Assessing Engraftment Following Fecal Microbiota Transplant

TL;DR

This paper reviews methods for quantifying microbiome engraftment after Fecal Microbiota Transplant, highlighting three criteria to assess engraftment extent and discussing their advantages and limitations.

Contribution

It introduces a comprehensive review of 46 studies, categorizes assessment approaches, and offers recommendations for standardized analysis of FMT engraftment.

Findings

Identified three main criteria for assessing engraftment: community coalescence, indicator features, and temporal stability.

Compared pros and cons of each assessment method with illustrative examples.

Provided terminology and guidelines for rigorous FMT engraftment evaluation.

Abstract

Fecal Microbiota Transplant (FMT) is an FDA approved treatment for recurrent Clostridium difficile infections, and is being explored for other clinical applications, from alleviating digestive and neurological disorders, to priming the microbiome for cancer treatment, and restoring microbiomes impacted by cancer treatment. Quantifying the extent of engraftment following an FMT is important in determining if a recipient didn't respond because the engrafted microbiome didn't produce the desired outcomes (a successful FMT, but negative treatment outcome), or the microbiome didn't engraft (an unsuccessful FMT and negative treatment outcome). The lack of a consistent methodology for quantifying FMT engraftment extent hinders the assessment of FMT success and its relation to clinical outcomes, and presents challenges for comparing FMT results and protocols across studies. Here we review 46 studies of FMT in humans and model organisms and group their approaches for assessing the extent to which an FMT engrafts into three criteria: 1) Chimeric Asymmetric Community Coalescence investigates microbiome shifts following FMT engraftment. 2) Donated Microbiome Indicator Features tracks donated microbiome features as a signal of engraftment with methods such as differential abundance testing based on the current sample collection, or tracking changes in feature abundances that have been previously identified. 3) Temporal Stability examines how resistant post-FMT recipient's microbiomes are to reverting back to their baseline microbiome. Investigated together, these criteria provide a clear assessment of microbiome engraftment. We discuss the pros and cons of each of these criteria, providing illustrative examples of their application. We also introduce key terminology and recommendations on how FMT studies can be analyzed for rigorous engraftment extent assessment.