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AGA Abstracts Tu1866 Effects of Probiotics on Serum Bile Acids in Patients With Ulcerative Colitis Shinji Sato, Hidenari Nagai, Hiroshi Morita, Wataru Yamamuro, Yoshinori Igarashi, Yasukiyo Sumino BACKGROUND/AIM: Evaluation of bile acids (BA) is a useful method for assessing changes of the intestinal flora in patients with ulcerative colitis (UC). During enterohepatic circulation, conjugated BA is deconjugated to free BA by intestinal bacteria. The presence of intestinal microflora (Clostridium and Eubacterium) leads to 7 alpha-dehydroxylation of cholic acid (CA) and chenodeoxycholic acid (CDCA), yielding deoxycholic acid (DCA) and lithocholic acid, respectively. It was reported that the Lachnospiraceae subgroup of Firmicutes (including Clostridium) are decreased in the colon of UC patients compared to controls without inflammatory bowel disease. We have already reported that the serum %CDCA is significantly higher in patients with UC than in healthy volunteers (HV), while serum %DCA is significantly lower in UC patients than in HV, and these changes do not depend on the activity or extent of UC. The aim of the present study was to elucidate the effects of probiotics in patients with UC by examining the serum BA profile. PATIENTS/METHODS: The study population was 27 patients in whom UC was diagnosed from endoscopic and histological findings. All patients underwent ileocolonoscopy with appropriate biopsies. They were divided into the following 2 groups based on endoscopic findings: 15 patients with distal UC (dUC) and diffuse changes extending from the rectum to the splenic flexure, and 12 patients with more extensive UC or pancolitis (pUC). Treatment was given with mesalazine or salazosulfapyridine (5-ASA) and all patients achieved remission. After entering remission, they were treated with by 5-ASA plus the probiotic Clostridium butyricum Miyairi (MIYA) (3 g/day) for 4 weeks. The control group was composed of 8 HV. Routine laboratory tests were performed on the basis of clinical need, while fasting serum samples for measurement of BA were obtained before and after treatment with 5-ASA plus MIYA for 4 weeks. Serum BA fractions were analyzed by HPLC. RESULTS: There were no significant differences of serum total BA among the 3 groups. Before treatment, %CDCA was significantly higher in the dUC and pUC groups than in the HV group, while %DCA was significantly lower than in the HV group. In the pUC group, %CDCA was significantly higher and %DCA was significantly lower than in the HV group after 4 weeks of probiotic treatment. In the dUC group, however, there was no significant difference of %CDCA or %DCA after 4 weeks compared with the HV group. There were no significant differences in the ratio of conjugated BA to total serum BA among the three groups. CONCLUSIONS: These results suggest that intestinal bacteria involved in the deconjugation of BA are restored when patients achieve remission of UC by treatment with 5-ASA, and that MIYA restored microflora involved in 7 alpha-dehydroxylation in the dUC group, but not in the pUC group. Tu1867 Effects of Pro- and Antibiotics on the Intestinal Homeostasis in a Computer Controlled Model of the Large Intestine Ateequr Rehman, Femke-Anouska Heinsen, Koen Venema, Marjorie Koenen, Stefan Schreiber, Stephan J. Ott Introduction: Antibiotic associated diarrhea and Clostridium difficile infection are frequent complications of broad spectrum antibiotic therapy. Probiotic bacteria are used as therapeutic and preventive agents in these disorders, but the exact functional mechanisms and the mode of action are poorly understood. Methods: The effects of antibiotic (Clindamycin) and probiotic (VSL#3) consecutively or a combination therapy of both at the same time were investigated and compared to controls without therapy using a standardized human fecal microbiota in a computer-controlled In Vitro model of the large intestine. Microbial metabol- ites (short chain fatty acids, lactate, branched chain fatty acids and ammonia) and the intestinal microbiota composition were analyzed. Results: Compared to controls and com- bination therapy, short chain fatty acids and lactate, but also ammonia and branched chain fatty acids, were increased under probiotic therapy. The metabolic pattern under combined therapy with anti- and probiotics had the most beneficial and consistent effect on intestinal metabolic profiles. The intestinal microbiota showed a decrease in several indigenous bacterial groups under antibiotic therapy, there was no significant recovery of these groups when the antibiotic therapy was followed by administration of probiotics. Simultaneous application of anti- and probiotics had a stabilizing effect on the intestinal microbiota with increased bifidobacteria and lactobacilli. Conclusion: Administration of probiotics parallel with the antibiotic therapy had a beneficial and stabilizing effect on the intestinal metabolic homeost- asis by decreasing toxic metabolites and protecting the endogenic microbiota from destruction as in the experiment with broad spectrum antibiotics. Probiotics could be a reasonable strategy in prevention of antibiotic associated disturbances of the intestinal homeostasis and disorders. Tu1868 Evaluation of Effects and Complications of Probiotics in Microscopic Colitis, a Double Blind Placebo Control Clinical Trial Amir Taheri, Ali Sadighi, Bahram Nikkhoo, Elham Farhangi Microscopic colitis is one of causes that induce chronic nonbloody watery diarrhea. Probiotics are useful organisms that have been used in many kind of diarrheal disease (e.g. IBD, IBS, traveler's diarrhea & etc), but effects of these resources have not been evaluated adequately in microscopic colitis. Only a couple of articles have been