- Email: [email protected]
Tu1985 A Prospective Controlled Pilot Study of Fecal Microbiota Transplantation for Chronic Refractory Pouchitis
that some metabolites strongly drive microbial community structure. Conclusions: The strong interconnectivity between the metabolome and microbiome suggests that: (a) mucosal metabolites are primarily of microbial origin; (b) metabolites should be more deeply interrogated as direct mediators of microbial-associated disease activity; and (c) metabolites may be a direct target for monitoring and therapeutically manipulating microbial community function in IBD and other microbiome-associated intestinal diseases.
Tu1986
Background: Increasing evidence suggests an important role of intestinal microbiota in Chronic Inflammatory bowel disease (IBD). Probiotics have been shown in recent studies to maintain remission in patients with active UC. The aim of this study is to deteremine the efficacy of Probiotics in patients with Active UC through a systematic review and metaanalysis. Methods: A search of Medline, Pubmed, and Embase databases between 1992 to November 2012 for studies that assessed the therapeutic efficacy of Probiotics in the treatment of active UC. Search terms were: Ulcerative Colitis, Inflammatory bowel Disease Colitis; medical interventions evaluated Probiotics, lactobacilli, bifidobact, Ecoli Nissle, Sarcomyces. Clinical outcome was defined by (validated) clinical activity indices and endoscopic and/or histological scores.We include only RCT or prospective studies using a probiotic as 1 treatment arm. All Patients included were diagnosed with UC. Studies were not differentiated based on strain type or strength . Exclusion criteria included: studies not in English, those with less than 10 patients, and case series/reports. A random effects model was used for this analysis. The data on pain relief was subsequently extracted, pooled, and analyzed. Results: Our initial review resulted in 41 potential articles. 29 studies were excluded as they did not meet our inclusion criteria.12 studies were identified for inclusion, however, 3 studies were excluded on further review as the type of symptom scale used were not uniform. Our final analysis included nine studies (5 RCTs, 4 Prospective trials) comprising 575 patients (575 in Probiotics group and 313 in Control Group). The pooled estimates of remission were 53% in the Probiotics group vs 30% in the Control group (OR 2.54, CI 95% (1.78 to 3.63) P,0.001). Patients were treated for a mean duration of treatment 2.5 months. Chi Square Test for heterogeneity among the studies was found to be significant (P= 0.19) Conclusion: Probiotics are efficacious in the treatment and induction of remission and prevention of relapse in patients with active UC. Further insight into the etiology of microorganisms involved in active UC and well designed studies will be required to confirm our finding. Future studies should be designed carefully and should focus on specific disease subtypes/location.
Tu1984 Chemically Defined Diet Alters the Protective Properties of FructoOligosaccharides and Isomalto-Oligosaccharides in a Rodent Model of Colitis Petya Koleva, Ali Ketabi, Rosica Valcheva, Michael Gänzle, Levinus A. Dieleman Introduction: Inflammatory bowel diseases are complex disorders associated with chronic intestinal inflammation. Intestinal bacteria contribute to the initiation and perpetuation of this chronic condition. The composition and metabolic activity of intestinal microbiota can be modified by different environmental factors such as diet. Dietary intervention with fructooligosaccharides (FOS) and isomalto-oligosaccharides (IMO) in HLA-B27 transgenic (TG) rats changed specific cecal microbiota, associated with reduction of spontaneous colitis, but their protective mechanisms remain unclear. However, the use of different non-digestible carbohydrates in combination with various dietary backgrounds may reveal the role of the diet and fibers in experimental IBD. Therefore, the aim of this study was to examine if feeding a chemically defined AIN76A diet, with high sucrose content, versus a standard rat chow diet, supplemented or not with FOS or IMO, can modify the effects of these prebiotics on colitis development and intestinal microbiota. Methods: Four weeks old rats were fed AIN76A diet or standard rat chow