RESUMO
PURPOSE: Obesity and its related severe comorbidities are increasing rapidly. The duodenal-jejunal bypass is an endoscopically implanted device (mimicking the Roux-en-Y gastric bypass) developed to support weight reduction and improve type 2 diabetes control. MATERIALS AND METHODS: Retrospective data analysis of consecutive patients undergoing duodenal-jejunal bypass (EndoBarrier®, DJB) implantation between 2013 and 2017 was performed to evaluate safety as well as short- and long-term efficacy. RESULTS: One hundred and twenty-one patients (mean BMI of 43.1 ± 7.2 kg/m2 and weight of 138.2 ± 28.6 kg) underwent DJB implantation. The mean dwelling time was 15.5 months, the mean total body weight loss (%TBWL) after explantation was 10.3% ± 7.9% (14.2 kg, p < 0.0001), and the mean BMI was 39.5 ± 7.3 kg/m2 (p < 0.0001). There was no significant weight gain 24 months after the explantation. Seventy-seven patients had type 2 diabetes mellitus (T2DM) with a mean HbA1c before implantation of 5.6% (n = 52). The mean HbA1c after explantation was 5.1% (p = 0.0001). Significant reductions in transaminase and lipid levels before and after explantation were observed. One complication occurred during implantation and another during explantation. In 16 patients, the device had to be extracted earlier than expected (7 for severe adverse events and 9 for adverse events; 13.2%). CONCLUSION: Despite an evident rate of adverse events, the DJB shows promise as a weight-loss procedure. Our results show that some patients implanted with the device maintained reduced weight even 24 months after explantation, while many improved T2DM control.
Assuntos
Diabetes Mellitus Tipo 2 , Derivação Gástrica , Obesidade Mórbida , Humanos , Diabetes Mellitus Tipo 2/cirurgia , Diabetes Mellitus Tipo 2/complicações , Obesidade Mórbida/cirurgia , Hemoglobinas Glicadas , Estudos Retrospectivos , Resultado do Tratamento , Obesidade/cirurgia , Obesidade/complicações , Duodeno/cirurgia , Jejuno/cirurgia , Derivação Gástrica/métodos , Redução de PesoRESUMO
BACKGROUND/AIMS: Upper gastrointestinal bleeding (UGIB) is the most common GI condition requiring hospitalization, and can be diagnosed by direct visualization. The present study aimed to evaluate the safety and feasibility of using the PillSense system (EnteraSense Ltd.), a novel diagnostic tool designed for the rapid in vivo detection of UGIB, in human volunteers. METHODS: In the present study, 10 volunteers swallowed a PillSense capsule, followed by 2 servings of an autologous blood preparation. Participants were monitored for capsule passage, overall tolerability of the procedure, and adverse events. RESULTS: The procedure was completed per the protocol established in the present study in 9/10 cases. In 9 of the subjects, after capsule ingestion, the device indicated the absence of blood with sensor output values of 1. After the ingestion of the first blood mixture, the sensor outputs of all devices increased from 2.8 to 4, indicating that each camera detected blood. The sensor output remained within that range after the ingestion of the second mixture; however, in one case, the baseline capsule signal was positive, because of a preexisting condition. The passage of the capsule was verified in all patients, and no adverse events were reported. CONCLUSION: The first trial of the PillSense system in human subjects demonstrated the feasibility, safety, and tolerability of utilizing this product as a novel, noninvasive, and easy-to-use triage tool for the diagnosis of patients suspected of having UGIB.
