Role of the Intestinal Microbiota in Clostridium difficile Infection and Recurrence
Lead Research Organisation:
University of Edinburgh
Department Name: Sch of Molecular. Genetics & Pop Health
Abstract
The human gut microbiota is often described as another organ of the body and plays an integral role in health, one such role is providing colonisation resistance against pathogens. However, the integrity of the microbiota is often lost after antibiotic treatment as the "good" bacteria are diminished, known as dysbiosis, and pathogens such as Clostridium difficile are able to invade, causing disease. Those who are >65, have been hospitalised or received antibiotic treatment are at a greater risk of infection. Clostridium difficile infection (CDI) can manifest as a range of conditions from mild diarrhoea to potentially fatal pseudomembranous colitis and is attributed to around 150 deaths in Scotland every year.
A faecal microbiota transplant (FMT) is the transfer of faecal matter from a "healthy" screened donor to the patient and they are successful in treating >90% of CDI cases however the success is undefined and comes with a plethora of safety concerns as it is not possible to identify all of the bacteria and viruses present in faeces. The gut microbiota is also being linked to conditions such as depression and obesity and it may be possible to transfer these conditions from the donor to the patient. A proposed solution is to identify the specific groups of bacteria which provide colonisation resistance and only transfer these groups to the patient.
This project will investigate the gut microbiota of patients with active CDI, those with recurring CDI, individuals who are colonised but healthy and healthy non-colonised individuals in order to identify which groups of bacteria could be providing colonisation resistance against C. difficile. To achieve this metataxonomic data of patient and volunteer microbiotas will be gathered via DNA isolation and Illumina 16s sequencing. The data will then be analysed and Python will be used to predict the functional characteristics of the microbiota. This information could be used to guide the development of probiotic cocktails which could be tailored to match a patient's specific needs and replace FMT.
A faecal microbiota transplant (FMT) is the transfer of faecal matter from a "healthy" screened donor to the patient and they are successful in treating >90% of CDI cases however the success is undefined and comes with a plethora of safety concerns as it is not possible to identify all of the bacteria and viruses present in faeces. The gut microbiota is also being linked to conditions such as depression and obesity and it may be possible to transfer these conditions from the donor to the patient. A proposed solution is to identify the specific groups of bacteria which provide colonisation resistance and only transfer these groups to the patient.
This project will investigate the gut microbiota of patients with active CDI, those with recurring CDI, individuals who are colonised but healthy and healthy non-colonised individuals in order to identify which groups of bacteria could be providing colonisation resistance against C. difficile. To achieve this metataxonomic data of patient and volunteer microbiotas will be gathered via DNA isolation and Illumina 16s sequencing. The data will then be analysed and Python will be used to predict the functional characteristics of the microbiota. This information could be used to guide the development of probiotic cocktails which could be tailored to match a patient's specific needs and replace FMT.
People |
ORCID iD |
Andrew Free (Primary Supervisor) | |
Amy Irvine (Student) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/N013166/1 | 01/10/2016 | 30/09/2025 | |||
1805056 | Studentship | MR/N013166/1 | 01/09/2016 | 30/04/2021 | Amy Irvine |
Description | NHS Collab |
Organisation | NHS Lothian |
Country | United Kingdom |
Sector | Public |
PI Contribution | I process patient samples for sequencing and analyse the data generated. |
Collaborator Contribution | Partners to this collaboration are responsible for collecting patient faecal samples, anonymising patients, collecting patient data from medical records and anonymising this data. |
Impact | The collaboration has so far resulted in the sequencing and further analysis of 97 patients samples, with a further 96 samples due to be sequenced in the coming weeks. A poster of the work generated by this collaboration is due to be presented at the FEMS congress in Glasgow this summer. |
Start Year | 2016 |
Description | Midlothian Science Festival |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | A number of people from the general public attended our table top event during a gala day at the science festival. The event was designed to teach people about the bacteria living in their guts, "good vs bad bugs". As the event was run through Science Grrl (Glasgow) people also had the option to takeaway postcards featuring female scientists. |
Year(s) Of Engagement Activity | 2017 |
Description | The Max Perutz Science Writing Award |
Form Of Engagement Activity | Engagement focused website, blog or social media channel |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | I wrote an entry which had to explain why my research matters aimed at a non-specialist audience. |
Year(s) Of Engagement Activity | 2019 |
Description | Three Minute Thesis |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Postgraduate students |
Results and Impact | I participated in the Three Minute Thesis Competition, a competition for research students to summarise their research to an intelligent lay audience in just three minutes. |
Year(s) Of Engagement Activity | 2019 |