Microbiome and Oral–Gut–Liver Axis in Cirrhosis: Experimental Research & Therapeutics

Understanding mechanisms. Developing diagnostics. Testing treatments to prevent complications.

Why do some people with cirrhosis deteriorate rapidly, and where can we intervene?

CIRROBIOME investigates how microbial communities, intestinal barrier damage and host responses contribute to infection, decompensation and organ dysfunction in cirrhosis. We connect discoveries in patients with experimental research to identify disease mechanisms, develop diagnostics and evaluate therapeutic approaches.

Led by Dr Vishal C Patel, our group is based at the Roger Williams Institute of Liver Studies (RW-ILS), in partnership with the Foundation for Liver Research, King’s College London and King’s College Hospital.

Our research programme

Our programme centres on the oral–gut–liver axis: how microbes and their products interact with the intestinal lining, immune system and liver to influence the course of disease.

We investigate these relationships across different stages of cirrhosis, from clinically stable disease to acute decompensation and acute-on-chronic liver failure. Our work combines detailed patient characterisation and biological sampling with microbiome profiling, experimental models and clinical trials.

Three key questions connect our projects:

1. What drives deterioration? We investigate microbial and host mechanisms that contribute to barrier failure, inflammation, infection and organ injury.
2. How can we identify clinically important changes earlier? We develop and evaluate approaches to pathogen detection, antimicrobial resistance profiling and biomarkers of tissue injury.
3. Can targeted intervention prevent complications? We assess strategies to modify microbial activity, protect the intestinal barrier and reduce the risk of clinical deterioration.

Our aim is to move from recognising disease-associated changes to understanding which processes can be meaningfully altered at scale to improve patient outcomes.

How the programme has developed

The programme grew from the Gut-Liver Axis in Liver Failure Syndromes study, established by Dr Patel during his doctoral research. By linking high resolution clinical information to well characterised biological samples, this study created a foundation for investigating microbial communities, intestinal inflammation and host immune disturbances in advanced chronic liver disease. In parallel, Dr Patel co-founded the Advanced Chronic Liver Disease clinical service at King’s College Hospital, recognising the need to provide specialist input to diagnose and manage the symptoms of advanced cirrhosis, working in continual partnership with local gastroenterology and hepatology teams, GP and community services.

Work that characterised oral–gut microbial overlap, virulence and antimicrobial resistance led to more specific questions about whether oral bacteria establish themselves in the intestine, which functions they carry, and how they may contribute to tissue injury. Subsequent research has now linked oral bacterial translocation and microbial collagenase activity to intestinal barrier damage. This foundational work provides the rationale for targeted experimental and therapeutic studies of the mouth and the gut.

The clinical burden of infection, together with the effects of antimicrobial exposure, prompted parallel work on antimicrobial resistance and clinical metagenomics to for rapid infection diagnostics. A complementary programme examines the host response to injury through cell-free DNA, inflammation and coagulation.

These projects inform one another. Patient studies identify clinically relevant patterns; experimental work tests possible mechanisms; and diagnostic and therapeutic studies assess their potential application with an increasing focus on prevention of complications and, ultimately, disease.

Our connected research areas

1. Microbial mechanisms and intestinal barrier function

We study how oral and intestinal microbial communities change in cirrhosis, and how these changes affect the host.

A central focus is oralisation of the gut microbiome: the increased presence and establishment of oral microbes in the intestine. We investigate microbial virulence, collagenase activity and metabolic functions that may damage the intestinal barrier or alter immune responses.

Our work combines metagenomic sequencing, microbial isolation and functional analysis with intestinal organoid and other experimental models. This allows us to examine specific microbial activities and test their effects on barrier integrity.

These oral-gut-liver axis studies identify potential targets for intervention and provide a mechanistic foundation for our oral health and microbiome modulation projects.

2. Infection diagnostics and antimicrobial resistance

The Rapid Infection Diagnostics in Cirrhosis (RIDiC) programme evaluates clinical metagenomic sequencing for detecting pathogens and antimicrobial resistance.

We investigate samples including blood and ascitic fluid, where microbial material may be scarce. A key task is to distinguish clinically meaningful findings from contamination and determine how sequencing results could support treatment decisions.

