RESUMO
Despite the decreased rates in inflammatory bowel disease (IBD) colectomies due to high advances in therapeutic options, a significant number of patients still require proctocolectomy with ileal pouch-anal anastomosis (IPPA) for ulcerative colitis (UC). Pouchitis is the most common complication in these patients, where up to 60% develop one episode of pouchitis in the first two years after UC surgery with IPAA with severe negative impact on their quality of life. Acute cases usually respond well to antibiotics, but 15% of patients will still develop a refractory disease that requires the initiation of advanced immunosuppressive therapies. For chronic idiopathic pouchitis, current recommendations suggest using the same therapeutic options as for IBD in terms of biologics and small molecules. However, the available data are limited regarding the effectiveness of different biologics or small molecules for the management of this condition, and all evidences arise from case series and small studies. Vedolizumab is the only biologic agent that has received approval for the treatment of adult patients with moderately to severely active chronic refractory pouchitis. Despite the fact that IBD treatment is rapidly evolving with the development of novel molecules, the presence of pouchitis represents an exclusion criterion in these trials. Recommendations for the approach of these conditions range from low to very low certainty of evidence, resulting from small randomized controlled trials and case series studies. The current review focuses on the therapeutic management of idiopathic pouchitis.
Assuntos
Doenças Inflamatórias Intestinais , Pouchite , Proctocolectomia Restauradora , Humanos , Pouchite/tratamento farmacológico , Pouchite/etiologia , Pouchite/diagnóstico , Doenças Inflamatórias Intestinais/cirurgia , Doenças Inflamatórias Intestinais/complicações , Doença Crônica , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Doença Aguda , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/cirurgia , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
Ulcerative colitis (UC) is a chronic immune-mediated disease that affects the entire colon and rectum with a relapsing and remitting course, causing lifelong morbidity. When medical treatment is ineffective, especially in cases of massive gastrointestinal bleeding, perforation, toxic megacolon, or carcinogenesis, surgery becomes the last line of defense to cure UC. Total colorectal resection and ileal pouch-anal anastomosis (IPAA) offer the best chance for long-term treatment. Pouchitis is the most common and troublesome postoperative complication. In this investigation, microsurgery is employed to create an ileal pouch model in experimental rats via IPAA surgery. Subsequently, a sustained rat model of pouchitis is established by inducing inflammation of the ileal pouch with dextran sulfate sodium (DSS). The successful establishment of rat pouchitis is validated through analysis of postoperative general status, weight, food and water intake, fecal data, as well as pouch tissue pathology, immunohistochemistry, and inflammatory factor analysis. This experimental animal model of pouchitis provides a foundation for studying the pathogenesis and treatment of the condition.
Assuntos
Bolsas Cólicas , Sulfato de Dextrana , Modelos Animais de Doenças , Pouchite , Proctocolectomia Restauradora , Animais , Pouchite/etiologia , Ratos , Proctocolectomia Restauradora/métodos , Proctocolectomia Restauradora/efeitos adversos , Bolsas Cólicas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Masculino , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/efeitos adversosRESUMO
Pouchitis is an acute or chronic inflammatory disease of the ileal reservoir. It is common after restorative proctocolectomy with ileal pouch-anal anastomosis, and treatment of chronic antibiotic-refractory pouchitis has proven challenging. Most cases of acute pouchitis evolve into chronic pouchitis. The aetiology of acute pouchitis is likely to be partly related to the gut microbiota, whereas the pathophysiology of chronic pouchitis involves abnormal interactions between genetic disposition, faecal stasis, the gut microbiota, dysregulated host immunity, surgical techniques, ischaemia and mesentery-related factors. Pouchoscopy with biopsy is the most valuable modality for diagnosis, disease monitoring, assessment of treatment response, dysplasia surveillance and delivery of endoscopic therapy. Triggering or risk factors, such as Clostridioides difficile infection and use of non-steroidal anti-inflammatory drugs, should be modified or eradicated. In terms of treatment, acute pouchitis usually responds to oral antibiotics, whereas chronic antibiotic-refractory pouchitis often requires induction and maintenance therapy with integrin, interleukin or tumour necrosis factor inhibitors. Chronic pouchitis with ischaemic features, fistulae or abscesses can be treated with hyperbaric oxygen therapy.
