The relationship between human colonic mucosal metabolism and mucin synthesis was explored, with particular reference to ulcerative colitis (UC) and pouchitis. A hypothesis was proposed, that UC and pouchitis result from impaired metabolism of butyrate, and that the outcome of this metabolic event was reduced mucosal protection via effects on mucin synthesis. The study aims were to assess mucosal metabolism in the ileum and colon in controls and in UC, and to assess the effects of agents that are effective therapy for UC on metabolism as measured by mucin synthesis. In histologically normal colonoscopic mucosal biopsies cultured <I>in vitro</I>, the rate of metabolism of butyrate was similar in the ascending (AC) and descending colon (DC). There was a higher rate of metabolism of glutamine in the ascending colon, in agreement with previous work which stressed the relatively greater dependence of the distal colon on butyrate as an energy source. The terminal ileum (TI), in controls had a surprisingly high rate of metabolism of butyrate, significantly higher than the AC, glutamine metabolism in controls was also greater than in the AC. In ulcerative colitis (UC) the most striking change in epithelial metabolism was an increase in the rate of glutamine metabolism in the descending colon. The rates of butyrate metabolism in UC were similar to those in controls, the ratio of butyrate:glutamine metabolism was non-significantly lower in the descending colon in UC as a result of the increased rate of glutamine metabolism. Rates of metabolism in the terminal ileum were similar in UC and controls. Butyrate, at concentrations that are likely to be physiologically and pharmacologically relevant, significantly increased mucin synthesis in colonic mucosal explants from histologically normal and diseased (UC) tissue. Glucocorticoids and nicotine similarly increased colonic mucin synthesis, whereas mineralocorticoids were without effect.

Objectives: Ileal pouch anal anastomosis (IPAA), the removal of the colon and formation of a reservoir from ileum, is the surgery of choice for ulcerative colitis and familial adenomatous polyposis. Yet, 10 to 35% of patients develop pouchitis, an inflammation of the pouch mucosa. Microbial imbalances are observed in pouchitis and inulin has been suggested as a prebiotic treatment. Our objectives were to determine the effect of inulin supplementation on quality of life (QOL), and its practicality and safety as a treatment in IPAA patients.<p> Methods: Adults with IPAA (n= 8) consented to a blinded, placebo-controlled trial of inulin supplementation. Baseline symptoms were measured for 1 month prior to supplementation, followed by a blinded low-dose (5 g of inulin) or placebo (maltodextrin) for 2 weeks and a higher-dose (10 g) for 5.5 months. Participants recorded any symptoms that they experienced in a diary and QOL was assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) at the beginning and end of the study.<p> Results: Two participants in the same group developed significant side effects on the 10 g supplementation; abdominal discomfort, severe gas, and small amounts of blood with defecation were reported. Unblinding determined that these participants were taking the active treatment (inulin); therefore, the study was stopped early. No differences were observed in SIBDQ scores.<p> Implications & Conclusions: In this pilot study, inulin appeared to be ineffective in improving QOL and may have contributed to unpleasant side effects. Future research should explore synbiotic therapy in IPAA, by combining prebiotics and probiotics for optimal results.

Objectives: Ileal pouch anal anastomosis (IPAA), the removal of the colon and formation of a reservoir from ileum, is the surgery of choice for ulcerative colitis and familial adenomatous polyposis. Yet, 10 to 35% of patients develop pouchitis, an inflammation of the pouch mucosa. Microbial imbalances are observed in pouchitis and inulin has been suggested as a prebiotic treatment. Our objectives were to determine the effect of inulin supplementation on quality of life (QOL), and its practicality and safety as a treatment in IPAA patients.<p> Methods: Adults with IPAA (n= 8) consented to a blinded, placebo-controlled trial of inulin supplementation. Baseline symptoms were measured for 1 month prior to supplementation, followed by a blinded low-dose (5 g of inulin) or placebo (maltodextrin) for 2 weeks and a higher-dose (10 g) for 5.5 months. Participants recorded any symptoms that they experienced in a diary and QOL was assessed using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ) at the beginning and end of the study.<p> Results: Two participants in the same group developed significant side effects on the 10 g supplementation; abdominal discomfort, severe gas, and small amounts of blood with defecation were reported. Unblinding determined that these participants were taking the active treatment (inulin); therefore, the study was stopped early. No differences were observed in SIBDQ scores.<p> Implications & Conclusions: In this pilot study, inulin appeared to be ineffective in improving QOL and may have contributed to unpleasant side effects. Future research should explore synbiotic therapy in IPAA, by combining prebiotics and probiotics for optimal results.

