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1.
Dig Endosc ; 35(6): 718-725, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36567638

RESUMO

OBJECTIVES: Patients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE). METHODS: A longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low-grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end-point was histopathologic progression to LGD, high-grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation. RESULTS: A total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long-segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow-up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil-to-lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77-2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09-1.36, P < 0.001), age (OR 1.03, 95% CI 1.02-1.05, P = 0.02), smoking (OR 1.66, 95% CI 1.09-2.75, P = 0.04), and renal failure (OR 1.51, 95% CI 0.93-2.43, P = 0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively. CONCLUSION: This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs.


Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Lesões Pré-Cancerosas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Esôfago de Barrett/patologia , Estudos Longitudinais , Lesões Pré-Cancerosas/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Hiperplasia , Endoscopia Gastrointestinal
2.
Dig Dis Sci ; 64(5): 1288-1295, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30565010

RESUMO

BACKGROUND: Bloating is one of the most bothersome symptoms of irritable bowel syndrome (IBS), but its association with other symptoms is not well described. AIMS: We investigated the association between symptoms of abdominal bloating, other IBS symptoms, psychological distress, and comorbid pain conditions. METHODS: We conducted a cross-sectional study on a large cohort of IBS patients with and without symptoms of abdominal bloating and healthy controls. Subjects were assessed for IBS and its subtypes, pain severity, symptoms severity, psychological disturbances, comorbidities, and dietary restrictions of three fluid groups. RESULTS: A total of 484 subjects were investigated. Compared with IBS - B, IBS + B subjects had higher rates of constipation (30% vs. 15%, p = 0.191) and lower rates of diarrhea, (70% vs. 85%, p = 0.191) although these were not statistically significant. Bloating severity correlated with IBS symptoms severity (r = 0.397, p = 0.000), pain severity (r = 0.364, p = 0.000), and both anxiety and somatization scores (r = 0.167, p = 0.015 and r = 0.219, p = 0.001, respectively). Prevalence of fibromyalgia and depression and somatization scores was significantly higher in IBS with bloating than in IBS without bloating. IBS patients with bloating reported more dietary restriction of three fluid groups to control their symptoms compared with healthy controls and IBS patients without bloating. CONCLUSIONS: Abdominal bloating in IBS is associated with increased symptoms and pain severity, somatization, depression, fibromyalgia, and altered dietary fluids composition. Recognizing and addressing these factors in the diagnosis and management of patients with IBS may improve clinical outcome.


Assuntos
Dor Abdominal/diagnóstico , Dor Abdominal/psicologia , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/psicologia , Índice de Gravidade de Doença , Dor Abdominal/epidemiologia , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Comorbidade , Estudos Transversais , Feminino , Humanos , Síndrome do Intestino Irritável/epidemiologia , Masculino , Pessoa de Meia-Idade
3.
Am J Hum Genet ; 96(5): 797-807, 2015 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-25957468

RESUMO

High-throughput sequencing technology has enabled population-based studies of the role of the human microbiome in disease etiology and exposure response. Distance-based analysis is a popular strategy for evaluating the overall association between microbiome diversity and outcome, wherein the phylogenetic distance between individuals' microbiome profiles is computed and tested for association via permutation. Despite their practical popularity, distance-based approaches suffer from important challenges, especially in selecting the best distance and extending the methods to alternative outcomes, such as survival outcomes. We propose the microbiome regression-based kernel association test (MiRKAT), which directly regresses the outcome on the microbiome profiles via the semi-parametric kernel machine regression framework. MiRKAT allows for easy covariate adjustment and extension to alternative outcomes while non-parametrically modeling the microbiome through a kernel that incorporates phylogenetic distance. It uses a variance-component score statistic to test for the association with analytical p value calculation. The model also allows simultaneous examination of multiple distances, alleviating the problem of choosing the best distance. Our simulations demonstrated that MiRKAT provides correctly controlled type I error and adequate power in detecting overall association. "Optimal" MiRKAT, which considers multiple candidate distances, is robust in that it suffers from little power loss in comparison to when the best distance is used and can achieve tremendous power gain in comparison to when a poor distance is chosen. Finally, we applied MiRKAT to real microbiome datasets to show that microbial communities are associated with smoking and with fecal protease levels after confounders are controlled for.


