ABSTRACT
BACKGROUND: To date, evidence for the efficacy of fecal microbiota transplantation (FMT) in recurrent Clostridium difficile infection (CDI) has been limited to case series and open-label clinical trials. OBJECTIVE: To determine the efficacy and safety of FMT for treatment of recurrent CDI. DESIGN: Randomized, controlled, double-blind clinical trial. (ClinicalTrials.gov: NCT01703494). SETTING: Two academic medical centers. PATIENTS: 46 patients who had 3 or more recurrences of CDI and received a full course of vancomycin for their most recent acute episode. INTERVENTION: Fecal microbiota transplantation with donor stool (heterologous) or patient's own stool (autologous) administered by colonoscopy. MEASUREMENTS: The primary end point was resolution of diarrhea without the need for further anti-CDI therapy during the 8-week follow-up. Safety data were compared between treatment groups via review of adverse events (AEs), serious AEs (SAEs), and new medical conditions for 6 months after FMT. Fecal microbiota analyses were performed on patients' stool before and after FMT and also on donors' stool. RESULTS: In the intention-to-treat analysis, 20 of 22 patients (90.9%) in the donor FMT group achieved clinical cure compared with 15 of 24 (62.5%) in the autologous FMT group (P = 0.042). Resolution after autologous FMT differed by site (9 of 10 vs. 6 of 14 [P = 0.033]). All 9 patients who developed recurrent CDI after autologous FMT were free of further CDI after subsequent donor FMT. There were no SAEs related to FMT. Donor FMT restored gut bacterial community diversity and composition to resemble that of healthy donors. LIMITATION: The study included only patients who had 3 or more recurrences and excluded those who were immunocompromised and aged 75 years or older. CONCLUSION: Donor stool administered via colonoscopy seemed safe and was more efficacious than autologous FMT in preventing further CDI episodes. PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases.
Subject(s)
Clostridioides difficile , Clostridium Infections/therapy , Diarrhea/therapy , Fecal Microbiota Transplantation , Clostridium Infections/microbiology , Colonoscopy , Diarrhea/microbiology , Double-Blind Method , Fecal Microbiota Transplantation/adverse effects , Fecal Microbiota Transplantation/methods , Female , Humans , Intention to Treat Analysis , Male , Middle Aged , Prospective Studies , Recurrence , Treatment OutcomeABSTRACT
We explored potential genetic risk factors implicated in nonalcoholic fatty liver disease (NAFLD) within a Caribbean-Hispanic population in New York City. A total of 316 individuals including 40 subjects with biopsy-proven NAFLD, 24 ethnically matched non-NAFLD controls, and a 252 ethnically mixed random sampling of Bronx County, New York were analyzed. Genotype analysis was performed to determine allelic frequencies of 74 known single-nucleotide polymorphisms (SNPs) associated with NAFLD risk based on previous genome-wide association study (GWAS) and candidate gene studies. Additionally, the entire coding region of PNPLA3, a gene showing the strongest association to NAFLD was subjected to Sanger sequencing. Results suggest that both rare and common DNA variations in PNPLA3 and SAMM50 may be correlated with NAFLD in this small population study, while common DNA variations in CHUK and ERLIN1, may have a protective interaction. Common SNPs in ENPP1 and ABCC2 have suggestive association with fatty liver, but with less compelling significance. In conclusion, Hispanic patients of Caribbean ancestry may have different interactions with NAFLD genetic modifiers; therefore, further investigation with a larger sample size, into this Caribbean-Hispanic population is warranted.
