Fecal microbiota transplantation restores gut microbiota diversity in children with active Crohn's disease: a prospective trial

Abstract

Background: Clinical data on oral fecal microbiota transplantation (FMT), a promising therapy for Crohn's disease (CD), are limited. Herein, we determined the short-term safety and feasibility of FMT for pediatric patients with active CD.

Methods: In this open-label, parallel-group, single-center prospective trial, patients with active CD were treated with oral FMT capsules combined with partial enteral nutrition (PEN) (80%). The control group comprised pediatric patients with active CD treated with PEN (80%) and immunosuppressants. Thirty-three patients (11.6 ± 1.82 years)-17 in the capsule and 16 in the control groups-were analyzed. Data regarding the adverse events, clinical reactions, intestinal microbiome composition, and biomarker parameters were collected and compared post-treatment.

Results: At week 10, the clinical and endoscopic remission rates did not differ between the two groups. By week 10, the mean fecal calprotectin level, C-reactive protein level, erythrocyte sedimentation rate, simple endoscopic score for CD, and pediatric CD activity index decreased significantly in the capsule group (all P < 0.05). The main adverse event was mild-to-moderate constipation. Core functional genera, Agathobacter, Akkermansia, Roseburia, Blautia, Subdoligranulum, and Faecalibacterium, were lacking pre-treatment. Post-treatment, the implantation rates of these core functional genera increased significantly, which positively correlated with the anti-inflammatory factor, interleukin (IL)-10, and negatively correlated with the pro-inflammatory factor, IL-6. The combination of these six functional genera distinguished healthy children from those with CD (area under the curve = 0.96).

Conclusions: Oral FMT capsules combined with PEN (80%) could be an effective therapy for children with active CD. The six core functional genera identified here may be candidate biomarkers for identifying children with CD.

Trial registration: ClinicalTrials.gov, retrospectively registered, ID# NCT05321758, NCT05321745, date of registration: 2022-04-04.

Keywords: Children; Core functional genera; Crohn’s disease; Efficacy and safety; Oral fecal microbiota capsules.

Fig. 1

Trial profile of patient inclusion. PEN: Partial enteral nutrition

Fig. 2

The trends of weight, weight percentile, height and BMI of the two groups before and after treatment (The comparison between the two groups was the Mann–Whitney test, Paired Wilcoxon rank sum test was used before and after treatment, ***P < 0.001)

Fig. 3

Changes in the parameters before and after treatment in the capsule group. Changes in the C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), fecal calprotectin (FCP) level, vitamin D level, pediatric Crohn’s disease activity index (PCDAI), and simple endoscopic score for Crohn’s disease (SES-CD) between the baseline and week 10

Fig. 4

Changes in the serum cytokine before and after treatment of the two groups. (The comparison between the two groups was the Mann-Whitney test, Paired Wilcoxon rank sum test was used before and after treatment, ***P < 0.001

Fig. 5

The dynamic changes in the gut microbiota before and after treatment in the capsule group. A Phylum level changes between the healthy donors and patients with CD at various time points. B Alpha diversity indices (Chao1, ACE, Shannon and Simpson) changes between the healthy donors and patients with CD at various time-points. There was a significant reduction in the alpha diversity in patients in the FMT 0W group compared with donors and patients in the FMT 10W group (Kruskal–Wallis H test, P < 0.001, with *P < 0.05, **P < 0.01, ***P < 0.001). C Principal coordinate analysis (PCoA) comparisons of the microbial communities between the healthy donors and patients with CD at various time-points. The FMT 10W and donor samples were significantly clustered together than the FMT 0W samples. D Comparison of the Gut Microbiome Health Indices (GMHIs) in the different groups. The GMHIs of patients in the FMT 0W group were significantly lower than those of the healthy donors and patients in the FMT 10W group (Wilcoxon signed-rank test, P < 0.001). E Comparison of the microbial dysbiosis index (MDI) in the different groups. The MDI of patients in the FMT 0W group was significantly lower than that of the healthy donors and patients in the FMT 10W group (Wilcoxon signed-rank test, P < 0.001). HD: healthy donor; FMT 0W: before treatment; FMT 5W: at week 5 after oral capsule treatment; FMT 10W: at week 10 after oral capsule treatment

Fig. 6

Implantation of the core functional genera (Agathobacter, Akkermansia, Roseburia, Blautia, Subdoligranulum, and Faecalibacterium) after oral capsule administration. A The relative abundance of the core functional genera between the healthy donors and patients with CD at various time-points. The level of significance was determined using the Wilcoxon rank-sum test, with *P < 0.05, **P < 0.01, ***P < 0.001. B Spearman correlation analysis revealed a correlation between core functional bacteria and cytokines. The red and blue areas’ represent positive and negative correlations, respectively, with *P < 0.05, **P < 0.01, ***P < 0.001. C The six core functional genera were assessed as potential markers to distinguish patients with CD from healthy children. The combined effects of the six bacterial genera showed an AUC of 0.98, indicating good performance. D The six core functional genera were assessed as potential gut markers to predict the efficacy of the CD therapy. The combined effects of the six bacterial genera showed an AUC of 0.93, indicating good performance. HD: healthy donor; FMT 0W: before treatment; FMT 5W: at week 5 after oral capsule treatment; FMT 10W: at week 10 after oral capsule treatment