of oligosaccharides is human breast milk and it is established that collostrial oligosaccharides modulate the enteric immune response. The aim of this study is to investigate the effect of DON on epithelial integrity and to test the hypothesis whether specific oligosaccharides can mitigate the DON related pathological effects at the intestinal epithelial layer. Using the human epithelial intestinal cell line Caco2 in a transwell system as an In Vitro model, we studied the effect of DON on transepithelial electrical resistance (TEER), lucifer yellow (LY) permeability, tight junction protein expression, cytokine release, intracellular inflammatory cascades (NF-κB), galectin expression and release (contain carbohydrate recognition domains) and cell viability. In this study the ability of short chain galacto-oligosaccharides (scGOS), to inhibit the DON-related effects was investigated. The TEER of Caco-2 cells was dosedependently reduced following DON exposure and a significant increase in LY permeability was observed after 24 hours. These alterations of the intestinal barrier function were associated with a reduction in the expression of tight junction proteins and an increase in IL-8 production. Interestingly, after 24 hours incubation with scGOS the DON-induced reduction of the intestinal barrier was inhibited and the increased IL-8 levels in the apical as well as the basolateral chamber induced by DON were significantly decreased. The mycotoxin DON impaired the intestinal barrier function and induced an inflammatory response of epithelial cells. We conclude that scGOS can restore the DON-induced effect on epithelial barrier function and exert an anti-inflammatory effect by reducing IL-8 levels. The results suggested that the intake of galacto-oligosaccharides can reduce the direct effects of DON on the intestinal epithelial integrity. Taken together, the use of specific oligosaccharides to restrict the pathological effects of the fungal toxin DON related to intestinal epithelial cells offers a promising concept for mycotoxin exposure intervention.

Sa2052 Putative IBD Prophylaxis in Addition to Metabolic Syndrome by Oligosaccharide Synthesize Enzyme Makoto Sasaki, Naotaka Ogasawara, Satoshi Koikeda, Yasushi Funaki, Mari Mizuno, Akihito Iida, Naohiko Kawamura, Kentaro Tokudome, Yasutaka Hijikata, Shinya Izawa, Ryuta Masui, Yoshihiro Kondo, Yasuhiro Tamura, Takashi Joh, Kunio Kasugai Background & Aims: Dietary fiber, which includes oligosaccharides, is known to promote good health via a lot of affects that improve intestinal microflora and lower blood glucose and cholesterol. We have reported a novel strategy in oligosaccharides production in the digestive tract and resulting in the improvement of bowel flora and metabolic markers including blood glucose and lipids (J Clin Biol Nutr. 41; 191-196, 2007, Diabetes Obes Metab. in press). The goal of this study is national health care by oligosaccharide synthesize enzyme, and the aim of this study is to examine the effects of oligosaccharide synthesize enzyme in the colitis model of DSS. Methods: Oligosaccharides synthesize enzyme, transglucosidase (TG) was administrated orally with bait before 7 days and for 5 days while 3% of DSS is administrated (TG(0); 0mg/kg/day, TG(15); 15mg/kg/day). Colonic inflammatory scales (body weight (BW), disease activity index (DAI) including BW, stool characteristic, and fecal blood on a scale of 0 to 4) were examined. Histological analysis and myeloperoxidase (MPO) activity were examined. The change of signaling pathway in the colon and intestinal microbiota was analyzed using DNA microarray technique and Terminal Restriction Fragment Length Polymorphism (T-RFLP) method respectively. Results: TG prevented the progression of colitis. Body weight loss of TG(0) and TG(15) was 17.3% and 10.5% respectively, and DAI was 3.75 and 3.17. The colon length (71.5mm) which was shortened by DSS was significantly improved by TG administration (76.1mm, p < 0.05). The histological colitis sore in TG(0) and TG(15) was 7.7 and 5.1 in the inflammatory score and 10.5 and 5.7 in the

AGA Abstracts

S-390