Assuntos
Genética Populacional , Microbiota/genética , Modelos Estatísticos , Simulação por Computador , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Filogenia , Polimorfismo de Nucleotídeo Único , Software
4.
Dig Dis Sci ; 63(7): 1890-1899, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29777439

RESUMO

BACKGROUND: Irritable bowel syndrome (IBS) has been associated with changes in the intestinal microbiota. Only a few studies have explored differences in the mucosa-associated microbiota between IBS patients and healthy controls (HC). AIMS: To characterize and compare the microbiota in mucosal and fecal samples from carefully selected patients with IBS-D and HC. METHODS: The cohort was composed of 23 diarrhea-predominant IBS (IBS-D) patients and 24 HC. Fresh stool samples were collected from participants prior to the collection of colonic mucosal samples from an unprepped bowel. After DNA extraction, 16S rRNA genes were sequenced by 454 pyrosequencing and analyzed using the QIIME pipeline. RESULTS: The fecal microbiota (luminal niche) of IBS-D patients was found to have reduced enteric richness compared to HC (P < 0.05), whereas no differences were observed between the two groups within the mucosal microbiota. Within the luminal niche, the relative proportions of Faecalibacterium genus were found to be lower in IBS-D than in HC and the Dorea genus was higher in IBS-D. None of the taxa proportions were significantly different in IBS-D patients versus HC using an FDR of ≤ 0.1 when analyzing samples that appeared in > 25% samples of either niche. CONCLUSION: Fecal and mucosal microbiota of IBS-D patients and HC are very similar and are not sufficient to explain the reported altered physiology and symptomatology of IBS-D. Future studies should investigate intestinal microbiome-dependent functional activity in addition to the fecal and mucosal-associated microbial composition.


Assuntos
Bactérias/isolamento & purificação , Diarreia/microbiologia , Fezes/microbiologia , Microbioma Gastrointestinal , Intestinos/microbiologia , Síndrome do Intestino Irritável/microbiologia , Bactérias/classificação , Bactérias/genética , Estudos de Casos e Controles , Diarreia/diagnóstico , Humanos , Síndrome do Intestino Irritável/diagnóstico , Ribotipagem
5.
Am J Gastroenterol ; 112(6): 900-902, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28572651

RESUMO

Irritable bowel syndrome (IBS) is one of the most common diagnoses made by healthcare providers. Yet the majority of patients with IBS are undiagnosed. The study by Sayuk et al. allows insight into the characteristics of different patient groups, e.g., with and without a formal diagnosis of diarrhea predominant IBS (IBS-D). We discuss the questions raised by this study regarding the importance of making a confident diagnosis, conveying it to patients and their implications for clinical practice.


Assuntos
Diarreia , Síndrome do Intestino Irritável , Humanos
6.
Am J Gastroenterol ; 112(1): 145-151, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27845337

RESUMO

OBJECTIVES: Bifidobacterium infantis 35624 is a probiotic that is used often in patients with irritable bowel syndrome (IBS). Non-patients with bowel symptoms may differ from patients with IBS in the impact of their bowel symptoms on illness severity, healthcare and treatment seeking behavior. The aim of this study is to assess the efficacy of B. infantis 35624 (109 c.f.u. per day) for the relief of abdominal discomfort and bloating in a non-patient population. METHODS: A double-blind, randomized, placebo-controlled, parallel study with a 2-week placebo run-in phase followed by a 4-week intervention phase was conducted at ten clinical centers (USA). Subjects were recruited from the general population by advertisement. The study randomized 302 subjects who experienced abdominal discomfort and bloating ≥2-times per week for at least three months but have not seen a physician or received prescribed medication for their symptoms in the past 12 months. Subjects were assessed for pre- to post-intervention changes in symptom severity (on a 6-point Likert scale; 0=none, 5=very severe) and frequency (symptoms-free days). RESULTS: A total of 275 subjects (mean age 42 years, 79% female, 74% Caucasian) provided evaluable data. Overall mean severity scores at baseline were 2.4 for abdominal discomfort and 2.5 for bloating with no significant differences between the placebo and probiotic groups. Both groups showed significant (P<0.05) improvement in abdominal discomfort and bloating scores over the 4-week intervention period. Mean severity symptom scores at the end of intervention showed no significant differences between the probiotic and the placebo groups in either abdominal discomfort or bloating (P>0.3). The frequency of abdominal bloating-free days was greater in the B. infantis 35624 group compared to the placebo group (P<0.05). Both regimens were well tolerated. CONCLUSIONS: Unlike previous clinical studies in patients with IBS, B. infantis 35624 did not show a significant improvement in the mean severity of symptoms of abdominal discomfort and bloating in a non-patient population. This may be explained by the high placebo effect and the lower impact of functional bowel symptoms in the non-patient population.


