Intestinal Microbiome Changes in Fecal Microbiota Transplant (FMT) vs. FMT Enriched with Lactobacillus in the Treatment of Recurrent Clostridioides difficile Infection

Abstract

Aim: In this study, we conducted a comparative study to explore the differences in therapeutic efficacy and intestinal microbiome of fecal microbiota transplant (FMT) vs. FMT in addition with Lactobacillus (FMT-L) for treatment of recurrent Clostridioides difficile infection (R-CDI).

Methods: We designed a double-blinded randomized comparative two-arm pilot multicenter study to assess the efficacy and impact in the intestinal microbiome of standard capsules of FMT vs. FMT-L enriched with 3 species of Lactobacillus for patients with R-CDI. A 90-day follow-up of 21 patients was performed, starting at the beginning of the study. From the selected patients, fecal samples were obtained at days 0, 3, 7, and 28 after treatment. Fecal samples and FMT were analyzed by 16S rRNA sequencing.

Results: We included 21 patients (13 in the FMT group and 8 in the FMT-L group). Overall, both groups had a reduction in bowel movements per day, from 8.6 to 3.2 in the first 48 h (62.7% reduction, p=0.001). No severe adverse reactions or recurrences were recorded. Firmicutes were the most abundant phylum in donors. A low relative abundance of Proteobacteria was detected and mostly found in patients even at higher proportions than the donor. The donor's pool also had relatively few Bacteroidetes, and some patients showed a higher abundance of this phylum. Based on the ANOSIM R values, there is a significant difference between the microbial communities of basal samples and samples collected on day 7 (p=0.045) and at day 28 (0.041).

Conclusion: Fecal microbiota transplant by capsules was clinically and genomically similar between traditional FMT and enriched FMT with Lactobacillus spp. Restoration of bacterial diversity and resolution of dysbiosis at days 7 and 28 were observed. Patients with a first episode of recurrence treated with FMT had an excellent response without severe adverse events; FMT should be considered as an early treatment during R-CDI.

Figure 1

Average bacterial composition at the phylum level. Distribution of bacterial families in the fecal microbiome transplant (FMT) group and the Lactobacillus-FMT (L-FMT) group. The label of each sample (e.g., FMT-5-0) denotes treatment (FMT or L-FMT), the assigned number of each patient, and days on treatment (0 = baseline, 3 = 3 days on treatment, 7 = 7 days on treatment, and 28 = 28 days of treatment). To facilitate comparison and visualization, the distribution of bacterial families of the donors is presented for the FMT group and the L-FMT group.

Figure 2

Average bacterial composition at the genera level. Distribution of bacterial genera in the fecal microbiota transplant (FMT) group and the Lactobacillus-FMT (L-FMT) group. The label of each sample (e.g., FMT-5-0) denotes treatment (FMT or L-FMT), the assigned number of each patient, and days on treatment (0 = baseline, 3 = 3 days on treatment, 7 = 7 days on treatment, and 28 = 28 days of treatment). To facilitate comparison and visualization, the distribution of bacterial families of the donors is presented for the FMT group and the L-FMT group.

Figure 3

Observed OTUs boxplot and Kruskal–Wallis pairwise comparisons.

Figure 4

Shannon diversity boxplot.

Figure 5

Principal coordinate plot of weighted UniFrac data. Colors keyed on the group: A (red), B (blue), C (orange), and D (green). Primary vector explains 25.8% of the variation between the groups. The first 3 vectors together exhibit 51.9% of the variation among the groups.