Pathophysiology Of Functional Gastrointestinal Disorders Research Articles

NON-PHARMACOLOGICAL MANAGEMENT OF FUNCTIONAL GASTROINTESTINAL DISORDERS THROUGH AYURVEDA: A REVIEW

Non-pharmacological management refers to the management without the use of medications. Gastrointestinal disorders, especially Functional Gastrointestinal Disorders (FGIDs), are common disorders characterized by persistent and recurrent gastrointestinal symptoms due to abnormal functioning of the enteric nervous system where no structural or organic pathology is identified. FGIDs are associated with motility disturbances, visceral hypersensitivity, altered mucosal and immune function, gut microbiota, etc. To fully understand the pathophysiology of FGIDs, it is important to comprehend the biopsychosocial behaviour, which focuses on understanding and treatment of the illness and the subjective sense of the patient's suffering. Globally, the most common FGIDs (irritable bowel syndrome and functional dyspepsia) alone affect 16–26% of the population. The non-pharmacological management includes reassurance, lifestyle modifications including observance of dinacharya (daily regimen), gut hygiene, ritucharya (seasonal regimen), psychotherapy, dietary interventions like intake of pathyaahara, implementing sadvritta, the ideal code of conduct, performing yoga, etc. Since gastrointestinal disorders are highly prevalent and pharmacological modalities are limited in contemporary medicine. Thus, a non-pharmacological approach can be preferred in today’s era for sustainable results. Ayurveda follows a holistic approach and has never considered an individual's physical, physiological, and psychological aspects as separate entities. Hence, the management of different diseases has been given under three modalities: daivavyapashraya, yuktivyapashraya, and satvavajaya chikitsa. Thus, in the non-pharmacological management of FGIDs, Ayurveda played a magnificent role.

Obesity and functional gastrointestinal disorders: What is the link?

Obesity and functional gastrointestinal disorders: What is the link?

Uloga odnosa između crevne mikrobiote i mozga u patogenezi funkcionalnih gastrointestinalnih poremećaja

The relation between the intestinal microbiota and the brain is an important field of research in the pathophysiology of functional gastrointestinal disorders (FGIDs). This group of diseases includes more than 40% of the population and is one of the most common reasons for the need of consulting a gastroenterologist. The interaction between the gut microbiota and the brain is a new terminology for defining functional gastrointestinal disorders, based on certain diagnostic criteria. The ROMA IV classification of diagnostic criteria divides functional gastrointestinal diseases into five anatomical regions including the esophagus, gastroduodenal tract, intestine, biliary tract, and anorectal region. Symptoms are usually based on gastrointestinal dysfunction such as gastroesophageal reflux disease (GERD), functional dysphagia, functional dyspepsia, gastroparesis, irritable bowel syndrome (IBS), functional constipation, diarrhea, and fecal incontinence. In this study, we observe at the mechanisms of interaction between gut microbes and brain function. Enteric microbiota (nonpathological microorganisms) has numerous synergistic actions with the human body. The microbiota can change and is different in each individual, as each individual has their own specific microbiome. From digesting food to protecting against pathogens, the intestinal microbiota plays an important role in maintaining immunity and homeostasis. Recently, studies have shown that one of the main impeler of the interaction between the gut and the brain is precisely the microbiome, and so the new term was created "axis of intestinal microbiota-brain". In the future, the general approach to the treatment of functional gastrointestinal disorders tends to be personalized, not only based on symptoms, but also on the underlying pathophysiology and psychology. Various mechanisms, including metabolic pathways, immune system, neural pathways, are involved in the relationship between the gut microbiota axis and the brain. We also discuss some future challenges in modifying the intestinal microbiota with probiotics, prebiotics and nutrition, precisely through this new relationship. Awareness of the relationship between intestinal bacteria and their hosts is crucial in the development of modern therapeutic strategies based on good microorganisms (pre/probiotics) for functional gastrointestinal disorders.

Functional Gastrointestinal Disorders in Patients With Epilepsy: Reciprocal Influence and Impact on Seizure Occurrence.