Assuntos
Dor Abdominal/terapia , Bifidobacterium longum subspecies infantis , Probióticos/uso terapêutico , Adulto , Método Duplo-Cego , Feminino , Flatulência , Humanos , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento
7.
Am J Physiol Gastrointest Liver Physiol ; 310(6): G417-26, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26702134

RESUMO

Recent studies have demonstrated differences in the intestinal microbiota between patients with irritable bowel syndrome (IBS) and healthy controls (HC), suggesting a role for the intestinal microbiota in the pathogenesis of IBS. Alterations in the microbiota have also been implicated in the pathogenesis of abdominal bloating, a commonly reported symptom in IBS. We investigated the relationship between the intestinal microbiota, abdominal bloating, and altered bowel patterns in a cohort of patients with IBS and HC. The 16S rRNA gene from fresh fecal samples was amplified and pyrosequenced by using Roche-454 Titanium chemistry. A Core Measurable Microbiome (CMM) was generated for Operational Taxonomic Unit (OTU) detected in >75% of all samples and compositional features of CMM were compared between groups by Linear Discriminant Analysis (LDA). IBS differentiated from HC by LDA using continuous variation in the species/OTUs or the CMM genera. When subcategorized based on bloating symptoms and bowel characteristics, the same subjects were also well differentiated from one another and from HC. ANOVA analysis showed quantitative species/OTU differences between the subgroups including IBS with and without bloating, and subtypes based on bowel characteristics. The clear LDA differentiation and the significant microbial taxa differences between the groups imply a significant association of the microbiota with bloating symptoms and bowel characteristics in IBS. These changes in the microbiota may serve as a biomarker for IBS and its clinical subtypes and suggest a role for the intestinal microbiota in the pathogenesis of the main symptoms of the disorder.


Assuntos
Cavidade Abdominal , Microbioma Gastrointestinal , Intestinos/microbiologia , Intestinos/fisiopatologia , Adulto , Estudos de Coortes , DNA Bacteriano/genética , Dilatação Patológica , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Síndrome do Intestino Irritável/microbiologia , Síndrome do Intestino Irritável/fisiopatologia , Masculino , Microbiota , Pessoa de Meia-Idade , RNA Ribossômico 16S/biossíntese , RNA Ribossômico 16S/genética , Adulto Jovem
8.
J Clin Gastroenterol ; 50(3): 227-32, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25930973

RESUMO

BACKGROUND: Recent studies demonstrated low-grade inflammation in patients with irritable bowel syndrome (IBS). However, these studies have been relatively small and do not enable examination of this factor in different subtypes of IBS and the possibility of confounding effects of comorbidities that may be associated with inflammatory responses. GOALS: To investigate the association between high-sensitive C-reactive protein (hs-CRP) and the diagnosis of IBS, IBS subtypes, symptoms' severity, and IBS-associated comorbidities. STUDY: This cross-sectional study uses data from a large matched case-control study of IBS subjects and healthy controls (HC). hs-CRP levels were measured in all subjects. IBS diagnosis was determined by Rome III criteria, negative screening blood tests, and normal colonoscopy. Subjects were evaluated for IBS severity and associated pain and psychological comorbidities. RESULTS: A total of 242 IBS patients and 244 HC were studied. Median hs-CRP levels in the IBS group were significantly higher than in HC (1.80; interquartile range, 0.7 to 4.04 mg/L vs. 1.20, interquartile range, 0.5 to 2.97 mg/L respectively, P<0.006). Levels were highest in IBS-D patients with greater disease severity. Hs-CRP levels mildly correlated with symptoms severity (r=0.169, P=0.009); this correlation was stronger for the IBS-D patients (r=0.27, P=0.006). IBS was a significant independent predictor (P=0.025) for higher hs-CRP levels, whereas other pain and psychological comorbidities were not. CONCLUSIONS: Given these observations of cross-sectional differences in hs-CRP between IBS subtypes and severity, independent of pain and comorbidities, more research is needed to explore a possible role of low-grade inflammation in the pathogenesis and/or clinical presentation of IBS.


