Abstract

Patients in the intensive care unit often lose a considerable fraction of their gut microbiome due to exposure to broad-spectrum antibiotics and other reasons. Dysbiosis often results in prolonged diarrhea and increase occurrence of multi-drug resistant pathogens in the colon with clinical consequences not yet well understood. Restoring the microbiome by fecal microbial transplantation (FMT) is a plausible therapeutic possibility, so far only documented in case reports and case series using very heterogeneous methodologies. Before FMT with critically ill patients can be tested in randomized controlled trials, there is a burning need to describe a standardized operating procedure (SOP) of the whole process, respecting the specifics of the critically ill population, such as the risk of the disrupted intestinal barrier and time-critical nature of the procedure. We describe the SOP that has been developed for experimental use in critically ill patients by a multidisciplinary team of intensivists, gastroenterologists, and microbiologists based on feedback from regulatory authority (State Institute for Drug Control of the Czech Republic). The hallmarks of these SOPs are multi-donor freshly frozen transplants guaranteed for 2 months consisting of seven aliquots from seven unrelated healthy donors and administered by a rectal tube. In this paper we discuss the rationale for this SOP and the process of its development in detail and release the full proposed SOP is in the form of an online appendix.

Highlights

  • The sayings on the connection between the proper function of the gastrointestinal tract (GIT) and longevity have been known for decades, a full scientific description of such claims based on scientific evidence is yet to be made

  • There we describe the development of a standard operating procedure for multi-donor fecal microbial transplantation in critically ill patients, starting from donor selection and finishing with post-procedure recipient care

  • Ill patients often suffer from rapid-onset intestinal dysbiosis resulting in prolonged diarrhea and potentially other adverse consequences

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Summary

Introduction

The sayings on the connection between the proper function of the gastrointestinal tract (GIT) and longevity have been known for decades, a full scientific description of such claims based on scientific evidence is yet to be made. The recent progress in 16S rRNA sequencing brought about proof that the microbiome composition of each individual is unique to such an extent, that it may be used in forensic disciplines [4,5]. This enormous microbiome diversity is pivotal to maintaining homeostasis [6,7]. The complex nature of these associations is yet to be understood, it is likely that two-way communication between microbiota and immune system exists [19] and is mediated by microbial-synthesized metabolites regulating host neuroimmune-inflammatory axes that could physiologically link gut with other organ systems, such as the brain [20] or liver [21]. Details of the interplay are summarized in a paper by Cibulkova et al [22]

Dysbiosis and Diarrhea in Intensive Care Patients
Procedure
Donor Selection and Rationale for Multi-Donor Strategy
Donor Stool Processing and Sample Preparation
Southern Way of Administration
Safety Considerations and Measures to Maximise Safety for Recipients
Findings
Conclusions
Full Text
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