Browsing by Author "Carco C"

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    Increasing Evidence That Irritable Bowel Syndrome and Functional Gastrointestinal Disorders Have a Microbial Pathogenesis
    (Frontiers Media S.A., 2020-09-09) Carco C; Young W; Gearry RB; Talley NJ; McNabb WC; Roy NC; Ianiro G
    The human gastrointestinal tract harbors most of the microbial cells inhabiting the body, collectively known as the microbiota. These microbes have several implications for the maintenance of structural integrity of the gastrointestinal mucosal barrier, immunomodulation, metabolism of nutrients, and protection against pathogens. Dysfunctions in these mechanisms are linked to a range of conditions in the gastrointestinal tract, including functional gastrointestinal disorders, ranging from irritable bowel syndrome, to functional constipation and functional diarrhea. Irritable bowel syndrome is characterized by chronic abdominal pain with changes in bowel habit in the absence of morphological changes. Despite the high prevalence of irritable bowel syndrome in the global population, the mechanisms responsible for this condition are poorly understood. Although alterations in the gastrointestinal microbiota, low-grade inflammation and immune activation have been implicated in the pathophysiology of functional gastrointestinal disorders, there is inconsistency between studies and a lack of consensus on what the exact role of the microbiota is, and how changes to it relate to these conditions. The complex interplay between host factors, such as microbial dysbiosis, immune activation, impaired epithelial barrier function and motility, and environmental factors, including diet, will be considered in this narrative review of the pathophysiology of functional gastrointestinal disorders.
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    Integrated multi-omic and symptom clustering reveals lower-gastrointestinal disorders of gut-brain interaction heterogeneity
    (Taylor and Francis Group, 2026-12-31) Dowrick JM; Roy NC; Carco C; James SC; Heenan PE; Frampton CMA; Fraser K; Young W; Cooney J; Trower T; Keenan JI; McNabb WC; Mullaney JA; Bayer SB; Talley NJ; Gearry RB; Angeli-Gordon TR
    Rome IV disorders of gut-brain interaction (DGBI) subtypes are known to be unstable and demonstrate high rates of non-treatment response, likely indicating patient heterogeneity. Cluster analysis, a type of unsupervised machine learning, can identify homogeneous sub-populations. Independent cluster analyses of symptom and biological data have highlighted its value in predicting patient outcomes. Integrated clustering of symptom and biological data may provide a unique multimodal perspective that better captures the complexity of DGBI. Here, integrated symptom and multi-omic cluster analysis was performed on a cohort of healthy controls and patients with lower-gastrointestinal tract DGBI. Cluster stability was assessed by considering how frequently pairs of participants appeared in the same cluster between different bootstrapped datasets. Functional enrichment analysis was performed on the biological signatures of stable DGBI-predominant clusters, implicating disrupted ammonia handling and metabolism as possible pathophysiologies present in a subset of patients with DGBI. Integrated clustering revealed subtypes that were not apparent using a singular modality, suggesting a symptom-only classification is prone to capturing heterogeneous sub-populations.