Cholecystectomy and Biliary Sphincterotomy Increase Fecal Bile Loss and Improve Lipid Profile in Dyslipidemia.

BACKGROUND AND AIMS: Bile is the only significant pathway for cholesterol elimination. Cholecystectomy (CS) increases fecal bile acid loss, and endoscopic biliary sphincterotomy (ES) is thought to have a similar effect. We speculated that a combined effect of ES + CS would further enhance fecal bile acid loss, potentially causing lipid profile changes in these patients. METHODS: Fecal bile acids and sterols were determined using gas chromatography in cohorts of post-CS + ES, post-CS and in healthy controls. The effect of ES + CS on blood lipid profile was assessed retrospectively in a single-center cohort of post-CS + ES patients, using a computerized database. Parameters of interest included demographics, medical history, and lipid profiles. RESULTS: Fecal primary bile acid concentrations were increased after CS + ES compared to CS and controls (cholic acid [CA] 1.4 ng/mg vs. 0.26 ng/mg, p = 0.02 vs. 0.23 ng/mg, p = 0.004, chenodeoxycholic acid [CDCA] 1.92 ng/mg vs. 0.39 ng/mg, p = 0.02 vs. 0.23 ng/mg, p = 0.01, respectively). Fecal cholesterol excretion was similar in all three groups. Baseline serum lipid profile and subsequent changes following CS + ES were correlated. In patients with baseline hypercholesterolemia (total cholesterol (TC) > 200 mg/dl), TC levels decreased by 28.5 mg/dl, and LDL levels decreased by 21.5 mg/dl. The effect was more pronounced in those with TC > 200 mg/dl, despite of statin intake. In patients with hypertriglyceridemia [triglycerides (TG) > 200 mg/dl], TG decreased by 67.8 mg/dl following ES + CS. Among patients without dyslipidemia or dyslipidemia with adequate response to statins, the effect of ES + CS on lipid profile was minor. CONCLUSIONS: Fecal bile acid loss increases following CS + ES. The effect on blood lipid profile depends on baseline TC and TG levels. Lipid profile is improved in dyslipidemic patients, while the impact of CS + ES is minimal on the normolipemic population.

Pouch Inflammation Is Associated With a Decrease in Specific Bacterial Taxa.

BACKGROUND & AIMS: Pouchitis is a common long-term complication in patients with ulcerative colitis (UC) undergoing proctocolectomy with ileal pouch-anal anastomosis. Because the inflammation occurs in a previously normal small bowel, studies of this process might provide information about the development of Crohn's disease. Little is known about the intestinal microbiome of patients with pouchitis. We investigated whether specific bacterial populations correlate with the pouch disease phenotype and inflammatory activity. METHODS: We performed a prospective study of patients with UC who underwent pouch surgery (N = 131) from 1981 through 2012 and were followed at Tel Aviv Medical Center. Patients were assigned to groups based on their degree and type of pouch inflammation. Patients with familial adenomatous polyposis after pouch surgery (n = 9), individuals with intact colons undergoing surveillance colonoscopy (n = 10), and patients with UC who did not undergo surgery (n = 9) served as controls. We collected demographic and disease activity data (based on the Pouchitis Disease Activity Index) and measured levels of C-reactive protein. Fecal samples were collected, levels of calprotectin were measured, and microbiota were analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. RESULTS: Increased proportions of the Fusobacteriaceae family correlated with increased disease activity and levels of C-reactive protein in patients with UC who underwent pouch surgery. In contrast, proportions of Faecalibacterium were reduced in patients with pouchitis vs controls; there was a negative correlation between proportion of Faecalibacterium and level of C-reactive protein. There was an association between antibiotic treatment, but not biologic or immunomodulatory therapy, with reduced proportions of 11 genera and with increased proportions of Enterococcus and Enterobacteriaceae. CONCLUSIONS: Reductions in protective bacteria and increases in inflammatory bacteria are associated with pouch inflammation in patients with UC who underwent pouch surgery. The finding that antibiotics exacerbate dysbiosis indicates that these drugs might not provide long-term benefit for patients with pouchitis. Additional studies of this form of dysbiosis could provide information about the pathogenesis of Crohn's disease.