Assuntos
Pouchite , Proctocolectomia Restauradora , Pouchite/terapia , Pouchite/etiologia , Pouchite/diagnóstico , Pouchite/fisiopatologia , Humanos , Proctocolectomia Restauradora/efeitos adversos , Microbioma Gastrointestinal , Doença Crônica , Antibacterianos/uso terapêutico , Fatores de Risco , Doença AgudaRESUMO
Pouchitis is the most common long-term complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis. Although several agents, including probiotics, steroids, and immunomodulators, have been used, the treatment of pouchitis remains challenging. Owing to the proven efficacy of biological therapy in inflammatory bowel disease, there is now growing evidence suggesting the potential benefits of biological therapy in refractory pouchitis. Here, we report the case of a 64-year-old woman with pouchitis due to ulcerative colitis who was successfully treated with ustekinumab (UST). The patient developed ulcerative pancolitis at the age of 35. Total colectomy and IPAA with J-pouch anastomosis were performed when the patient was 47 years old. Ileotomy closure was performed 6 months later. Postoperatively, the patient developed steroid-dependent pouchitis. Three years later, she developed steroid-induced diabetes. The patient has been taking 3mg of steroid for 20 years;therefore, her lifetime total steroid dose was 21g. The patient had over 20 episodes of bloody diarrhea a day. The last pouchoscopy in 20XX-9 revealed inflammatory stenosis with deep ulcerations of the afferent limb just before the ileoanal pouch junction. In July 20XX, when we took over her treatment, the policy of treatment was to withdraw her from steroids. Pouchoscopy revealed a widened but still tight afferent limb through which the scope could easily pass, and the ileoanal pouch still showed erosive ileitis without ulcers. Thiopurine administration and steroid tapering were initiated. Steroid tapering increased the erythrocyte sedimentation rate (ESR). As ESR increased, her arthritis exacerbated. Six months after the end of steroid administration, the patient consented to UST treatment. On April 20XX+1, the patient received her first 260-mg UST infusion. At this point, she experienced 14-15 episodes of muddy bloody stools. She had no abdominal pain;however, she experienced shoulder pain. Gradually, UST affected both pouchitis and arthritis. UST treatment was continued at 90mg subcutaneously every 12 weeks without abdominal pain recurrence. Eight months after the first UST infusion, nonsteroidal anti-inflammatory drugs were no longer necessary for shoulder pain. Follow-up pouchoscopy performed 14 months after UST optimization revealed a normal afferent limb without ulcerations in either segment. Pouchitis remission was maintained for over 2 years.
Assuntos
Artrite , Colite Ulcerativa , Bolsas Cólicas , Pouchite , Proctocolectomia Restauradora , Feminino , Humanos , Pessoa de Meia-Idade , Artrite/complicações , Artrite/cirurgia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Colite Ulcerativa/complicações , Pouchite/tratamento farmacológico , Pouchite/etiologia , Proctocolectomia Restauradora/efeitos adversos , Dor de Ombro/complicações , Dor de Ombro/cirurgia , Esteroides/efeitos adversos , Ustekinumab/uso terapêuticoRESUMO
Pouchitis is defined as inflammation of the ileal pouch created during a restorative proctocolectomy with ileal pouch-anal anastomosis. Although the incidence of this inflammatory condition is high, the exact etiology often remains unclear and the management challenging. In this review, we summarize the clinical presentation, pathogenesis, diagnosis, and management of this common complication.
Assuntos
Pouchite , Proctocolectomia Restauradora , Pouchite/diagnóstico , Pouchite/etiologia , Pouchite/terapia , Humanos , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Bolsas Cólicas/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Colite Ulcerativa/cirurgia , Colite Ulcerativa/diagnósticoRESUMO
BACKGROUND & AIMS: Pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC); however, clinical and environmental risk factors for pouchitis remain poorly understood. We explored the relationship between specific clinical factors and the incidence of pouchitis. METHODS: We established a population-based cohort of all adult persons in Denmark undergoing proctocolectomy with IPAA for UC from 1996-2020. We used Cox proportional hazard modeling to assess the impact of antibiotic, nonsteroidal anti-inflammatory drug (NSAID) exposure, and appendectomy on diagnosis of acute pouchitis in the first 2 years after IPAA surgery. RESULTS: Among 1616 eligible patients, 46% developed pouchitis in the first 2 years after IPAA. Antibiotic exposure in the 12 months before IPAA was associated with an increased risk of pouchitis (adjusted hazard ratio [aHR], 1.41; 95% confidence interval [CI], 1.22-1.64) after adjusting for anti-tumor necrosis factor alpha use and sex. Compared with persons without any antibiotic prescriptions in the 12 months before IPAA, the risk of pouchitis was increased in those with 1 or 2 courses of antibiotics in that period (aHR, 1.30; 95% CI, 1.11-1.52) and 3 or more courses (aHR, 1.77; 95% CI, 1.41-2.21). NSAID exposure in the 12 months before IPAA and appendectomy were not associated with risk of acute pouchitis (P = .201 and P = .865, respectively). CONCLUSIONS: In this population-based cohort study, we demonstrated that antibiotic exposure in the 12 months before IPAA is associated with an increased risk of acute pouchitis. Future prospective studies may isolate specific microbial changes in at-risk patients to drive earlier interventions.
