The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome

Negin Kazemian,Gane Ka-Shu Wong,Amir Hossein Zeinali Kalkhoran,Dina Kao,Sepideh Pakpour,Aarushi Sehgal,Faizan Muhammad Khalid,Milad Ramezankhani,Apurva Narayan

doi:10.1038/s41598-020-75162-x

Abstract

Fundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridioides difficile infections (rCDI) and other dysbiosis-related conditions. In this study, stool samples were collected from donors and rCDI patients one week prior to FMT (pre-FMT), as well as from patients one week following FMT (post-FMT). Using metagenomic sequencing and machine learning, our results suggested that FMT outcome is not only dependent on the ecological structure of the recipients, but also the interactions between the donor and recipient microbiomes at the taxonomical and functional levels. We observed that the presence of specific bacteria in donors (Clostridioides spp., Desulfovibrio spp., Odoribacter spp. and Oscillibacter spp.) and the absence of fungi (Yarrowia spp.) and bacteria (Wigglesworthia spp.) in recipients prior to FMT could predict FMT success. Our results also suggested a series of interlocked mechanisms for FMT success, including the repair of the disturbed gut ecosystem by transient colonization of nexus species followed by secondary succession of bile acid metabolizers, sporulators, and short chain fatty acid producers.

Highlights

Fundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridioides difficile infections and other dysbiosis-related conditions
We investigated whether FMT super-donors exists for recurrent Clostridioides difficile infections (rCDI) treatment, or whether the donor-recipient compatibility and short-term fluctuations in the gut microbiomes of both donors and recipients have profound implications in FMT success
Our results showed that successful FMT is associated with the colonization of bile acid metabolizers, short chain fatty acids (SCFAs) producers, and sporulating bacterial genera, since the diversity (Wilcoxon signed-rank test, p = 0.003, p = 0.00014, and p = 0.015, respectively) and community structures of associated bacteria within each community significantly increased after successful FMT (ANOSIM, R = 0.670, R = 0.759, and R = 0.872, respectively) but not the failed ones (ANOSIM, R = 0.091, R = 0.117, and R = 0.134, respectively) (Fig. 3)

Summary

Introduction

Fundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridioides difficile infections (rCDI) and other dysbiosis-related conditions. A study by Meader et al.[30] showed that bacteriophages alone weren’t sufficient to eradicate CDI These studies emphasize that in order to uncover mechanisms involved in FMT efficacy, it is fundamental to include the relative contribution of all domains and consider the microbiome-associated ecosystem heterogeneity in both donors and recipients. To this end, we investigated whether FMT super-donors exists for rCDI treatment, or whether the donor-recipient compatibility and short-term fluctuations in the gut microbiomes (a combination of bacteria, fungi, archaea, and viruses) of both donors and recipients have profound implications in FMT success

Methods

Results

Conclusion