New research on why ‘poo’ transplants effectively treat C. diff could lead to more treatments for similar conditions

Experts have uncovered a new molecular reason why faecal transplants are highly effective in treating infections such as C. difficile (a nasty bacteria that can infect the bowel), which could lead to more targeted treatments for this and other similar diseases.

C. diff is a bacterium that can infect the bowel and cause diarrhoea

The study, published today in Gastroenterology, was led by experts from the University of Nottingham and Nottingham Trent University.

Clostridium difficile, also known as C. difficile or C. diff, is a bacterium that can infect the bowel and cause diarrhoea. The infection most commonly affects people who have recently been treated with antibiotics. It can spread easily to others.

A stool transplant - or to give it its full title "a faecal microbiota transplant" (FMT) - aims to repopulate the patient's gut with the microbes from a healthy person, making it a successful therapy against C. diff and other similar diseases. An FMT is only considered if a patient suffers recurring bouts of the infection or has not responded to traditional treatments. FMT is effective in at least 80% of cases in treating the condition.

After a poo "sample" is produced, it is mixed with water. There are two routes for getting the sample into the required location in the bowel - down through the mouth straight into the stomach, or as a colonoscopy, up through the rectum.

Whilst the technique is highly effective in treating the infection, little is still known about how it does so. In this new study, a team of experts set out to understand how FMT works at a molecular level.

Dr Tanya Monaghan, Clinical Associate Professor, Honorary Consultant in Gastroenterology, and Anne McLaren Fellow in the School of Medicine at the University of Nottingham, and co-lead author of the research said: “It is not fully understood how an FMT works at a molecular level. That is a problem because if we knew how it worked at this level, then we could refine the treatment, which would mean a full transplant may not be needed.”

The team used blood samples from two clinical FMT trials which were undertaken in Canada by co-lead Dr Dina Kao (University of Alberta) and collaborator Prof Christine Lee (University of British Columbia). From these data, they could see that following successful FMTs, there were alterations in patient microRNAs in the blood.

MicroRNAs are a class of short non-coding RNA molecules. With more than 2,000 microRNAs discovered in humans to date, many of them have already been implicated in common human disorders.

Dr Christos Polytarchou, Associate Professor in the School of Science and Technology at Nottingham Trent University, and co-author of the research, said: “MicroRNAs are characterised as master regulators of gene expression. A single microRNA can modulate multiple RNA and protein molecules, affecting a vast array of cell functions.“

The researchers wanted to specifically look at whether microRNAs changed following a successful FMT.

The team, which also included investigators from the universities of Vanderbilt (Prof Borden Lacy and Dr Nick Markham) and Clemson (Dr Anna Seekatz), discovered that following successful transplant, there was an increase in specific microRNAs in the blood, which resembled similar changes also seen in the human and mouse intestine.

Dr Polytarchou added: “We found that C. diff utilises its toxins to highjack the molecular mechanism important for microRNA maturation, a process important for microRNA activity. We went on to identify specific microRNAs, which contribute to disease pathogenesis.“ The team then looked at whether or not the combination of specific microRNAs could protect bowel cells from the damage that is induced by toxins from the bacteria, and they could.

Dr Monaghan said: “We have discovered a new mechanism by which the transplants work, which will now help us to develop a new method of therapeutics, which specifically target microRNAs. MicroRNA-based drugs are already being investigated to treat cancers, heart abnormalities, and kidney disease, but this is the first time microRNAs have been looked at as a means to treat C. diff infections. If used with antimicrobials, microRNA drugs could be extremely effective in treating C. diff and potentially other diseases”

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‘Fecal microbiota transplantation for recurrent Clostridioides difficile infection associates with functional alterations in circulating microRNAs’ by Tanya M. Monaghan, Anna M. Seekatz, Nicholas O. Markham, Tung On Yau, Maria Hatziapostolou, Tahseen Jilani, Niki Christodoulou, Brandi Roach, Eleni Birli, Odette Pomenya, Thomas Louie, D. Borden Lacy, Peter Kim, Christine Lee, Dina Kao, Christos Polytarchou.
Nottingham Trent University (NTU) was named University of the Year 2019 in the Guardian University Awards. The award was based on performance and improvement in the Guardian University Guide, retention of students from low-participation areas and attainment of BME students. NTU was also the Times Higher Education University of the Year 2017, and The Times and Sunday Times Modern University of the Year 2018. These awards recognise NTU for its high levels of student satisfaction, its quality of teaching, its engagement with employers, and its overall student experience.
The university has been rated Gold in the Government’s Teaching Excellence Framework – the highest ranking available. It is one of the largest UK universities. With nearly 32,000 students and more than 4,000 staff located across four campuses, the University contributes £900m to the UK economy every year. With an international student population of more than 3,000 from around 100 countries, the University prides itself on its global outlook. The university is passionate about creating opportunities and its extensive outreach programme is designed to enable NTU to be a vehicle for social mobility. NTU is among the UK’s top five recruiters of students from disadvantaged backgrounds and was awarded University of the Year in the UK Social Mobility Awards 2019.

The University of Nottingham is a research-intensive university with a proud heritage, consistently ranked among the world's top 100. Studying at the University of Nottingham is a life-changing experience and we pride ourselves on unlocking the potential of our students. We have a pioneering spirit, expressed in the vision of our founder Sir Jesse Boot, which has seen us lead the way in establishing campuses in China and Malaysia - part of a globally connected network of education, research and industrial engagement. The University’s state-of-the-art facilities and inclusive and disability sport provision is reflected in its status as The Times and Sunday Times Good University Guide 2021 Sports University of the Year. We are ranked eighth for research power in the UK according to REF 2014. We have six beacons of research excellence helping to transform lives and change the world; we are also a major employer and industry partner - locally and globally. Alongside Nottingham Trent University, we lead the Universities for Nottingham initiative, a pioneering collaboration which brings together the combined strength and civic missions of Nottingham’s two world-class universities and is working with local communities and partners to aid recovery and renewal following the COVID-19 pandemic.