- Email: [email protected]
Sa1782 Solitary Therapy With Metronidazole (MTZ) or Vancomycin (VCO) for C. difficile Infection (CDI) Results in Similar Outcomes of Disease
AGA Abstracts
fecal BA loss, which occurs in the absence of any absorptive defect within the terminal ileum, is due to increased BA synthesis, resulting from impaired FGF19 ileal production or hepatic actions. We aimed to investigate whether BA-induced expression of FGF19 in the ileum is reduced in patients with low SeHCAT retention. Methods: Patients being investigated for unexplained diarrhea (n=16) were prospectively recruited and gave informed consent at colonoscopy to give additional ileal biopsies. All had SeHCAT tests. Groups of 2-3 biopsies (explants) were incubated separately for 6h with either BA-free culture media (unstimulated controls), chenodeoxycholate (CDCA) or glyco-CDCA (GCDCA), both at 50uM. After RNA extraction and cDNA synthesis, FGF19 expression was quantified relative to GAPDH by RT-PCR. Results: SeHCAT 7d retention values were <15% in 7 patients, indicating primary BAD, and >15% in 9 who were normal diarrhea controls. Previous studies had shown no significant difference in baseline unstimulated FGF19 expression between these groups and this was confirmed with the unstimulated control samples (p=0.76). Median stimulation overall was 184-fold with CDCA and 373-fold with GCDCA. A positive correlation was found between SeHCAT retention and the magnitude of the fold change in FGF19 expression stimulated by either CDCA (r=0.50, n=16, p=0.02) or by GCDCA (r=0.76, n=7, p=0.02). These relationships were still present when the fold changes were normalized to the baseline FGF19 expression found in the unstimulated explants. Conclusion: Ileal explants from patients with lower SeHCAT 7d retention have a lower response to both CDCA and GCDCA. As uptake of GCDCA is dependent on carrier-mediated apical BA uptake but CDCA is not, this implies there is no defect in apical BA uptake, but abnormalities elsewhere in the FGF19 response. A reduced capacity to induce ileal FGF19 expression in response to absorbed BA is proposed to lead to the excess BA production and fecal BA losses found in primary BAD.
with intestinal failure and the need for intestinal transplantation in SBS patients in the absence of CD. The aim of the present study was to establish a murine SBS model for studying the influence of genetic risk factors, especially NOD2, on peri-operative outcome, mucosal adaptation and transepithelial transport. Material and Methods: Male C57BL6/J wild-type (wt) and NOD2 knock-out (ko) mice (body weight (BW) 30-34g) were anaesthetized by i.p. injection of ketamine and xylazine. Mice were orally intubated with a 22-gauge cannula and mechanically ventilated with room air (300μl and 130 breaths/min). Mice were placed on a heating plate and body temperature was continuously monitored. After midline incision, the small bowel was resected 10-12cm proximal to the ileocecal junction and immediately after the cecum. Intestinal continuity was restored by an end-to-end anastomosis. Control mice received simple transection without resection. Mice were rescued with s.c. injection of 1ml Ringer's lactate and 5mg/kg BW carprofen and received a standard liquid diet ad libitum 1-7d p.o.. Wellness and BW were scored daily. At 7 and 14d p.o., intestine was harvested 1-2cm proximal from anastomosis for histological examinations and gene expression analyses of ion transporters (DRA; SLC26A3, NHE3; SLC9A3), mucin2 and lysozyme. Results: Wt and ko mice had similar survival rates of 70% (wt) and 71% (ko). Both strains got diarrhea. Ko mice displayed more severe weight loss (maximal 21±1.9%, d9) compared to wt (maximal 13±3.4%, d9) and both groups suffered from more and prolonged weight loss than their related sham controls (maximal 9±2.6% (ko) vs. maximal 7±1.9% (wt), d1). Both groups showed signs of mucosal adaptation such as an increase in villus height (128±12.6% (wt) and 150±18.2% (ko), 14d) and diameter. qPCR revealed increased intestinal expression levels of DRA (0h vs. 14d, p=0.01) and decreased amounts of lysozyme (0h vs. d14, p=0.02) and mucin2 (0h vs. d14, p=0.006) in wt mice. NHE3 was not significantly altered. Conclusions: A clinical relevant model of ileocecal recection was successfully established in mice to study genetic risk factors for SBS. Loss of NOD2 results in worse clinical adaptation in SBS mice. The underlying mechanisms are presently unknown. Future studies will address transepithelial transport, barrier function and potential immune mediators of mucosal adaptation in short bowel conditions.
