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Irritable bowel syndrome (IBS) is a symptom-based disorder of chronic abdominal pain and altered bowel habits. The pathogenesis of IBS is multifactorial, leading to the potential for the development of diverse treatment strategies. This mechanistic heterogeneity suggests that available therapies will only prove effective in a subset of IBS sufferers. Current US Food and Drug Administration (FDA) approved therapies for IBS with diarrhea (IBS-D) and IBS with constipation (IBS-C) are reviewed. Limited symptom responses and side effect experiences lead to considerable patient dissatisfaction with currently available IBS treatments. Only a small percentage of IBS patients are on prescription therapies underscoring the potential market and need for additional therapeutic options.Expanding on currently available therapies, the serotonergic and endogenous opioid receptor systems continue to be a focus of future IBS treatment development. Additional novel emerging therapies include the endogenous cannabinoid system, bile acid secretion and sequestration, and exploit our enhanced understanding of visceral sensory signaling and intestinal secretomotor function.While challenges remain for the future development of IBS therapies, the diverse etiologies underlying the disorder present an opportunity for novel therapies. Hence, great potential is anticipated for future IBS treatment options.

BACKGROUND. Obesity is associated with increased risk for various gastrointestinal and liver diseases. However, the relationship between obesity and abnormal bowel habits is poorly understood. AIMS. To investigate the relationship between Body Mass Index (BMI) and bowel habit, controlling for clinical, demographic and dietary factors, in a representative sample of the United States adult population. METHODS. Data were extracted from the 2009–2010 National Health and Nutrition Examination Survey (NHANES). Survey responses were included in this study if respondents completed the bowel health questionnaire (BHQ), were ≥20 years of age, and did not report history of inflammatory bowel disease, celiac disease, or colon cancer. BMI was divided into the following categories: underweight, normal weight, overweight, obese, and severely obese. Stepwise logistic regression provided risk ratios of constipation and diarrhoea controlling for confounding factors (dietary, life-style, psychological and medical). RESULTS. A total of 5,126 respondents completed the BHQ, had BMI data available, and met eligibility criteria. Of these, 70 (1.40%) were underweight, 1,350 (26.34%) were normal weight, 1,731 (33.77%) were overweight, 1,097 (21.40%) were obese, and 878 (17.13%) were severely obese. Up to 8.5% of obese and 11.5% of severely obese individuals had chronic diarrhoea, compared to 4.5% of normal weight individuals. Stepwise regression revealed that severe obesity was independently associated with increased risk of diarrhoea. CONCLUSIONS. In conclusion, this study provides strong evidence that obesity is positively associated with chronic diarrhoea in a nationally representative US adult population after adjusting for several known confounding factors

Unexplained, multi-system somatic symptoms and syndromes, the hallmark features of somatization, are prevalent in patients with functional gastrointestinal disorders (FGIDs). We studied outpatients attending a gastroenterology clinic to see whether current somatic symptom burdens (a somatization state measure) or number of prior functional diagnoses (a somatization trait measure) could predict the presence of an FGID over structural gastrointestinal disease, and whether the predictive value was dependent on comorbid depression or anxiety disorders.Clinical data from 327 consecutive new referrals to an outpatient gastroenterology practice were reviewed, 187 with an FGID and 140 with a structural illness. Somatization state and trait were measured by using self-reported current symptoms and functional diagnoses recorded in the medical history, respectively. Psychiatric comorbidity (depression or anxiety disorders) was extracted from chart review.FGID subjects endorsed more somatization state symptoms, had more somatization trait diagnoses, and had greater likelihood of psychiatric comorbidity (P.001 for each). Logistic regression analysis adjusting for age and sex differences showed that each of these features independently predicted the likelihood of an FGID over structural disease (P.05 for each). When high ratings on the somatization measures were present together with psychiatric comorbidity, the positive predictive value exceeded 0.95.Higher burdens of either current somatic symptoms or functional diagnoses in the medical history are strong predictors of an FGID in outpatients presenting with gastrointestinal complaints. The mechanism is not solely dependent on a relationship with affective disorders, which independently predicts FGID, at least in part, through another path.