RESUMO
Background: Tumor necrosis factor-alpha (TNF-α) agonists revolutionized therapeutic algorithms in inflammatory bowel disease (IBD) management. However, approximately every third IBD patient does not respond to this therapy in the long term, which delays efficient control of the intestinal inflammation. Methods: We analyzed the power of serum biomarkers to predict the failure of anti-TNF-α. We collected serum of 38 IBD patients at therapy prescription and 38 weeks later and analyzed them with relation to therapy response (no-, partial-, and full response). We used enzyme-linked immunosorbent assay to quantify 16 biomarkers related to gut barrier (intestinal fatty acid-binding protein, liver fatty acid-binding protein, trefoil factor 3, and interleukin (IL)-33), microbial translocation, immune system regulation (TNF-α, CD14, lipopolysaccharide-binding protein, mannan-binding lectin, IL-18, transforming growth factor-ß1 (TGF-ß1), osteoprotegerin (OPG), insulin-like growth factor 2 (IGF-2), endocrine-gland-derived vascular endothelial growth factor), and matrix metalloproteinase system (MMP-9, MMP-14, and tissue inhibitors of metalloproteinase-1). Results: We found that future full-responders have different biomarker profiles than non-responders, while partial-responders cannot be distinguished from either group. When future non-responders were compared to responders, their baseline contained significantly more TGF-ß1, less CD14, and increased level of MMP-9, and concentration of these factors could predict non-responders with high accuracy (AUC = 0.938). Interestingly, during the 38 weeks, levels of MMP-9 decreased in all patients, irrespective of the outcome, while OPG, IGF-2, and TGF-ß1 were higher in non-responders compared to full-responders both at the beginning and the end of the treatment. Conclusions: The TGF-ß1 and CD14 can distinguish non-responders from responders. The changes in biomarker dynamics during the therapy suggest that growth factors (such as OPG, IGF-2, and TGF-ß) are not markedly influenced by the treatment and that anti-TNF-α therapy decreases MMP-9 without influencing the treatment outcome.
Assuntos
Fator de Crescimento Insulin-Like II , Fator de Crescimento Transformador beta1 , Humanos , Metaloproteinase 9 da Matriz , Inibidores do Fator de Necrose Tumoral , Fator A de Crescimento do Endotélio VascularRESUMO
Inflammatory bowel diseases (IBD) are systemic immune-mediated conditions with predilection for the gastrointestinal tract and include Crohn's disease and ulcerative colitis. Despite the advances in the fields of basic and applied research, the etiopathogenesis remains largely unknown. As a result, only one third of the patients achieve endoscopic remission. A substantial portion of the patients also develop severe clinical complications or neoplasia. The need for novel biomarkers that can enhance diagnostic accuracy, more precisely reflect disease activity, and predict a complicated disease course, thus, remains high. Genomic and transcriptomic studies contributed substantially to our understanding of the immunopathological pathways involved in disease initiation and progression. However, eventual genomic alterations do not necessarily translate into the final clinical picture. Proteomics may represent a missing link between the genome, transcriptome, and phenotypical presentation of the disease. Based on the analysis of a large spectrum of proteins in tissues, it seems to be a promising method for the identification of new biomarkers. This systematic search and review summarize the current state of proteomics in human IBD. It comments on the utility of proteomics in research, describes the basic proteomic techniques, and provides an up-to-date overview of available studies in both adult and pediatric IBD.
Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Adulto , Criança , Proteômica/métodos , Doenças Inflamatórias Intestinais/metabolismo , Colite Ulcerativa/metabolismo , Doença de Crohn/metabolismo , Biomarcadores/metabolismoRESUMO
BACKGROUND: Ustekinumab, is a new therapy for patients with IBD, especially for patients suffering from Crohn's disease (CD) who did not respond to anti-TNF treatment. To shed light on the longitudinal effect of ustekinumab on the immune system, we investigated the effect on skin and gut microbiota composition, specific immune response to commensals, and various serum biomarkers. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 11 patients with IBD who were monitored over 40 weeks of ustekinumab therapy and 39 healthy controls (HC). We found differences in the concentrations of serum levels of osteoprotegerin, TGF-ß1, IL-33, and serum IgM antibodies against Lactobacillus plantarum between patients with IBD and HC. The levels of these biomarkers did not change in response to ustekinumab treatment or with disease improvement during the 40 weeks of observation. Additionally, we identified differences in stool abundance of uncultured Subdoligranulum, Faecalibacterium, and Bacteroides between patients with IBD and HC. CONCLUSION/SIGNIFICANCE: In this preliminary study, we provide a unique overview of the longitudinal monitoring of fecal and skin microbial profiles as well as various serum biomarkers and humoral and cellular response to gut commensals in a small cohort of patients with IBD on ustekinumab therapy.