Sa1779 Soluble Plantain (Banana) Fibre Inhibits Epithelial Cell Damage in Response to Clostridium difficile and Its Toxins Hannah L. Simpson, Jonathan M. Rhodes, Barry J. Campbell
Sa1781
Background: Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and carries significant mortality. Epithelial adherence contributes to its pathogenicity (PLoS ONE 2013;8:e78404). We have previously shown that soluble non-starch polysaccharides (NSP) from plantain bananas (Musa spp.) inhibit the epithelial adherence of a range of diarrhoeal pathogens, both in vitro and in vivo (J. Nutr. Biochem. 2013; 24:97-103) via an interaction with the epithelium that involves enhanced chloride secretion (PLoS ONE 2014; 9:e87658). Aim: To evaluate soluble plantain fibre for its potential inhibitory effect against C.difficile bacterium, spore and toxin interaction with intestinal epithelial cells. Methods: Human intestinal epithelial Caco2 cell monolayers were pre-incubated (30min) with plantain NSP (2.5-20 mg/mL) prior to infection with 13 C. difficile clinical isolates or 5 purified spore preparations (2h; multiplicity of infection MOI of 100), or treatment with purified native C.difficile Toxin A (TcdA) or Toxin B (TcdB); 0-100 ng/mL over 24h. C.difficile bacterium and spore adherence were determined by quantification of colony forming units (CFUs). C.difficile toxin and bacterium-mediated cellular effects (adenylate kinase release as a measure of cytotoxicity, caspase-3 activation and IL-8 release) were also monitored in the presence and absence of plantain NSP. Results: Plantain NSP caused dose-related inhibition of intestinal epithelial adherence of all C. difficile clinical isolates (inhibition at plantain NSP at 10 mg/mL, 52.2±3.0 to 98.6±1.0%; all P<0.001;) and all C. difficile spore preparations (27.9±5.4% to 33.8±6.9% inhibition; all P≤ 0.05). Plantain NSP at 10 mg/mL also caused 38-64% inhibition of toxic and pro-inflammatory effects of C.difficile toxins on epithelial cells (see Table) and 25-88% inhibition of the toxic and pro-inflammatory effects of whole C.difficile bacteria (Table). Conclusions: Soluble plantain NSP at concentrations readily achievable in the human distal colon inhibits C.difficile bacterium, spore and toxin interaction with intestinal epithelial cells. These results suggest that soluble dietary fibres, such as plantain, acting as "contrabiotics", could be developed as potential prophylaxis or treatment for C.difficile infection (CDI).
Chronic Heart Failure Is Associated With Bowel Wall Edema, Reduced Intestinal Blood Flow, Gastrointestinal Symptoms and Bacterial Growth Juergen Bauditz, Stefan D. Anker, Alexander Swidsinski, Anja Sandek, Wolfram Doehner, Anja Sandek Background: We previously demonstrated that chronic heart failure (CHF) is associated with morphological and functional intestinal changes. We now investigated whether bowel wall thickening in CHF is also associated with clinical gastrointestinal symptoms (GIS), bowel alterations and changes in blood flow in the abdominal arteries. Aim: To measure bowel wall thickness (BWT), arterial intestinal blood flow (BF), gastrointestinal symptoms, histological changes and juxtamucosal bacterial growth in CHF. Methods: We investigated 85 subjects (65 patients, 25 controls). BWT and intestinal BF were measured using ultrasound. The Gastrointestinal Symptom Rating Scale was employed for evaluation of GIS. Sigmoidal biopsies for histological evaluation, investigation of juxtamucosal bacteria and bacteria in stool by fluorescence in situ hybridization were studied in a subgroup of patients. Serum lipopolysaccharide-(LPS)-antibodies were measured. Results: Bowel wall thickness of all colonic segments and the ileum was significantly increased in CHF (p<0.003 for all parts) and corresponded to bowel wall edema in histology. Patients showed a 30-43% reduced mean systolic BF in the superior and inferior mesenteric arteries (SMA and IMA) and celiac trunk (CT) compared to controls (all p<0.007). CHF patients more often suffered from repletion, flatulences, intestinal murmurs and burping as compared to controls (all p<0.04). Patients with lower CT BF had more abdominal discomfort and immunoglobulin A-antiLPS (r=0.76, p<0.02). Anti-LPS-response correlated with increased growth of juxtamucosal and not stool bacteria. Patients with intestinal murmurs had greater BWT of sigmoid/ descending colon (p<0.05). Conclusions: Bowel wall edema together with reduced intestinal blood flow may cause gastrointestinal symptoms and juxtamucosal bacterial growth in chronic heart failure. Sa1782 Solitary Therapy With Metronidazole (MTZ) or Vancomycin (VCO) for C. difficile Infection (CDI) Results in Similar Outcomes of Disease Muhammad S. Mansoor, Paul Feuerstadt Introduction: Guidelines for C. difficile infection (CDI) treatment advise MTZ for mild disease, VCO for severe and combination MTZ and VCO (Combo) in severe-complicated pts. In practice, medication adjustments are made in response to changes in clinical status. We hypothesize that pts in a tertiary care hospital who receive one unaltered therapy with MTZ or VCO will have similar outcomes but Combo will have worsened outcomes as a result of disease severity. Methods: Consecutive pts who had a +C. difficile toxin assay at Yale-New Haven Hospital between 4/10 and 5/14 were identified. For each patient we recorded