published in this field and most of them have been done on Collagenous colitis and with low sample volume. Regarding to previous research that has been performed in Kurdistan province of Iran, incidence of microscopic colitis (especially Lymphocytic colitis) seems to be very high in this area, so we decided to perform a double blind clinical trial on patients with microscopic colitis in order to evaluate the effects and complication of probiotics in these patients. Fifty two patients with microscopic colitis (46 with Lymphocytic & 6 with Collagenous colitis) were enrolled in this study (27 in Probiotic and 25 in Placebo group).All patients received Loperamide 1mg daily. Patients in Probiotic group also received probiotics and patients in placebo groups received placebo with same appearance twice daily for 4 weeks. [Both S-852 AGA Abstracts probiotics and placebos had been made by wren laboratories in England under trade name of Optibac, and probiotics had been consisted of Lactobacillus rhamnosus Rosell-11, Lactoba- cillus acidophilus Rosell-52, Bifidobacterium longum Rosell-175, Lactococcus lactis Rosell- 1058, Bifidobacterium breve Rosell-70, Bifidobacterium bifidum Rosell-71.And concentra- tion of probiotics was 2.5billion in each capsule i.e. 5 billion daily for each patient]. Severity of abdominal pain (by vas system),frequency of defecation and frequency of nocturnal defecation Along with complications were assessed before and after treatment in both groups. Patients were match for age, sex, proportion of lymphocytic to Collagenous colitis and also severity of symptoms in both groups before treatment. In patients with lymphocytic colitis abdominal pain and frequency of defecation (both in days and nights) were decreased more significantly in probiotics group than in placebo group. (p<0.001).But in patients with Collagenous colitis such dramatic differences were not seen between two groups. (p>0.01).Neither in Probiotic nor in placebo group, serious complications, were not seen in this study. Only one of patients in Probiotic group terminated the study before ending because of intensifying of her diarrhea. Other complications were minimal and same statistic- ally in both groups. This study showed that probiotics are effective and safe in treatment of lymphocytic colitis but they were not significantly effective in patients with Colla- genous colitis. Tu1869 Effect of Probiotic Treatment on Visceral Hypersensitivity in Irritable Bowel Syndrome Annemieke Yvonne Thijssen, Daisy Jonkers, Cees H. Clemens, Ad Masclee Introduction: Alterations in gut microbiota composition and visceral hypersensitivity have been proposed as pathophysiological factors in Irritable Bowel syndrome (IBS). Visceral hypersensitivity is a hallmark of IBS, present in up to 60% of IBS patients. Probiotics are considered to have therapeutic potential in IBS with respect to control of symptoms. Animal studies point to a beneficial effect of lactobacilli strains on visceral perception, but human data in IBS are lacking. In a larger study on the effect of a probiotic dairy product containing Lactobacillus casei strain Shirota (LcS) on IBS symptoms, we performed a side study to evaluate visceral perception in IBS patients. Materials and methods: IBS patients between 18 and 65 years of age, fulfilling the Rome II criteria, were included in a randomized placebo controlled double blind trial. Probiotic and placebo product were provided by Yakult Europe, Almere, NL. Patients had to take 2 bottles daily for 8 weeks, containing at least 6.5 x 109 CFU living Lactobacillus casei Shirota per bottle (65 ml). Rectal perception was studied at week 0 (before intervention) and week 8 (at the end of intervention) using a barostat, with a phasic ascending pressure distension protocol. Perception of urge and pain was scored on a Visual Analogue Scale (0-100 mm). Dynamic compliance was calculated by dividing the highest change in volume during a pressure step by the change in pressure. Results: Of the 80 patients included in the main study, 21 patients agreed to participate: 8 patients (5F; 40 ± 16 yrs) in the probiotic and 13 patients (7F; 43 ± 12 yrs) in the placebo group. Demographic data did not differ between treatment groups. Rectal compliance did not differ significantly before and after treatment for both treatment groups (probiotic week 0: 33 ± 29 ml/mmHg; probiotic week 8: 33 ± 22 ml/mmHg; placebo week 0: 25 ± 18 ml/mmHg; placebo week 8: 27 ± 21 ml/mmHg). In the probiotic group, perception of urge during the highest pressures (32-40 mmHg) did decrease significantly in week 8 compared to week 0 (from 65 ± 27 mm to 53 ± 23 mm respectively, p < 0.05), in contrast to the placebo group, where no difference in urge perception scores could be detected after treatment (55 ± 24 mm; 50 ± 22 mm respectively). Pain scores at higher pressures were not different between groups nor after probiotic or placebo compared to before treatment. Conclusions: Treatment with LcS in IBS patients did not affect pain perception scores but beneficially and significantly influenced urge perception scores. Tu1933 Early Predictors for the Need for Abundant Fluid Therapy in Patients With Acute Pancreatitis Enrique de-Madaria, Neftalí Moya-Hoyo, Inmaculada Lopez-Font, Gema Soler-Sala, Laura Sempere-Robles, Félix Lluís, Juan Martínez, Miguel Pérez-Mateo It has been claimed that Blood Urea Nitrogen (BUN) and hematocrit are useful to guide fluid therapy in acute pancreatitis (AP), but there is no direct data to support this statement. Primary aim: to determine the capacity of BUN, creatinine, hematocrit, leucocytes and the number of SIRS criteria (NSIRS) determined at emergency room to predict a high need for fluid therapy in the first 48h of admission. Secondary aim: to describe the outcome of