OBJECTIVE Nonalcoholic steatohepatitis (NASH) is a morbid liver disease with limited treatment. Depression and anxiety have been associated recently with insulin resistance and inflammatory states, factors that are relevant to the development of NASH. We hypothesized that depression and anxiety would be more prevalent in NASH patients and predict more severe histological findings on liver biopsy. METHODS Histories of major depressive disorder (MDD) and generalized anxiety disorder (GAD) were determined using a structured interview and DSM-IV criteria in 36 NASH subjects and 36 matched controls without liver disease who had undergone cholecystectomy. Histological changes on liver biopsy in NASH subjects were age-adjusted and compared in subjects with and without psychiatric disorders. A multivariate model incorporating other potential risk factors for NASH (female sex, body mass index, waist-to-hip ratio, and presence of diabetes) was used to determine independent effects of MDD and GAD on severity of histological findings. RESULTS NASH subjects had significantly increased lifetime rates of MDD (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.4-10.2; p = .018) and GAD (OR 5.0, 95% CI, 1.7-14.9; p = .005). The onset of psychiatric illness preceded diagnosis of liver disease by 18 to 20 years. Each psychiatric disorder was associated with more severe histological features (p < .05 for each), the effect of GAD on fibrosis stage persisting in the multivariate model. CONCLUSIONS MDD and GAD are overrepresented in NASH subjects and are associated with more advanced liver histological abnormalities. Additional investigation will be required to determine if depression and anxiety affect the development or progression of NASH and serve as modifiable risk factors.

Autoimmune enteropathy (AIE) is characterized by chronic intractable diarrhea, weight loss from malabsorption, and immune-mediated damage to the intestinal mucosa. The syndrome initially was described in 1982 in a male child (1, 2). Walker-Smith formulated a set of diagnostic criteria for the disorder that remain in use: (a) small intestinal villous atrophy, (b) unresponsiveness to dietary restriction, and (c) circulating enterocyte antibodies and/or associated autoimmune conditions (3). AIE also occurs in the setting of immunoglobulin deficiencies, a known risk factor for the development of autoimmune disorders (4, 5). The first published cases of adult-onset AIE appeared in 1997 when Corazza et al. described two subjects aged 38 and 47 years with severe diarrhea and malabsorption, small bowel villous atrophy, no response to gluten-free diet, and circulating antienterocyte antibodies (6, 7). Only occasional case reports of adults with this disorder have appeared since, and similarly to pediatric cases, adultonset AIE has been associated with autoimmunity and immunoglobulin deficiency. AIE likely is but one manifestation of a more diffuse autoimmune disorder of the gastrointestinal system with heterogeneous manifestations including gastritis, colitis, hepatitis, and pancreatitis, as well as a variety of autoantibodies, such as anti–parietal cell antibodies and anti–goblet cell antibodies (4, 8, 9). Leon et al. recently coined the term generalized autoimmune gut disorder (GAGD) for those whose autoimmune gastrointestinal damage extends beyond the small intestine

The US Multi-Society Task Force on Colorectal Cancer published guidelines for colonoscopy screening and surveillance in 2008 and affirmed them in 2012. Characteristics associated with guideline adherence among US gastroenterologists have not been assessed.Assess awareness and adherence of US gastroenterologists with national guidelines for colonoscopy screening and surveillance and predictors of adherence to guidelines.A Web-based survey was administered to gastroenterologists in various practice settings across the USA.A total of 306 gastroenterologists completed the survey; 86 % reported awareness of the guidelines. Low-volume colonoscopists (20/month) were less likely to be aware of the guidelines (OR 0.26, p = 0.03) compared to high-volume colonoscopists (100/month). Those completing training before 1990 were less likely to report following guidelines (OR 0.37, p = 0.01). Adherence with guidelines was then assessed via clinical scenarios. Compared to physicians finishing training in 1991-2010, less adherence was seen in those finishing before 1990 (OR 0.75, p0.001) or currently in training (OR 0.72, p = 0.004). Compared to the Western USA, less adherence was seen in the Midwest (OR 0.69, p = 0.001), Northeast (OR 0.63, p0.001), and South (OR 0.59, p0.001). Lower adherence was seen among non-academic physicians (OR 0.72, p = 0.001) and low-volume colonoscopists (OR 0.52, p0.001).There is poor adherence with colonoscopy screening and surveillance guidelines among US gastroenterologists. Poor adherence was associated with being in training or finishing training before 1990, practicing in the South, non-academic settings, and low colonoscopy volume. These findings can target interventions for quality improvement in colorectal cancer screening and surveillance.