Assuntos
Antibacterianos , Colite Ulcerativa , Pouchite , Proctocolectomia Restauradora , Humanos , Pouchite/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Proctocolectomia Restauradora/efeitos adversos , Colite Ulcerativa/cirurgia , Dinamarca/epidemiologia , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Fatores de Risco , Incidência , Estudos de Coortes , Adulto Jovem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Apendicectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Modelos de Riscos ProporcionaisAssuntos
Ciprofloxacina , Metronidazol , Pouchite , Humanos , Pouchite/tratamento farmacológico , Metronidazol/uso terapêutico , Ciprofloxacina/uso terapêutico , Pontuação de Propensão , Anti-Infecciosos/uso terapêutico , Antibacterianos/uso terapêutico , Resultado do Tratamento , Proctocolectomia RestauradoraRESUMO
BACKGROUND: Radiographic imaging of the abdomen and pelvis plays an important role in the diagnosis and management of ileal pouch disorders with modalities including CT, MRI, contrasted pouchography, and defecography. OBJECTIVES: To perform a systematic review of the literature and describe applications of cross-sectional imaging, pouchography, defecography, and ultrasonography. DATA SOURCES: PubMed, Google Scholar, and Cochrane database. STUDY SELECTION: Relevant articles on endoscopy in ileal pouches published between January 2003 and June 2023 in English were included on the basis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. INTERVENTION: Main abdominal and pelvic imaging modalities and their applications in the diagnosis of ileal pouch disorders were included. MAIN OUTCOME MEASURES: Accuracy in characterization of ileal pouch disorders. RESULTS: CT is the test of choice for the evaluation of acute anastomotic leaks, perforation, and abscess(es). MRI of the pelvis is suitable for the assessment of chronic anastomotic leaks and their associated fistulas and sinus tracts, as well as for the penetrating phenotype of Crohn's disease of the pouch. CT enterography and magnetic resonance enterography are useful in assessing intraluminal, intramural, and extraluminal disease processes of the pouch and prepouch ileum. Water-soluble contrast pouchography is particularly useful for evaluating acute or chronic anastomotic leaks and outlines the shape and configuration of the pouch. Defecography is the key modality to evaluate structural and functional pouch inlet and outlet obstructions. Ultrasonography can be performed to assess the pouch in experienced IBD centers. LIMITATIONS: This is a qualitative, not quantitative, review of mainly case series and case reports. CONCLUSIONS: Abdominopelvic imaging, along with clinical and endoscopic evaluation, is imperative for accurately assessing structural, inflammatory, functional, and neoplastic disorders. See video from symposium .