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sTu1866

Effects of Probiotics on Serum Bile Acids in Patients With Ulcerative ColitisShinji Sato, Hidenari Nagai, Hiroshi Morita, Wataru Yamamuro, Yoshinori Igarashi,Yasukiyo Sumino

BACKGROUND/AIM: Evaluation of bile acids (BA) is a useful method for assessing changesof the intestinal flora in patients with ulcerative colitis (UC). During enterohepatic circulation,conjugated BA is deconjugated to free BA by intestinal bacteria. The presence of intestinalmicroflora (Clostridium and Eubacterium) leads to 7 alpha-dehydroxylation of cholic acid(CA) and chenodeoxycholic acid (CDCA), yielding deoxycholic acid (DCA) and lithocholicacid, respectively. It was reported that the Lachnospiraceae subgroup of Firmicutes (includingClostridium) are decreased in the colon of UC patients compared to controls withoutinflammatory bowel disease. We have already reported that the serum%CDCA is significantlyhigher in patients with UC than in healthy volunteers (HV), while serum%DCA is significantlylower in UC patients than in HV, and these changes do not depend on the activity or extentof UC. The aim of the present study was to elucidate the effects of probiotics in patientswith UC by examining the serum BA profile. PATIENTS/METHODS: The study populationwas 27 patients in whom UC was diagnosed from endoscopic and histological findings. Allpatients underwent ileocolonoscopy with appropriate biopsies. They were divided into thefollowing 2 groups based on endoscopic findings: 15 patients with distal UC (dUC) anddiffuse changes extending from the rectum to the splenic flexure, and 12 patients with moreextensive UC or pancolitis (pUC). Treatment was givenwithmesalazine or salazosulfapyridine(5-ASA) and all patients achieved remission. After entering remission, they were treatedwith by 5-ASA plus the probiotic Clostridium butyricum Miyairi (MIYA) (3 g/day) for 4weeks. The control group was composed of 8 HV. Routine laboratory tests were performedon the basis of clinical need, while fasting serum samples for measurement of BA wereobtained before and after treatment with 5-ASA plus MIYA for 4 weeks. Serum BA fractionswere analyzed by HPLC. RESULTS: There were no significant differences of serum total BAamong the 3 groups. Before treatment, %CDCA was significantly higher in the dUC andpUC groups than in the HV group, while %DCA was significantly lower than in the HVgroup. In the pUC group, %CDCA was significantly higher and %DCA was significantlylower than in the HV group after 4 weeks of probiotic treatment. In the dUC group, however,there was no significant difference of %CDCA or %DCA after 4 weeks compared with theHV group. There were no significant differences in the ratio of conjugated BA to total serumBA among the three groups. CONCLUSIONS: These results suggest that intestinal bacteriainvolved in the deconjugation of BA are restored when patients achieve remission of UC bytreatment with 5-ASA, and thatMIYA restoredmicroflora involved in 7 alpha-dehydroxylationin the dUC group, but not in the pUC group.