Introduction: The complex relationship between the microbiota-gut-brain axis (MGBA) and epilepsy has been increasingly investigated in preclinical studies. Conversely, evidence from clinical studies is still scarce. In recent years, the pivotal role of MGBA dysregulation in the pathophysiology of functional gastrointestinal disorders (FGID) has been recognized. With this background, we aimed to investigate the prevalence of FGID in patients with epilepsy (PWE) and the possible impact of bowel movement abnormalities on seizure recurrence.Methods: A total of 120 PWE and 113 age-, sex-, and BMI-matched healthy subjects (HS) were consecutively enrolled. A questionnaire to evaluate the presence of FGID (according to Rome III diagnostic criteria) was administrated to all participants. In a subgroup of drug-resistant patients, we administered an ad-hoc questionnaire combining Bristol stool charts and seizure diaries to evaluate seizure trends and bowel movement changes.Results: A higher prevalence of FGID in PWE (62.5%) than in HS (39.8%) was found (p < 0.001). The most frequently observed disorder was constipation, which was significantly higher in PWE than in HS (43.3 vs. 21.2%, p < 0.001), and was not associated with anti-seizure medication intake according to multivariable analysis. In drug-resistant patients, most seizures occurred during periods of altered bowel movements, especially constipation. A significant weak negative correlation between the number of days with seizures and the number of days with normal bowel movements was observed (p = 0.04). According to multivariable logistic regression analysis, FGID was significantly associated with temporal lobe epilepsy as compared with other lobar localization (p = 0.03).Conclusions: Our clinical findings shed new light on the complex relationship between epilepsy and the MGBA, suggesting a bidirectional link between bowel movement abnormalities and seizure occurrence. However, larger studies are required to better address this important topic.

Gut microbiota dysbiosis in functional gastrointestinal disorders: Underpinning the symptoms and pathophysiology.

Functional gastrointestinal disorders (FGIDs), currently known as disorders of gut–brain interaction, are emerging microbiota–gut–brain abnormalities that are prevalent worldwide. The pathogenesis of FGIDs is heterogeneous and is intertwined with gut microbiota and its derived molecule‐modulated mechanisms, including gut dysmotility, visceral hypersensitivity, gut immune abnormalities, abnormal secretion, and impaired barrier function. There has been phenomenal progress in understanding the role of gut microbiota in FGIDs by underpinning the species alternations between healthy and pathological conditions such as FGIDs. However, the precise gut microbiota‐directed cellular and molecular pathogeneses of FGIDs are yet enigmatic. Determining the mechanistic link between the gut microbiota and gastrointestinal (GI) diseases has been difficult due to (i) the lack of robust animal models imitating the various aspects of human FGID pathophysiology; (ii) the absence of longitudinal human and/or animal studies to unveil the interaction of the gut microbiota with FGID‐relevant pathogenesis; (iii) uncertainty about connections between human and animal studies; and (iv) insufficient data supporting a holistic view of disease‐specific pathophysiological changes in FGID patients. These unidentified gaps open possibilities to explore pathological mechanisms directed through gut microbiota dysbiosis in FGIDs. The current treatment options for dysbiotic gut microbiota are limited; dietary interventions, antibiotics, probiotics, and fecal microbiota transplantation are the front‐line clinical options. Here, we review the contribution of gut microbiota and its derived molecules in gut homeostasis and explore the possible pathophysiological mechanisms involved in FGIDs leading to potential therapeutics options.

Animal Models for Functional Gastrointestinal Disorders.

Functional gastrointestinal disorders (FGID), such as functional dyspepsia (FD) and irritable bowel syndrome (IBS) are characterized by chronic abdominal symptoms in the absence of an organic, metabolic or systemic cause that readily explains these complaints. Their pathophysiology is still not fully elucidated and animal models have been of great value to improve the understanding of the complex biological mechanisms. Over the last decades, many animal models have been developed to further unravel FGID pathophysiology and test drug efficacy. In the first part of this review, we focus on stress-related models, starting with the different perinatal stress models, including the stress of the dam, followed by a discussion on neonatal stress such as the maternal separation model. We also describe the most commonly used stress models in adult animals which brought valuable insights on the brain-gut axis in stress-related disorders. In the second part, we focus more on models studying peripheral, i.e., gastrointestinal, mechanisms, either induced by an infection or another inflammatory trigger. In this section, we also introduce more recent models developed around food-related metabolic disorders or food hypersensitivity and allergy. Finally, we introduce models mimicking FGID as a secondary effect of medical interventions and spontaneous models sharing characteristics of GI and anxiety-related disorders. The latter are powerful models for brain-gut axis dysfunction and bring new insights about FGID and their comorbidities such as anxiety and depression.