demographics, medical co-morbidities, basic lab data at diagnosis, treatments of CDI and various outcomes. Pts who received only-MTZ (PO and/or IV), VCO or Combo therapy without any treatment changes were separated into groups. Independent comparisons were made between MZO and VCO as well as VCO and Combo using SPSS (23.0). Results: Of 798 pts originally identified with CDI, 63.5% met inclusion criteria receiving one therapy with 374, 98 and 35, receiving MTZ, VCO and Combo, respectively. From those excluded, in 18.7% (% of the entire cohort) VCO was added to MTZ, 2.4% had MTZ added to VCO and 13.8% had MTZ switched to VCO. The remaining excluded pts received rifaximin, fidaxomicin or nitazoxanide. MTZ dosing was exclusively 500 mg Tid while 91.8% of pts received VCO 125 Qid, 4.2% 250 mg Qid and 4.2% 500 mg Qid. In our study population, there were no significant differences in demographics, Charlson score or medical co-morbidities. When comparing MZO with VCO, pts receiving VCO had previous CDI more often (20.4%, 3.2%, p<0.001). Pts receiving Combo were more likely to have a fever (30.0%, 9.9%, p<0.01) or respiratory rate > 20 (46.7%, 23.5%, p<0.05) at diagnosis compared with VCO. Those receiving VCO had a higher WBC compared with MZO (14.0 ± 8.8, 11.0 ± 6.4, p<0.001). 90-day recurrence of infection was higher in VCO (13.5%, 8.0%, p<0.04) with lower frequency of resolution of diarrhea during hospitalization (73.0%, 86.3%, p<0.05)
Sa1780 The Influence of NOD2 Gene Mutation on the Intestinal Adaptation and PeriOperative Outcome in a Murine Model of Short Bowel Syndrome Peggy Bodammer, Maria Witte, Karen Bannert, Daniel M. Bastmeyer, Katja Bovensiepen, Holger Schäffler, Georg Lamprecht Background and Aims: Short bowel syndrome (SBS) is the condition of malabsorption of nutrients, fluids and electrolytes in patients after massive bowel resection. The intracellular pattern recognition receptor Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is a risk gene for Crohn's disease (CD) which in turn is a frequent indication for small bowel surgery. However, recent studies show that NOD2 mutations are associated
AGA Abstracts
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compared with MZO. Combo had higher ICU requirement (68.6%, 38.5%, p<0.01), 30day colectomy (5.7%, 0.0%, p<0.05), sepsis within 30-days (31.4%, 10.2%, p< 0.001) and 30-day mortality (34.3%, 8.2%, p<0.001) with a lower readmission rate within 90-days (31.4%, 49.0%, p<0.01) compared with VCO. Conclusions: Solitary therapy with VCO for those with higher WBC and/or recurrent disease and MTZ for the less severe resulted in similar overall outcomes. It is likely clinicians judgment to keep pts on one therapy reflects appropriate response and this might predict these outcomes. As would be expected with the most severe disease, Combo therapy was associated with worse outcomes and these pts require more aggressive management. Sa1783 The Impact of Medications on Small Intestinal Bacterial Overgrowth Sheevani Bhalsod, Seth Lipka, Roshanak Rabbanifard, Jennifer Leigh, Jae Chung, Marc Levin, Kiran Joglekar, Ambuj Kumar, Jay J. Mamel Introduction: Small intestinal bacterial overgrowth (SIBO) occurs when native/non-native bacteria exceed 105 colony-forming units per milliliter in the small intestine. Currently, there is little data regarding a relationship between SIBO and statin therapy, PPI, probiotic, and opioids. The purpose of this study is to evaluate the effect of medications on SIBO status. Methods: We conducted a retrospective cohort study using the electronic health records of 416 patients that underwent SIBO lactulose hydrogen and methane breath testing. Charts were reviewed for demographics (age, sex, race, and BMI) and medications such as statins, PPI, probiotics, and opioids. T-test and logistic regression assessed association between dependent and independent variables. The results were summarized as mean difference (MD) and standard deviation (SD), or odds ratio(OR) and 95% confidence intervals (CI). Results: Of the 416 patients enrolled in this study, 198 (47%) tested positive for SIBO. The mean age of SIBO(+ve) patients was 51.9 +/- 18.6 and SIB-(-ve) patients was 53.9 +/- 17.6. The mean BMI of SIBO(+ve) patients was 26.5 +/- 6.4 vs 26.1 +/- 6.6 in SIBO(-ve). 49 (24.7%) of the SIBO(+ve) patients were male compared to 55 (25.2%) of the SIBO(-ve) patients. Our data indicated no significant association between the use of statins, PPI, probiotics or opioids on SIBO status. 103 (24.7%) patients used statin therapy with a 29.8% incidence of SIBO compared to 19.7% without SIBO. Of the 186 (44.7%) patients on PPI, there were 41.4% SIBO(+ve) vs 47.7% SIBO(-ve). 50 (12%) patients used probiotics, with an 11.6% incidence of SIBO(+ve) vs 12.3% SIBO(-ve). Of the 59 (14.2%) patients on opioids, there were 12.6% SIBO(+ve) vs 15.6% SIBO(-ve). Conclusion: In this retrospective study, our data did not reveal a significant association between statins, PPI, probiotics, and opioids on SIBO status. Prior published data have yielded conflicting results on association between PPI and risk of developing SIBO and our data supports no association between PPI use and risk of developing SIBO. In addition, even though it is well known that opioids can induce bowel dysfunction, our data does not signify a risk of developing SIBO for patients on opioids.
