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Functional GI Disorders & Gut Brain Axis

THE ROLES OF THE MICROBIOTA IN FUNCTIONAL GI DISORDERS AND THE GUT-BRAIN AXIS

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Functional intestinal disorders constitute the most globally prevalent GI disorders and reflect, at least in part, disruption of the bidirectional gut-brain axis. Our laboratory investigates the pathogenesis and pathophysiology of these heterogeneous disorders. Our current focus is on the role of the microbiota in these conditions using humanized preclinical models as well as clinical studies. We are particularly interested in the role of dietary components and microbial metabolites in (a) the generation of visceral pain and (b) the modulation and disruption of intestinal motility – both hallmark features of functional GI disorders. Psychiatric comorbidity is very common in these disorders and our work extends to the investigation of how the intestinal microbiota influences brain function and contributes to the psychiatric comorbidity in functional disorders using humanized preclinical models. Our clinical work involves investigation of dietary manipulation of the microbiota including gliadin and when provocation in IBS with alleged wheat sensitivity, and prebiotics and probiotics in the treatment of functional GI disorders.

Lab Website: https://bercik-collins.com

Premysl Bercik: https://experts.mcmaster.ca/display/bercikp

Stephen Collins:  https://experts.mcmaster.ca/display/scollins

Giada De Palma: https://experts.mcmaster.ca/display/depalma

THE ROLE OF THE EXTRINSIC NERVOUS SYSTEM IN FUNCTIONAL GI DISORDERS

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The Chen-Huizinga lab is focused on better understanding and treating complex chronic gastrointestinal motility disorders. The lab utilizes several approaches including assessment of autonomic function, high resolution manometry, ultrasound, barostat  and cutaneous electrical recording techniques to characterize these disorders and ultimately develop a composite  set of markers  to phenotype patients and develop novel  personalized therapies involving neuro modulatory approaches and regulation of autonomic function.  See also “Clinical Research” page on this website.

Selected Papers

1. Ali MK, Liu L, Chen JH & Huizinga JD (2021). Optimizing Autonomic Function Analysis via Heart Rate Variability Associated With Motor Activity of the Human Colon. Front Physiol 12, 1–14; doi: 10.3389/fphys.2021.619722.

2. Huizinga JD, Hussain A & Chen JH (2022). Generation of Gut Motor Patterns Through Interactions Between Interstitial Cells of Cajal and the Intrinsic and Extrinsic Autonomic Nervous Systems. Adv Exp Med Biol 1383, 205–212.

3. Liu L, Milkova N, Nirmalathasan S, Ali MK, Sharma K, Huizinga JD & Chen JH (2022). Diagnosis of dysmotility associated with autonomic dysfunction in patients with chronic refractory constipation. Nature’s Scientific Reports 12:12051, doi.org/10.1038/s41598–022.

INVESTIGATING THE ROLE OF THE MICROBIOTA IN DISEASES INVOLVING THE GUT-BRAIN AXIS

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The gut-brain axis in the bidirectional link between the enteric and central nervous systems and is essential for the maintenance of gastrointestinal homeostasis. The development of the enteric nervous system and the navigation of extrinsic nerves to targets in the gastrointestinal tract begin during fetal life and continue to develop into the postnatal period, with ongoing plasticity into adulthood. Alterations in the gut-brain axis contribute to the pathophysiology of the highly common disorders of gut-brain interaction (DGBI). In children, DGBI such as gastroesophageal reflux disease, abdominal pain and constipation are among the most common diagnoses for which children require medical attention.

There has been increasing recognition that the intestinal microbiota and gut-brain axis interact during critical periods, with implications for normal development and function. The Ratcliffe Lab has previously shown that the early postnatal development of the ENS is disrupted in germ-free mice, with reductions in nerve density, changes in neuronal chemical coding and altered patterns of motility. The potential for the intestinal microbiota to participate in neuronal programming has drawn attention to the importance of studying neurodevelopmental processes in the context of the microbiota milieu.

The overarching theme of projects in the Ratcliffe Lab is to identify modifiable factors that can influence gut-brain axis development, such as interactions with the host microbiome, exposure to medications/substances and nutritional components. Our research program is supported by the infrastructure of the Farncombe Family Digestive Health Research Institute, by a network of local, national and international collaborators, and by outreach to community partners. Long-term, we strive to make major advances in our understanding of the prevention and management of DGBI while providing a rich learning environment for undergraduate, graduate and postgraduate trainees.

Elyanne Ratcliffe: https://experts.mcmaster.ca/display/ratcli

Lab Website:   https://www.ratcliffelab.com/