Assuntos
Bolsas Cólicas , Imageamento por Ressonância Magnética , Humanos , Bolsas Cólicas/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Defecografia/métodos , Ultrassonografia/métodos , Tomografia Computadorizada por Raios X/métodos , Pouchite/diagnóstico por imagem , Pouchite/diagnóstico , Pouchite/etiologia , Fístula Anastomótica/diagnóstico por imagem , Fístula Anastomótica/etiologia , Fístula Anastomótica/diagnóstico , Complicações Pós-Operatórias/diagnóstico por imagem , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/cirurgiaAssuntos
Bolsas Cólicas , Pouchite , Proctocolectomia Restauradora , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Pouchite/etiologia , Pouchite/prevenção & controle , Bolsas Cólicas/efeitos adversos , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Metanálise como Assunto , Anastomose Cirúrgica/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Restorative proctocolectomy with IPAA improves the quality of life in patients with ulcerative colitis by the removal of diseased large bowel and preservation of the natural route of defecation. Although the surgery may improve preexisting extraintestinal manifestations in the joints, skin, and eyes, extraintestinal manifestations, particularly primary sclerosing cholangitis, can persist after colectomy. OBJECTIVES: A systematic review of diagnosis and treatment of liver, joint, skin, and eye manifestations in patients with restorative proctocolectomy and IPAA for ulcerative colitis. DATA SOURCES: PubMed, Google Scholar, and Cochrane database. STUDY SELECTION: Relevant articles on primary sclerosing cholangitis and extraintestinal manifestations in ileal pouches published between January 2001 and July 2023 in English were included on the basis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. INTERVENTION: Diagnosis and treatment of primary sclerosing cholangitis and extraintestinal manifestations in patients with restorative proctocolectomy and IPAA were included. MAIN OUTCOME MEASURES: Association between primary sclerosing cholangitis, extraintestinal manifestations, and inflammatory disorders of the pouch and their management. RESULTS: Primary sclerosing cholangitis and extraintestinal manifestations are associated with pouchitis, particularly chronic pouchitis. Primary sclerosing cholangitis is associated with chronic pouchitis, enteritis, and possible pouch neoplasia. However, the disease severity and course of primary sclerosing cholangitis and pouchitis do not appear to be parallel. Despite the fact that oral vancomycin or budesonide have been used to treat primary sclerosing cholangitis-associated pouchitis, their impact on the disease course of primary sclerosing cholangitis is not known. Biological therapy for chronic inflammatory disorders of the pouch may also be beneficial for the concurrent extraintestinal manifestations of the joints, skin, and eyes. However, studies on the correlation between the severity of inflammatory pouch disorders and the severity of joint, skin, and eye diseases are lacking. LIMITATIONS: This is a qualitative, not quantitative, review of case series and case reports. CONCLUSIONS: Primary sclerosing cholangitis and extraintestinal manifestations of the joints, skin, and eyes appear to be associated with inflammatory disorders of the ileal pouch. Although the treatment of pouchitis does not seem to affect the disease course of primary sclerosing cholangitis, effective therapy of inflammatory pouch disorders, particularly with biologics, likely benefits concurrent disorders of the joints, skin, and eyes. See video from the symposium .
Assuntos
Colangite Esclerosante , Colite Ulcerativa , Pouchite , Proctocolectomia Restauradora , Colangite Esclerosante/complicações , Colangite Esclerosante/cirurgia , Humanos , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Pouchite/etiologia , Pouchite/terapia , Pouchite/diagnóstico , Colite Ulcerativa/complicações , Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversos , Oftalmopatias/etiologia , Dermatopatias/etiologiaRESUMO
BACKGROUND: IPAA is often required for patients with ulcerative colitis or familial adenomatous polyposis after colectomy. This procedure reduces but does not completely eliminate the risk of neoplasia. OBJECTIVE: This study focuses on the histopathology of neoplasia in the ileal pouch, rectal cuff, and anal transition zone. DATA SOURCES: We performed a MEDLINE search for English-language studies published between 1981 and 2022 using the PubMed search engine. The terms "ileal pouch-anal anastomosis," "pouchitis," "pouch dysplasia," "pouch lymphoma," "pouch squamous cell carcinoma," "pouch adenocarcinoma," "pouch neoplasia," "dysplasia of rectal cuff," and "colitis-associated dysplasia" were used. STUDY SELECTION: Human studies of neoplasia occurring in the pouch and para-pouch were selected, and the full text was reviewed. Comparisons were made within and across studies, with key concepts selected for inclusion in this article. CONCLUSIONS: Neoplasia in the pouch is a rare complication in patients with IPAA. Annual endoscopic surveillance is recommended for familial adenomatous polyposis patients and ulcerative colitis patients with a history of prior dysplasia or carcinoma. In familial adenomatous polyposis, dysplastic polyps of the pouch are visible and readily amenable to endoscopic removal; however, glandular dysplasia in the setting of ulcerative colitis may be invisible on endoscopy. Therefore, random biopsies and adequate tissue sampling of the pouch and rectal cuff are recommended in this setting. The histological diagnosis of IBD-associated dysplasia can be challenging and should be confirmed by at least 1 expert GI pathologist. See video from the symposium.