Sa1785 The Impact of Hypertension, Hyperlipidemia, Diabetes, and Psychiatric History on Small Intestinal Bacterial Overgrowth Sheevani Bhalsod, Seth Lipka, Roshanak Rabbanifard, Jennifer Leigh, Jae Chung, Marc Levin, Kiran Joglekar, Ambuj Kumar, Jay J. Mamel Introduction: Small intestinal bacterial overgrowth (SIBO) occurs when native/non-native bacteria exceed 105 colony-forming units per milliliter in the small intestine. Currently, there is little data regarding a relationship between SIBO and certain factors such as age, sex, race, BMI and medical conditions such as hypertension, hyperlipidemia, diabetes, and psychiatric history. The purpose of this study is to evaluate the association between specific medical conditions and SIBO. Methods: We conducted a retrospective cohort study using electronic health records of 416 patients that underwent SIBO lactulose hydrogen and methane breath testing. Charts were reviewed for demographics (age, sex, BMI, race) and past medical histories including hypertension, hyperlipidemia, diabetes, and psychiatric history. T-test and logistic regression assessed association between dependent and independent variables. The results were summarized as mean difference (MD) and standard deviation (SD), or odds ratio (OR) and 95% confidence intervals (CI). Results: Of the 416 patients enrolled in this study, 198 (47%) tested positive for SIBO. The mean age of SIBO(+ve) patients was 51.9 +/- 18.6 and SIBO(-ve) patients was 53.9 +/- 17.6. The mean BMI of SIBO(+ve) patients was 26.5 +/- 6.4 vs 26.1 +/- 6.6 in SIBO(-ve). Fourty-nine (24.7%) of the SIBO(+ve) patients were male compared to 55 (25.2%) of the SIBO(-ve) patients. In our database, there were 58 (13.9%) diabetic patients and of those 13.1% SIBO(+ve) vs 14.7% SIBO(-ve). Comparing the 87 (21%) patients with hypertension, there were 15.7% SIBO(+ve) vs 25.7% SIBO(-ve) with OR 0.54(0.33, 0.88; p=0.01). Of the 147 (35.3%) patients with hyperlipidemia, 39.4% SIBO(+ve) vs 31.4% SIBO(-ve). Of the 119 (28.6%) patients with a psychiatric history, 26.3% SIBO(+ve) vs 30.7% SIBO(-ve). Conclusion: In this retrospective study, there was a protective effect against SIBO in the hypertensive patients. Whether this is related to hypertension itself, or medications used to treat hypertension remains to be further delineated in future studies. Sex, age, race, BMI, hyperlipidemia, diabetes, and psychiatric history did not signify a risk for SIBO.
Sa1784 Gallstones, Lactose Malabsorption and Methanogenic Flora: A Strange Trio Francesca Mangiola, Fabio Del Zompo, Daniela Feliciani, Teresa Di Rienzo, Giovanna D'Angelo, Cristiana sensi, Roberto Persiani, Domenico D'ugo, Francesco Franceschi, Antonio Gasbarrini, Veronica Ojetti BACKGROUND AND AIM Cholelithiasis, is defined as the presence of stones in the gallbladder and is one of the most common digestive diseases, affecting 9-19% of the general population, with a female prevalence. The most common symptom is postprandial biliary colic,. Cholecystectomy, usually laparoscopic, is the definitive treatment of choice. The altered composition and excretion of bile in the duodenum is very irritating for the intestinal mucosa, altering the brush border with a possible interference on the lactose absorption. The aim of this study was to assess the prevalence of lactose malabsorption through a H2/ CH4 lactose breath test (LBT) in subjects affected by gallstones. MATERIAL AND METHODS Twenty (4M/16F; mean age 55±8yrs) subjects, scheduled to undergo cholecystectomy in the following month for gallstones, have performed a H2/CH4 LBT in our Gastroenterology Unit according to the guidelines. We have considered a positive LBT when there was a peak of H2>20 ppm over baseline. RESULTS 14 out of 20 (70%) pts resulted lactose malabsorbers with an H2 mean peak value of 73±23 ppm (Table 1). The most interesting data was that 90% (18/20) of these pts produced high levels of CH4, with a mean basal value of 8±5 ppm and a mean peak value of 28 ± 12 ppm (Table 2). CONCLUSION We found a high prevalence of lactose malabsorption in patients affected by gallstones, confirming the hypothesis that an alteration of bile composition could destroy the lactase enzyme on the brush border. The high prevalence of methanogenic flora observed in these pts could be a cause or a consequence of the formation of gallbladder stones. Further studies are needed to better understand these interesting findings.
Sa1786 Loss of PTPN2 in the Intestinal Epithelium of Mice Only Fractionally Affects Inflammation in DSS Colitis but Leads to Epithelial Transformations When Repeatedly Treated With DSS Stephanie Kasper, Marianne R. Spalinger, Irina Leonardi, Alexandra Gerstgrasser, Kirstin Atrott, Isabelle Frey-Wagner, Michael Fried, Gerhard Rogler, Michael Scharl Background: Mice featuring a knock-out of the inflammatory bowel disease (IBD) susceptibility gene protein tyrosine phosphatase non-receptor type 2 (PTPN2), die from systemic inflammation. We have previously shown that T-cell specific loss of PTPN2 leads to more severe DSS colitis and systemic inflammation. To examine the role of PTPN2 in the colonic epithelium in vivo, we generated mice exhibiting a loss of PTPN2 in intestinal epithelial cells (IEC) and induced DSS colitis. Methods: PTPN2flox/floxxVilCre mice and control littermates were used. Acute colitis was induced by either 2% or 2.5% DSS treatment for 7 days.
