The gut microbiome response to trauma

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What does each milestone mean?

    1 = Clinical need
    2 = Idea
    3 = Proof of concept
    4 = Proof of feasibility
    5 = Proof of value
    6 = Initial clinical trials
    7 = Validation of solution
    8 = Approval and launch
    9 = Clinical use
    10 = Standard of care

Aim

The aim of this project is to characterise changes in the gut microbiome during a patient’s stay on the ICU. Our understanding of such changes will lay the groundwork for the formulation of novel ecological interventions including faecal transplants and smart probiotics.

Lay Summary

In healthy people the gut especially the colon is home to a rich and largely stable collection of bacteria known as the microbiome. These bacteria are often considered ‘good bacteria’ as they perform many functions including the digestion of nutrients. However, in the long-stay ICU patient, a disruption in bacterial variation in the digestive tract may occur. Indeed, it is possible for some of the ‘good bacteria’ to disappear leaving only a single or just a few bacterial species present. Studies so far have used a method of detecting bacteria in faecal samples which provides insufficient information on the numbers and types of bacteria present and their potential antibiotic resistance. Following a pioneering study using direct analysis of bacterial DNA in faecal samples (a process called metagenomics), we will analyse gut bacteria in ICU patients to provide information with the intention of understanding and improving patient management.

Background

Long-stay patients in the intensive care unit (ICU) are among the sickest and most vulnerable in the hospital. Once in the ICU, they are subjected to numerous procedures and administration of many drugs. In healthy individuals, the human gut is home to a wide variety of bacteria and their genes (the human microbiome). However, in the long-stay ICU patient, there is a disruption in bacterial diversity. Indeed, studies using genetic detection of bacterial DNA have demonstrated that fewer types of bacteria are present and antibiotic-resistant bacteria may predominate. However, these genetic methods used have provided little information on the bacteria. Thanks to our recent groundbreaking experience of the direct genetic sequencing of DNA extracted from clinical samples we will explore bacteria in the gut of the ICU patient.

Method

Patients who are over 18 years of age and expected to stay on the ICU for more than 48 hours will be approached for participation in the study. Following consent, the first faecal sample passed on ICU and each calendar day thereafter will be collected until patient discharge from (or death on) the ICU. DNA extraction, quality control of extracted DNA, preparation of sequencing libraries and deep shotgun metagenomic sequencing will be carried out on these samples. From the sequence files, we will identify sequences that align to the human reference genome and exclude them from further analysis or deposition in public data repositories. We will then perform a range of analyses relevant to clinical microbiology and microbial ecology.

Research Team

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Beryl Oppenheim
Anna Casey
Fenella Halstead
Amy Bamford
Robert Goulden
Mark Pallen
Nicholas Thomson
Willem van Schaik
Ebenezer Foster-Nyarko
George M. Savva

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