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Blizard Institute - Faculty of Medicine and Dentistry
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Neurogastroenterology group

YAKULT Study (Investigator Lead Study)

Investigation of the effect of L. casei Shirota on preventing abdominal symptoms and small intestinal bacterial overgrowth in patients with gastro-oesophageal reflux disease(GORD) newly treated with proton pump inhibitors(PPI): A randomised controlled pilot trial.

EGIS study (Commercial Study):

A Multi-Centre, Randomized, Placebo-Controlled, Efficacy Study of Prebiotic Galacto-oligosaccharides on Gastrointestinal Symptom Severity in Patients with Irritable Bowel Syndrome.

Lead: Qasim Aziz
Professor of Neurogastroenterology
Director of the Wingate Institute

Neurogastroenterology is a discipline of gastroenterology, aimed at understanding the neuromuscular control of gastrointestinal function, with particular emphasis on brain-gut interactions. The Neurogastroenterology Group is a multidisciplinary collaboration of experts, both clinicians and scientists, including adult and paediatric neurogastroenterologists, GI pathologists, physiologists, psychologists and psychiatrists, surgeons, immunologists, neuroscientists, and physicists. They are working across the Blizard Institute, Barts and The London School of Medicine and Dentistry, and Barts Health NHS Trust to advance basic scientific study and translate this knowledge to enhance patient care.

There are four major areas of our research on the gastrointestinal system: pain, neurodegeneration and ageing, reflux, obesity and connective tissue, all addressed by the neurogastroenterology group. The activities of the group span the disciplines of Gastroenterology, Gastrointestinal surgery, Psychiatry, Pharmacology, Neuroscience, Neurology, Immunology, Nutrition and Endocrinology. Many of our members are specialists in one or more of these areas and/or disciplines. The approaches comprise Molecular and Cellular, Experimental and Translational, and Population-based medicine, providing a vertical and horizontal matrix between our research themes. Our many collaborations clearly demonstrate the high level of national and international outreach. Our publication record emphasises our multidisciplinary approach. We provide state-of-the-art research facilities that promote sharing of resources within the campus. We have both individual and collective projects addressing four levels of investigation in each programme.

The four levels are:

  1. Fundamental research on function of human sensorimotor cells and systems
  2. Understanding disease in humans
  3. New diagnostics, therapies and personalized medicine
  4. Health service delivery and dissemination

 

 

 

Pain Programme

Principal investigators: Qasim Aziz, Madusha Peiris, Daniel Sifrim, Charles Knowles, Dr Rubina Aktar

 

Pain

  1. Fundamental research on function of human sensorimotor cells and systems
    1. Mechanical and chemical mechanisms of peripheral stimulus detection in the gut
    2. Central processes
    3. Psycho-physiological interactions
  2. Understanding disease in humans
    1. Oesophageal sensitization
    2. Inflammatory Bowel Disease
    3. Chronic unexplained abdominal pain syndromes (inc. Irritable Bowel Syndrome)
    4. Chronic pelvic pain in women
    5. Post-operative pain
    6. Connective tissue disorders and pain
    7. New diagnostics, therapies and personalized medicine
  3. Cell-based – on individual sensory neurones
    1. Organ-based – interaction between neurones and other cell types
    2. RCT and concept studies
    3. Stratification studies
  4. Health service delivery and dissemination
    1. Community and self-help management strategies

Neurodegeneration and Ageing Programme

Principal investigators: Gareth Sanger

Young mice and old mice

 
  1. Fundamental research on human sensorimotor cells and systems
    1. Effects of ageing on colonic reflex movements and peristalsis
    2. Neuromuscular/secretory interactions with enteric bacteria
    3. Colorectal sensory pathway
  2. Understanding disease in humans
    1. Effects of ageing on neuromuscular activity, neurodegeneration and intestinal reflex functions
    2. Differential neuropharmacology in ageing – ‘pharmacochronetics’
    3. Exploration of rare diseases (including paediatric disorders, Chagas’ disease) – used also as exemplars for common complex diseases to show mechanism of disease and treatment
    4. Definition of neurodegenerative/ neuromuscular changes during chronic inflammation
    5. Secondary neuromuscular diseases including Parkinson’s
  3. New diagnostics, therapies and personalized medicine
    1. In vivo diagnostics: cost effective developments in less invasive methods of assessing colonic sensing and motility
    2. Development and trialling of age and disease-targeted drugs for chronic constipation and pseudo-obstruction, using models with proven translatable value
    3. Development and trialling of less invasive, extracorporeal neuromodulatory treatments for chronic constipation
    4. Development and trialling of pharmaconutrients / probiotics
    5. Neuroprotection or replacement in primary and secondary enteric neuropathies
  4. Health service delivery and dissemination
    1. Post trial effectiveness studies of interventional therapies e.g. neuromodulation
    2. Development of evidence-based NHS algorithms for management of common conditions e.g. constipation

