Systemic Disease Associations with Disorders of Gut–Brain Interaction and Gastrointestinal Transit: A Review

Moudgal, Rohitha; Schultz, Andrew W.; Shah, Eric D.

doi:10.2147/ceg.s283685

Cited by 10 publications

(4 citation statements)

References 97 publications

(98 reference statements)

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“…MPS III patients have also been found to be particularly susceptible to extrapyramidal side effects (e.g., dystonia, ataxia) of certain behaviour management treatments (i.e., risperidone, olanzapine, or lamotrigine) [58]. There may be a burden of medication in MPS III patients due to the need to ameliorate symptoms of multiple conditions and polypharmacy, defined as taking more than five medications at any one time, has been identified as a risk factor for developing GI conditions and GI motility delays [59]. A study assessing sleep disturbance in MPS III children lists two participants as taking 5-10 concurrent medications to manage sleep, epilepsy, seizures, pain, GI symptoms and other conditions [60].…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal Manifestations in Mucopolysaccharidosis Type III: Review of Death Certificates and the Literature

Thomas

Ramaswami

Cleary

et al. 2021

JCM

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Background: Mucopolysaccharidosis type III (MPS III, Sanfilippo disease) is a life-limiting recessive lysosomal storage disorder caused by a deficiency in the enzymes involved in degrading glycosaminoglycan heparan sulfate. MPS III is characterized by progressive deterioration of the central nervous system. Respiratory tract infections have been reported as frequent and as the most common cause of death, but gastrointestinal (GI) manifestations have not been acknowledged as a cause of concern. The aim of this study was to determine the incidence of GI problems as a primary cause of death and to review GI symptoms reported in published studies. Methods: Causes of death from 221 UK death certificates (1957–2020) were reviewed and the literature was searched to ascertain reported GI symptoms. Results: GI manifestations were listed in 5.9% (n = 13) of death certificates. Median (IQR) age at death was 16.7 (5.3) years. Causes of death included GI failure, GI bleed, haemorrhagic pancreatitis, perforation due to gastrostomies, paralytic ileus and emaciation. Twenty-one GI conditions were reported in 30 studies, mostly related to functional GI disorders, including diarrhoea, dysphagia, constipation, faecal incontinence, abdominal pain/distension and cachexia. Conclusions: GI manifestations may be an under-recognized but important clinical feature of MPS III. Early recognition of GI symptoms and timely interventions is an important part of the management of MPS III patients.

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Section: Discussionmentioning

confidence: 99%

Gastrointestinal Manifestations in Mucopolysaccharidosis Type III: Review of Death Certificates and the Literature

Thomas

Ramaswami

Cleary

et al. 2021

JCM

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“…The term “functional” will depend in reality on the exclusion of organic and specific motility disorders as well as systemic and metabolic diseases 4 by meticulous investigations. These may include: (1) different combinations of endoscopy including biopsy (to exclude morphologically or histologically distinguishable disorders like cancer, Helicobacter pylori and other chronic infections, celiac disease, microscopic colitis, eosinophilic GI disorders, disaccharidase deficiency); (2) motility studies including manometry of different GI areas (to differentiate functional dyspepsia [FD] from gastroparesis or functional constipation [FC] and constipation predominant irritable bowel syndrome [IBS-C] from slow colon transit due to visceral neuromyopathy); (3) pH-metry with impedance study of the esophagus (to exclude gastroesophageal reflux disease [GERD]), exclusion diets (for food intolerance or allergy); or (4) investigations to diagnose small intestinal bacterial overgrowth (SIBO), bile acid diarrhea and subtle pancreatic exocrine insufficiency.…”

Section: The Extent Of Organic Disease Exclusion Needed For Defining ...mentioning

confidence: 99%

Epidemiology of Disorders of the Gut-Brain Interaction: An Appraisal of the Rome IV Criteria and Beyond