Are functional gastrointestinal disorders a clinically significant comorbid factor for acute respiratory infection in children?

Rationale: Functional gastrointestinal disorders (FGID) are highly prevalent in children worldwide. Current concept of FGID pathophysiology implies contributions from various mechanisms. Information in the role of acute respiratory infections in the development of FGID in children is lacking.Aim: To determine the prevalence of FGID in children hospitalized to the department of infectious diseases with acute respiratory tract infections (ARTI) and their association with demographic, medical biological factors and clinical manifestations.Materials and methods: We performed observational and cross-sectional study with continuous patient sampling. The study included 180 ARTI patients, whose mothers agreed to fill in the proposed questionnaire of 41 items. The diagnosis of FGID during in-hospital stay was made based on clinical data in accordance with the Rome criteria IV (2016) and by standard collection of the information from the parents. The stool characteristics were assessed with the Bristol scale. The rate of recurrent ARTI was assessed by the resistance index of above 0.5. We considered clinical symptoms of ARTI at the admittance, the rates of bacterial complications and the need in antibacterial treatment.Results: The prevalence of FGID in hospitalized children with ARTI below 4 years of age (n = 134) was 35.1% (95% confidence interval [CI]) 27.0– 43.9); they had higher rates of functional diarrhea (14.9%, 95% CI 9.4–22.1) and constipation (14.2%, 95% CI 8.8–21.3). Among those above 4 years of age (n = 46), FGID were diagnosed in 50% (95% CI 34.9–65.1) of the cases; with most frequent symptoms being abdominal pain (39.1%, 95% CI 25.1–54.6) and irritable bowel syndrome (10.8%). Irrespective of their age, the children with FGID had higher rates of ARTI recurrence (by 34.0%, 95% CI 20.0–48.1; relative risk 1.98, 95% CI 1.47–2.69; odds ratio 4.13, 95% CI 2.18–7.85) and intestinal infections in their past history, compared to those without any gastrointestinal symptoms during the index hospitalization. In children with FGID, ARTI were more frequently complicated by otitis and they had higher requirement in antibiotics. The mothers of the infants and toddlers with FGID had lower educational level (smaller proportion of those with high school education) and were less satisfied with their home and living conditions, whereas their fathers were older and more frequently employed in vehicle operations and less frequently were occupied in communication-related professions.Conclusion: Acute respiratory infections, especially recurring, may plaу a significant role in the development and maintenance of FGID in children. Further studies are necessary, which may result in useful information for the development of tailored strategies to treatment and prevention.

Gut‐Brain Axis Exploration

The pathophysiology of functional gastrointestinal disorders (FGIDs) is associated with dysfunction at various levels of the gut-brain axis. Hypervigilance can result in an increased tendency to report pain. In the present study, we aimed to explore whether hypervigilance can influence attentional processing in postural control in children with FGIDs. Fifty-nine participants classified into healthy subjects, those with FGIDs, and those with organic diseases (Org) based on Rome IV criteria were enrolled. Postural control under 6 sensory conditions was evaluated using a stabilometric platform. The mean velocity of the center of pressure (CoP) displacement in the anteroposterior direction and the mediolateral direction, the length of the CoP trajectory, and the sway area were also measured. With visual and somatosensorial normal inputs, participants with FGIDs showed a higher number of anteroposterior (FGIDs: 4[interquartile range [IQR] 3-7], control [Cntl] 3 [IQR 3-4], P < 0.05) latero-lateral oscillations (FGIDs: 3 [IQR 3-6], Cntl 3 [IQR 2-3], P < 0.05) and a higher perimeter value (FGIDs: 148 [IQR 121-240], Cntl 124 [IQR 111-140], P = 0.056) compared to healthy subjects. With normal visual but altered somatosensorial input, subjects with FGIDs showed higher values of all parameters (anteroposterior: FGIDs 6[IQR 5-8], Cntl and Org 5 [IQR 4-6], P < 0.05; latero-lateral FGIDs 6 [IQR 4-8], Cntl 4 [IQR 4-5], Org 4[IQR 3-5], P < 0.05; perimeter FGIDs 253 [IQR 167-305], Cntl 185 [IQR 161-217], Org 176 [IQR 142-219], P < 0.05; area FGIDs 98 [IQR 81-233], Cntl 86 [IQR 59-114], Org 56 [IQR 41-97], P < 0.05). The higher number of oscillations in subjects with FGIDs who had normal visual input could be expression of alteration in attention and therefore hypervigilance as hypothesized in the context of gut-brain axis alterations.