diet supplemented with 8 g/kg of body weight IMO, FOS or not for 12 weeks. Cecal contents and tissues were collected at necropsy. Effects of IMO and FOS on intestinal inflammation were assessed by quantifying mucosal IL-1 β and microscopic colitis. Cecal content was analysed for microbiota composition by quantitative PCR and for short chain fatty acids (SCFA) by GC. Results: Both FOS and IMO failed to reduce colitis in the presence of AIN76A diet, as assessed by histology and mucosal IL1β. Quantification of dominant bacterial groups in cecum showed that copy numbers of bifidobacteria and Enterobacteriaceae were stimulated by FOS versus control and IMO treatment regardless of the background diet, while copy numbers of Clostridium cluster IV were decreased. Moreover, rat chow diet rather than prebiotic treatments, mediated a significant increase of gene copy numbers of clostridial clusters XI and XIVa, as well as butyratekinase compared to rats on AIN76A diet. Higher concentration of total SCFA were observed in cecal contents of rats on rat chow compared to the chemically defined diet. AIN76A diet increased the relative proportions of propionate and branched-chain fatty acids irrespectively the prebiotic treatment. Conclusions: This is the first study to show that the protective effects of fibers on colitis development depend on the background diet. The SCFA composition, particularly the relative concentration of branched-chain fatty acids, was highly correlated to inflammation. Although diet modifies cecal microbiota, our study indicates that these parameters are not associated with colitis reduction. Tu1985 A Prospective Controlled Pilot Study of Fecal Microbiota Transplantation for Chronic Refractory Pouchitis Jonathan Landy, Hafid O. Al-Hassi, Elizabeth R. Mann, Simon T. Peake, Simon D. McLaughlin, Paul J. Ciclitira, Susan K. Clark, Stella C. Knight, Ailsa L. Hart
Tu1987 Faecalibacterium prausnitzii Inhibits Interleukin-17 to Ameliorates Colorectal Colitis in Rats Chenggong Yu
Background: Fecal microbiota transplantation (FMT) is an effective therapy for Clostridium difficile and possibly inflammatory bowel diseases (IBD). Published data of FMT for inflammatory bowel diseases are reported in case series and case reports. To our knowledge, there are no controlled studies of FMT for IBD. We aimed to conduct a prospective study of FMT for chronic refractory pouchitis. Methods: Patients with clinically, endoscopically and histologically confirmed chronic refractory pouchitis; with a pouch disease activity index (PDAI>7) were included. Donors were nominated by the participating patients and were screened by clinical history and serology for HAV, HBV, HCV, HEV, Treponema, HIV, HTLV I/II and stool for M,C+S, C. difficile toxin and parasites. Thirty grams of fresh donor stool was collected and homogenised with 50ml of sterile saline within six hours of nasogasric administration of FMT. Stool samples were also collected from patients for analysis of coliform sensitivities before and 4 weeks after FMT. PDAI and Cleveland global quality of life score (CGQoL ) were recorded prior to FMT and four weeks after FMT. Results: Eight patients with chronic refractory pouchitis who had undergone restorative proctocolectomy for ulcerative colitis underwent FMT. Three patients had ESBL resistant coliforms on stool analysis prior toFMT. Two of these patients demonstrated a change to ciprofloxacin sensitive coliform following FMT. The mean PDAI prior to FMT was 12. The mean CGQoL was 0.45. At 4 weeks following FMT, no patient had achieved a clinical remission (mean PDAI 11). No improvement in CGQoL was seen (mean 0.44). Conclusion: FMT via nasogastric administration was not effective in achieving clinical remission for chronic refractory pouchitis with no change in PDAI or CGQoL identified at 4 weeks after FMT. However, in two patients with ESBL resistant coliform, ciprofloxacin sensitivity was regained following FMT and these patients have subsequently been maintained on ciprofloxacin. This suggests FMT may alter the pouch microbiota. Further molecular microbiological analysis is being undertaken to determine the effect FMT had on these patients' microbiota. In addition, further studies of FMT are required to assess the effect of different methods of FMT that may be more efficacious for this group of patients.