Tu1867

Effects of Pro- and Antibiotics on the Intestinal Homeostasis in a ComputerControlled Model of the Large IntestineAteequr Rehman, Femke-Anouska Heinsen, Koen Venema, Marjorie Koenen, StefanSchreiber, Stephan J. Ott

Introduction: Antibiotic associated diarrhea and Clostridium difficile infection are frequentcomplications of broad spectrum antibiotic therapy. Probiotic bacteria are used as therapeuticand preventive agents in these disorders, but the exact functional mechanisms and the modeof action are poorly understood. Methods: The effects of antibiotic (Clindamycin) andprobiotic (VSL#3) consecutively or a combination therapy of both at the same time wereinvestigated and compared to controls without therapy using a standardized human fecalmicrobiota in a computer-controlled In Vitro model of the large intestine. Microbial metabol-ites (short chain fatty acids, lactate, branched chain fatty acids and ammonia) and theintestinal microbiota composition were analyzed. Results: Compared to controls and com-bination therapy, short chain fatty acids and lactate, but also ammonia and branched chainfatty acids, were increased under probiotic therapy. The metabolic pattern under combinedtherapy with anti- and probiotics had the most beneficial and consistent effect on intestinalmetabolic profiles. The intestinal microbiota showed a decrease in several indigenous bacterialgroups under antibiotic therapy, there was no significant recovery of these groups whenthe antibiotic therapy was followed by administration of probiotics. Simultaneous applicationof anti- and probiotics had a stabilizing effect on the intestinal microbiota with increasedbifidobacteria and lactobacilli. Conclusion: Administration of probiotics parallel with theantibiotic therapy had a beneficial and stabilizing effect on the intestinal metabolic homeost-asis by decreasing toxic metabolites and protecting the endogenic microbiota from destructionas in the experiment with broad spectrum antibiotics. Probiotics could be a reasonablestrategy in prevention of antibiotic associated disturbances of the intestinal homeostasisand disorders.

Tu1868

Evaluation of Effects and Complications of Probiotics in Microscopic Colitis, aDouble Blind Placebo Control Clinical TrialAmir Taheri, Ali Sadighi, Bahram Nikkhoo, Elham Farhangi

Microscopic colitis is one of causes that induce chronic nonbloody watery diarrhea. Probioticsare useful organisms that have been used in many kind of diarrheal disease (e.g. IBD, IBS,traveler's diarrhea & etc), but effects of these resources have not been evaluated adequatelyin microscopic colitis. Only a couple of articles have been published in this field and mostof them have been done on Collagenous colitis and with low sample volume. Regarding toprevious research that has been performed in Kurdistan province of Iran, incidence ofmicroscopic colitis (especially Lymphocytic colitis) seems to be very high in this area, sowe decided to perform a double blind clinical trial on patients with microscopic colitis inorder to evaluate the effects and complication of probiotics in these patients. Fifty twopatients with microscopic colitis (46 with Lymphocytic & 6 with Collagenous colitis) wereenrolled in this study (27 in Probiotic and 25 in Placebo group).All patients receivedLoperamide 1mg daily. Patients in Probiotic group also received probiotics and patients inplacebo groups received placebo with same appearance twice daily for 4 weeks. [Both