Assuntos
Proteína C-Reativa/metabolismo , Síndrome do Intestino Irritável/sangue , Síndrome do Intestino Irritável/epidemiologia , Transtornos Mentais/epidemiologia , Doenças Musculares/epidemiologia , Índice de Gravidade de Doença , Adulto , Ansiedade/sangue , Ansiedade/epidemiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Comorbidade , Constipação Intestinal/sangue , Constipação Intestinal/etiologia , Estudos Transversais , Depressão/sangue , Depressão/epidemiologia , Diarreia/sangue , Diarreia/etiologia , Síndrome de Fadiga Crônica/sangue , Síndrome de Fadiga Crônica/epidemiologia , Feminino , Fibromialgia/sangue , Fibromialgia/epidemiologia , Humanos , Inflamação/sangue , Síndrome do Intestino Irritável/complicações , Masculino , Transtornos Mentais/sangue , Pessoa de Meia-Idade , Transtornos de Enxaqueca/sangue , Transtornos de Enxaqueca/epidemiologia , Doenças Musculares/sangue , Dor Pélvica/sangue , Dor Pélvica/epidemiologia , Prevalência , Transtornos Somatoformes/sangue , Transtornos Somatoformes/epidemiologia , Avaliação de Sintomas , Síndrome da Disfunção da Articulação Temporomandibular/sangue , Síndrome da Disfunção da Articulação Temporomandibular/epidemiologia , Adulto Jovem
9.
Am J Gastroenterol ; 110(9): 1339-46, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26303129

RESUMO

OBJECTIVES: Dysbiosis leading to abnormal intestinal fermentation has been suggested as a possible etiological mechanism in irritable bowel syndrome (IBS). We aimed to investigate the location and magnitude of altered intestinal bacterial fermentation in IBS and its clinical subtypes. METHODS: IBS patients who satisfied the Rome III criteria (114) and 33 healthy controls (HC) were investigated. Intestinal fermentation was assessed using two surrogate measures: intestinal intraluminal pH and fecal short-chain fatty acids (SCFAs). Intraluminal pH and intestinal transit times were measured in the small and large bowel using a wireless motility capsule (SmartPill) in 47 IBS and 10 HC. Fecal SCFAs including acetate, propionate, butyrate, and lactate were analyzed by capillary gas chromatography in all enrolled subjects. Correlations between intestinal pH, fecal SCFAs, intestinal transit time, and IBS symptom scores were analyzed. RESULTS: Colonic intraluminal pH levels were significantly lower in IBS patients compared with HC (total colonic pH, 6.8 for IBS vs. 7.3 for HC, P=0.042). There were no differences in total and segmental pH levels in the small bowel between IBS patients and HC (6.8 vs. 6.8, P=not significant). The intraluminal colonic pH differences were consistent in all IBS subtypes. Total SCFA level was significantly lower in C-IBS patients than in D-IBS and M-IBS patients and HC. The total SCFA level in all IBS subjects was similar with that of HC. Colonic pH levels correlated positively with colon transit time (CTT) and IBS symptoms severity. Total fecal SCFAs levels correlated negatively with CTT and positively with stool frequency. CONCLUSIONS: Colonic intraluminal pH is decreased, suggesting higher colonic fermentation, in IBS patients compared with HC. Fecal SCFAs are not a sensitive marker to estimate intraluminal bacterial fermentation.


