Dynamic changes in short- and long-term bacterial composition following fecal microbiota transplantation for recurrent Clostridium difficile infection.

Alexa Weingarden,Antonio González,Dan Knights,Tatsuya Unno,Rob Knight,Alexander Khoruts,Donna Berg-Lyons,Gregory Humphry,Yoshiki Vázquez-Baeza,Johnthomas Kang,Sophie Weiss,Aleh Bobr,Michael J Sadowsky

doi:10.1186/s40168-015-0070-0

Abstract

BackgroundFecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) that often fails standard antibiotic therapy. Despite its widespread recent use, however, little is known about the stability of the fecal microbiota following FMT.ResultsHere we report on short- and long-term changes and provide kinetic visualization of fecal microbiota composition in patients with multiply recurrent CDI that were refractory to antibiotic therapy and treated using FMT. Fecal samples were collected from four patients before and up to 151 days after FMT, with daily collections until 28 days and weekly collections until 84 days post-FMT. The composition of fecal bacteria was characterized using high throughput 16S rRNA gene sequence analysis, compared to microbiota across body sites in the Human Microbiome Project (HMP) database, and visualized in a movie-like, kinetic format. FMT resulted in rapid normalization of bacterial fecal sample composition from a markedly dysbiotic state to one representative of normal fecal microbiota. While the microbiome appeared most similar to the donor implant material 1 day post-FMT, the composition diverged variably at later time points. The donor microbiota composition also varied over time. However, both post-FMT and donor samples remained within the larger cloud of fecal microbiota characterized as healthy by the HMP.ConclusionsDynamic behavior is an intrinsic property of normal fecal microbiota and should be accounted for in comparing microbial communities among normal individuals and those with disease states. This also suggests that more frequent sample analyses are needed in order to properly assess success of FMT procedures.Electronic supplementary materialThe online version of this article (doi:10.1186/s40168-015-0070-0) contains supplementary material, which is available to authorized users.

Highlights

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) that often fails standard antibiotic therapy
Dynamic behavior is an intrinsic property of normal fecal microbiota and should be accounted for in comparing microbial communities among normal individuals and those with disease states
Four patients (CD1 to CD4) with recurrent CDI were treated with FMT using material obtained from a single donor but from different time points, and fecal samples were collected from these patients before and after the procedure as well as from the donor at times of donation

Summary

Introduction

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI) that often fails standard antibiotic therapy. Fecal microbiota transplantation (FMT) has emerged in recent years as a highly effective treatment for refractory. BioTechnology Institute, 1479 Gortner Ave, 140 Gortner Labs, St. Paul, MN. One recent study suggests the microbiota of patients after FMT may not fully recover until 16 weeks after the procedure [9]. This type of analysis, is complicated by the fact that the microbial communities are intrinsically dynamic and affected by daily fluctuations in the host’s diet, activities, and health [10,11,12]

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Discussion

Conclusion