Abstract

Intestinal microbial dysbiosis is hypothesized to facilitate Clostridium difficile colonization and to be a factor in the pathogenesis of ulcerative colitis (UC). Fecal microbial transplantation (FMT) is used to restore a healthy gut microbiome and decrease symptoms associated with these conditions. We conducted an uncontrolled prospective study in patients with recurrent C. difficile or refractory UC to characterize the effect of colonoscopic FMT on the fecal microbiome. Fecal DNA was extracted from the donor pre-transplant and from the recipient pre-transplant, 1 week, and 3 months after FMT. Quantitative PCR was performed using universal and group specific primers to amplify portions of the 16S rRNA gene for total bacteria and common gut bacteria Escherichia coli, Faecalibacterium prausnitzii, Clostridium coccoides-Eubacterium rectales, and Bacteroidetes. UC patients underwent flexible sigmoidoscopy at 3 months post-transplant. Patients were followed for 1 year after FMT with phone calls. The patients treated for C. difficile (n = 9) had a marked reduction in the relative abundance of F. prausnitzii (dCt = −17.0 ± 2.7) compared to their donors (dCt = −5.9 ± 3.1, n = 9, P < 0.0001). The relative abundance of F. prausnitzii was significantly increased in the recipients both at one week (dCt = −7.5 ± 2.0, n = 8, P = 0.0002) and 3 months (dCt = −7.5 ± 1.5, n = 4, P = 0.019). These patients also had a reduced relative abundance of Bacteroidetes (dCt = −15.7 ± 3.2) compared to their donors (dCt = −6.6 ± 3.9, n = 9, P < 0.0001). The relative abundance of Bacteroidetes was significantly increased in the recipients at one week (dCt = −7.2 ± 5.3, n = 8, P = 0.0097) but did not reach significance at 3 months (dCt = −11.4 ± 3.3, n = 4, P = 0.11). Differences in the relative abundances of other bacterial categories did not reach significance. With the exception of one patient, who subsequently underwent surgery and antibiotic treatment for rectal cancer, none of the patients had recurrence of C. difficile during the study period. The patients treated for UC (n = 5) also had a lower relative abundance of F. prausnitzii (dCt = −9.1 ± 3.6) compared to their donors (dCt = −4.7 ± 1.5, P = 0.0367), but no significant differences in the relative abundances of the other 3 bacterial categories. Increases in the relative abundances of F. prausnitzii at one week (dCt = −4.6 ± 2.9, n = 5, P = 0.075) and 3 months (dCt = −4.7 ± 1.9, n = 4, P = 0.15) post-transplant did not reach significance. In the UC patients, the baseline Mayo score was 4.6 ± 3.4 (n= 5), and the 3-month post-FMT score was 3.0 ± 1.0 (P = 0.87) in the 3 patients who underwent follow up sigmoidoscopy. Our results confirm that FMT is effective in preventing further recurrence of C. difficile. It also demonstrates that FMT replenishes F. prausnitzii in patients with recurrent C. difficile and patients with refractory UC.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call