Assuntos
Bactérias/metabolismo , Colo/metabolismo , Fermentação/fisiologia , Síndrome do Intestino Irritável/metabolismo , Adolescente , Adulto , Colo/microbiologia , Ácidos Graxos Voláteis/análise , Fezes/química , Feminino , Seguimentos , Humanos , Concentração de Íons de Hidrogênio , Síndrome do Intestino Irritável/etiologia , Síndrome do Intestino Irritável/microbiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
J Clin Gastroenterol ; 49 Suppl 1: S56-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26447966

RESUMO

Irritable bowel syndrome (IBS) is the most prevalent and the best studied functional gastrointestinal disorder. The etiology and the pathogenesis of IBS are still not clear; however, recent studies have implicated a role for alterations in the intestinal microbiota (dysbiosis) in the pathophysiology of the disorder. Epidemiological observations have demonstrated that the development of IBS symptoms is often preceded by a disruption of the individual's normal intestinal microbiota, and microbiological studies have demonstrated compositional differences in the intestinal microbiota between patients with IBS patients and healthy controls. In addition, animal studies and a few recent human clinical studies have demonstrated that compositional changes in the intestinal microbiota in IBS are associated with relevant abnormal gastrointestinal and brain-gut axis functions that are often observed in patients with IBS. This article discusses points of interest from the current research on the microbiota-gut-brain interactions in IBS and highlights the relevance of the emerging data to our understanding of the disorder and the clinical implications for patients' care.


Assuntos
Disbiose/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Síndrome do Intestino Irritável/microbiologia , Animais , Encéfalo/microbiologia , Encéfalo/fisiopatologia , Disbiose/complicações , Disbiose/microbiologia , Humanos , Intestinos/microbiologia , Intestinos/fisiopatologia , Síndrome do Intestino Irritável/fisiopatologia , Probióticos/uso terapêutico
11.
J Clin Gastroenterol ; 49 Suppl 1: S69-73, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26447969

RESUMO

This paper describes the consensus opinion of the participants in the 4th Triennial Yale/Harvard Workshop on Probiotic Recommendations. The recommendations update those of the first 3 meetings that were published in 2006, 2008, and 2011. Recommendations for the use of probiotics in necrotizing enterocolitis, childhood diarrhea, inflammatory bowel disease, irritable bowel syndrome and Clostridium difficile diarrhea are reviewed. In addition, we have added recommendations for liver disease for the first time. As in previous publications, the recommendations are given as A, B, or C ratings.


Assuntos
Diarreia/terapia , Enterocolite Necrosante/terapia , Síndrome do Intestino Irritável/terapia , Hepatopatias/terapia , Probióticos/normas , Adulto , Criança , Clostridioides difficile , Diarreia/microbiologia , Enterocolite Necrosante/microbiologia , Enterocolite Pseudomembranosa/microbiologia , Enterocolite Pseudomembranosa/terapia , Humanos , Síndrome do Intestino Irritável/microbiologia , Hepatopatias/microbiologia , Probióticos/uso terapêutico
12.
N Engl J Med ; 364(1): 22-32, 2011 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-21208106

RESUMO

BACKGROUND: Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS. METHODS: In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study. RESULTS: Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among patients who had IBS without constipation, treatment with rifaximin for 2 weeks provided significant relief of IBS symptoms, bloating, abdominal pain, and loose or watery stools. (Funded by Salix Pharmaceuticals; ClinicalTrials.gov numbers, NCT00731679 and NCT00724126.).


Assuntos
Antibacterianos/uso terapêutico , Síndrome do Intestino Irritável/tratamento farmacológico , Rifamicinas/uso terapêutico , Dor Abdominal/tratamento farmacológico , Dor Abdominal/etiologia , Idoso , Antibacterianos/efeitos adversos , Diarreia/tratamento farmacológico , Diarreia/etiologia , Método Duplo-Cego , Feminino , Humanos , Síndrome do Intestino Irritável/complicações , Masculino , Pessoa de Meia-Idade , Rifamicinas/efeitos adversos , Rifaximina
13.
Am J Physiol Gastrointest Liver Physiol ; 305(8): G529-41, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23886861