Assuntos
Doença de Crohn , Microbiota , Humanos , Ustekinumab/uso terapêutico , Projetos Piloto , Inibidores do Fator de Necrose Tumoral , Doença de Crohn/terapia , BiomarcadoresRESUMO
Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract that have been linked to microbiome dysbiosis and immune system dysregulation. We investigated the longitudinal effect of anti-TNF therapy on gut microbiota composition and specific immune response to commensals in IBD patients. The study included 52 patients tracked over 38 weeks of therapy and 37 healthy controls (HC). To characterize the diversity and composition of the gut microbiota, we used amplicon sequencing of the V3V4 region of 16S rRNA for the bacterial community and of the ITS1 region for the fungal community. We measured total antibody levels as well as specific antibodies against assorted gut commensals by ELISA. We found diversity differences between HC, Crohn's disease, and ulcerative colitis patients. The bacterial community of patients with IBD was more similar to HC at the study endpoint, suggesting a beneficial shift in the microbiome in response to treatment. We identified factors such as disease severity, localization, and surgical intervention that significantly contribute to the observed changes in the gut bacteriome. Furthermore, we revealed increased IgM levels against specific gut commensals after anti-TNF treatment. In summary, this study, with its longitudinal design, brings insights into the course of anti-TNF therapy in patients with IBD and correlates the bacterial diversity with disease severity in patients with ulcerative colitis (UC).
Assuntos
Fezes/microbiologia , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/microbiologia , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Anticorpos/sangue , Biodiversidade , Estudos de Casos e Controles , Feminino , Fungos/genética , Microbioma Gastrointestinal/genética , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/cirurgia , Interleucina-17/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Metagenômica , RNA Ribossômico 16S/genética , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Second-generation thrombopoietin receptor agonists (TPO-RAs) are emerging as the new standard for managing thrombocytopenia (TCP) in patients with chronic liver diseases (CLDs) undergoing scheduled procedures. However, practical guidance for their routine use in CLD patients undergoing specific invasive procedures is lacking. METHODS: These practice guidelines were developed by the Initiative Group for Central European Hepatologic Collaboration (CEHC), composed of nine hepatologist/gastroenterologist experts from Central Europe. Using an adapted Delphi process, the CEHC group selected ten invasive procedures most relevant to the hepatology/gastroenterology setting in the region. Consensus recommendations for each invasive procedure are reported as a final percentage of expert panel responses. RESULTS: A consensus was agreed that TPO-RAs should be considered for raising platelet count in CLD patients undergoing scheduled abdominal surgery, high-bleeding risk dentistry, endoscopic polypectomy, endoscopic variceal ligation, liver biopsy, liver surgery, liver transplantation and percutaneous ablation, but it was also agreed that they are less beneficial or not necessary for endoscopy without intervention and paracentesis. CONCLUSIONS: Using a modified Delphi method, experts reached an agreement for TCP management in CLD patients undergoing ten invasive procedures. These practice guidelines may help with decision making and patient management in areas where clinical evidence is absent or limited.
RESUMO
BACKGROUND: Vedolizumab demonstrated different placental pharmacokinetics than other immunoglobulin G1 antibodies, leading to lower drug levels in cord blood in contrast to maternal blood at the time of delivery. The placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor agents. Current evidence on the placental pharmacokinetics of vedolizumab and ustekinumab is limited. We aimed to assess the placental transfer of ustekinumab and vedolizumab in pregnant patients with inflammatory bowel disease. METHODS: Consecutive women from a prospective observational study who were exposed to ustekinumab or vedolizumab within 2 months prior to conception or during pregnancy were included. Ustekinumab and vedolizumab levels were measured in maternal and cord blood at the time of delivery. RESULTS: Drug levels were available in 31 infant-mother pairs (15 exposed to ustekinumab and 16 to vedolizumab). The median maternal and newborn ustekinumab levels were 5.3 mg/l and 10.3 mg/l, respectively (the median infant-to-maternal ratio was 1.7), while the median maternal and cord vedolizumab levels were 7.3 mg/l and 4.5 mg/l (the median infant-to-maternal ratio was 0.66). The ustekinumab levels in cord blood positively correlated with the maternal levels at delivery (ρ = 0.751, p = 0.001). However, no correlation with the timing of the last drug administration was found. In contrast, the vedolizumab levels in cord blood demonstrated significant positive correlation with the maternal levels (ρ = 0.831, p < 0.001) along with the gestational week of the last infusion (ρ = 0.736, p = 0.001). CONCLUSION: Vedolizumab demonstrated different placental pharmacokinetics, leading to lower drug levels in cord blood compared to maternal blood at delivery; in contrast, the placental transfer of ustekinumab seems to have a pattern similar to anti-tumour necrosis factor (TNF) agents.