INTRODUÇÃO: A bolsite tem sido descrita como a complicação mais comum após a realização de bolsa ileal por retocolite ulcerativa. A etiologia da bolsite não está clara, mas sua resolução ocasional com metronidazol e/ou ciprofloxacina sugere que a estase fecal e a superproliferação bacteriana possam estar envolvidas na sua patogênese. Poucos estudos analisaram culturas microbianas de amostras teciduais. Além disso, várias alterações na morfologia da mucosa são vistas após a construção das bolsas ileais, como inflamação aguda e crônica com atrofia vilosa, hiperplasia de criptas, metaplasia colônica e displasias. OBJETIVO: O objetivo deste estudo é caracterizar a microflora das bolsas ileais de pacientes operados por RCU com e sem bolsites, além de caracterizar as alterações histopatológicas mais freqüentes nas bolsas ileais e correlacioná-las com possíveis fatores de risco para o desenvolvimento de bolsites. MÉTODOS: Quarenta e um pacientes foram envolvidos no estudo, divididos em três grupos: o grupo sem bolsite (NB) não apresentava inflamação da bolsa ileal ao momento da avaliação (n=20; 12 mulheres; média de idade, 47.5 anos); o grupo BNA apresentava bolsite e incluía pacientes sem uso de antibióticos (n=14; 10 mulheres; média de idade, 47 anos) e o grupo BA incluía pacientes com bolsite fazendo uso de antibióticos (n= 7; 4 mulheres; média de idade, 41 anos). Foi realizada avaliação endoscópica da bolsa ileal com coleta de fezes e amostras teciduais para análise microbiológica e histopatológica. RESULTADOS: Houve tendência a concentrações aumentadas de Bacteroides sp em pacientes com bolsites (p=0,072). No entanto, concentrações significativamente mais elevadas foram observadas no grupo BA (p=0,018) comparativamente ao grupo NB. A presença de anaeróbios estritos na flora associada à mucosa aumentou o risco para desenvolvimento de bolsites (p=0,048). Foram observadas concentrações significativamente elevadas de Propionibacterium sp em pacientes com bolsites (p=0,009) e de Candida sp (p=0,043) e Fusobacterium sp (p=0,045) no grupo BA comparativamente ao grupo NB. A metaplasia colônica foi encontrada em 15 (36,6%) dos 41 pacientes: 5 (25%) do grupo NB, 8 (57,1%) do grupo BNA e 2 (28,6%) do grupo BA. No entanto, nenhuma correlação foi estabelecida entre sua presença e a ocorrência de bolsites (p=0,17). O grau de atrofia mucosa da bolsa ileal correlacionou-se com o tempo de seguimento pós-operatório (p=0,055). CONCLUSÕES: Concentrações elevadas de Bacteroides sp na flora associada à mucosa parecem aumentar o risco de desenvolvimento de bolsites; ao mesmo tempo, há um aumento na probabilidade de sua ocorrência à medida em que aumenta a concentração de anaeróbios na bolsa ileal; O grau de atrofia da mucosa, a presença de metaplasia colônica, o grau de inflamação aguda ou crônica não parecem constituir fatores de risco para o desenvolvimento de bolsites; quanto maior o tempo de seguimento pós-operatório, maior o grau de atrofia da mucosa / INTRODUCTION: Pouchitis has been described as the most common complication after ileal pouch-anal anastomosis for ulcerative colitis. The etiology of pouchitis is not clear, but its occasional resolution with metronidazole and/or ciprofloxacin suggests that fecal stasis and bacterial overgrowth may be involved in the disease process. Few studies have analyzed microbial cultures from tissue biopsy samples. Furthermore, many changes in mucosal morphology are seen after ileal pouch construction, like acute and chronic inflammation with villus atrophy, crypt hyperplasia, colonic metaplasia and dysplasia. AIM: The aim of this study is to characterize microflora of ileal pouches in patients with and without pouchitis and evaluate the most frequent histopatological changes in ileal pouches and correlate them with possible risk factors for the development of pouchitis. METHODS: Fortyone patients were enrolled in the study, divided into three groups: the no-pouchitis group (NB) had no pouchitis at the time of evaluation (n = 20; 14 females; mean age, 47.5 years), the pouchitis group (BNA) had pouchitis but included patients not taking any antibiotics (n = 14; 10 females; mean age, 47 years), and the pouchitis+antibiotics group (BA) included patients who had pouchitis and who were taking some type of antibiotics (n = 7; 4 males; mean age, 41 years). Ileal pouch endoscopy was performed, and fecal and tissue biopsy samples were collected for microbiological and histopathological analysis. RESULTS: There was a trend toward higher tissue biopsy concentrations of Bacteroides sp in patients with pouchitis (p=0,072). However, significantly higher concentrations were observed in group BA (p=0,018) comparatively to group NB. The presence of strict anaerobes