RESUMO

The pathophysiology of irritable bowel syndrome (IBS) is believed to involve alterations in the brain-gut axis; however, the etiological triggers and mechanisms by which these changes lead to symptoms of IBS remain poorly understood. Although IBS is often considered a condition without an identified "organic" etiology, emerging evidence suggests that alterations in the gastrointestinal microbiota and altered immune function may play a role in the pathogenesis of the disorder. These recent data suggest a plausible model in which changes in the intestinal microbiota and activation of the enteric immune system may impinge upon the brain-gut axis, causing the alterations in gastrointestinal function and the clinical symptoms observed in patients with IBS. This review summarizes the current evidence for altered intestinal microbiota and immune function in IBS. It discusses the potential etiological role of these factors, suggests an updated conceptual model for the pathogenesis of the disorder, and identifies areas for future research.


Assuntos
Intestinos/imunologia , Intestinos/microbiologia , Síndrome do Intestino Irritável/microbiologia , Humanos
14.
Gastroenterology ; 143(5): 1179-1187.e3, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22885331

RESUMO

BACKGROUND & AIMS: Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and cost. Statistical analyses of the most recent data are necessary to guide GI research, education, and clinical practice. We estimate the burden of GI disease in the United States. METHODS: We collected information on the epidemiology of GI diseases (including cancers) and symptoms, along with data on resource utilization, quality of life, impairments to work and activity, morbidity, and mortality. These data were obtained from the National Ambulatory Medical Care Survey; National Health and Wellness Survey; Nationwide Inpatient Sample; Surveillance, Epidemiology, and End Results Program; National Vital Statistics System; Thompson Reuters MarketScan; Medicare; Medicaid; and the Clinical Outcomes Research Initiative's National Endoscopic Database. We estimated endoscopic use and costs and examined trends in endoscopic procedure. RESULTS: Abdominal pain was the most common GI symptom that prompted a clinic visit (15.9 million visits). Gastroesophageal reflux was the most common GI diagnosis (8.9 million visits). Hospitalizations and mortality from Clostridium difficile infection have doubled in the last 10 years. Acute pancreatitis was the most common reason for hospitalization (274,119 discharges). Colorectal cancer accounted for more than half of all GI cancers and was the leading cause of GI-related mortality (52,394 deaths). There were 6.9 million upper, 11.5 million lower, and 228,000 biliary endoscopies performed in 2009. The total cost for outpatient GI endoscopy examinations was $32.4 billion. CONCLUSIONS: GI diseases are a source of substantial morbidity, mortality, and cost in the United States.


Assuntos
Endoscopia do Sistema Digestório/estatística & dados numéricos , Gastroenteropatias/diagnóstico , Gastroenteropatias/epidemiologia , Hospitalização/estatística & dados numéricos , Qualidade de Vida , Endoscopia do Sistema Digestório/economia , Gastroenteropatias/mortalidade , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/epidemiologia , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Incidência , Medicaid/estatística & dados numéricos , Medicare/estatística & dados numéricos , Programa de SEER/estatística & dados numéricos , Taxa de Sobrevida , Estados Unidos/epidemiologia , Estatísticas Vitais
15.
Am J Gastroenterol ; 108(8): 1322-31, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23711626