RESUMO
BACKGROUND AND AIMS: Ulcerative colitis (UC) is a chronic inflammatory disease. Fecal microbial transplantation (FMT) is a promising alternative treatment. METHODS: This multicenter, open-label, noninferiority trial randomized patients with active left-sided UC (Mayo score 4-10) equally to FMT or 5-aminosalicylic acid (5-ASA) enemas. FMT enemas were administered five times in the first week and then once weekly for 5 weeks. 5-ASA enemas were administered daily for 2 weeks and then every other day. The primary study endpoint was clinical remission, with a total Mayo score ≤2 at week 12 with no subscore >1. RESULTS: Sixty-one patients were screened; 45 were enrolled and randomized to FMT (n = 23) or 5-ASA (n = 22). Twenty-one FMT and 22 5-ASA patients completed at least the week 4 study visit and were included in the mITT analysis. Twelve FMT (57%) and eight 5-ASA patients achieved the primary study endpoint. FMT noninferiority with 10% margin was confirmed (95% CI: -7.6%, 48.9%). Adverse events occurred in 12 FMT (57%) and 13 5-ASA (59%) patients. Increased microbial diversity persisted 3 months after FMT. CONCLUSION: FMT is an effective treatment for left-sided UC and increased recipient microbiome diversity. Targeted microbiome modification may improve FMT efficacy. Further investigation is needed to guide donor and patient selection.
RESUMO
Ulcerative colitis (UC) is an inflammatory bowel disease, and intestinal bacteria are implicated in the pathogenesis of this disorder. The administration of aminosalicylates (5-ASA) is a conventional treatment that targets the mucosa, while fecal microbial transplantation (FMT) is a novel treatment that directly targets the gut microbiota. The aim of this study was to identify changes in fecal bacterial composition after both types of treatments and evaluate clinical responses. Sixteen patients with active left-sided UC underwent enema treatment using 5-ASA (n = 8) or FMT (n = 8) with a stool from a single donor. Fecal microbiota were analyzed by 16S rDNA high-throughput sequencing, and clinical indices were used to assess the efficacy of treatments. 5-ASA therapy resulted in clinical remission in 50% (4/8) of patients, but no correlation with changes in fecal bacteria was observed. In FMT, remission was achieved in 37.5% (3/8) of patients and was associated with a significantly increased relative abundance of the families Lachnospiraceae, Ruminococcaceae, and Clostridiaceae of the phylum Firmicutes, and Bifidobacteriaceae and Coriobacteriaceae of the phylum Actinobacteria. At the genus level, Faecalibacterium, Blautia, Coriobacteria, Collinsela, Slackia, and Bifidobacterium were significantly more frequent in patients who reached clinical remission. However, the increased abundance of beneficial taxa was not a sufficient factor to achieve clinical improvement in all UC patients. Nevertheless, our preliminary results indicate that FMT as non-drug-using method is thought to be a promising treatment for UC patients.
Assuntos
Colite Ulcerativa/microbiologia , Colite Ulcerativa/terapia , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Mesalamina/administração & dosagem , Mesalamina/uso terapêutico , Administração Tópica , Adulto , Idoso , Bactérias/classificação , Biodiversidade , Colite Ulcerativa/tratamento farmacológico , Análise Discriminante , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Masculino , Mesalamina/farmacologia , Pessoa de Meia-Idade , Análise de Componente Principal , Doadores de TecidosRESUMO
BACKROUND: Capsule colonoscopy might present an alternative to colonoscopy for colorectal neoplasia screening. AIM: To assess the accuracy of second-generation capsule colonoscopy (CCE2) for colorectal neoplasia detection compared with conventional colonoscopy (CC). METHODS: From 2011-2015, we performed a multicenter, prospective, cross-over study evaluating the use of CCE2 as a possible colorectal cancer (CRC) screening test based on the assessment of the method's characteristics (accuracy) and safety and patient acceptance of the routine. Enrolled participants fulfilled the CRC screening population criteria if they were asymptomatic, were older than 50, and had no personal or familial history of colorectal neoplasia. The primary outcome was accuracy for the detection of polyps ≥ 6 mm. Secondary outcomes were accuracy for all polyps, polyps ≥ 10 mm, adenomas ≥ 10 mm, and cancers, the quality of bowel cleansing, safety, and CCE2 acceptability by the screening population. RESULTS: A total of 236 individuals were examined; 11 patients (5%) were excluded. Therefore, 225 subjects (95%) were considered in the intention-to-screen (ITS) group. A total of 201 patients (89%) completed both examinations successfully (per protocol group). In the ITS group, polyps were diagnosed during CC in 114 subjects (51%); polyps ≥ 6 mm, polyps ≥ 10 mm, and adenomas ≥ 10 mm were diagnosed in 34 (15%), 16 (7%), and 11 (5%) patients, respectively. The sensitivity of CCE2 for polyps ≥ 6 mm, polyps ≥ 10 mm, and adenomas ≥ 10 mm was 79% (95% confidence interval (CI): 62-91%), 88% (95% CI: 62-98%), and 100% (95% CI: 72-100%), respectively. CONCLUSION: Second-generation capsule colonoscopy is a safe, noninvasive, and sensitive method for colorectal neoplasia detection although CC remains the preferred method for considerable proportion of subjects. CCE2 may therefore be accepted as the primary screening test for colorectal cancer screening.
