Fecal Microbiota Transplantation: Current Status in Treatment of GI and Liver Disease.

Fecal microbiota transplantation was originally introduced as a method to repair intestinal microbiota following failure of multiple treatments of recurrent Clostridiumdifficile infection with antibiotics. However, it is hypothesized that intestinal dysbiosis may contribute to the pathogenesis of many diseases, especially those involving the gastrointestinal tract. Therefore, fecal microbiota transplantation is increasingly being explored as a potential treatment that aims to optimize microbiota composition and functionality. Here, we review the current state of fecal microbiota transplantation development and applications in conditions of greatest interest to a gastroenterologist.

Stool Based Testing for Colorectal Cancer: an Overview of Available Evidence.

PURPOSE OF REVIEW: The goal of this review is to summarize stool-based testing for colorectal cancer (CRC). The key questions answered in this review were the advantages and limitations of each available stool-based test for CRC and to examine their comparative efficacy. RECENT FINDINGS: Guaiac-based fecal occult blood testing (gFOBT) is no longer a relevant test for CRC screening. fecal immunochemical testing (FIT) tests, especially quantitative assays, are clearly a reliable stool-based test. Multitarget DNA (mtsDNA) stool testing may represent a viable option as well, although cost and test characteristics are yet fully defined. FIT and mtsDNA represent the options for stool-based CRC screening. In larger screening centers, quantitative FIT assays represent an attractive option for stool-based testing. Qualitative FIT has applicability in smaller centers. Although a large validation trial showed promising results for mtsDNA, further head-to-head trials with FIT will help define the ultimate role of mtsDNA. Ultimately, however, the best test for CRC screening is the one performed stool-based CRC screening as an initial or alternative option can increase participation in CRC screening.

Inflammatory Bowel Disease Affects the Outcome of Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection.

BACKGROUND & AIMS: A significant fraction of patients with recurrent Clostridium difficile infections (CDI) have inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) can break the cycle of CDI recurrence and can be performed without evaluation of the colon. We evaluated the efficacy of colonoscopic FMT in patients with and without IBD, and whether we could identify IBD in patients during this procedure. METHODS: We collected clinical meta-data and colonoscopy results from 272 consecutive patients that underwent FMT for recurrent CDI at the University of Minnesota from 2008 through 2015. Patients had at least 2 spontaneous relapses of CDI following their initial episode and did not clear the infection after 1 extended antibiotic regimen. We collected random mucosal biopsies from patients' right colons to identify lymphocytic or collagenous colitis during the FMT procedure. Failure or success in clearing CDI was determined within or at 2 months after the FMT. RESULTS: Of patients undergoing FMT, 15% had established IBD and 2.6% were found to have IBD during the FMT procedure. A single colonoscopic FMT cleared CDI from 74.4% of patients with IBD and 92.1% of patients without IBD (P = .0018). Patients had similar responses to FMT regardless of immunosuppressive therapy. More than one-quarter of patients with IBD (25.6%) had a clinically significant flare of IBD after FMT. Lymphocytic colitis was documented in 7.4% of patients with endoscopically normal colon mucosa; only 3 of these patients (20%) required additional treatment for colitis after clearance of CDI. CONCLUSIONS: Based on an analysis of 272 patients, FMT is somewhat less effective in clearing recurrent CDI from patients with IBD, compared with patients without IBD, regardless of immunosuppressive therapy. More than 25% of patients with IBD have a disease flare following FMT. Lymphocytic colitis did not affect the outcome of FMT, but a small fraction of these patients required pharmacologic treatment after the procedure.

Single-session laparoscopic cholecystectomy and ERCP: a valid option for the management of choledocholithiasis.

BACKGROUND AND AIMS: The option for performing ERCP and laparoscopic cholecystectomy (LC) for the management of choledocholithiasis in the same operative session is often overlooked. We compared the success, safety, and cost of ERCP and LC when performed in either a single session or in separate sessions. METHODS: We conducted a retrospective cohort study at a U.S. tertiary care hospital. We identified patients undergoing ERCP and LC between April 2011 and August 2014 in either a single operative session (n = 33) or in 2 separate sessions within a 30-day period (n = 80). Technical success, total anesthesia duration, operative time, length of hospitalization, cost of care, and morbidity and mortality were evaluated. RESULTS: Bile duct clearance was achieved in all patients at ERCP in the same-session cohort. The separate versus single-session groups, respectively, did not differ in terms of total procedure times (mean ± SD = 142 ± 64 vs 142 ± 58 min; t test, P =.98), anesthesia duration (251 ± 64 vs 225 ± 69 min; P =.06), or overall cost (49.3 ± 24.5 vs 42.3 ± 23.2 ×1000 USD; P =.167), but hospitalization was longer in the separate-sessions group (6.2 ± 3.3 vs 4.8 ± 2.6 days; P =.03). The rates of adverse events were similarly low (7% vs 2%, P =.70). CONCLUSIONS: Performing single-session ERCP and LC is safe, effective, economically viable, and reduces hospital stay compared with performing ERCP and LC during separate sessions.

Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients.

OBJECTIVES: Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients. METHODS: A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT. RESULTS: Cases included adult (75) and pediatric (5) patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3-46 months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19), oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT, but two patients developed unrelated infections and five had self-limited diarrheal illness in which no causal organism was identified. One patient had a superficial mucosal tear caused by the colonoscopy performed for the FMT, and three patients reported mild, self-limited abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy related to course of UC >100 days after FMT. CONCLUSIONS: This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs. Importantly, there were no related infectious complications in these high-risk patients.

Cilofexor in Patients With Compensated Cirrhosis Due to Primary Sclerosing Cholangitis: An Open-Label Phase 1B Study.

INTRODUCTION: This proof-of-concept, open-label phase 1b study evaluated the safety and efficacy of cilofexor, a potent selective farnesoid X receptor agonist, in patients with compensated cirrhosis due to primary sclerosing cholangitis. METHODS: Escalating doses of cilofexor (30 mg [weeks 1-4], 60 mg [weeks 5-8], 100 mg [weeks 9-12]) were administered orally once daily over 12 weeks. The primary endpoint was safety. Exploratory measures included cholestasis and fibrosis markers and pharmacodynamic biomarkers of bile acid homeostasis. RESULTS: Eleven patients were enrolled (median age: 48 years; 55% men). The most common treatment-emergent adverse events (TEAEs) were pruritus (8/11 [72.7%]), fatigue, headache, nausea, and upper respiratory tract infection (2/11 [18.2%] each). Seven patients experienced a pruritus TEAE (one grade 3) considered drug-related. One patient temporarily discontinued cilofexor owing to peripheral edema. There were no deaths, serious TEAEs, or TEAEs leading to permanent discontinuation. Median changes (interquartile ranges) from baseline to week 12 (predose, fasting) were -24.8% (-35.7 to -7.4) for alanine transaminase, -13.0% (-21.9 to -8.6) for alkaline phosphatase, -43.5% (-52.1 to -30.8) for γ-glutamyl transferase, -12.7% (-25.0 to 0.0) for total bilirubin, and -21.2% (-40.0 to 0.0) for direct bilirubin. Least-squares mean percentage change (95% confidence interval) from baseline to week 12 at trough was -55.3% (-70.8 to -31.6) for C4 and -60.5% (-81.8 to -14.2) for cholic acid. Fasting fibroblast growth factor 19 levels transiently increased after cilofexor administration. DISCUSSION: Escalating doses of cilofexor over 12 weeks were well tolerated and improved cholestasis markers in patients with compensated cirrhosis due to primary sclerosing cholangitis (NCT04060147).

Adult Intestinal Toxemia Botulism in a Patient With Crohn's Disease.

Adult intestinal toxemia botulism (ITB) is a rare illness that can be fatal if not recognized. ITB can occur when botulinum neurotoxin-producing clostridia colonize the intestine. Underlying intestinal abnormalities associated with dysbiosis are likely a prerequisite for colonization. Dysbiosis seems necessary for spore germination and neurotoxin production. Botulism neurotoxins are the most lethal poisons known and are classified into 7 serotypes: A through G. The clinical presentation consists of cranial nerve abnormalities and descending flaccid paralysis. Prompt recognition and treatment with botulism antitoxin and supportive measures is often successful, but delayed recognition can be fatal. In this study, we present a case of a 40-year-old woman with Crohn's disease who developed ITB. This is the first case in literature to report adult intestinal botulism from Clostridium botulinum producing toxin B and F in the same patient.

Treatment of recurrent Clostridium difficile infection using fecal microbiota transplantation in patients with inflammatory bowel disease.

We recently compared results of fecal microbiota transplantation (FMT) in patients with refractory, recurrent Clostridium difficile infection (rCDI), with and without underlying inflammatory bowel disease (IBD). Here we extend this cohort and analyze outcomes in greater detail by subtype of IBD. We find that FMT is generally effective in breaking the cycle of CDI recurrence, but its effects on overall IBD progression are much less predictable. We discuss several challenges intrinsic to this complex clinical situation and outline the next steps that can address these challenges going forward.