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fecal BA loss, which occurs in the absence of any absorptive defect within the terminal ileum, is due to increased BA synthesis, resulting from impaired FGF19 ileal production or hepatic actions. We aimed to investigate whether BA-induced expression of FGF19 in the ileum is reduced in patients with low SeHCAT retention. Methods: Patients being investigated for unexplained diarrhea (n=16) were prospectively recruited and gave informed consent at colonoscopy to give additional ileal biopsies. All had SeHCAT tests. Groups of 2-3 biopsies (explants) were incubated separately for 6h with either BA-free culture media (unstimulated controls), chenodeoxycholate (CDCA) or glyco-CDCA (GCDCA), both at 50uM. After RNA extraction and cDNA synthesis, FGF19 expression was quantified relative to GAPDH by RT-PCR. Results: SeHCAT 7d retention values were <15% in 7 patients, indicating primary BAD, and >15% in 9 who were normal diarrhea controls. Previous studies had shown no significant difference in baseline unstimulated FGF19 expression between these groups and this was confirmed with the unstimulated control samples (p=0.76). Median stimulation overall was 184-fold with CDCA and 373-fold with GCDCA. A positive correlation was found between SeHCAT retention and the magnitude of the fold change in FGF19 expression stimulated by either CDCA (r=0.50, n=16, p=0.02) or by GCDCA (r=0.76, n=7, p=0.02). These relationships were still present when the fold changes were normalized to the baseline FGF19 expression found in the unstimulated explants. Conclusion: Ileal explants from patients with lower SeHCAT 7d retention have a lower response to both CDCA and GCDCA. As uptake of GCDCA is dependent on carrier-mediated apical BA uptake but CDCA is not, this implies there is no defect in apical BA uptake, but abnormalities elsewhere in the FGF19 response. A reduced capacity to induce ileal FGF19 expression in response to absorbed BA is proposed to lead to the excess BA production and fecal BA losses found in primary BAD.
with intestinal failure and the need for intestinal transplantation in SBS patients in the absence of CD. The aim of the present study was to establish a murine SBS model for studying the influence of genetic risk factors, especially NOD2, on peri-operative outcome, mucosal adaptation and transepithelial transport. Material and Methods: Male C57BL6/J wild-type (wt) and NOD2 knock-out (ko) mice (body weight (BW) 30-34g) were anaesthetized by i.p. injection of ketamine and xylazine. Mice were orally intubated with a 22-gauge cannula and mechanically ventilated with room air (300μl and 130 breaths/min). Mice were placed on a heating plate and body temperature was continuously monitored. After midline incision, the small bowel was resected 10-12cm proximal to the ileocecal junction and immediately after the cecum. Intestinal continuity was restored by an end-to-end anastomosis. Control mice received simple transection without resection. Mice were rescued with s.c. injection of 1ml Ringer's lactate and 5mg/kg BW carprofen and received a standard liquid diet ad libitum 1-7d p.o.. Wellness and BW were scored daily. At 7 and 14d p.o., intestine was harvested 1-2cm proximal from anastomosis for histological examinations and gene expression analyses of ion transporters (DRA; SLC26A3, NHE3; SLC9A3), mucin2 and lysozyme. Results: Wt and ko mice had similar survival rates of 70% (wt) and 71% (ko). Both strains got diarrhea. Ko mice displayed more severe weight loss (maximal 21±1.9%, d9) compared to wt (maximal 13±3.4%, d9) and both groups suffered from more and prolonged weight loss than their related sham controls (maximal 9±2.6% (ko) vs. maximal 7±1.9% (wt), d1). Both groups showed signs of mucosal adaptation such as an increase in villus height (128±12.6% (wt) and 150±18.2% (ko), 14d) and diameter. qPCR revealed increased intestinal expression levels of DRA (0h vs. 14d, p=0.01) and decreased amounts of lysozyme (0h vs. d14, p=0.02) and mucin2 (0h vs. d14, p=0.006) in wt mice. NHE3 was not significantly altered. Conclusions: A clinical relevant model of ileocecal recection was successfully established in mice to study genetic risk factors for SBS. Loss of NOD2 results in worse clinical adaptation in SBS mice. The underlying mechanisms are presently unknown. Future studies will address transepithelial transport, barrier function and potential immune mediators of mucosal adaptation in short bowel conditions.
