Abstract
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.
Highlights
Functional gastrointestinal disorders (FGIDs) have been described as disorders of gut-brain interactions and are common in clinical practice, and in the community (Black et al, 2020b; Sperber et al, 2021a)
It has been estimated that the prevalence of FGIDs worldwide is 40% based on Rome IV criteria (Sperber et al, 2021b)
Further subdivision of patients occurs based on the main stool form observed using the Bristol Stool Form Scale: constipationpredominant irritable bowel syndrome (IBS) (IBS-C), diarrhea-predominant IBS (IBS-D), IBS with a mixture of stool patterns (IBS-M), and IBS with the stool pattern unclassified (IBS-U) (Drossman, 2016)
Summary
Functional gastrointestinal disorders (FGIDs) have been described as disorders of gut-brain interactions and are common in clinical practice, and in the community (Black et al, 2020b; Sperber et al, 2021a). Gut microbial dysbiosis leads to the activation of the gut immune response and causes epithelial barrier dysfunction, which induces gut dysmotility and visceral hypersensitivity (Barbara et al, 2016b; Singh et al, 2021d) These findings reinforce the idea of impaired intestinal barrier function being a core pathophysiological mechanism behind FGIDs. Further, psychological comorbidities, including anxiety, depression, and stress, are often correlated with FGIDs and likely contribute to the altered pathophysiology of gut-brain interactions (Ghoshal, 2020). We selected 184 references for inclusion in this review due to their relevance in regard to the scope of this manuscript and based on the authors’ insight, research experience, and clinical practices in managing these disorders
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