Inflammatory bowel disease (IBD) is characterized by recurrent inflammation in the gastrointestinal mucosa. It has been shown that Faecalibacterium prausnitzii (F. prausnitzii), one of the dominant intestinal bacterial flora, may protect colonic mucosa against chronic inflammation and the devel-opment of IBD, with the underlying mechanisms unclear. The IL-23/Th17/IL-17 pathway has been proposed to be critical in the development of IBD. Therefore, the impacts of F. prausnitzii and its metabolites on the IL-23/Th17/IL-17 pathway in human monocytes and a rat model of colitis were determined in this study. The colitis was induced by 2,4,6-trinitrobenzene sulfonic acid in the rats, representing similar features as those in patients with IBD. F. prausnitzii, its culture medium (con-taining complete metabolites), and one of its metabolite butyric acid were used to treat the rats in vivo, as well as rat splenocytes and human monocytes in vitro. Inflammatory cytokines were measured in colon tissue, plasma and cell culture medium. Results showed that both F. prausnitzii and butyric acid increased plasma anti-inflammatory cytokines (IL-10 and IL-12) and suppressed IL-17 levels in both plasma and colonic mucosa, with ameliorated colonic colitis lesion. This inhibition on IL-17 release has also been observed in both rat splenocytes and human venous blood monocytes in vitro. The culture supernatant of F. prausnitzii also suppressed Th17 cell differentiation induced by TGF-beta and IL-6 in vitro. The present data show that the metabolites in the culture supernatant of F. prausnitzii exerted stronger anti-inflammatory effects than the bacterium itself in both in vivo and in vitro experiments. However, the anti-inflammatory effect of the culture supernatant occurs via different pathways from that of F. prausnitzii, and thus, both F. prausnitzii and its metabolites are required for protection against the development of IBD, suggesting a potential for using F. prausnitzii and metabolic products, eg. butyric acid, in the treatment of IBD. Tu1988 Impact of the Commensal Bacterium Faecalibacterium prausnitzii in a Non Active Inflammation Murine Model Rebeca Martin, Florian Chain, Jun Lu, Jennifer Jury, Jean Jacques Gratadoux, Elena F. Verdu, Premysl Bercik, Harry Sokol, Luis G. Bermúdez-Humarán, Philippe Langella Background: Recent evidence supports the presence of low grade inflammation in a wide array of diseases such as diabetes, obesity and non alcoholic fatty liver disease. Irritable bowel syndrome (IBS) is the prototypical functional disorder of the gastrointestinal tract. It
S-897
AGA Abstracts
AGA Abstracts
Efficacy of Probiotics in the Treatment of Patients With Active Ulcerative Colitis (UC): Systemic Review and Meta Analysis Mikram Jafri, Rimsha Hasan, Haroon Kamran, Javed N. Sadiq, Amit Bhanvadia, Frank G. Gress
Tu1986
Background: Increasing evidence suggests an important role of intestinal microbiota in Chronic Inflammatory bowel disease (IBD). Probiotics have been shown in recent studies to maintain remission in patients with active UC. The aim of this study is to deteremine the efficacy of Probiotics in patients with Active UC through a systematic review and metaanalysis. Methods: A search of Medline, Pubmed, and Embase databases between 1992 to November 2012 for studies that assessed the therapeutic efficacy of Probiotics in the treatment of active UC. Search terms were: Ulcerative Colitis, Inflammatory bowel Disease Colitis; medical interventions evaluated Probiotics, lactobacilli, bifidobact, Ecoli Nissle, Sarcomyces. Clinical outcome was defined by (validated) clinical activity indices and endoscopic and/or histological scores.We include only RCT or prospective studies using a probiotic as 1 treatment arm. All Patients included were diagnosed with UC. Studies were not differentiated based on strain type or strength . Exclusion criteria included: studies not in English, those with less than 10 patients, and case series/reports. A random effects model was used for this analysis. The data on pain relief was subsequently extracted, pooled, and analyzed. Results: Our initial review resulted in 41 potential articles. 29 studies were excluded as they did not meet our inclusion criteria.12 studies were identified for inclusion, however, 3 studies were excluded on further review as the type of symptom scale used were not uniform. Our final analysis included nine studies (5 RCTs, 4 Prospective trials) comprising 575 patients (575 in Probiotics group and 313 in Control Group). The pooled estimates of remission were 53% in the Probiotics group vs 30% in the Control group (OR 2.54, CI 95% (1.78 to 3.63) P,0.001). Patients were treated for a mean duration of treatment 2.5 months. Chi Square Test for heterogeneity among the studies was found to be significant (P= 0.19) Conclusion: Probiotics are efficacious in the treatment and induction of remission and prevention of relapse in patients with active UC. Further insight into the etiology of microorganisms involved in active UC and well designed studies will be required to confirm our finding. Future studies should be designed carefully and should focus on specific disease subtypes/location.