Sa1779 Soluble Plantain (Banana) Fibre Inhibits Epithelial Cell Damage in Response to Clostridium difficile and Its Toxins Hannah L. Simpson, Jonathan M. Rhodes, Barry J. Campbell
Sa1781
Background: Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and carries significant mortality. Epithelial adherence contributes to its pathogenicity (PLoS ONE 2013;8:e78404). We have previously shown that soluble non-starch polysaccharides (NSP) from plantain bananas (Musa spp.) inhibit the epithelial adherence of a range of diarrhoeal pathogens, both in vitro and in vivo (J. Nutr. Biochem. 2013; 24:97-103) via an interaction with the epithelium that involves enhanced chloride secretion (PLoS ONE 2014; 9:e87658). Aim: To evaluate soluble plantain fibre for its potential inhibitory effect against C.difficile bacterium, spore and toxin interaction with intestinal epithelial cells. Methods: Human intestinal epithelial Caco2 cell monolayers were pre-incubated (30min) with plantain NSP (2.5-20 mg/mL) prior to infection with 13 C. difficile clinical isolates or 5 purified spore preparations (2h; multiplicity of infection MOI of 100), or treatment with purified native C.difficile Toxin A (TcdA) or Toxin B (TcdB); 0-100 ng/mL over 24h. C.difficile bacterium and spore adherence were determined by quantification of colony forming units (CFUs). C.difficile toxin and bacterium-mediated cellular effects (adenylate kinase release as a measure of cytotoxicity, caspase-3 activation and IL-8 release) were also monitored in the presence and absence of plantain NSP. Results: Plantain NSP caused dose-related inhibition of intestinal epithelial adherence of all C. difficile clinical isolates (inhibition at plantain NSP at 10 mg/mL, 52.2±3.0 to 98.6±1.0%; all P<0.001;) and all C. difficile spore preparations (27.9±5.4% to 33.8±6.9% inhibition; all P≤ 0.05). Plantain NSP at 10 mg/mL also caused 38-64% inhibition of toxic and pro-inflammatory effects of C.difficile toxins on epithelial cells (see Table) and 25-88% inhibition of the toxic and pro-inflammatory effects of whole C.difficile bacteria (Table). Conclusions: Soluble plantain NSP at concentrations readily achievable in the human distal colon inhibits C.difficile bacterium, spore and toxin interaction with intestinal epithelial cells. These results suggest that soluble dietary fibres, such as plantain, acting as "contrabiotics", could be developed as potential prophylaxis or treatment for C.difficile infection (CDI).
Chronic Heart Failure Is Associated With Bowel Wall Edema, Reduced Intestinal Blood Flow, Gastrointestinal Symptoms and Bacterial Growth Juergen Bauditz, Stefan D. Anker, Alexander Swidsinski, Anja Sandek, Wolfram Doehner, Anja Sandek Background: We previously demonstrated that chronic heart failure (CHF) is associated with morphological and functional intestinal changes. We now investigated whether bowel wall thickening in CHF is also associated with clinical gastrointestinal symptoms (GIS), bowel alterations and changes in blood flow in the abdominal arteries. Aim: To measure bowel wall thickness (BWT), arterial intestinal blood flow (BF), gastrointestinal symptoms, histological changes and juxtamucosal bacterial growth in CHF. Methods: We investigated 85 subjects (65 patients, 25 controls). BWT and intestinal BF were measured using ultrasound. The Gastrointestinal Symptom Rating Scale was employed for evaluation of GIS. Sigmoidal biopsies for histological evaluation, investigation of juxtamucosal bacteria and bacteria in stool by fluorescence in situ hybridization were studied in a subgroup of patients. Serum lipopolysaccharide-(LPS)-antibodies were measured. Results: Bowel wall thickness of all colonic segments and the ileum was significantly increased in CHF (p<0.003 for all parts) and corresponded to bowel wall edema in histology. Patients showed a 30-43% reduced mean systolic BF in the superior and inferior mesenteric arteries (SMA and IMA) and celiac trunk (CT) compared to controls (all p<0.007). CHF patients more often suffered from repletion, flatulences, intestinal murmurs and burping as compared to controls (all p<0.04). Patients with lower CT BF had more abdominal discomfort and immunoglobulin A-antiLPS (r=0.76, p<0.02). Anti-LPS-response correlated with increased growth of juxtamucosal and not stool bacteria. Patients with intestinal murmurs had greater BWT of sigmoid/ descending colon (p<0.05). Conclusions: Bowel wall edema together with reduced intestinal blood flow may cause gastrointestinal symptoms and juxtamucosal bacterial growth in chronic heart failure. Sa1782 Solitary Therapy With Metronidazole (MTZ) or Vancomycin (VCO) for C. difficile Infection (CDI) Results in Similar Outcomes of Disease Muhammad S. Mansoor, Paul Feuerstadt Introduction: Guidelines for C. difficile infection (CDI) treatment advise MTZ for mild disease, VCO for severe and combination MTZ and VCO (Combo) in severe-complicated pts. In practice, medication adjustments are made in response to changes in clinical status. We hypothesize that pts in a tertiary care hospital who receive one unaltered therapy with MTZ or VCO will have similar outcomes but Combo will have worsened outcomes as a result of disease severity. Methods: Consecutive pts who had a +C. difficile toxin assay at Yale-New Haven Hospital between 4/10 and 5/14 were identified. For each patient we recorded