RESUMO

OBJECTIVES: Luminal serine-proteases lead to increased colonic paracellular permeability and visceral hypersensitivity in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Other proteases, namely cysteine-proteases (CPs), increase airway permeability by digesting epithelial tight junction proteins. In this study, we focused on constipation-predominant IBS (IBS-C) and we aimed to (i) evaluate CP levels in two cohorts of IBS patients, (ii) test if IBS-C fecal supernatant (FSN) affects permeability, and visceral sensitivity after repeated administrations in mice, and (iii) evaluate occludin expression in IBS-C colonic biopsies. METHODS: Fecal CP activity was determined using selective substrate and inhibitor (E64). The effect of papain, as positive control, and IBS-C FSN administrations were evaluated on colonic paracellular permeability and mucosal occludin levels in mice and T84 monolayers. Occludin protein levels were evaluated in IBS-C colonic biopsies. Sensitivity to colorectal distension (CRD) was measured after repeated administrations of IBS-C FSN. RESULTS: We found in a subset of IBS-C patients an enhanced fecal CP activity, in comparison with healthy controls and IBS-D patients. CP activity levels positively correlated with disease severity and abdominal pain scoring. This association was confirmed by receiver operating characteristic curve analysis. In mice, repeated application of IBS-C FSN into colon triggered increased permeability, linked to the enzymatic degradation of occludin, and was associated with enhanced visceral sensitivity to CRD. Finally, occludin levels were found decreased in colonic biopsies from IBS-C patients, and IBS-C FSNs were able to degrade recombinant human occludin in vitro. All these effects were abolished by preincubation of IBS-C FSN with a CP inhibitor, E64. CONCLUSIONS: These data suggest that luminal CPs may represent a new factor contributing to the genesis of symptoms in IBS.


Assuntos
Cisteína Proteases/metabolismo , Síndrome do Intestino Irritável/enzimologia , Síndrome do Intestino Irritável/patologia , Junções Íntimas/enzimologia , Junções Íntimas/patologia , Dor Abdominal/enzimologia , Dor Abdominal/patologia , Adulto , Análise de Variância , Animais , Biópsia , Western Blotting , Estudos de Casos e Controles , Células Cultivadas , Constipação Intestinal/enzimologia , Constipação Intestinal/patologia , Eletromiografia , Fezes/enzimologia , Feminino , Humanos , Absorção Intestinal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Ocludina/metabolismo , Medição da Dor , Reação em Cadeia da Polimerase , Curva ROC , Inquéritos e Questionários
16.
ACG Case Rep J ; 10(12): e01169, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38089533

RESUMO

Aseptic abscess syndrome is a rare clinical entity mainly associated with systemic inflammatory conditions, particularly inflammatory bowel disease. The syndrome is characterized by an inflammatory infiltrate predominantly consisting of neutrophils, most commonly in the liver and spleen. We present a case of a patient with symptomatic diversion colitis diagnosed with a clinical and histological presentation consistent with aseptic abscess syndrome of the liver. Treatment and resolution of the inflamed colon was associated with complete disappearance of the liver lesions and normalization of liver enzymes. To the best of our knowledge, this is the first report suggesting the unique link between diversion colitis and aseptic liver abscess.

18.
J Nutr ; 142(5): 962-74, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22457389

RESUMO

First defined in the mid-1990s, prebiotics, which alter the composition and activity of gastrointestinal (GI) microbiota to improve health and well-being, have generated scientific and consumer interest and regulatory debate. The Life Sciences Research Organization, Inc. (LSRO) held a workshop, Prebiotics and the Health Benefits of Fiber: Future Research and Goals, in February 2011 to assess the current state of the science and the international regulatory environment for prebiotics, identify research gaps, and create a strategy for future research. A developing body of evidence supports a role for prebiotics in reducing the risk and severity of GI infection and inflammation, including diarrhea, inflammatory bowel disease, and ulcerative colitis as well as bowel function disorders, including irritable bowel syndrome. Prebiotics also increase the bioavailability and uptake of minerals and data suggest that they reduce the risk of obesity by promoting satiety and weight loss. Additional research is needed to define the relationship between the consumption of different prebiotics and improvement of human health. New information derived from the characterization of the composition and function of different prebiotics as well as the interactions among and between gut microbiota and the human host would improve our understanding of the effects of prebiotics on health and disease and could assist in surmounting regulatory issues related to prebiotic use.