Tu1984 Chemically Defined Diet Alters the Protective Properties of FructoOligosaccharides and Isomalto-Oligosaccharides in a Rodent Model of Colitis Petya Koleva, Ali Ketabi, Rosica Valcheva, Michael Gänzle, Levinus A. Dieleman Introduction: Inflammatory bowel diseases are complex disorders associated with chronic intestinal inflammation. Intestinal bacteria contribute to the initiation and perpetuation of this chronic condition. The composition and metabolic activity of intestinal microbiota can be modified by different environmental factors such as diet. Dietary intervention with fructooligosaccharides (FOS) and isomalto-oligosaccharides (IMO) in HLA-B27 transgenic (TG) rats changed specific cecal microbiota, associated with reduction of spontaneous colitis, but their protective mechanisms remain unclear. However, the use of different non-digestible carbohydrates in combination with various dietary backgrounds may reveal the role of the diet and fibers in experimental IBD. Therefore, the aim of this study was to examine if feeding a chemically defined AIN76A diet, with high sucrose content, versus a standard rat chow diet, supplemented or not with FOS or IMO, can modify the effects of these prebiotics on colitis development and intestinal microbiota. Methods: Four weeks old rats were fed AIN76A diet or standard rat chow diet supplemented with 8 g/kg of body weight IMO, FOS or not for 12 weeks. Cecal contents and tissues were collected at necropsy. Effects of IMO and FOS on intestinal inflammation were assessed by quantifying mucosal IL-1 β and microscopic colitis. Cecal content was analysed for microbiota composition by quantitative PCR and for short chain fatty acids (SCFA) by GC. Results: Both FOS and IMO failed to reduce colitis in the presence of AIN76A diet, as assessed by histology and mucosal IL1β. Quantification of dominant bacterial groups in cecum showed that copy numbers of bifidobacteria and Enterobacteriaceae were stimulated by FOS versus control and IMO treatment regardless of the background diet, while copy numbers of Clostridium cluster IV were decreased. Moreover, rat chow diet rather than prebiotic treatments, mediated a significant increase of gene copy numbers of clostridial clusters XI and XIVa, as well as butyratekinase compared to rats on AIN76A diet. Higher concentration of total SCFA were observed in cecal contents of rats on rat chow compared to the chemically defined diet. AIN76A diet increased the relative proportions of propionate and branched-chain fatty acids irrespectively the prebiotic treatment. Conclusions: This is the first study to show that the protective effects of fibers on colitis development depend on the background diet. The SCFA composition, particularly the relative concentration of branched-chain fatty acids, was highly correlated to inflammation. Although diet modifies cecal microbiota, our study indicates that these parameters are not associated with colitis reduction. Tu1985 A Prospective Controlled Pilot Study of Fecal Microbiota Transplantation for Chronic Refractory Pouchitis Jonathan Landy, Hafid O. Al-Hassi, Elizabeth R. Mann, Simon T. Peake, Simon D. McLaughlin, Paul J. Ciclitira, Susan K. Clark, Stella C. Knight, Ailsa L. Hart
Tu1987 Faecalibacterium prausnitzii Inhibits Interleukin-17 to Ameliorates Colorectal Colitis in Rats Chenggong Yu
Background: Fecal microbiota transplantation (FMT) is an effective therapy for Clostridium difficile and possibly inflammatory bowel diseases (IBD). Published data of FMT for inflammatory bowel diseases are reported in case series and case reports. To our knowledge, there are no controlled studies of FMT for IBD. We aimed to conduct a prospective study of FMT for chronic refractory pouchitis. Methods: Patients with clinically, endoscopically and histologically confirmed chronic refractory pouchitis; with a pouch disease activity index (PDAI>7) were included. Donors were nominated by the participating patients and were screened by clinical history and serology for HAV, HBV, HCV, HEV, Treponema, HIV, HTLV I/II and stool for M,C+S, C. difficile toxin and parasites. Thirty grams of fresh donor stool was collected and homogenised with 50ml of sterile saline within six hours of nasogasric administration of FMT. Stool