AIM: To determine if diabetes mellitus (DM) is associated with increased risk of colorectal adenomas in younger subjects. METHODS: This was a retrospective cohort study of 375 patients undergoing index colonoscopy at a single tertiary care center in the United States. Three cohorts of patients matched for exam date and gender were compared: (1) ages 40-49 years with DM; (2) ages 40-49 years without DM; and (3) ages 50-59 years without DM. Data collected included demographics, co-morbidities, colonoscopy and pathology results. Adenoma detection rates (ADR) were calculated and compared. Conditional logistic regression analysis was performed to determine the association between each cohort and ADR. RESULTS: One hundred and twenty-five patients ages 40-49 with DM met study eligibility criteria. Patients in the other two cohorts were randomly selected, matching for date of exam and gender. ADR was 14.4% in those ages 40-49 years without DM, 30.4% in those ages 40-49 years with DM, and 32.0% in those ages 50-59 years without DM. Compared to those ages 40-49 years without DM, ADR was higher in those ages 40-49 years with DM (OR = 3.1; 95%CI: 1.5-6.4; P = 0.002) and those ages 50-59 years without DM (OR = 2.9; 95%CI: 1.5-5.6; P = 0.002). There was no difference between the ADR in those ages 40-49 years with DM and those ages 50-59 years without DM (P = 0.83). CONCLUSION: DM was associated with higher risk of colorectal adenomas in patients ages 40-49 years. These subjects harbored as many adenomas as those at the standard screening age of 50-59 years without DM.

OBJECTIVES To identify factors responsible for premature antidepressant discontinuation that would assist in designing management strategies for patients with functional gastrointestinal disorders. Antidepressants are being used increasingly to manage patients with functional gastrointestinal disorders; poor patient adherence to treatment regimens, particularly in the period shortly after antidepressant initiation, is common and interferes with success. METHODS Clinical records were reviewed from 172 outpatients who attended a university-based practice and who had been prescribed antidepressants to manage their functional gastrointestinal symptoms. Survival analysis methods were used to determine independent predictors of premature antidepressant discontinuation (within 6 months of initiation). Logistic regression analyses were used to see if the same predictors were responsible for side effects or poor treatment response. RESULTS Premature antidepressant discontinuation occurred in 41 (23.8%) subjects. Somatization features (state or trait) and history of depression or an anxiety disorder were the most significant predictors of premature discontinuation (p < or = .01 for each). Advancing age and female sex also were independent predictors (p < .05 for each). Somatization features and psychiatric illness were each linked to poor treatment response, whereas somatization features most consistently were associated with antidepressant side effects. CONCLUSIONS Failure to maintain treatment occurs in nearly a quarter of outpatients given antidepressants for functional gastrointestinal disorders. Somatization features and history of depression or anxiety most significantly interfered with treatment by predicting side effects, poor treatment response, and premature antidepressant discontinuation. Management algorithms should include specific strategies targeted at patients with these risk factors for poor treatment adherence.

OBJECTIVES: Increased risk for colorectal cancer (CRC) has been associated with type 2 diabetes. Despite several studies linking insulin resistance to increased CRC risk, there are limited data on colorectal adenoma risk in diabetic women. We hypothesized that diabetic women would have increased rates of colorectal adenomas relative to a group of nondiabetic women. METHODS: Colorectal adenoma rates were determined in 100 estrogen-negative women with type 2 diabetes mellitus and compared with 500 nondiabetic, estrogen-negative controls. Adenomas were defined as any adenoma or advanced adenoma (villous or tubulovillous features, size >1 cm or high-grade dysplasia). A multivariate model including age, race, diabetes, hypertension, hypercholesterolemia, body mass index, and nonsteroidal anti-inflammatory drug status was used to determine the independent effects of diabetes on colorectal adenoma incidence. RESULTS: Diabetics as compared with nondiabetics had greater rates of any adenoma (37% vs 24%, p = 0.009) and advanced adenomas (14% vs 6%, p = 0.009). Two hundred forty-five obese subjects compared with 355 nonobese subjects had a higher rate of any adenoma (32% vs 22%, p = 0.001). Obese diabetics compared with nonobese, nondiabetics had greater rates of any adenoma (42% vs 23%, p ≤ 0.001 ) and advanced adenomas (19% vs 7%, p ≤ 0.001). Multivariate analysis showed that adenomas and advanced adenomas were independently predicted by diabetes (p < 0.05) and adenomas by age. DISCUSSION: Women with type 2 diabetes mellitus had higher rates of colorectal adenomas as compared with lean and nondiabetic women. This finding adds to the evidence that type 2 diabetes is an important factor in the progression of the adenoma-carcinoma sequence.