Reflux Disease Programme

Principal Investigators: Daniel Sifrim, Philip Woodland

 

Reflux disease

  1. Fundamental research on function of human sensorimotor cells and systems
           1. Role of dilated intercellular spaces in oesophageal permeability
           2. Acid sensing molecules in the oesophageal epithelium
           3. Oesophagal sensory neurons and receptors

  2. Understanding disease in humans
           1. Epithelial permeability in reflux disease
           2. Oesophageal neuro-epithelial sensory mechanisms in patients unresponsive to acid suppression therapy
           3. Aetiology and role of hypomotility in reflux disease– sensory or motor?
           4. Supragastric belching and rumination in refractory GORD

  3. New diagnostics, therapies and personalized medicine
            1. New methods for diagnosis of reflux (salivary components, new parameters in catheter and wireless reflux monitoring)
            2. Topical protection of the oesophageal mucosa
            3. New prokinetics
            4. Improvement in the valve function of the lower oesophageal sphincter and reduction of transient LOS relaxations
            5. LOS electrical stimulation

  4. Health service delivery and dissemination
            1. Guidelines for management of patients with reflux disease not responding to standard medical treatment.

Enteric Neurobiology Programme

Principal Investigators: Dr Madusha Peiris and Dr Rubina Aktar

Enteric Nervous System:

Fundamental research on function of human and mouse sensorimotor cells and systems:
• Peripheral mechanisms of mechanical and chemical induced gut pain pathways.
• Identification of novel molecular targets for motility, sensory and inflammatory gut disorders.

Understanding molecular mechanisms of human gut diseases:
• Oesophageal sensitization
• Inflammatory Bowel Disease
• Irritable Bowel Syndrome 

Obesity and Appetite Regulation:

Fundamental research on function of human sensorimotor cells and systems
• Nutrient receptor mechanisms in the gut epithelium
• Enteroendocrine communication between the gut and the CNS

Understanding disease in humans
• Changes in enteroendocrine cell function in obesity
• Stress and neuroendocrine responses

New diagnostics, therapies and personalized medicine
• Mechanism of action of bariatric surgery
• Cell-based – vagal afferent neurons and enteroendocrine cells
• Organ-based – enteroendocrine-vagal-brain communication
• Clinical trials of anti-obesity treatments in obese patients

Role of Microbiota in regulating enteric nervous system:

Characterising the effect of microbial populations on:
• Neuronal subtypes innervating the gut
• Function and activity of ENS mediated processes e.g. motility, secretion and sensory signalling.
• Enteroendocrine cell populations and downstream activity/interaction with ENS

Connective Tissue and Extracellular Matrix Programme      

Principal Investigator: Qasim Aziz

 

Connective tissueConnective tissue 

 

 

  1. Fundamental research on human sensorimotor cells and systems
    1. How connective tissue components are distributed in the gastrointestinal tract and sensory nervous system
    2. Contribution of tenascins to gut function: sensation, motility, secretion, coordinated activity
  2. Understanding disease in humans
    1. Cross-correlating epidemiology of Joint Hypermobility Syndrome and Functional Gastrointestinal Disorders
    2. Changes in enteric tenascins in disease
  3. New diagnostics, therapies and personalized medicine
    1. Development and trialling of treatments suited to altered motility and sensation in Joint Hypermobility Syndrome
  4. Health service delivery and dissemination
    1. Development of evidence-based NHS algorithms for management of common co-morbidities e.g. constipation, upper GI symptoms
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