samples were also collected from patients for analysis of coliform sensitivities before and 4 weeks after FMT. PDAI and Cleveland global quality of life score (CGQoL ) were recorded prior to FMT and four weeks after FMT. Results: Eight patients with chronic refractory pouchitis who had undergone restorative proctocolectomy for ulcerative colitis underwent FMT. Three patients had ESBL resistant coliforms on stool analysis prior toFMT. Two of these patients demonstrated a change to ciprofloxacin sensitive coliform following FMT. The mean PDAI prior to FMT was 12. The mean CGQoL was 0.45. At 4 weeks following FMT, no patient had achieved a clinical remission (mean PDAI 11). No improvement in CGQoL was seen (mean 0.44). Conclusion: FMT via nasogastric administration was not effective in achieving clinical remission for chronic refractory pouchitis with no change in PDAI or CGQoL identified at 4 weeks after FMT. However, in two patients with ESBL resistant coliform, ciprofloxacin sensitivity was regained following FMT and these patients have subsequently been maintained on ciprofloxacin. This suggests FMT may alter the pouch microbiota. Further molecular microbiological analysis is being undertaken to determine the effect FMT had on these patients' microbiota. In addition, further studies of FMT are required to assess the effect of different methods of FMT that may be more efficacious for this group of patients.
Inflammatory bowel disease (IBD) is characterized by recurrent inflammation in the gastrointestinal mucosa. It has been shown that Faecalibacterium prausnitzii (F. prausnitzii), one of the dominant intestinal bacterial flora, may protect colonic mucosa against chronic inflammation and the devel-opment of IBD, with the underlying mechanisms unclear. The IL-23/Th17/IL-17 pathway has been proposed to be critical in the development of IBD. Therefore, the impacts of F. prausnitzii and its metabolites on the IL-23/Th17/IL-17 pathway in human monocytes and a rat model of colitis were determined in this study. The colitis was induced by 2,4,6-trinitrobenzene sulfonic acid in the rats, representing similar features as those in patients with IBD. F. prausnitzii, its culture medium (con-taining complete metabolites), and one of its metabolite butyric acid were used to treat the rats in vivo, as well as rat splenocytes and human monocytes in vitro. Inflammatory cytokines were measured in colon tissue, plasma and cell culture medium. Results showed that both F. prausnitzii and butyric acid increased plasma anti-inflammatory cytokines (IL-10 and IL-12) and suppressed IL-17 levels in both plasma and colonic mucosa, with ameliorated colonic colitis lesion. This inhibition on IL-17 release has also been observed in both rat splenocytes and human venous blood monocytes in vitro. The culture supernatant of F. prausnitzii also suppressed Th17 cell differentiation induced by TGF-beta and IL-6 in vitro. The present data show that the metabolites in the culture supernatant of F. prausnitzii exerted stronger anti-inflammatory effects than the bacterium itself in both in vivo and in vitro experiments. However, the anti-inflammatory effect of the culture supernatant occurs via different pathways from that of F. prausnitzii, and thus, both F. prausnitzii and its metabolites are required for protection against the development of IBD, suggesting a potential for using F. prausnitzii and metabolic products, eg. butyric acid, in the treatment of IBD. Tu1988 Impact of the Commensal Bacterium Faecalibacterium prausnitzii in a Non Active Inflammation Murine Model Rebeca Martin, Florian Chain, Jun Lu, Jennifer Jury, Jean Jacques Gratadoux, Elena F. Verdu, Premysl Bercik, Harry Sokol, Luis G. Bermúdez-Humarán, Philippe Langella Background: Recent evidence supports the presence of low grade inflammation in a wide array of diseases such as diabetes, obesity and non alcoholic fatty liver disease. Irritable bowel syndrome (IBS) is the prototypical functional disorder of the gastrointestinal tract. It
S-897
AGA Abstracts
AGA Abstracts
Efficacy of Probiotics in the Treatment of Patients With Active Ulcerative Colitis (UC): Systemic Review and Meta Analysis Mikram Jafri, Rimsha Hasan, Haroon Kamran, Javed N. Sadiq, Amit Bhanvadia, Frank G. Gress