Assuntos
Polipose Adenomatosa do Colo , Bolsas Cólicas , Proctocolectomia Restauradora , Humanos , Polipose Adenomatosa do Colo/patologia , Polipose Adenomatosa do Colo/cirurgia , Polipose Adenomatosa do Colo/complicações , Bolsas Cólicas/efeitos adversos , Bolsas Cólicas/patologia , Proctocolectomia Restauradora/efeitos adversos , Colite Ulcerativa/patologia , Colite Ulcerativa/complicações , Colite Ulcerativa/cirurgia , Pouchite/patologia , Pouchite/etiologia , Pouchite/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/etiologia , Adenocarcinoma/cirurgia , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/complicaçõesRESUMO
BACKGROUND: Chronic antibiotic refractory pouchitis after restorative proctocolectomy with IPAA, characterized by at least 4 weeks of pouchitis symptoms that have not responded to standard antibiotic therapy, presents a therapeutic challenge for patients and health care providers. OBJECTIVE: The aim of this narrative review was to summarize the current evidence regarding the management of chronic antibiotic refractory pouchitis. DATA SOURCES: Studies were identified through a search of the PubMed database from the National Library of Medicine. STUDY SELECTION: We included case series, cohort studies, randomized controlled trials, and systematic reviews with meta-analyses that addressed chronic antibiotic refractory pouchitis management, with prioritization of data published within the past 3 to 5 years. INTERVENTION: Studies examining pharmacologic and select nonpharmacologic interventions were included. MAIN OUTCOME MEASURE: Outcomes measures included clinical, endoscopic, and histologic end points. RESULTS: Mesalamine has demonstrated efficacy in symptom improvement but no improvement in quality of life. Budesonide has demonstrated high rates of clinical remission that have mostly been sustained in a small number of patients. Anti-tumor necrosis factor therapies have demonstrated efficacy in reaching clinical and even endoscopic end points, although rates of treatment discontinuation were not insignificant. Limited evidence is encouraging for the use of ustekinumab in achieving clinical response. Data for vedolizumab are favorable across clinical, endoscopic, and histologic end points, including one of the only randomized, placebo-controlled trials. Nonmedication therapies, including hyperbaric oxygen therapy and fecal microbiota transplant, have undergone limited evaluation, and concerns about the ultimate accessibility of these therapies remain. LIMITATIONS: Overall, studies assessing therapeutic options for chronic antibiotic refractory pouchitis are mostly limited to case series and retrospective studies with small sample sizes. CONCLUSIONS: Biologic therapies have demonstrated efficacy in the management of chronic antibiotic refractory pouchitis and offer a steroid-sparing option for refractory disease. Nonpharmacologic therapies, including hyperbaric oxygen and fecal microbiota transplant, require further exploration. See video from symposium .
Assuntos
Antibacterianos , Pouchite , Proctocolectomia Restauradora , Pouchite/tratamento farmacológico , Pouchite/terapia , Humanos , Antibacterianos/uso terapêutico , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Doença Crônica , Transplante de Microbiota Fecal/métodos , Medicina Baseada em EvidênciasRESUMO
BACKGROUND: Restorative proctocolectomy and IPAA have become the surgical procedure of choice in pediatric patients with medically refractory colitis or familial adenomatous polyposis. OBJECTIVE: This systematic review aims to assess the diagnosis and treatment of pouch disorders in pediatric patients who undergo IPAA. DATA SOURCES: A literature search was performed using MEDLINE, Google Scholar, and Embase for all publications describing outcomes of pediatric IPAA. STUDY SELECTION: Studies between January 1, 2000, and September 7, 2022, published in English were included. Studies were excluded on the basis of title, abstract, and full-length review. INTERVENTIONS: IPAA. MAIN OUTCOME MEASURES: Pouch disorders described include anastomotic leaks, pouch strictures, pouch failure, pouchitis, cuffitis, and de novo Crohn's disease of the pouch. RESULTS: Thirty-three studies were included in this review, all of which were retrospective in nature. The outcomes of 2643 pediatric patients were included in the 33 studies. LIMITATIONS: Management is largely informed by clinical practices in adult patients with scant data on treatment efficacy in children. CONCLUSIONS: The reported incidence of disorders of the pouch in children varies widely and is likely attributable to differences in definitions and follow-up periods across studies. Pouchitis was the most frequently described outcome. The overall rate of pouch failure in children is relatively low, with de novo Crohn's disease of the pouch being the most significant risk factor. Multicenter prospective studies are needed in the pediatric population to accurately identify risk factors, standardize the assessment of pouch complications, and determine effective treatment strategies. See video from the symposium .
