R-BiOME: Tackling AMR via microbiome modulation boosting immunity

The R-Biome network conducts cutting-edge research with novel technological solutions including AI, to provide innovative ways to tackle AMR. Boosting immunity by modulation of ouR microBiOME via non-traditional therapeutics such as phage-therapy. Reducing the incidence of infection and antibiotic prescription in chronic diseases impacting the most vulnerable in society. 

Dr Lindsey Edwards, Primary Investigator at the Centre for Host-Microbiome Interactions and Scientific Director of the Faecal Microbiota Transplant Research Programme at the Institute of Liver Studies, King’s College London.

Drug-resistant infections are once again a leading cause of death worldwide.1 The intestinal microbiota is the largest reservoir of Multidrug-Resistant Organisms (MDROs). Microbiome perturbations and disrupted host immunity, increase susceptibility to infections and drive AMR, but also underpin many chronic diseases.2 Chronic diseases are estimated to kill 41 million people annually worldwide, 74% of all deaths globally.3 Jeopardizing our ability to treat patients safely, burdens healthcare systems, driving-up costs and complexifying the delivery of care for the most vulnerable in society. Children, the elderly, burn victims, cancer patients and those with chronic diseases are particularly at risk and AMR is more deadly to these vulnerable patient populations.4,5,6,7,8  There is an evolving crisis of chronic liver disease in the UK with the prevalence and mortality increasing exponentially, representing 2–3% of all deaths globally.9,10,11  Most liver disease deaths arise following infection and patients are particularly at risk of developing AMR.12,13 Carriage of MDROs in liver disease was directly linked to worsening of 28-day mortality and increased hospital admissions (both p<0.001). Before Covid-19, antibiotic-resistant bloodstream infections had risen by 35%,14 costing the NHS ~£180million/year.15now exacerbated post-pandemic.16,17

Raising awareness is critical to driving change and tackling health issues. From conception, this network has integrated participation, knowledge and perception from the public, patients and key stakeholders. Utilising processes of mutual learning embodying our mission of ‘science with society’. We have established citizen science projects. The Phage Collection Project is engaging the public to assist in the search for new phages in environmental water sources as a treatment for AMR. We are encouraging the public to donate poo to stool banks and partnering with the BBC, Operation Ouch! and the National Poo Museum to challenge taboos and perceptions. We have a successful track record of patient engagement. Following NIHR funding, we conducted patient workshops with Dr Dorey KCL Public Engagement Manager, the British Liver Trust and with academic artists from Boston University facilitating an animation launched at the Houses of Parliament. We will create a bespoke patient/public network, committed and passionate to counter AMR, co-creating outputs and playing crucial roles in shaping the research landscape and driving policy impacts. Creating opportunities for patient dialogue throughout the life of the network and ensuring outputs are representative viewpoints in a medium that will maximise engagement with patients and wider society. 

We expect our programme of work to be upscaled and used in different geographic and socioeconomic settings. Our network aims to enable shared biobanking, data/protocols, knowledge transfer and resources. For example, partnering with The Gates Foundation, Phase-Genomics is building a repository of virus genomes and their bacterial hosts that is “orders of magnitude” larger than what’s already known enabling tracking of AMR through the global ecosystems providing an invaluable resource. Faecal Microbiota treatment for example is a relatively low-cost sustainable intervention.

We expect to deliver tangible outputs such as policy documents, position statements, government white papers, synthesising existing evidence, preliminary data and co-identifying research gaps to facilitate the development of transdisciplinary funding proposals. We aim to develop standards, legislation and investment in infrastructure. We are developing a transdisciplinary cross-institutional MSc in AMR; alongside a bespoke mentoring scheme with opportunities for exchange programmes; facilitating cross-pollination and transdisciplinary working. Shaped by stakeholders to produce skilled practitioners, researchers, and change-makers. We are ensuring representation and raising awareness, critical to driving change and tackling health issues. Utilising processes of mutual learning embodying our mission of ‘science with society’. We will create a bespoke patient/public network passionate about countering AMR.

Children, elderly, cancer patients and those with chronic diseases (estimated to kill 41million, 74% of all deaths globally) are particularly at risk of AMR, which is deadly to the most vulnerable patient populations, particularly in the lowest socioeconomic bracket. We will work to connect AMR researchers and non-academic stakeholders actively engaging third-sector industry, regulatory stakeholders, and other end users of research. Enabling timely high-impact research and treatments that meet the needs of policymakers, practitioners, industry, civil and broader society. We expect to deliver tangible outputs such as policy documents, position statements, government white papers and publications. We have a roadmap to Policy Impact in holding a Policy Lab, an innovative workshop uniting stakeholders and policymakers to discuss the evidence and barriers/facilitators to plan for successful implementation and scaling-up. Work is already being undertaken in conjunction with the Policy Institute at KCL to estimate the potential impact both on healthcare provision and reduction in loss of life and the potential of cost savings to the NHS. Treating AMR infections costs an estimated £180 million/year in the UK. The Lancet Commission, on Liver Disease, suggested that tackling liver disease alone could have an estimated cost saving of £11.7 billion to the NHS. 