Assuntos
Fibras na Dieta/uso terapêutico , Alimento Funcional , Enteropatias , Prebióticos , Bactérias/metabolismo , Neoplasias do Colo/dietoterapia , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/prevenção & controle , Diarreia/dietoterapia , Diarreia/epidemiologia , Diarreia/prevenção & controle , Enterocolite Pseudomembranosa/dietoterapia , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/prevenção & controle , Gastroenterite/dietoterapia , Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Saúde Global , Objetivos , Humanos , Doenças Inflamatórias Intestinais/dietoterapia , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/prevenção & controle , Enteropatias/dietoterapia , Enteropatias/epidemiologia , Enteropatias/prevenção & controle , Mucosa Intestinal/metabolismo , Intestinos/microbiologia , Obesidade/dietoterapia , Obesidade/epidemiologia , Obesidade/prevenção & controle , Saúde Pública , Fatores de Risco , Comportamento de Redução do Risco
19.
Dig Liver Dis ; 54(12): 1657-1661, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35853820

RESUMO

BACKGROUND: This study evaluated the prevalence of cardiovascular risk-factors in patients with mesenteric panniculitis. AIMS: To determine whether cardiovascular risk-factors and mesenteric panniculitis are associated. METHODS: Retrospective, matched case-control study of patients referred to Meir Medical Center, Israel, 2014-2019, who underwent computerized tomography scan, were diagnosed mesenteric panniculitis by radiologic criteria. They were compared to two, matched case-control groups: hospitalized patients without mesenteric panniculitis and the general population based on Israeli Ministry of Health surveys. Patients with active malignancy, IBD or significant intra-abdominal morbidity were excluded. RESULTS: Of 376 patients with mesenteric panniculitis diagnosed by computerized tomography, 187 were included. Compared to hospital patients, they had higher incidence of dyslipidemia (77.5%/56.7%), hypertension (52.4%/40.6%), obesity (body mass index>30) (60.4%/30.5%) and nonalcoholic fatty liver disease (42.2%/16.6%). Similar differences were observed compared to the general population. In multivariable logistic regression, dyslipidemia, obesity, and nonalcoholic fatty liver disease were independent predictors for mesenteric panniculitis. CONCLUSIONS: Patients with mesenteric panniculitis have more cardiovascular risk-factors compared to a case-control group and to the general population. This suggests that mesenteric panniculitis is clinically significant and may be part of the metabolic morbidity burden. This association should be further explored.


Assuntos
Doenças Cardiovasculares , Hepatopatia Gordurosa não Alcoólica , Paniculite Peritoneal , Humanos , Paniculite Peritoneal/diagnóstico por imagem , Paniculite Peritoneal/epidemiologia , Estudos Retrospectivos , Estudos de Casos e Controles , Hepatopatia Gordurosa não Alcoólica/complicações , Doenças Cardiovasculares/epidemiologia , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Obesidade/complicações
20.
Am J Physiol Gastrointest Liver Physiol ; 301(5): G799-807, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21737778

RESUMO

Alterations in the intestinal microbiota have been suggested as an etiological factor in the pathogenesis of irritable bowel syndrome (IBS). This study used a molecular fingerprinting technique to compare the composition and biodiversity of the microbiota within fecal and mucosal niches between patients with diarrhea-predominant IBS (D-IBS) and healthy controls. Terminal-restriction fragment (T-RF) length polymorphism (T-RFLP) fingerprinting of the bacterial 16S rRNA gene was used to perform microbial community composition analyses on fecal and mucosal samples from patients with D-IBS (n = 16) and healthy controls (n = 21). Molecular fingerprinting of the microbiota from fecal and colonic mucosal samples revealed differences in the contribution of T-RFs to the microbiota between D-IBS patients and healthy controls. Further analysis revealed a significantly lower (1.2-fold) biodiversity of microbes within fecal samples from D-IBS patients than healthy controls (P = 0.008). No difference in biodiversity in mucosal samples was detected between D-IBS patients and healthy controls. Multivariate analysis of T-RFLP profiles demonstrated distinct microbial communities between luminal and mucosal niches in all samples. Our findings of compositional differences in the luminal- and mucosal-associated microbiota between D-IBS patients and healthy controls and diminished microbial biodiversity in D-IBS fecal samples further support the hypothesis that alterations in the intestinal microbiota may have an etiological role in the pathogenesis of D-IBS and suggest that luminal and mucosal niches need to be investigated.


Assuntos
Colo/microbiologia , Diarreia/microbiologia , Mucosa Intestinal/microbiologia , Síndrome do Intestino Irritável/microbiologia , Metagenoma/genética , Adulto , DNA Bacteriano/genética , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
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