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Pharmacogenetics and the treatment of functional gastrointestinal disorders.

ABSTRACT: The diagnosis and management of functional gastrointestinal disorders (FGIDs) remain very challenging. In the era of precision medicine, it is important to individualize the treatment of these conditions by providing targeted and effective therapies while minimizing the risk of medication side effects. By using genetic information that predicts and affects the responses to specific medications, it is anticipated that the science of pharmacogenetics in FGIDs will advance the practice of precision medicine. The pathophysiology of FGIDs is complex, involving the interaction between predisposing genetic and environmental factors. Studies have shown that genetic polymorphisms may contribute to the variable responses to specific medications among individuals with FGIDs. Genetic variations in the CYP450 system can affect the metabolism and, hence, the pharmacokinetics of drugs used to treat FGIDs. Polymorphisms in the genes controlling proteins that are involved in the direct action of medications targeting the serotonergic, cannabinoid, adrenergic and bile acid pathways can affect the pharmacologic effects of the medications. In this review, we summarize the published literature on the pharmacogenetics of FGIDs and address the potential clinical utility and future challenges in this field. Since it was the dominant topic in the majority of the articles relevant to FGIDs, our review will focus on irritable bowel syndrome.

SUBMITTER: Halawi H

PROVIDER: S-EPMC5591464 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Pharmacogenetics and the treatment of functional gastrointestinal disorders.

Halawi Houssam H Camilleri Michael M

Pharmacogenomics 20170707 11

The diagnosis and management of functional gastrointestinal disorders (FGIDs) remain very challenging. In the era of precision medicine, it is important to individualize the treatment of these conditions by providing targeted and effective therapies while minimizing the risk of medication side effects. By using genetic information that predicts and affects the responses to specific medications, it is anticipated that the science of pharmacogenetics in FGIDs will advance the practice of precision ...[more]

PMID: 28686075

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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.

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.

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Pharmacogenetics and the treatment of functional gastrointestinal disorders.

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Pharmacogenetics and the treatment of functional gastrointestinal disorders.

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