RESUMO
Crohn's disease (CD), ulcerative colitis (UC) and inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC-IBD), share three major pathogenetic mechanisms of inflammatory bowel disease (IBD)-gut dysbiosis, gut barrier failure and immune system dysregulation. While clinical differences among them are well known, the underlying mechanisms are less explored. To gain an insight into the IBD pathogenesis and to find a specific biomarker pattern for each of them, we used protein array, ELISA and flow cytometry to analyze serum biomarkers and specific anti-microbial B and T cell responses to the gut commensals. We found that decrease in matrix metalloproteinase (MMP)-9 and increase in MMP-14 are the strongest factors discriminating IBD patients from healthy subjects and that PSC-IBD patients have higher levels of Mannan-binding lectin, tissue inhibitor of metalloproteinases 1 (TIMP-1), CD14 and osteoprotegerin than patients with UC. Moreover, we found that low transforming growth factor-ß1 (TGF-ß1) is associated with disease relapse and low osteoprotegerin with anti-tumor necrosis factor-alpha (TNF-α) therapy. Patients with CD have significantly decreased antibody and increased T cell response mainly to genera Eubacterium, Faecalibacterium and Bacteroides. These results stress the importance of the gut barrier function and immune response to commensal bacteria and point at the specific differences in pathogenesis of PSC-IBD, UC and CD.
Assuntos
Biomarcadores/sangue , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Adulto , Colangite Esclerosante/complicações , Colite Ulcerativa/complicações , Colite Ulcerativa/metabolismo , Doença de Crohn/complicações , Doença de Crohn/metabolismo , Disbiose/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
AIM: To evaluate risk factors for primary sclerosing cholangitis (PSC) recurrence (rPSC) after orthotopic liver transplantation (OLT) in patients with well-preserved colons. METHODS: We retrospectively evaluated the medical records of all patients transplanted for PSC in our center between July 1994 and May 2015 and selected 47 with follow-up of at least 60 mo for further analysis based on strict inclusion and exclusion criteria. rPSC was confirmed by magnetic resonance or endoscopic retrograde cholangiopancreatography and liver biopsy. All patients were evaluated by protocolary pre-OLT colonoscopy with randomized mucosal biopsies. Colonoscopy was repeated annually after OLT. Both organ donors and recipients were human leukocyte antigen (HLA) typed by serological and/or DNA methods. All input data were thoroughly analyzed employing relevant statistical methods. RESULTS: Altogether, 31 men and 16 women with a median (range) age of 36 (15-68) years at the time of OLT and a median follow-up of 122 (60-249) mo were included. rPSC was confirmed in 21/47 (44.7%) of patients, a median 63 (12-180) mo after transplantation. De novo colitis [rPSC in 11/12, P ≤ 0.05, hazard ratio (HR): 4.02, 95% confidence interval (CI): 1.58-10.98] and history of acute cellular rejection (rPSC in 14/25, P ≤ 0.05; HR: 2.66, 95%CI: 1.03-7.86) showed strong positive associations with rPSC. According to the univariate analysis, overlapping features of autoimmune hepatitis (rPSC in 5/5, P ≤ 0.05) and HLA-DRB1*07 in the donor (rPSC in 10/15, P ≤ 0.05) represent other potential risk factors for rPSC, while the HLA-DRB1*04 (rPSC in 0/6, P ≤ 0.05), HLA-DQB1*03 (rPSC in 1/11, P ≤ 0.05), and HLA-DQB1*07 (rPSC in 0/7, P ≤ 0.05) recipient alleles may have protective roles. CONCLUSION: De novo colitis and acute cellular rejection are clinical conditions significantly predisposed towards recurrence of PSC after liver transplantation.