Fecal microbiome signatures of pancreatic cancer patients.

Pancreatic cancer (PC) is a leading cause of cancer-related death in developed countries, and since most patients have incurable disease at the time of diagnosis, developing a screening method for early detection is of high priority. Due to its metabolic importance, alterations in pancreatic functions may affect the composition of the gut microbiota, potentially yielding biomarkers for PC. However, the usefulness of these biomarkers may be limited if they are specific for advanced stages of disease, which may involve comorbidities such as biliary obstruction or diabetes. In this study we analyzed the fecal microbiota of 30 patients with pancreatic adenocarcinoma, 6 patients with pre-cancerous lesions, 13 healthy subjects and 16 with non-alcoholic fatty liver disease, using amplicon sequencing of the bacterial 16S rRNA gene. Fourteen bacterial features discriminated between PC and controls, and several were shared with findings from a recent Chinese cohort. A Random Forest model based on the microbiota classified PC and control samples with an AUC of 82.5%. However, inter-subject variability was high, and only a small part of the PC-associated microbial signals were also observed in patients with pre-cancerous pancreatic lesions, implying that microbiome-based early detection of such lesions will be challenging.

Interactions between the intestinal microbiota and bile acids in gallstones patients.

Cholecystectomy, surgical removal of the gallbladder, changes bile flow to the intestine and can therefore alter the bidirectional interactions between bile acids (BAs) and the intestinal microbiota. We quantified and correlated BAs and bacterial community composition in gallstone patients scheduled for cholecystectomy before and after the procedure, using gas-liquid chromatography and 16S rRNA amplicon sequencing, followed by quantitative real-time polymerase chain reaction of the phylum Bacteroidetes. Gallstone patients had higher overall concentrations of faecal BAs and a decreased microbial diversity, accompanied by a reduction in the beneficial genus Roseburia and an enrichment of the uncultivated genus Oscillospira, compared with controls. These two genera may thus serve as biomarkers for symptomatic gallstone formation. Oscillospira was correlated positively with secondary BAs and negatively with primary BAs, while the phylum Bacteroidetes showed an opposite trend. Cholecystectomy resulted in no substantial change in patients' faecal BAs. However, bacterial composition was significantly altered, with a significant increase in the phylum Bacteroidetes. Given that cholecystectomy has been associated with a higher risk of colorectal cancer and that members of the Bacteroidetes are increased in that disease, microbial consequences of cholecystectomy should be further explored.

Can Colonoscopy Aspirates be a Substitute for Fecal Samples in Analyses of the Intestinal Microbiota?

There is a growing interest in the study of the human gut microbiota, as correlations between changes in bacterial profiles and diseases are increasingly discovered. Studies in this field generally use fecal samples, but it is often easier to obtain colon content aspirates during colonoscopy. This study used automated ribosomal internal spacer analysis (ARISA) to examine the extent to which the microbiota of colon aspirate samples obtained after bowel cleansing can reflect interindividual differences and serve as a proxy for fecal samples. Pre-bowel preparation fecal samples as well as colonoscopy aspirate samples from the cecum and rectum were obtained from 19 subjects. DNA was extracted from all samples, and comparative analysis was performed, including analysis of similarity (ANOSIM) and nonmetric multidimensional scaling. ANOSIM confirmed that samples from the same individual were well separated from samples from different individuals. Significantly larger differences were found between samples from different individuals than between samples of the same individual (R = 0.7605, p < 0.0001). These findings show that post-bowel preparation aspirates maintain a strong individual signature. Colonoscopy aspirates can therefore serve as a substitute for fecal samples in studies comparing the microbiota of different clinical study groups, especially when fecal samples are unavailable.