in tissue-associated flora increased the risk of development of pouchitis (p=0,048). There were significantly higher fecal concentrations of Propionibacterium sp in patients with pouchitis (p=0,009), and of Candida sp (p=0,043) and Fusobacterium sp (p=0,045) in group BA in comparison to group NB. Colonic metaplasia was found in 15 (36,6%) of 41 patients: 5 (25%) of group NB, 8 (57,1%) of group BNA and 2 (28,6%) of group BA. However, no correlation was established between its presence with pouchitis (p=0,17). Atrophy degree of ileal pouch mucosa correlated well with time of postoperative follow-up (p=0,055). CONCLUSIONS: A higher risk of developing pouchitis seems to be associated to higher concentrations of Bacteroides sp, as well as an increased concentration of anaerobic bacteria in the ileal pouch. The degree of mucosal atrophy, the presence of colonic metaplasia and the degree of acute or chronic inflammation does not seem to constitute risk factors for the development of pouchitis; the longer the time of postoperative follow-up, the greater the degree of mucosal atrophy

INTRODUÇÃO: A bolsite tem sido descrita como a complicação mais comum após a realização de bolsa ileal por retocolite ulcerativa. A etiologia da bolsite não está clara, mas sua resolução ocasional com metronidazol e/ou ciprofloxacina sugere que a estase fecal e a superproliferação bacteriana possam estar envolvidas na sua patogênese. Poucos estudos analisaram culturas microbianas de amostras teciduais. Além disso, várias alterações na morfologia da mucosa são vistas após a construção das bolsas ileais, como inflamação aguda e crônica com atrofia vilosa, hiperplasia de criptas, metaplasia colônica e displasias. OBJETIVO: O objetivo deste estudo é caracterizar a microflora das bolsas ileais de pacientes operados por RCU com e sem bolsites, além de caracterizar as alterações histopatológicas mais freqüentes nas bolsas ileais e correlacioná-las com possíveis fatores de risco para o desenvolvimento de bolsites. MÉTODOS: Quarenta e um pacientes foram envolvidos no estudo, divididos em três grupos: o grupo sem bolsite (NB) não apresentava inflamação da bolsa ileal ao momento da avaliação (n=20; 12 mulheres; média de idade, 47.5 anos); o grupo BNA apresentava bolsite e incluía pacientes sem uso de antibióticos (n=14; 10 mulheres; média de idade, 47 anos) e o grupo BA incluía pacientes com bolsite fazendo uso de antibióticos (n= 7; 4 mulheres; média de idade, 41 anos). Foi realizada avaliação endoscópica da bolsa ileal com coleta de fezes e amostras teciduais para análise microbiológica e histopatológica. RESULTADOS: Houve tendência a concentrações aumentadas de Bacteroides sp em pacientes com bolsites (p=0,072). No entanto, concentrações significativamente mais elevadas foram observadas no grupo BA (p=0,018) comparativamente ao grupo NB. A presença de anaeróbios estritos na flora associada à mucosa aumentou o risco para desenvolvimento de bolsites (p=0,048). Foram observadas concentrações significativamente elevadas de Propionibacterium sp em pacientes com bolsites (p=0,009) e de Candida sp (p=0,043) e Fusobacterium sp (p=0,045) no grupo BA comparativamente ao grupo NB. A metaplasia colônica foi encontrada em 15 (36,6%) dos 41 pacientes: 5 (25%) do grupo NB, 8 (57,1%) do grupo BNA e 2 (28,6%) do grupo BA. No entanto, nenhuma correlação foi estabelecida entre sua presença e a ocorrência de bolsites (p=0,17). O grau de atrofia mucosa da bolsa ileal correlacionou-se com o tempo de seguimento pós-operatório (p=0,055). CONCLUSÕES: Concentrações elevadas de Bacteroides sp na flora associada à mucosa parecem aumentar o risco de desenvolvimento de bolsites; ao mesmo tempo, há um aumento na probabilidade de sua ocorrência à medida em que aumenta a concentração de anaeróbios na bolsa ileal; O grau de atrofia da mucosa, a presença de metaplasia colônica, o grau de inflamação aguda ou crônica não parecem constituir fatores de risco para o desenvolvimento de bolsites; quanto maior o tempo de seguimento pós-operatório, maior o grau de atrofia da mucosa / INTRODUCTION: Pouchitis has been described as the most common complication after ileal pouch-anal anastomosis for ulcerative colitis. The etiology of pouchitis is not clear, but its occasional resolution with metronidazole and/or ciprofloxacin suggests that fecal stasis and bacterial overgrowth may be involved in the disease process. Few studies have analyzed microbial cultures from tissue biopsy samples. Furthermore, many changes in mucosal morphology are seen after ileal pouch construction, like acute and chronic inflammation with villus atrophy, crypt hyperplasia, colonic metaplasia and dysplasia. AIM: The aim of this study is to characterize microflora of