Assuntos
Colangite Esclerosante/patologia , Doenças Inflamatórias Intestinais/epidemiologia , Transplante de Fígado , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Colangiopancreatografia Retrógrada Endoscópica , Colangite Esclerosante/diagnóstico por imagem , Colangite Esclerosante/cirurgia , Colo/diagnóstico por imagem , Colo/patologia , Colonoscopia , Feminino , Seguimentos , Humanos , Doenças Inflamatórias Intestinais/diagnóstico por imagem , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Doadores de Tecidos/estatística & dados numéricos , Adulto JovemRESUMO
Primary sclerosing cholangitis (PSC) is a progressive disease of the biliary tree which represents one of the most frequent indications for orthotopic liver transplantation (OLTx) in developed countries. LTx is currently the only curative procedure for PSC. Concomitant inflammatory bowel disease (IBD) is present in approximately 70 % of patients with PSC. Such colitis in PSC has specific clinical and etiological features and is considered as a distinct phenotype of IBD often referred to as "PSC-IBD". The phenotype usually manifests as mild extensive colitis with right-sided predominance. Other morphological features, such as back- wash ileitis and rectal sparing, are also increasingly prevalent in PSC-IBD. Moreover, patients with PSC-IBD have increased risk towards developing colorectal neoplasia which tend to be highly progressive. Therefore, total colonoscopy employing multiple random biopsies or chromoendoscopy should be performed every 1-2 years once PSC-IBD is diagnosed. Even detection of low-grade dysplasia in colonic mucosa should lead towards prophylactic colectomy consideration in patients with PSC-IBD. Recommendations regarding pharmacological therapy are based on the similar principles as in Crohn´s disease and ulcerative colitis. However, status of the liver disease should always be taken into account. Proctocolectomy with ileal pouch-anal anastomosis (IPAA) is a method of choice in the field of surgical therapy of PSC-IBD. The clinical course of PSC-IBD may deteriorate after OLTx despite immunosuppressive therapy administration. IBD can even develop de-novo after OLTx and may significantly influence the risk ratio for PSC recurrence in the liver graft. Key words: inflammatory bowel disease - primary sclerosing cholangitis - PSC-IBD.
Assuntos
Colangite Esclerosante , Colite Ulcerativa , Doenças Inflamatórias Intestinais , Colangite Esclerosante/complicações , Colite Ulcerativa/complicações , Humanos , Doenças Inflamatórias Intestinais/complicações , FenótipoRESUMO
Human gut microbiota, complex ecosystem of microbes associated with human gut, is essential for the development of the host's immune system and many other physiological functions. Recently, numerous diseases and syndromes were associated with disruption of this ecosystem thus stressing its importance in maintaining the host's health. Growing evidence suggests that by manipulating the gut microbiota, some of these diseases could be treated or even prevented. These manipulations include changes in diet, use of probiotics, prebiotics, antibiotics and fecal microbiota transplantation (FMT). The successes in FMT treatment of recurrent infection of Clostridium difficile led recently to a great interest in extending this treatment modality to other diseases with proven disruption of gut microbiota, such as ulcerative colitis or metabolic syndrome. Key words: Clostridium difficile - dysbiosis - fecal microbial transplantation - microbiota - prebiotics - probiotics.
Assuntos
Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Clostridioides difficile , Infecções por Clostridium/terapia , Disbiose , Humanos , MicrobiotaRESUMO
AIM: To characterize the gut bacterial microbiota of patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). METHODS: Stool samples were collected and relevant clinical data obtained from 106 study participants, 43 PSC patients with (n = 32) or without (n = 11) concomitant inflammatory bowel disease, 32 UC patients, and 31 healthy controls. The V3 and V4 regions of the 16S ribosomal RNA gene were sequenced on Illumina MiSeq platform to cover low taxonomic levels. Data were further processed in QIIME employing MaAsLin and LEfSe tools for analysis of the output data. RESULTS: Microbial profiles in both PSC and UC were characterized by low bacterial diversity and significant change in global microbial composition. Rothia, Enterococcus, Streptococcus, Veillonella, and three other genera were markedly overrepresented in PSC regardless of concomitant inflammatory bowel disease (IBD). Rothia, Veillonella and Streptococcus were tracked to the species level to identify Rothia mucilaginosa, Streptococcus infantus, S. alactolyticus, and S. equi along with Veillonella parvula and V. dispar. PSC was further characterized by decreased abundance of Adlercreutzia equolifaciens and Prevotella copri. Decrease in genus Phascolarctobacterium was linked to presence of colonic inflammation regardless of IBD phenotype. Akkermansia muciniphila, Butyricicoccus pullicaecorum and Clostridium colinum were decreased in UC along with genus Roseburia. Low levels of serum albumin were significantly correlated with enrichment of order Actinomycetales. CONCLUSION: PSC is associated with specific gut microbes independently of concomitant IBD and several bacterial taxa clearly distinguish IBD phenotypes (PSC-IBD and UC).