S-852AGA Abstracts

probiotics and placebos had been made by wren laboratories in England under trade nameof Optibac, and probiotics had been consisted of Lactobacillus rhamnosus Rosell-11, Lactoba-cillus acidophilus Rosell-52, Bifidobacterium longum Rosell-175, Lactococcus lactis Rosell-1058, Bifidobacterium breve Rosell-70, Bifidobacterium bifidum Rosell-71.And concentra-tion of probiotics was 2.5billion in each capsule i.e. 5 billion daily for each patient]. Severityof abdominal pain (by vas system),frequency of defecation and frequency of nocturnaldefecation Along with complications were assessed before and after treatment in both groups.Patients were match for age, sex, proportion of lymphocytic to Collagenous colitis and alsoseverity of symptoms in both groups before treatment. In patients with lymphocytic colitisabdominal pain and frequency of defecation (both in days and nights) were decreased moresignificantly in probiotics group than in placebo group. (p<0.001).But in patients withCollagenous colitis such dramatic differences were not seen between two groups.(p>0.01).Neither in Probiotic nor in placebo group, serious complications, were not seenin this study. Only one of patients in Probiotic group terminated the study before endingbecause of intensifying of her diarrhea. Other complications were minimal and same statistic-ally in both groups. This study showed that probiotics are effective and safe in treatmentof lymphocytic colitis but they were not significantly effective in patients with Colla-genous colitis.

Tu1869

Effect of Probiotic Treatment on Visceral Hypersensitivity in Irritable BowelSyndromeAnnemieke Yvonne Thijssen, Daisy Jonkers, Cees H. Clemens, Ad Masclee

Introduction: Alterations in gut microbiota composition and visceral hypersensitivity havebeen proposed as pathophysiological factors in Irritable Bowel syndrome (IBS). Visceralhypersensitivity is a hallmark of IBS, present in up to 60% of IBS patients. Probiotics areconsidered to have therapeutic potential in IBS with respect to control of symptoms. Animalstudies point to a beneficial effect of lactobacilli strains on visceral perception, but humandata in IBS are lacking. In a larger study on the effect of a probiotic dairy product containingLactobacillus casei strain Shirota (LcS) on IBS symptoms, we performed a side study toevaluate visceral perception in IBS patients. Materials and methods: IBS patients between18 and 65 years of age, fulfilling the Rome II criteria, were included in a randomized placebocontrolled double blind trial. Probiotic and placebo product were provided by Yakult Europe,Almere, NL. Patients had to take 2 bottles daily for 8 weeks, containing at least 6.5 x 109CFU living Lactobacillus casei Shirota per bottle (65 ml). Rectal perception was studied atweek 0 (before intervention) and week 8 (at the end of intervention) using a barostat, witha phasic ascending pressure distension protocol. Perception of urge and pain was scoredon a Visual Analogue Scale (0-100 mm). Dynamic compliance was calculated by dividingthe highest change in volume during a pressure step by the change in pressure. Results: Ofthe 80 patients included in the main study, 21 patients agreed to participate: 8 patients(5F; 40 ± 16 yrs) in the probiotic and 13 patients (7F; 43 ± 12 yrs) in the placebo group.Demographic data did not differ between treatment groups. Rectal compliance did not differsignificantly before and after treatment for both treatment groups (probiotic week 0: 33 ±29 ml/mmHg; probiotic week 8: 33 ± 22 ml/mmHg; placebo week 0: 25 ± 18 ml/mmHg;placebo week 8: 27 ± 21 ml/mmHg). In the probiotic group, perception of urge during thehighest pressures (32-40 mmHg) did decrease significantly in week 8 compared to week 0(from 65 ± 27 mm to 53 ± 23 mm respectively, p < 0.05), in contrast to the placebo group,where no difference in urge perception scores could be detected after treatment (55 ± 24mm; 50 ± 22 mm respectively). Pain scores at higher pressures were not different betweengroups nor after probiotic or placebo compared to before treatment. Conclusions: Treatmentwith LcS in IBS patients did not affect pain perception scores but beneficially and significantlyinfluenced urge perception scores.

Tu1933

Early Predictors for the Need for Abundant Fluid Therapy in Patients WithAcute PancreatitisEnrique de-Madaria, Neftalí Moya-Hoyo, Inmaculada Lopez-Font, Gema Soler-Sala, LauraSempere-Robles, Félix Lluís, Juan Martínez, Miguel Pérez-Mateo

It has been claimed that Blood Urea Nitrogen (BUN) and hematocrit are useful to guidefluid therapy in acute pancreatitis (AP), but there is no direct data to support this statement.Primary aim: to determine the capacity of BUN, creatinine, hematocrit, leucocytes and thenumber of SIRS criteria (NSIRS) determined at emergency room to predict a high need forfluid therapy in the first 48h of admission. Secondary aim: to describe the outcome of