Alongside RIDiC, our long-read metagenomics work examines microbial communities and resistance genes in advanced liver disease. We investigate how the oral and intestinal reservoirs of resistance relate to disease severity and antimicrobial exposure.

Together, these projects connect microbial ecology with the clinical need for timely diagnosis, targeted treatment and effective antimicrobial stewardship.

3. Host responses, cell-free DNA and organ injury

We investigate how tissue injury, immune activation and coagulation disturbances interact in chronic liver failure.

Our cell-free DNA programme examines extracellular DNA as both a potential contributor to disease mechanisms and a source of information about injured tissues. This includes work on neutrophil extracellular traps, inflammation and immunothrombosis.

Molecular and epigenetic profiling help us investigate the origins of circulating DNA and its relationship to organ dysfunction. Complementary studies of haemostasis examine how these processes influence coagulation.

This work extends the programme’s focus from microbial activity and barrier damage to the host consequences of injury, with the aim of identifying useful biomarkers and potential therapeutic targets.

4. Therapeutic modulation and prevention

We connect mechanistic research with studies that evaluate whether intervention can alter the course of cirrhosis.

Our oral health programme investigates whether modifying the oral microbial environment can influence downstream processes along the oral–gut–liver axis. Experimental studies of microbial activity and barrier function support the development of interventions for evaluation in patients.

This work sits alongside mechanistic studies of rifaximin, including the completed RIFSYS trial, collaborative research on faecal microbiota transplantation, and other microbiome-modulating therapeutics. These approaches allow us to examine how treatment changes microbial function and host responses, as well as its clinical effects.

Prevention is also a central aim of BOPPP, the NIHR-funded multicentre trial co-led by Dr Patel, which is evaluating non-selective beta-blockers in people with cirrhosis and small oesophageal varices.

These studies provide complementary routes towards the same goal: preventing complications through interventions supported by biological understanding and clinical evidence.

Our contribution to the RW-ILS strategy

CIRROBIOME contributes to the Institute’s Cirrhosis and Gut–Liver–Brain Axis Strategic Research Theme, which Dr Patel co-leads.

Our particular contribution lies in oral–gut microbial mechanisms, intestinal barrier biology, infection diagnostics, antimicrobial resistance and host injury. This expertise complements work across the wider theme on the pathways linking liver disease with systemic and neurological complications.

We support the Institute’s translational aims by connecting patient cohorts and biobanking with experimental investigation and clinical studies. Collaboration across RW-ILS and King’s Health Partners enables questions arising in clinical care to inform laboratory research, and allows laboratory findings to be assessed for their relevance to patients.

Developing researchers is a core part of this contribution. Through doctoral supervision and clinical research fellowships, we help build the expertise needed to sustain interdisciplinary liver research.

People, training and research culture

Building a research group means investing in people. We bring clinicians and scientists together in an unparalleled way that drives inter-disciplinary working and cross-pollination, and work to widen opportunities for those whose potential can otherwise go unrecognised.

Training and individual development is embedded in our programme. Researchers develop their own questions within connected areas of work, with opportunities to learn across clinical, laboratory and computational disciplines. Doors are opened to accelerate collaborative efforts with other clinical and academic groups and institutions. Creating an environment that encourages and enables people from different backgrounds to excel is central to the ethos of - and a priority for - the group.

Current doctoral projects include:

• Intestinal barrier dysfunction in cirrhosis: investigating interactions between microbes, the intestinal lining and host responses, , including utilisation of experimental models.
• The microbiome and antimicrobial resistance: using long-read metagenomics to characterise microbial communities and resistance genes in advanced liver disease.
• Cell-free DNA and immunothrombosis: examining the relationships between extracellular DNA, neutrophil extracellular traps, inflammation and coagulation dysfunction.

Clinical research fellowships support developing projects in oral health, microbiome modulation and experimental therapeutics. Dr Patel also leads the RW-ILS Pre-Doctoral Clinical Research Fellowship Scheme, which supports clinicians to develop research skills and projects, with progression towards doctoral training where appropriate.

Our aim is to develop independent researchers who can question assumptions, assess evidence critically and collaborate across disciplines. We value different routes into science and recognise that clinical experience, bench-based technical expertise and computational insight each contribute to better research.