Gut-Microbiome-On-A-Chip as a Personalized Patient Model to Predict Fecal Microbiota Transplant Compatibility for Vancomycin-Resistant Enterococci: An Original Research Protocol

Abstract

Introduction: Antimicrobial resistance, specifically vancomycin-resistant enterococci (VRE), has recently emerged as a leading threat to public health due to its high resistance to antibiotics, specifically vancomycin. Without proper treatment, VRE in the gut can infect the bloodstream and may become life-threatening. Fecal microbiota transplant (FMT) has recently become promising in decolonizing VRE, however it still varies in success. The goal of this proposal is to investigate the use of gut-microbiome-on-a-chip (GMoC) to develop a personalized patient model that can predict FMT compatibility between recipient and donor in vitro without placing the recipient at risk of adverse side events.

Methods: A personalized GMoC model is developed replicating the gut microbiome of the FMT recipient. Patient intestinal epithelial cells, endothelial cells, and fecal samples will be cultured to develop the gut and microbiome within the GMoC.
A multiplex polymerase chain reaction (mPCR) technique will be carried out pre and post-FMT to compare the quantification of VRE vanA and vanB genes on the GMoC. The decrease of VRE by 85% after FMT will demonstrate successful compatibility between FMT recipient and donor.

Anticipated Results: If the FMT recipient and donor are compatible, we will observe a minimum of a 85% decrease, as observed in current literature, in the quantification of VRE genes on the GMoC post-FMT. If FMT recipient and donor are not compatible, we will observe a maximum of a 85% decrease in VRE genes on the GMoC post-FMT.

Discussion: Rigorous validity and physiological relevance support this research protocol that allows for thorough testing that surpasses traditional in vitro culture methods and animal models. Limitations include cost, length of the research protocol, and inability to control all physiological conditions.

Conclusion: By leveraging the ability of gut-microbiome-on-a-chip to accurately recapitulate the human gut in an in vitro model, FMT procedures can be tested for success without placing the FMT recipient at risk of adverse side events. This original approach to precision medicine highlights the possibilities of GMoC and other microfluidic in vitro cell culture systems to improve the success of various health procedures.