Assuntos
Pouchite , Proctocolectomia Restauradora , Humanos , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Criança , Pouchite/diagnóstico , Pouchite/terapia , Pouchite/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Bolsas Cólicas/efeitos adversos , Colite Ulcerativa/cirurgia , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/terapia , Polipose Adenomatosa do Colo/cirurgia , Polipose Adenomatosa do Colo/diagnóstico , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/terapia , Doença de Crohn/diagnóstico , Doença de Crohn/cirurgia , Doença de Crohn/terapia , Doença de Crohn/complicaçõesRESUMO
Bile acids (BAs) are cholesterol-derived molecules that aid in digestion and nutrient absorption, regulate host metabolic processes, and influence physiology of the gut microbiota. Both the host and its microbiome contribute to enzymatic modifications that shape the chemical diversity of BAs in the gut. Several bacterial species have been reported to conjugate standard amino acids to BAs, but it was not known if bacteria conjugate BAs to other amine classes. Here, we show that Bacteroides fragilis strain P207, isolated from a bacterial bloom in the J-pouch of a patient with ulcerative colitis pouchitis, conjugates standard amino acids and the neuroactive amines γ-aminobutyric acid (GABA) and tyramine to deoxycholic acid. We extended this analysis to other human gut isolates and identified species that are competent to conjugate GABA and tyramine to primary and secondary BAs, and further identified diverse BA-GABA and BA-tyramine amides in human stool. A longitudinal metabolomic analysis of J-pouch contents of the patient from whom B. fragilis P207 was isolated revealed highly reduced levels of secondary bile acids and a shifting BA amide profile before, during, and after onset of pouchitis, including temporal changes in several BA-GABA amides. Treatment of pouchitis with ciprofloxacin was associated with a marked reduction of nearly all BA amides in the J-pouch. Our study expands the known repertoire of conjugated bile acids produced by bacteria to include BA conjugates to GABA and tyramine and demonstrates that these molecules are present in the human gut. IMPORTANCE BAs are modified in multiple ways by host enzymes and the microbiota to produce a chemically diverse set of molecules that assist in the digestive process and impact many physiological functions. This study reports the discovery of bacterial species that conjugate the neuroactive amines, GABA and tyramine, to primary and secondary BAs. We further present evidence that BA-GABA and BA-tyramine conjugates are present in the human gut, and document a shifting BA-GABA profile in a human pouchitis patient before, during, and after inflammation and antibiotic treatment. GABA and tyramine are common metabolic products of the gut microbiota and potent neuroactive molecules. GABA- and tyramine-conjugated BAs may influence receptor-mediated regulatory mechanisms of humans and their gut microbes, and absorption of these molecules and their entry into enterohepatic circulation may impact host physiology at distal tissue sites. This study defines new conjugated bile acids in the human gut.
Assuntos
Ácidos e Sais Biliares , Pouchite , Humanos , Aminoácidos , Ácido gama-Aminobutírico , Aminas , Catálise , AmidasRESUMO
BACKGROUND: Clinical, nonspecific pouchitis is common after restorative proctocolectomy for ulcerative colitis, but its cause is unknown. A possible lack of protection for the ileal mucosa in its role as a reservoir for colonic-type bacteria may be the missing piece in defining the causes of pouchitis. OBJECTIVE: The study aimed to review the causes of pouchitis and introduce the hypothesis that inadequate mucus protection in the pouch, combined with a predisposition to abnormal inflammation, is the most common cause of nonspecific pouchitis. DATA SOURCES: Review of PubMed and MEDLINE for articles discussing pouchitis and intestinal mucus. STUDY SELECTION: Studies published from 1960 to 2023. The main search terms were "pouchitis," and "intestinal mucus," whereas Boolean operators were used with multiple other terms to refine the search. Duplicates and case reports were excluded. MAIN OUTCOME MEASURES: Current theories about the cause of pouchitis, descriptions of the role of mucus in the physiology of intestinal protection, and evidence of the effects of lack of mucus on mucosal inflammation. RESULTS: The crossreference of "intestinal mucus" with "pouchitis" produced 9 references, none of which discussed the role of mucus in the development of pouchitis. Crossing "intestinal mucus" with "pouch" resulted in 32 articles, combining "pouchitis" with "barrier function" yielded 37 articles, and "pouchitis" with "permeability" yielded only 8 articles. No article discussed the mucus coat as a barrier to bacterial invasion of the epithelium or mentioned inadequate mucus as a factor in pouchitis. However, an ileal pouch produces a colonic environment in the small bowel, and the ileum lacks the mucus protection needed for this sort of environment. This predisposes pouch mucosa to bacterial invasion and chronic microscopic inflammation that may promote clinical pouchitis in patients prone to an autoimmune response. LIMITATIONS: No prior studies address inadequate mucus protection and the origin of proctitis. There is no objective way of measuring the autoimmune tendency in patients with ulcerative colitis. CONCLUSIONS: Studies of intestinal mucus in the ileal pouch and its association with pouchitis are warranted.