demographics, medical co-morbidities, basic lab data at diagnosis, treatments of CDI and various outcomes. Pts who received only-MTZ (PO and/or IV), VCO or Combo therapy without any treatment changes were separated into groups. Independent comparisons were made between MZO and VCO as well as VCO and Combo using SPSS (23.0). Results: Of 798 pts originally identified with CDI, 63.5% met inclusion criteria receiving one therapy with 374, 98 and 35, receiving MTZ, VCO and Combo, respectively. From those excluded, in 18.7% (% of the entire cohort) VCO was added to MTZ, 2.4% had MTZ added to VCO and 13.8% had MTZ switched to VCO. The remaining excluded pts received rifaximin, fidaxomicin or nitazoxanide. MTZ dosing was exclusively 500 mg Tid while 91.8% of pts received VCO 125 Qid, 4.2% 250 mg Qid and 4.2% 500 mg Qid. In our study population, there were no significant differences in demographics, Charlson score or medical co-morbidities. When comparing MZO with VCO, pts receiving VCO had previous CDI more often (20.4%, 3.2%, p<0.001). Pts receiving Combo were more likely to have a fever (30.0%, 9.9%, p<0.01) or respiratory rate > 20 (46.7%, 23.5%, p<0.05) at diagnosis compared with VCO. Those receiving VCO had a higher WBC compared with MZO (14.0 ± 8.8, 11.0 ± 6.4, p<0.001). 90-day recurrence of infection was higher in VCO (13.5%, 8.0%, p<0.04) with lower frequency of resolution of diarrhea during hospitalization (73.0%, 86.3%, p<0.05)
Sa1780 The Influence of NOD2 Gene Mutation on the Intestinal Adaptation and PeriOperative Outcome in a Murine Model of Short Bowel Syndrome Peggy Bodammer, Maria Witte, Karen Bannert, Daniel M. Bastmeyer, Katja Bovensiepen, Holger Schäffler, Georg Lamprecht Background and Aims: Short bowel syndrome (SBS) is the condition of malabsorption of nutrients, fluids and electrolytes in patients after massive bowel resection. The intracellular pattern recognition receptor Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) is a risk gene for Crohn's disease (CD) which in turn is a frequent indication for small bowel surgery. However, recent studies show that NOD2 mutations are associated
AGA Abstracts
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compared with MZO. Combo had higher ICU requirement (68.6%, 38.5%, p<0.01), 30day colectomy (5.7%, 0.0%, p<0.05), sepsis within 30-days (31.4%, 10.2%, p< 0.001) and 30-day mortality (34.3%, 8.2%, p<0.001) with a lower readmission rate within 90-days (31.4%, 49.0%, p<0.01) compared with VCO. Conclusions: Solitary therapy with VCO for those with higher WBC and/or recurrent disease and MTZ for the less severe resulted in similar overall outcomes. It is likely clinicians judgment to keep pts on one therapy reflects appropriate response and this might predict these outcomes. As would be expected with the most severe disease, Combo therapy was associated with worse outcomes and these pts require more aggressive management. Sa1783 The Impact of Medications on Small Intestinal Bacterial Overgrowth Sheevani Bhalsod, Seth Lipka, Roshanak Rabbanifard, Jennifer Leigh, Jae Chung, Marc Levin, Kiran Joglekar, Ambuj Kumar, Jay J. Mamel Introduction: Small intestinal bacterial overgrowth (SIBO) occurs when native/non-native bacteria exceed 105 colony-forming units per milliliter in the small intestine. Currently, there is little data regarding a relationship between SIBO and statin therapy, PPI, probiotic, and opioids. The purpose of this study is to evaluate the effect of medications on SIBO status. Methods: We conducted a retrospective cohort study using the electronic health records of 416 patients that underwent SIBO lactulose hydrogen and methane breath testing. Charts were reviewed for demographics (age, sex, race, and BMI) and medications such as statins, PPI, probiotics, and opioids. T-test and logistic regression assessed association between dependent and independent variables. The results were summarized as mean difference (MD) and standard deviation (SD), or odds ratio(OR) and 95% confidence intervals (CI). Results: Of the 416 patients enrolled in this study, 198 (47%) tested positive for SIBO. The mean age of SIBO(+ve) patients was 51.9 +/- 18.6 and SIB-(-ve) patients was 53.9 +/- 17.6. The mean BMI of SIBO(+ve) patients was 26.5 +/- 6.4 vs 26.1 +/- 6.6 in SIBO(-ve). 49 (24.7%) of the SIBO(+ve) patients were male compared to 55 (25.2%) of the SIBO(-ve) patients. Our data indicated no significant association between the use of statins, PPI, probiotics or opioids on SIBO status. 103 (24.7%) patients used statin therapy with a 29.8% incidence of SIBO compared to 19.7% without SIBO. Of the 186 (44.7%) patients on PPI, there were 41.4% SIBO(+ve) vs 47.7% SIBO(-ve). 50 (12%) patients used probiotics, with an 11.6% incidence of SIBO(+ve) vs 12.3% SIBO(-ve). Of the 59 (14.2%) patients on opioids, there were 12.6% SIBO(+ve) vs 15.6% SIBO(-ve). Conclusion: In this retrospective study, our data did not reveal a significant association between statins, PPI, probiotics, and opioids on SIBO status. Prior published data have yielded conflicting results on association between PPI and risk of developing SIBO and our data supports no association between PPI use and risk of developing SIBO. In addition, even though it is well known that opioids can induce bowel dysfunction, our data does not signify a risk of developing SIBO for patients on opioids.