Increasing Evidence That Irritable Bowel Syndrome and Functional Gastrointestinal Disorders Have a Microbial Pathogenesis.

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.

Herbal Therapies in Functional Gastrointestinal Disorders: A Narrative Review and Clinical Implication.

The pathophysiology of functional gastrointestinal disorders (FGIDs) is still unclear and various complex mechanisms have been suggested to be involved. In many cases, improvement of symptoms and quality of life (QoL) in patients with FGIDs is difficult to achieve with the single-targeted treatments alone and clinical application of these treatments can be challenging owing to the side effects. Herbal preparations as complementary and alternative medicine can control multiple treatment targets of FGIDs simultaneously and relatively safely. To date, many herbal ingredients and combination preparations have been proposed across different countries and together with a variety of traditional medicine. Among the herbal therapies that are comparatively considered to have an evidence base are iberogast (STW-5) and peppermint oil, which have been mainly studied and used in Europe, and rikkunshito and motilitone (DA-9701), which are extracted from natural substances in traditional medicine, are the focus of this review. These herbal medications have multi-target pharmacology similar to the etiology of FGIDs, such as altered intestinal sensory and motor function, inflammation, neurohormonal abnormality, and have displayed comparable efficacy and safety in controlled trials. To achieve the treatment goal of refractory FGIDs, extensive and high quality studies on the pharmacological mechanisms and clinical effects of these herbal medications as well as efforts to develop new promising herbal compounds are required.

Estado y rasgo de ansiedad en escolares y adolescentes colombianos con y sin desórdenes gastrointestinales funcionales

Introducción: la fisiopatología de los desórdenes gastrointestinales funcionales (DGF) incluye un eje intestino-cerebro alterado.&#x0D; Objetivo: determinar la prevalencia y posibles asociaciones de ansiedad en niños con DGF.&#x0D; Metodología: estudio de prevalencia realizado en ciudades colombianas en niños entre 8 y 18 años a quienes se les identificaron DGF según los Criterios de Roma III y ansiedad por medio del State Trait Anxiety Inventory for Children. Se incluyeron variables sociodemográficas y familiares. El análisis estadístico incluyó medidas de tendencia central, análisis uni- y multivariados, y regresión logística, teniendo en cuenta una p &lt; 0,05 como significativa.&#x0D; Resultados: se incluyeron 1496 niños, 12,7 ± 2,1 años, 50,5 % niñas, 79,9 % con ansiedad transitoria y 51,5 % con tendencia a experimentar estados de ansiedad. Hubo predominio para el estado-ansiedad en adolescentes masculinos y para el rasgo-ansiedad en adolescentes femeninas con algún DGF. Los posibles factores de riesgo fueron la edad y el sexo para estado-ansiedad, y la edad, el sexo y los DGF para el rasgo-ansiedad.&#x0D; Conclusiones: cerca de la mitad de los niños tuvo tendencia a presentar estados de ansiedad, con predominio de las adolescentes femeninas y con factores de riesgo como la edad, el sexo y tener algún DGF.

Colonic hypersensitivity and low-grade inflammation in a spontaneous animal model for functional gastrointestinal disorders.

A complex interplay between a failing intestinal barrier and low-grade inflammation leading to sensorimotor disturbances is an often-cited mechanism in the pathogenesis of functional gastrointestinal disorders (FGID). However, the cause-consequence relationship between these features has not been clearly established. We previously described jejunal alterations in the normoglycemic BB-rat (BBDP-N) model proposing this model as a suitable animal model to study FGID pathophysiology. The current study explores colonic permeability, inflammation, and sensitivity of the BB-rat. Colonic tissue of BBDP-N and control (BBDR) rats at 50, 90, 110, 160, and 220days (n≥7 per group) was used to assess intestinal permeability in Ussing chambers and inflammation, including infiltration by eosinophils, mast cells, and eosinophil peroxidase (EPO) activity. Anxiety-like symptoms were evaluated at 50, 90, and 220days and colonic sensitivity at 160 and 220days by measuring the visceromotor response (VMR) to isobaric colorectal distensions. Lamina propria eosinophil and mast cell infiltration and increased EPO activity were demonstrated from 90days onward. Increased permeability and myenteric ganglionitis were observed in the oldest BBDP-N rats. At 220days, the VMR was significantly increased suggesting colonic hypersensitivity. At the same age, increased anxiety-like behavior was observed. We demonstrated a lamina propria eosinophil and mast cell infiltration preceding visceral hypersensitivity in the colon of the BBDP-N rat, reminiscent of patients with FGID. These findings help elucidating pathogenetic pathways in FGID and further validate the BBDP-N rat as an attractive model to study pathophysiology and therapy of FGID.