Assuntos
Colite Ulcerativa , Bolsas Cólicas , Pouchite , Proctocolectomia Restauradora , Humanos , Pouchite/etiologia , Pouchite/prevenção & controle , Colite Ulcerativa/cirurgia , Colite Ulcerativa/complicações , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Íleo/cirurgia , Bolsas Cólicas/efeitos adversos , Mucosa Intestinal/cirurgia , Inflamação/complicaçõesRESUMO
BACKGROUND: Structural and inflammatory adverse sequelae are common after restorative proctocolectomy and IPAA. On rare occasions, neoplasia can occur in patients with ileal pouches. Pouchoscopy plays a key role in the diagnosis, differential diagnosis, disease monitoring, assessment of treatment response, surveillance, and delivery of therapy. OBJECTIVE: A systematic review of the literature was performed, and principles and techniques of pouchoscopy were described. DATA SOURCES: PubMed, Google Scholar, and Cochrane databases. STUDY SELECTION: Relevant articles on endoscopy in ileal pouches published between January 2000 and May 2023 were included based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. INTERVENTION: Diagnostic, surveillance, and therapeutic endoscopy in ileal pouch disorders were included. MAIN OUTCOME MEASURES: Accurate characterization of the ileal pouch in healthy or diseased states. RESULTS: The main anatomic structures of a J- or S-pouch are the stoma closure site, prepouch ileum, inlet, tip of the "J," pouch body, anastomosis, cuff, and anal transition zone. Each anatomic location can be prone to the development of structural, inflammatory, or neoplastic disorders. For example, ulcers and strictures are common at the stoma closure site, inlet, and anastomosis. Leaks are commonly detected at the tip of the "J" and anastomosis. Characterization of the anastomotic distribution of inflammation is critical for the differential diagnosis of subtypes of pouchitis and other inflammatory disorders of the pouch. Neoplastic lesions, albeit rare, mainly occur at the cuff, anal transition zone, or anastomosis. LIMITATIONS: This is a qualitative, not quantitative, review of mainly case series. CONCLUSIONS: Most structural, inflammatory, and neoplastic disorders can be reliably diagnosed with a careful pouchoscopy. The endoscopist and other clinicians taking care of pouch patients should be familiar with the anatomy of the ileal pouch and be able to recognize common abnormalities. See video from symposium.
Assuntos
Bolsas Cólicas , Pouchite , Proctocolectomia Restauradora , Humanos , Bolsas Cólicas/efeitos adversos , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Pouchite/etiologia , Pouchite/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Endoscopia Gastrointestinal/métodos , Íleo/cirurgia , Íleo/patologiaRESUMO
Altered microbiota and impaired host immune function have been linked to the pathogenesis of pouchitis. We used 16S rRNA gene sequencing and RNA sequencing data from a previous randomized clinical trial (RCT) on fecal microbiota transplantation (FMT) therapy in 26 chronic pouchitis patients with one-year follow-up. We analyzed changes in both luminal and mucosal microbiota composition, as well as in host mucosal gene expression to gain insights into the host-microbiota interactions possibly underlying clinical outcomes of the patients. Antibiotic type and pattern of use were significant drivers of the luminal microbiota at baseline. Differential gene expression analysis indicated transition from ileal to colonic gene expression in the pouch, and upregulation in inflammation- and immune system-related pathways in the pouch. At 4 weeks, the non-relapsed FMT patients had a lower microbiota dissimilarity to the donor than the non-relapsed placebo patients (p = .02). While two FMT-treated patients showed a shift toward the donor's microbiota during the one-year follow-up, the overall FMT microbiota modulation effect was low. Patient's luminal and mucosal microbiota profiles were unstable in both FMT and placebo groups. Expression of the chemokine receptor CXCR4 was downregulated at 52 weeks compared to the baseline in the non-relapsed patients in both FMT and placebo groups. Microbiota modulation by FMT seems to be low in this patient group. The microbiota composition or alterations did not explain the relapse status of the patients. Some evidence for remission-related host gene expression pattern was found; specifically, CXCR4 expression may have a role in sustained remission.