Ray,

Ghoshal

2024

Gut and Liver

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Disorders of the gut-brain interaction (DGBIs) are presently classified into mutually exclusive anatomical area-related symptom-based categories according to the Rome IV criteria. The pathophysiology of visceral nociception, which contributes to the wide range of symptoms of DGBIs, involves complex psychobiological processes arising from the bidirectional interactions of multiple systems at the gut and brain levels, which affect symptom expression and illness behaviors. The attitude toward an illness and expression of pain and bowel habit vary across cultures with variable interpretation based on sociocultural beliefs, which may not tally with the medical definitions. Thus, psychological factors impact DGBI definitions, their severity and health care utilization. Due to the poor localization and multisegment referral of visceral pain, the anatomical site of pain may not correspond to the affected segment, and there may be a variable degree of overlap among symptoms. The somewhat restrictively defined Rome IV criteria assume one-to-one correlation of symptoms with underlying pathophysiology and ignore overlapping DGBIs, nonstandardized symptom categories, and change or shift in category over time. The microorganic nature of DGBIs resulting from systemic, metabolic or motility disorders, gut dysbiosis and inflammation are not addressed in the Rome IV criteria. Although there is a multidimensional clinical profile that does address these factors, it is not followed rigorously in practice. Threshold changes for diagnostic criteria or addition/deletion of symptoms leads to wide variation among different DGBI criteria resulting in uncertain comparability of results. Although the Rome IV criteria are excellent for research studies and therapeutic trials in homogenous populations, further improvement is needed for their wider applicability in clinical practice.

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“…The agent might also act differently at the presynaptic and postsynaptic levels, as seen in the case of opposing effects of mGluR signaling in amygdala and hippocampus. Examining the interactive roles of multiple organs might also be essential for us to gain deeper understanding of the unforeseen trade-offs indicated by the emergent role of the gut microbiome on neurological disorders, such as depression and autism (145)(146)(147)(148)(149). Even within a given brain region, there are still notable differences in gene expression across cell types, thus, differences in signaling pathways, as shown with ASD (150).…”

Section: Biological Factors Can Influence Phenotypic Trade-offsmentioning

confidence: 99%

Phenotypic Trade-Offs: Deciphering the Impact of Neurodiversity on Drug Development in Fragile X Syndrome

et al. 2021

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Fragile X syndrome (FXS) is the most common single-gene cause of intellectual disability and autism spectrum disorder. Individuals with FXS present with a wide range of severity in multiple phenotypes including cognitive delay, behavioral challenges, sleep issues, epilepsy, and anxiety. These symptoms are also shared by many individuals with other neurodevelopmental disorders (NDDs). Since the discovery of the FXS gene, FMR1, FXS has been the focus of intense preclinical investigation and is placed at the forefront of clinical trials in the field of NDDs. So far, most studies have aimed to translate the rescue of specific phenotypes in animal models, for example, learning, or improving general cognitive or behavioral functioning in individuals with FXS. Trial design, selection of outcome measures, and interpretation of results of recent trials have shown limitations in this type of approach. We propose a new paradigm in which all phenotypes involved in individuals with FXS would be considered and, more importantly, the possible interactions between these phenotypes. This approach would be implemented both at the baseline, meaning when entering a trial or when studying a patient population, and also after the intervention when the study subjects have been exposed to the investigational product. This approach would allow us to further understand potential trade-offs underlying the varying effects of the treatment on different individuals in clinical trials, and to connect the results to individual genetic differences. To better understand the interplay between different phenotypes, we emphasize the need for preclinical studies to investigate various interrelated biological and behavioral outcomes when assessing a specific treatment. In this paper, we present how such a conceptual shift in preclinical design could shed new light on clinical trial results. Future clinical studies should take into account the rich neurodiversity of individuals with FXS specifically and NDDs in general, and incorporate the idea of trade-offs in their designs.

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Systemic Disease Associations with Disorders of Gut–Brain Interaction and Gastrointestinal Transit: A Review

Cited by 10 publications

References 97 publications

Gastrointestinal Manifestations in Mucopolysaccharidosis Type III: Review of Death Certificates and the Literature

Gastrointestinal Manifestations in Mucopolysaccharidosis Type III: Review of Death Certificates and the Literature

Epidemiology of Disorders of the Gut-Brain Interaction: An Appraisal of the Rome IV Criteria and Beyond

Phenotypic Trade-Offs: Deciphering the Impact of Neurodiversity on Drug Development in Fragile X Syndrome

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