Background & Aims Weight loss following pharmacotherapy varies greatly. We aimed to examine associations of quantitative gastrointestinal and psychological traits with obesity, and to validate the ability of these traits to predict responses of obese individuals to pharmacotherapy. Methods In a prospective study, we measured gastric emptying (GE) of solids and liquids, fasting and postprandial gastric volume, satiation by nutrient drink test (volume to fullness and maximal tolerated volume), satiety following an ad-libitum buffet meal, gastrointestinal hormones, and psychological traits in 328 normal weight, overweight, or obese adults. We also analyzed data from 181 previously studied adults to assess associations between a subset of traits with body mass index and waist circumference. Latent dimensions associated with overweight or obesity were appraised by principal component analyses. We performed a proof-of-concept, placebo-controlled trial of extended-release phentermine and topiramate in 24 patients, to validate associations between quantitative traits and response to weight-loss therapy. Results In the prospective study, obesity was associated with fasting gastric volume (P=.03), accelerated GE (P<.001 for solids and P=.011 for liquids), lower postprandial levels of peptide tyrosine tyrosine (P=.003), and higher postprandial levels of glucagon-like peptide 1 (P<.001). In a combined analysis of data from all studies, obesity was associated with higher volume to fullness (n=509; P=.038) and satiety with abnormal waist circumference (n=271; P=.016). Principal component analysis identified latent dimensions that accounted for ∼81% of the variation among overweight and obese subjects, including satiety or satiation (21%), gastric motility (14%), psychological factors (13%), and gastric sensorimotor factors (11%). The combination of phentermine and topiramate caused significant weight loss, slowed GE, and decreased calorie intake; weight loss in response to phentermine and topiramate was significantly associated with calorie intake at the prior satiety test. Conclusion Quantitative traits are associated with high body mass index; they can distinguish obesity phenotypes and, in a proof-of-concept clinical trial, predicted response to pharmacotherapy for obesity.

Background & Aims There is an unclear relationship among bowel symptoms, excretion of unconjugated fecal bile acid (UBA), and colonic transit in irritable bowel syndrome (IBS). We measured total and main individual UBA in fecal samples of patients with IBS, and assessed relationships among stool frequency or consistency, fecal UBA (total and individual), and colonic transit. Methods In a study of 30 healthy volunteers (controls), 31 subjects with IBS with diarrhea (IBS-D), and 30 with IBS with constipation (IBS-C) were placed on 4-day diets containing 100 g fat; we measured stool characteristics, total fecal UBA and fat levels, and overall colonic transit. We assessed univariate associations of total and individual levels of fecal UBA with phenotype (controls, IBS-D, IBS-C) using the Kruskal-Wallis test; associations between endpoints were assessed using Spearman correlations. With response surface regression models, we assessed relationships between stool, colonic transit, and fecal total and secretory UBA. Results There was a significant association between total fecal UBA and phenotype (P=.029); the association was greater for IBS-D than IBS-C, compared with controls. Fecal levels of primary UBAs (cholic and chenodeoxycholic acids) were higher in subjects with IBS-D, compared with controls (both P<.01). Levels of fecal secretory UBAs (chenodeoxycholic acids, P=.019; deoxycholic acid, P=.025) were lower in subjects with IBS-C compared with controls, whereas levels of the nonsecretory UBA, lithocholic acid, were higher (P=.020). There were significant univariate associations between stool number and form and total fecal UBA (including percentages of lithocholic acid, chenodeoxycholic acids, and cholic acid), fecal fat, and colonic transit at 24 and 48 h after eating. In the regression models, the relative contribution of colonic transit was consistently greater, and largely independent of the contribution of bile acids. Conclusions Measurements of individual UBAs identify changes associated with stool characteristics in patients with IBS; these effects are independent of the effects of colonic transit.

