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Immune Activation in Functional Gastrointestinal Disorders.

ABSTRACT: There is growing appreciation that functional gastrointestinal disorders (FGIDs) such as functional dyspepsia and irritable bowel syndrome are heterogeneous conditions linked by subtle inflammation within the gastrointestinal (GI) tract. The literature suggests that while the symptoms of these diseases may manifest with similar clinical presentations, there are significant differences in triggers and disease severity among patients classified into the same subtype. It is hypothesized that the subtle inflammation observed in these patients is related to an imbalance in GI homeostasis. Disruption of the delicate homeostatic balance within the GI tract can result from any number or combination of factors, including dysbiosis, loss of barrier integrity, genetic predisposition, or immune responses to dietary or luminal antigens. This article discusses the interplay between the immune system, microbiota, and luminal environment in FGIDs. In addition, the article proposes emerging immune pathways, including those involving T-helper type 17 response and innate lymphoid cells, as potential regulators of the subtle inflammation characteristic of FGIDs that warrant investigation in future studies.

SUBMITTER: Burns G

PROVIDER: S-EPMC6883739 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Immune Activation in Functional Gastrointestinal Disorders.

Burns Grace G Pryor Jennifer J Holtmann Gerald G Walker Marjorie M MM Talley Nicholas J NJ Keely Simon S

Gastroenterology & hepatology 20191001 10

There is growing appreciation that functional gastrointestinal disorders (FGIDs) such as functional dyspepsia and irritable bowel syndrome are heterogeneous conditions linked by subtle inflammation within the gastrointestinal (GI) tract. The literature suggests that while the symptoms of these diseases may manifest with similar clinical presentations, there are significant differences in triggers and disease severity among patients classified into the same subtype. It is hypothesized that the su ...[more]

PMID: 31802978

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Project description:ObjectiveTo investigate the illness perception characteristics of Chinese patients with functional gastrointestinal disorders (FGID), and the mediating role between symptoms, psychopathology, and clinical outcomes.MethodsSix illness groups from four outpatient departments of a general hospital in China were recruited, including the FGID patient group. The modified and validated Chinese version of the illness perception questionnaire-revised was utilized, which contained three sections: symptom identity, illness representation, and causes. The 12-item short-form health survey was utilized to reflect the physical and mental health-related quality of life (HRQoL). The Toronto alexithymia scale was used to measure the severity of alexithymia. Additional behavioral outcome about the frequency of doctor visits in the past 12 months was measured. Pathway analyses with multiple-group comparisons were conducted to test the mediating role of illness perception.ResultsOverall, 600 patients were recruited. The illness perceptions of FGID patients were characterized as with broad non-gastrointestinal symptoms (6.8 ± 4.2), a negative illness representation (more chronic course, worse consequences, lower personal and treatment control, lower illness coherence, and heavier emotional distress), and high numbers of psychological and culture-specific attributions. Fit indices of the three hypothesized path models (for physical and mental HRQoL and doctor-visit frequency, respectively) supported the mediating role of illness perceptions. For example, the severity of alexithymia and non-gastrointestinal symptoms had significant negative effect on mental quality of life through both direct (standardized effect: -0.085 and -0.233) and indirect (standardized effect: -0.045 and -0.231) influence via subscales of consequences, emotional representation, and psychological and risk factor attributions. Multi-group confirmatory factor analysis showed similar psychometric properties for FGID patients and the other disease group.ConclusionThe management of FGID patients should take into consideration dysfunctional illness perceptions, non-gastrointestinal symptoms, and emotion regulation.

Project description:Functional gastrointestinal disorders (FGIDs) have been re-named as disorders of gut-brain interactions. These conditions are not only common in clinical practice, but also in the community. In reference to the Rome IV criteria, the most common FGIDs, include functional dyspepsia (FD) and irritable bowel syndrome (IBS). Additionally, there is substantial overlap of these disorders and other specific gastrointestinal motility disorders, such as gastroparesis. These disorders are heterogeneous and are intertwined with several proposed pathophysiological mechanisms, such as altered gut motility, intestinal barrier dysfunction, gut immune dysfunction, visceral hypersensitivity, altered GI secretion, presence and degree of bile acid malabsorption, microbial dysbiosis, and alterations to the gut-brain axis. The treatment options currently available include lifestyle modifications, dietary and gut microbiota manipulation interventions including fecal microbiota transplantation, prokinetics, antispasmodics, laxatives, and centrally and peripherally acting neuromodulators. However, treatment that targets the pathophysiological mechanisms underlying the symptoms are scanty. Pharmacological agents that are developed based on the cellular and molecular mechanisms underlying pathologies of these disorders might provide the best avenue for future pharmaceutical development. The currently available therapies lack long-term effectiveness and safety for their use to treat motility disorders and FGIDs. Furthermore, the fundamental challenges in treating these disorders should be defined; for instance, 1. Cause and effect cannot be disentangled between symptoms and pathophysiological mechanisms due to current therapies that entail the off-label use of medications to treat symptoms. 2. Despite the knowledge that the microbiota in our gut plays an essential part in maintaining gut health, their exact functions in gut homeostasis are still unclear. What constitutes a healthy microbiome and further, the precise definition of gut microbial dysbiosis is lacking. More comprehensive, large-scale, and longitudinal studies utilizing multi-omics data are needed to dissect the exact contribution of gut microbial alterations in disease pathogenesis. Accordingly, we review the current treatment options, clinical insight on pathophysiology, therapeutic modalities, current challenges, and therapeutic clues for the clinical care and management of functional dyspepsia, gastroparesis, irritable bowel syndrome, functional constipation, and functional diarrhea.

Dataset Information

Immune Activation in Functional Gastrointestinal Disorders.

Publications

Immune Activation in Functional Gastrointestinal Disorders.

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