Specific fungi associated with response to capsulized fecal microbiota transplantation in patients with active ulcerative colitis

Abstract

Objective: Fecal microbiota transplantation (FMT) is a novel microbial treatment for patients with ulcerative colitis (UC). In this study, we performed a clinical trial of capsulized FMT in UC patients to determine the association between the gut fungal community and capsulized FMT outcomes.

Design: This study recruited patients with active UC (N = 22) and healthy individuals (donor, N = 9) according to the criteria. The patients received capsulized FMT three times a week. Patient stool samples were collected before (week 0) and after FMT follow-up visits at weeks 1, 4, and 12. Fungal communities were analysed using shotgun metagenomic sequencing.

Results: According to metagenomic analysis, fungal community evenness index was greater in samples collected from patients, and the overall fungal community was clustered among the samples collected from donors. The dominant fungi in fecal samples collected from donors and patients were Ascomycota and Basidiomycota. However, capsulized FMT ameliorated microbial fungal diversity and altered fungal composition, based on metagenomic analysis of fecal samples collected before and during follow-up visits after capsulized FMT. Fungal diversity decreased in samples collected from patients who achieved remission after capsulized FMT, similar to samples collected from donors. Patients achieving remission after capsulized FMT had specific enrichment of Kazachstania naganishii, Pyricularia grisea, Lachancea thermotolerans, and Schizosaccharomyces pombe compared with patients who did not achieve remission. In addition, the relative abundance of P. grisea was higher in remission fecal samples during the follow-up visit. Meanwhile, decreased levels of pathobionts, such as Candida and Debaryomyces hansenii, were associated with remission in patients receiving capsulized FMT.

Conclusion: In the metagenomic analysis of fecal samples from donors and patients with UC receiving capsulized FMT, shifts in gut fungal diversity and composition were associated with capsulized FMT and validated in patients with active UC. We also identified the specific fungi associated with the induction of remission. ClinicalTrails.gov (NCT03426683).

Keywords: capsule administration; fecal microbiota transplantation; metagenomics; mycobiota; ulcerative colitis.

Figure 1

Gut fungal community in the donors. (A) Sector diagram showed the overall fungal community structure at the phylum level. (B) The percentage of different fungi at the class level. (C) Sector diagram showed the composition of the fungal genera.

Figure 2

Dysbiosis of gut fungal communities in UC patients. (A) α-diversity indices in UC patients and donors were analyzed, including observed OTUs, Chao 1, and Shannon and Pielou’s evenness indices. The asterisk indicated statistical differences between the two groups, *p ≤ 0.05,**p ≤ 0.01,. (B) Clusters of gut fungal communities were analyzed using PCA of the fungal species by the Euclidean distance. The top 7 species were fitted to PCA with a significance cutoff at p < 0.05.

Figure 3

Changes in fungi in UC patients. Overall fungal community structures at the genera (A) and species (B) levels. (C) Relative abundances of genera (C) and species (D) were significantly different between UC patients and donors.

Figure 4

Changes of gut fungal communities of UC patients after FMT. (A) α-diversity indices in UC patients were analyzed during the follow-up visits, including observed OTUs, Chao 1, and Shannon and Pielou’s evenness indices. (B) Clusters of gut fungal community were analyzed using PCA of the Euclidean distance of OTU abundance. The top ten genera were fitted to PCA with a statistical significance of p < 0.05. Relative abundances of the top 15 genus (C) and species (D) in samples from donors and patients before and after FMT. (E) The significant change in relative abundances of genera in samples from patients between week 0 and other time points after FMT. (F) The significant change in relative abundances of species in samples from patients between week 0 and other time points after FMT.

Figure 5

Alterations in gut fungal taxa associated with Rm after FMT. (A) α-diversity indices in samples from donors and patients who received remission (Rm) or not (NRm) were analyzed, including Observed species, Chao 1, Shannon, and Pielou’s evenness. (B) Clusters of gut fungal community were analyzed using PCA of the Euclidean distance of OTU abundance. The circle represented the donor, the triangle represented patients who received remission (Rm), and the inverted triangle represented patients who did not receive remission (NRm). (C–E) The changes in relative abundances of fungal species were assessed by the paired rank-sum test between week 0 and other time points (weeks 1, 4, and 12) (p < 0.05). Box plots showed the species significantly changed in the Rm group at different time points. (F) The relative abundance of fungal species in remission patients at different time points.