Background Gastric emptying (GE) is measured in pharmacodynamic and diagnostic studies. Aims To assess inter- and intra-subject coefficients of variation (COV) of scintigraphic GE measurements in healthy subjects, and associations of GE with gender and BMI. Methods Data from participants with scintigraphic measurements of gastric emptying of solids were analyzed. Primary endpoints were gastric emptying T1/2 (GE T1/2) and GE at 1, 2, 3 and 4 hours. Results The patient cohort consisted of 105 males and 214 females; at least 2 studies were performed in 47 subjects [16 males (M), 32 females (F)]. Inter-subject COV (COVinter) for GE T1/2 were similar in M and F: overall 24.5% (M 26.0%, F 22.5%); COV are predictably lowest for GE at 4h (COVinter 9.6%). COVintra for T1/2 and GE4h were overall 23.8% and 12.6%, and were similar to COVinter values. Gender (but not age or body mass index [BMI]) was significantly associated with GE T1/2 [p<0.001, F 127.6 ± 28.7 (SD) min; M 109.9 ± 28.6 min] and with GE at 1h and 2h. Repeat GE T1/2 values in 47 participants were significantly correlated (r= 0.459, p<0.001) with median difference of −6 min (mean −1.6, range −56 to 72 min). Bland-Altman plots showed Δ GE T1/2 similarly distributed across mean GE T1/2 100–155 minutes, and across studies conducted 90 to 600 days apart. Conclusion Inter-subject variations in scintigraphic GE results are only slightly higher than the intra-subject measurements, which are also reproducible over time in healthy volunteers. Gender, but not BMI, is significantly associated with GE results.

The purpose of this expert review is to synthesize the existing evidence on the management of Clostridium difficile infection in patients with underlying inflammatory bowel disease. The evidence reviewed in this article is a summation of relevant scientific publications, expert opinion statements, and current practice guidelines. This review is a summary of expert opinion in the field without a formal systematic review of evidence. Best Practice Advice 1: Clinicians should test patients who present with a flare of underlying inflammatory bowel disease for Clostridium difficile infection. Best Practice Advice 2: Clinicians should screen for recurrent C difficile infection if diarrhea or other symptoms of colitis persist or return after antibiotic treatment for C difficile infection. Best Practice Advice 3: Clinicians should consider treating C difficile infection in inflammatory bowel disease patients with vancomycin instead of metronidazole. Best Practice Advice 4: Clinicians strongly should consider hospitalization for close monitoring and aggressive management for inflammatory bowel disease patients with C difficile infection who have profuse diarrhea, severe abdominal pain, a markedly increased peripheral blood leukocyte count, or other evidence of sepsis. Best Practice Advice 5: Clinicians may postpone escalation of steroids and other immunosuppression agents during acute C difficile infection until therapy for C difficile infection has been initiated. However, the decision to withhold or continue immunosuppression in inflammatory bowel disease patients with C difficile infection should be individualized because there is insufficient existing robust literature on which to develop firm recommendations. Best Practice Advice 6: Clinicians should offer a referral for fecal microbiota transplantation to inflammatory bowel disease patients with recurrent C difficile infection.

Altered bile acid (BA) concentrations in the colon may cause diarrhea or constipation. BA malabsorption (BAM) accounts for >25% of patients with irritable bowel syndrome (IBS) with diarrhea and chronic diarrhea in Western countries. As BAM is increasingly recognized, proper diagnostic methods are desired in clinical practice to help direct the most effective treatment course for the chronic bowel dysfunction. This review appraises the methodology, advantages and disadvantages of 4 tools that directly measure BAM: 14C-glycocholate breath and stool test, 75Selenium HomotauroCholic Acid Test (SeHCAT), 7 α-hydroxy-4-cholesten-3-one (C4) and fecal BAs. 14C-glycocholate is a laborious test no longer widely utilized. 75SeHCAT is validated, but not available in the United States. Serum C4 is a simple, accurate method that is applicable to a majority of patients, but requires further clinical validation. Fecal measurements to quantify total and individual fecal BAs are technically cumbersome and not widely available. Regrettably, none of these tests are routinely available in the U.S., and a therapeutic trial with a BA binder is used as a surrogate for diagnosis of BAM. Recent data suggest there is an advantage to studying fecal excretion of the individual BAs and their role in BAM; this may constitute a significant advantage of the fecal BA method over the other tests. Fecal BA test could become a routine addition to fecal fat measurement in patients with unexplained diarrhea. In summary, availability determines the choice of test among C4, SeHCAT and fecal BA; more widespread availability of such tests would enhance clinical management of these patients.