Assuntos
Bactérias/isolamento & purificação , Colangite Esclerosante/complicações , Colite Ulcerativa/complicações , Colo/microbiologia , Disbiose/microbiologia , Microbioma Gastrointestinal , Adulto , Idoso , Bactérias/genética , Colangite Esclerosante/microbiologia , Colite Ulcerativa/microbiologia , Disbiose/etiologia , Fezes/microbiologia , Feminino , Voluntários Saudáveis , Humanos , Mucosa Intestinal/microbiologia , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/isolamento & purificação , Análise de Sequência de RNARESUMO
BACKGROUND: Most patients with Crohn's disease (CD) require one or more operations during their lifetime. Repeated resections and surgical complications may result in short gut in a subset of patients, typically those with extensive small bowel disease or a penetrating CD phenotype. The effects of short bowel syndrome (SBS) can range in seriousness from mild to life-threatening advanced intestinal failure. Worldwide, CD is the second leading indication for intestinal transplantation (ITx) in SBS, but the overall incidence of ITx is quite low. Key Messages: Currently, total parenteral nutrition (TPN) is the preferred treatment option for patients with SBS because of its superior survival outcome. However, TPN can fail from loss of venous access due to catheter-associated thromboses, recurrent catheter-related blood stream infections, or intestinal-failure-associated liver dysfunction. Three types of transplantations are available for CD patients - small bowel alone, liver plus small bowel and multivisceral, which includes other intra-abdominal organs. An abdominal wall transplant is required in case of abdominal wall defects or lack of free intra-abdominal space. The current 5-year survival rate of 54% following ITx of the isolated small bowel appears worse than that associated with TPN. However, outcomes are substantially improving because of surgical and technical advances and progress in medical therapy. On the other hand, ITx carries the risk of both complications (e.g., rejection, infections, and post transplant lymphoproliferative disorders) and adverse events associated with immunosuppression. CD recurrence has been reported in a few patients, but this primarily histologic recurrence might not be of great clinical importance. CONCLUSIONS: ITx has become a well-established treatment for those who fail on TPN and who have life-threatening complications. Fortunately, it concerns only a small proportion of CD patients, but it does offer reasonable survival and quality of life. Primary management of patients with small bowel failure should be provided by a center experienced in medical intestinal rehabilitation, nutrition, and transplantation of other solid organs.
Assuntos
Doença de Crohn/cirurgia , Enteropatias/cirurgia , Intestino Delgado/transplante , Síndrome do Intestino Curto/cirurgia , Adulto , Doença de Crohn/complicações , Humanos , Terapia de Imunossupressão/efeitos adversos , Enteropatias/etiologia , Nutrição Parenteral Total , Qualidade de Vida , Síndrome do Intestino Curto/etiologia , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Intestinal transplantation represents a suitable treatment for patients with intestinal failure who then develop life-threatening complications of total parenteral nutrition and for some patients with complex abdominal disorders not suitable for conventional treatment. METHODS: prior to launch of the clinical program, preparation started in 2006 initially with extensive experimentation carried out on pigs. The clinical phase involved a specialized, multidisciplinary team who examined 23 patients being considered for transplantation. Seven patients were put on a waiting list and one female, due to the improvement of her medical status, was unlisted. The first ever intestinal transplantation was done in 2014. RESULTS: three out of six transplanted patients are alive with 380 days of actual survival; median 131 days (63-763). Two patients are on a full oral diet and nutritionally independent with an excellent quality of life. One female is nutritionally independent but with the need for partial supplemental parenteral rehydration due to the stomal output. CONCLUSION: intestinal transplantation is a suitable treatment for highly selected patients with intestinal failure who meet specific listing criteria.