Exploring mechanisms of intestinal microbiota transplantation on prevention of invasive disease in patients with intestinal colonisation of multidrug-resistant organisms
File(s)
Author(s)
Ghani, Rohma
Type
Thesis
Abstract
Background
The intestinal microbiome has an important function in the defence against infectious diseases. Intestinal colonisation with multidrug-resistant organisms (MDROs) is a risk factor for invasive disease which leads to higher morbidity than drug-sensitive infections. Intestinal Microbiota Transplantation (IMT) is a modality to restore the gut microbiome. We utilised IMT in MDRO colonised patients and observed both clinical outcomes and effect on microbiota diversity, gene expression, metabolites expression and markers of gut barrier function.
Methods
A retrospective study was performed to identify at risk groups and a literature review was performed to refine the IMT process for MDRO colonised patients. IMT was performed on patients with risk factors for invasive disease who had known intestinal MDRO colonisation and clinical outcomes were assessed 6 months pre- and post-IMT. Metataxonomic profiles were performed on these patient stool samples. Additional stool from donor, pre-and post-IMT samples underwent metagenomic and metabonomic testing.
Results
Renal transplant and pre-hematopoietic cell transplant patients were identified as the highest risk of developing invasive MDRO disease with a worse outcome profile. Guidelines for the use of IMT for MDRO colonised patients were constructed with careful consideration of administration and donor stool preparation. Post-IMT patients had fever bloodstream infections, shorter hospital admissions and reduced antibiotic usage. IMT increased intestinal microbiota alpha diversity and reduced the burden of Enterococci but not Gram-negative pathobionts. Blautia producta and Coprococcus catus, two commensal bacteria, increased post-IMT. The short-chain fatty acid, valerate was higher in concentration in stool in patients who did not develop invasive infection post-IMT. Serum levels of TNF-α and IL-8, proinflammatory cytokines associated with gut barrier permeability both reduced post-IMT.
Conclusion
The microbiome may play a role in protection against infection, and manipulation of the composition may be a key facet of preventing infection in at risk groups.
The intestinal microbiome has an important function in the defence against infectious diseases. Intestinal colonisation with multidrug-resistant organisms (MDROs) is a risk factor for invasive disease which leads to higher morbidity than drug-sensitive infections. Intestinal Microbiota Transplantation (IMT) is a modality to restore the gut microbiome. We utilised IMT in MDRO colonised patients and observed both clinical outcomes and effect on microbiota diversity, gene expression, metabolites expression and markers of gut barrier function.
Methods
A retrospective study was performed to identify at risk groups and a literature review was performed to refine the IMT process for MDRO colonised patients. IMT was performed on patients with risk factors for invasive disease who had known intestinal MDRO colonisation and clinical outcomes were assessed 6 months pre- and post-IMT. Metataxonomic profiles were performed on these patient stool samples. Additional stool from donor, pre-and post-IMT samples underwent metagenomic and metabonomic testing.
Results
Renal transplant and pre-hematopoietic cell transplant patients were identified as the highest risk of developing invasive MDRO disease with a worse outcome profile. Guidelines for the use of IMT for MDRO colonised patients were constructed with careful consideration of administration and donor stool preparation. Post-IMT patients had fever bloodstream infections, shorter hospital admissions and reduced antibiotic usage. IMT increased intestinal microbiota alpha diversity and reduced the burden of Enterococci but not Gram-negative pathobionts. Blautia producta and Coprococcus catus, two commensal bacteria, increased post-IMT. The short-chain fatty acid, valerate was higher in concentration in stool in patients who did not develop invasive infection post-IMT. Serum levels of TNF-α and IL-8, proinflammatory cytokines associated with gut barrier permeability both reduced post-IMT.
Conclusion
The microbiome may play a role in protection against infection, and manipulation of the composition may be a key facet of preventing infection in at risk groups.
Version
Open Access
Date Issued
2024-01
Date Awarded
2024-09
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Marchesi, Julian
Davies, Frances
Thursz, Mark
Sponsor
National Institute for Health Research (Great Britain)
Grant Number
P68710
Publisher Department
Department of Metabolism, Digestion and Reproduction
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)