ileal pouches in patients with and without pouchitis and evaluate the most frequent histopatological changes in ileal pouches and correlate them with possible risk factors for the development of pouchitis. METHODS: Fortyone patients were enrolled in the study, divided into three groups: the no-pouchitis group (NB) had no pouchitis at the time of evaluation (n = 20; 14 females; mean age, 47.5 years), the pouchitis group (BNA) had pouchitis but included patients not taking any antibiotics (n = 14; 10 females; mean age, 47 years), and the pouchitis+antibiotics group (BA) included patients who had pouchitis and who were taking some type of antibiotics (n = 7; 4 males; mean age, 41 years). Ileal pouch endoscopy was performed, and fecal and tissue biopsy samples were collected for microbiological and histopathological analysis. RESULTS: There was a trend toward higher tissue biopsy concentrations of Bacteroides sp in patients with pouchitis (p=0,072). However, significantly higher concentrations were observed in group BA (p=0,018) comparatively to group NB. The presence of strict anaerobes in tissue-associated flora increased the risk of development of pouchitis (p=0,048). There were significantly higher fecal concentrations of Propionibacterium sp in patients with pouchitis (p=0,009), and of Candida sp (p=0,043) and Fusobacterium sp (p=0,045) in group BA in comparison to group NB. Colonic metaplasia was found in 15 (36,6%) of 41 patients: 5 (25%) of group NB, 8 (57,1%) of group BNA and 2 (28,6%) of group BA. However, no correlation was established between its presence with pouchitis (p=0,17). Atrophy degree of ileal pouch mucosa correlated well with time of postoperative follow-up (p=0,055). CONCLUSIONS: A higher risk of developing pouchitis seems to be associated to higher concentrations of Bacteroides sp, as well as an increased concentration of anaerobic bacteria in the ileal pouch. The degree of mucosal atrophy, the presence of colonic metaplasia and the degree of acute or chronic inflammation does not seem to constitute risk factors for the development of pouchitis; the longer the time of postoperative follow-up, the greater the degree of mucosal atrophy

In severe cases of ulcerative colitis (UC) unresponsive to current treatment options, patients require a complete proctocolectomy, or surgical removal of the colon. Ileal pouch anal anastomosis (IPAA) has become the preferred surgical technique for patients who require surgery, as this method restores rectal function. This procedure is also used to treat colorectal cancers such as adenocarcinoma and familial adenomatous polyposis (FAP). The surgery involves an abdominal colectomy with the construction of an ileal pouch created from folded tissue recovered from the ileal portion of the small intestine. Up to 50% of patients who require IPAA surgery experience an episode of pouchitis, a non-specific inflammation of the constructed ileal pouch with unknown etiology. Several hypotheses have been proposed regarding the pathogenesis of pouchitis. Current theories include bacterial overgrowth due to fecal stasis, microbial imbalance (dysbiosis), immune alteration, genetic susceptibility, metaplasia, ischemic complications of surgery, a recurrence of UC, or even a novel form of inflammatory bowel disease. The efficacy of antibiotics and probiotics in treating pouchitis and maintaining remission underscores the importance of gut microbiota in the development of this condition. In the study, we aimed to characterize the intestinal bacterial communities that inhabit IPAA pouches of both UC and FAP patients, in an effort to investigate the hypothesis that bacterial dysbiosis is involved in the pathogenesis of pouchitis. Mucosal biopsy and stool samples were analyzed from patients with UC and pouchitis (UCP), healthy UC controls (HUC) and healthy pouches with a background of FAP (FAP). Samples were examined through analysis of terminal restriction fragment length polymorphisms (TRF) and DNA sequencing. The data presented here demonstrate that a microbial imbalance exists in pouchitis, as bacterial communities in pouchitis differ significantly from healthy UC pouches and pouches constructed for FAP. Both methods identified potential groups of organisms that may play a role in the development of pouchitis, including decreases in protective Lactobacillus and Bacteroides and increases in mucin-degrading Clostridium and Akkermansia. A better understanding of the factors driving the pathogenesis of pouchitis will not only benefit patients with this disease, but also lead to a better understanding of the complex relationship that exists between the human host and the diverse community of organisms that inhabit the gastrointestinal tract.