We have a Roadmap to Policy Impact and Engagement. The Policy Institute will hold a Policy Lab, an innovative workshop uniting stakeholders and policymakers to discuss the evidence and barriers/facilitators to establish a plan for successful implementation and scaling-up. Alongside a Route to market strategy, regulations, legislation and standardisation. Our GMP manufacturing unit and commercial partners will help develop the pipeline from breakthrough product candidates, designed to address AMR, to production and prescription in the clinic. We will develop standards, legislation and investment in infrastructure through the regulatory/standards boards we sit on, and our ability to lobby government. For example, we are working with the NIBSC Regulatory Science Research Unit using Reference Reagents standardising global pipelines of AMR detection and reporting. Dr Edwards is an elected steering committee member of the (EurFMT network) that implements safety and quality requirements for FMT in a legal context.

Future-proofing our efforts requires workforce planning and training. Raising an army of AM-Resistance activists via a transdisciplinary MSc in AMR and a bespoke early career researchers mentorship programme. With opportunities for exchange programmes; facilitating cross-pollination and transdisciplinary working. Shaped by stakeholders to produce skilled practitioners, researchers, and change-makers. 

We will be able to measure impact according to the number of tangible outputs we have achieved, such as policy documents, position statements, government white papers, publications, developed standards, legislation, students trained and infrastructure. With the Policy Institute we will estimate the impact on healthcare provision, reduction in loss of life, and potential cost savings. We will collect data conducting quasi-experimentation against historical data. Alongside our randomised controlled trials to determine have we reduced infections, AMR transmission rates or prescription of antibiotics etc. We will conduct focus groups to ascertain societal impact and improved quality of life for our patients. Examples from our FMT trial:

“It was like a game-changer for me – stopped me from having infections every couple of weeks. I was in and out of hospital all the time having to take antibiotics with my liver disease and they were making me really ill – now I’m so much better and I don’t have to go to the hospital all the time”

“Thank you for this - you have given us something really important and that’s hope – and if we can pass that hope on to other people to help them that’s such a good thing”

FMT or microbiome modulation could have a profoundly positive impact on both health and the economy, yet there is no infrastructure in place to deliver these treatments. This means it is not currently possible to conduct wider clinical trials, or to roll out this life-saving treatment across the NHS or global health systems. Realising the potential of microbiome-modulation requires strategic investment in expanding the existing infrastructure. Some of these critical changes are longer-term, others could make a difference right now, such as simultaneously collecting stool samples and blood samples.

The development of infrastructure and capability would need to include the following: Advertising & promotion, Donor recruitment, Stool bank facilities, Donor screening facilities, FMT manufacturing facilities, Governance & Regulation, a national database, workforce development and training.

The UK is in a strong position to lead with existing health system infrastructure, world-leading research organisations, and manufacturing capabilities including several MHRA (Medicines and Healthcare products Regulatory Agency) licensed Good Manufacturing Practice compliant manufacturing facilities, including at at Guy’s, King’s and St Thomas’. There must be investment to develop existing infrastructure and capabilities to and ensure we build the promise of these exciting new treatments. 

The R-Biome network is composed of individuals and organisations who passionately want to develop practical and scalable solutions to the global health crisis of AMR. We believe microbiome modulation and boosting our health resilience could have a profoundly positive impact on both health and the economy, yet there is limited infrastructure in place to deliver these treatments. Governance & Regulation, workforce development and training are required to scale. The lack of infrastructure means, at present, it is not possible to conduct wider clinical trials or to roll out this life-saving treatment across global health systems. Realising the potential of microbiome-modulation requires strategic investment in expanding the existing infrastructure. Some of these critical changes are longer-term, others could make an immediate difference. The R-BiOME members leverage great expertise and insight gained through research, and policy initiatives. However, being part of the Trinity challenge and having access to expert collaborators, members, mentors and resources can greatly catalyse our capability to tackle the global challenges of AMR.

The R-Biome network is composed of individuals and organisations who passionately want to develop practical and scalable solutions to the global health crisis of AMR. We believe microbiome modulation and boosting our health resilience could have a profoundly positive impact on both health and the economy, yet there is limited infrastructure in place to deliver these treatments. Governance & Regulation, workforce development and training are required to scale. The lack of infrastructure means, at present, it is not possible to conduct wider clinical trials or to roll out this life-saving treatment across global health systems. Realising the potential of microbiome-modulation requires strategic investment in expanding the existing infrastructure. Some of these critical changes are longer-term, others could make an immediate difference. The R-BiOME members leverage great expertise and insight gained through research, and policy initiatives. However, being part of the Trinity challenge and having access to expert collaborators, members, mentors and resources can greatly catalyse our capability to tackle the global challenges of AMR.