Assuntos
Colite Ulcerativa , Microbioma Gastrointestinal , Microbiota , Pouchite , Humanos , Transplante de Microbiota Fecal/efeitos adversos , Pouchite/terapia , Pouchite/metabolismo , Colite Ulcerativa/terapia , Expressão Gênica , FezesRESUMO
BACKGROUND: Patients with medically-refractory ulcerative colitis or advanced neoplasia are often offered an ileal-pouch-anal anastomosis to restore bowel continuity. However, up to 50% of patients can suffer from inflammatory conditions of the pouch, some of which require biological therapy to treat. The aim of this study was to determine the efficacy of each biological agent for the treatment of inflammatory conditions of the pouch. MATERIALS AND METHODS: A comprehensive literature search was performed in the major databases from inception through February 11, 2020, for studies assessing the efficacy of biologics in chronic antibiotic-refractory pouchitis (CARP) and Crohn's disease (CD) of the pouch. Both prospective and retrospective studies were included. The primary outcomes of interest were complete and partial responses were defined within each study. χ 2 test was used to compare variables. RESULTS: Thirty-four studies were included in the systematic review and meta-analysis. Sixteen studies (N=247) evaluated the use of infliximab (IFX), showing complete response in 50.7% and partial response in 28.1% for CARP, and complete response in 66.7% and partial response in 20% for CD of the pouch. Seven studies (n=107) assessed the efficacy of adalimumab. For CARP, 33.3% of patients had a complete response, and 38.1% had a partial response, whereas for CD of the pouch, 47.7% experienced a complete response, and 24.6% had a partial response. Three studies (n=78) reported outcomes with the use of ustekinumab, showing 50% complete response and 3.8% partial response for CARP. For the CD of the pouch, 5.8% had a complete response and 78.8% had a partial response. Seven studies (n=151) reported the efficacy of vedolizumab, showing 28.4% complete response and 43.2% partial response in patients with CARP, whereas 63% of patients experienced partial response in CD of the pouch. IFX had higher rates of complete response in CARP compared with adalimumab ( P =0.04) and compared with vedolizumab ( P =0.005), but not compared with ustekinumab ( P =0.95). There were no new safety signals reported in any of the studies. CONCLUSIONS: Biologics are safe and efficacious in the treatment of chronic, refractory inflammatory conditions of the pouch. IFX seems to be more efficacious than adalimumab and vedolizumab for CARP. Further prospective, head-to-head evaluations are needed to compare biological therapies in the treatment of CARP and CD of the pouch.
Assuntos
Anticorpos Monoclonais , Produtos Biológicos , Pouchite , Proctocolectomia Restauradora , Humanos , Adalimumab/uso terapêutico , Produtos Biológicos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Infliximab/uso terapêutico , Resposta Patológica Completa , Pouchite/tratamento farmacológico , Pouchite/cirurgia , Estudos Retrospectivos , Ustekinumab/uso terapêutico , Anticorpos Monoclonais/uso terapêuticoRESUMO
IMPORTANCE: The Gram-negative bacterium Bacteroides fragilis is a common member of the human gut microbiota that colonizes multiple host niches and can influence human physiology through a variety of mechanisms. Identification of genes that enable B. fragilis to grow across a range of host environments has been impeded in part by the relatively limited genetic tractability of this species. We have developed a high-throughput genetic resource for a B. fragilis strain isolated from a UC pouchitis patient. Bile acids limit microbial growth and are altered in abundance in UC pouches, where B. fragilis often blooms. Using this resource, we uncovered pathways and processes that impact B. fragilis fitness in bile and that may contribute to population expansions during bouts of gut inflammation.