Sa1785 The Impact of Hypertension, Hyperlipidemia, Diabetes, and Psychiatric History on Small Intestinal Bacterial Overgrowth Sheevani Bhalsod, Seth Lipka, Roshanak Rabbanifard, Jennifer Leigh, Jae Chung, Marc Levin, Kiran Joglekar, Ambuj Kumar, Jay J. Mamel Introduction: Small intestinal bacterial overgrowth (SIBO) occurs when native/non-native bacteria exceed 105 colony-forming units per milliliter in the small intestine. Currently, there is little data regarding a relationship between SIBO and certain factors such as age, sex, race, BMI and medical conditions such as hypertension, hyperlipidemia, diabetes, and psychiatric history. The purpose of this study is to evaluate the association between specific medical conditions and SIBO. Methods: We conducted a retrospective cohort study using electronic health records of 416 patients that underwent SIBO lactulose hydrogen and methane breath testing. Charts were reviewed for demographics (age, sex, BMI, race) and past medical histories including hypertension, hyperlipidemia, diabetes, and psychiatric history. T-test and logistic regression assessed association between dependent and independent variables. The results were summarized as mean difference (MD) and standard deviation (SD), or odds ratio (OR) and 95% confidence intervals (CI). Results: Of the 416 patients enrolled in this study, 198 (47%) tested positive for SIBO. The mean age of SIBO(+ve) patients was 51.9 +/- 18.6 and SIBO(-ve) patients was 53.9 +/- 17.6. The mean BMI of SIBO(+ve) patients was 26.5 +/- 6.4 vs 26.1 +/- 6.6 in SIBO(-ve). Fourty-nine (24.7%) of the SIBO(+ve) patients were male compared to 55 (25.2%) of the SIBO(-ve) patients. In our database, there were 58 (13.9%) diabetic patients and of those 13.1% SIBO(+ve) vs 14.7% SIBO(-ve). Comparing the 87 (21%) patients with hypertension, there were 15.7% SIBO(+ve) vs 25.7% SIBO(-ve) with OR 0.54(0.33, 0.88; p=0.01). Of the 147 (35.3%) patients with hyperlipidemia, 39.4% SIBO(+ve) vs 31.4% SIBO(-ve). Of the 119 (28.6%) patients with a psychiatric history, 26.3% SIBO(+ve) vs 30.7% SIBO(-ve). Conclusion: In this retrospective study, there was a protective effect against SIBO in the hypertensive patients. Whether this is related to hypertension itself, or medications used to treat hypertension remains to be further delineated in future studies. Sex, age, race, BMI, hyperlipidemia, diabetes, and psychiatric history did not signify a risk for SIBO.
Sa1784 Gallstones, Lactose Malabsorption and Methanogenic Flora: A Strange Trio Francesca Mangiola, Fabio Del Zompo, Daniela Feliciani, Teresa Di Rienzo, Giovanna D'Angelo, Cristiana sensi, Roberto Persiani, Domenico D'ugo, Francesco Franceschi, Antonio Gasbarrini, Veronica Ojetti BACKGROUND AND AIM Cholelithiasis, is defined as the presence of stones in the gallbladder and is one of the most common digestive diseases, affecting 9-19% of the general population, with a female prevalence. The most common symptom is postprandial biliary colic,. Cholecystectomy, usually laparoscopic, is the definitive treatment of choice. The altered composition and excretion of bile in the duodenum is very irritating for the intestinal mucosa, altering the brush border with a possible interference on the lactose absorption. The aim of this study was to assess the prevalence of lactose malabsorption through a H2/ CH4 lactose breath test (LBT) in subjects affected by gallstones. MATERIAL AND METHODS Twenty (4M/16F; mean age 55±8yrs) subjects, scheduled to undergo cholecystectomy in the following month for gallstones, have performed a H2/CH4 LBT in our Gastroenterology Unit according to the guidelines. We have considered a positive LBT when there was a peak of H2>20 ppm over baseline. RESULTS 14 out of 20 (70%) pts resulted lactose malabsorbers with an H2 mean peak value of 73±23 ppm (Table 1). The most interesting data was that 90% (18/20) of these pts produced high levels of CH4, with a mean basal value of 8±5 ppm and a mean peak value of 28 ± 12 ppm (Table 2). CONCLUSION We found a high prevalence of lactose malabsorption in patients affected by gallstones, confirming the hypothesis that an alteration of bile composition could destroy the lactase enzyme on the brush border. The high prevalence of methanogenic flora observed in these pts could be a cause or a consequence of the formation of gallbladder stones. Further studies are needed to better understand these interesting findings.
Sa1786 Loss of PTPN2 in the Intestinal Epithelium of Mice Only Fractionally Affects Inflammation in DSS Colitis but Leads to Epithelial Transformations When Repeatedly Treated With DSS Stephanie Kasper, Marianne R. Spalinger, Irina Leonardi, Alexandra Gerstgrasser, Kirstin Atrott, Isabelle Frey-Wagner, Michael Fried, Gerhard Rogler, Michael Scharl Background: Mice featuring a knock-out of the inflammatory bowel disease (IBD) susceptibility gene protein tyrosine phosphatase non-receptor type 2 (PTPN2), die from systemic inflammation. We have previously shown that T-cell specific loss of PTPN2 leads to more severe DSS colitis and systemic inflammation. To examine the role of PTPN2 in the colonic epithelium in vivo, we generated mice exhibiting a loss of PTPN2 in intestinal epithelial cells (IEC) and induced DSS colitis. Methods: PTPN2flox/floxxVilCre mice and control littermates were used. Acute colitis was induced by either 2% or 2.5% DSS treatment for 7 days.
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