The Digestive Health among Participants of the Woodstock Rock Festival in Poland-A Cross-Sectional Survey.

Alterations of gut microbiota, intestinal barrier and the gut-brain axis may be involved in pathophysiology of functional gastrointestinal disorders. Our aim was to assess the prevalence of digestive tract symptoms and identify common variables potentially disrupting the gut-brain axis among participants of the Woodstock Festival Poland, 2017. In total 428 people filled in a questionnaire assessing health of their digestive tract. The investigator collected answers on an electronic device, while the study participant responded using a paper version of the same questionnaire. Liver and gallbladder related symptoms were the most prevalent among our study group (n = 266, 62%), however symptoms related to altered intestinal permeability were found to be the most intensive complaints. In females the intensity of gastrointestinal complaints was higher compared to men (p < 0.05), as well as the incidence of factors with the potential to alter gut-brain axis (p < 0.0001). Chronic psychological distress, intake of non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics, were the most common associations with gastrointestinal symptoms, which were the most prevalent in females. Further attention should be focused on stress as one of the main factors negatively influencing public health.

Understanding Neurogastroenterology From Neuroimaging Perspective: A Comprehensive Review of Functional and Structural Brain Imaging in Functional Gastrointestinal Disorders.

This review provides a comprehensive overview of brain imaging studies of the brain-gut interaction in functional gastrointestinal disorders (FGIDs). Functional neuroimaging studies during gut stimulation have shown enhanced brain responses in regions related to sensory processing of the homeostatic condition of the gut (homeostatic afferent) and responses to salience stimuli (salience network), as well as increased and decreased brain activity in the emotional response areas and reduced activation in areas associated with the top-down modulation of visceral afferent signals. Altered central regulation of the endocrine and autonomic nervous responses, the key mediators of the brain-gut axis, has been demonstrated. Studies using resting-state functional magnetic resonance imaging reported abnormal local and global connectivity in the areas related to pain processing and the default mode network (a physiological baseline of brain activity at rest associated with self-awareness and memory) in FGIDs. Structural imaging with brain morphometry and diffusion imaging demonstrated altered gray- and white-matter structures in areas that also showed changes in functional imaging studies, although this requires replication. Molecular imaging by magnetic resonance spectroscopy and positron emission tomography in FGIDs remains relatively sparse. Progress using analytical methods such as machine learning algorithms may shift neuroimaging studies from brain mapping to predicting clinical outcomes. Because several factors contribute to the pathophysiology of FGIDs and because its population is quite heterogeneous, a new model is needed in future studies to assess the importance of the factors and brain functions that are responsible for an optimal homeostatic state.

Role of Gut Microbiota-Gut Hormone Axis in the Pathophysiology of Functional Gastrointestinal Disorders.

Gut microbiota exert a pivotal influence on various functions including gastrointestinal (GI) motility, metabolism, nutrition, immunity, and the neuroendocrine system in the host. These effects are mediated by not only short-chain fatty acids produced by microbiota but also gut hormones and inflammatory signaling by enteroendocrine and immune cells under the influence of the microbiota. GI motility is orchestrated by the enteric nervous system and hormonal networks, and disturbance of GI motility plays an important role in the pathophysiology of functional gastrointestinal disorders (FGIDs). In this context, microbiota-associated mediators are considered to act on specific receptors, thus affecting the enteric nervous system and, subsequently, GI motility. Thus, the pathophysiology of FGIDs is based on alterations of the gut microbiota/gut hormone axis, which have crucial effects on GI motility.

Functional gastrointestinal disorders in newborns: nutritional perspectives.

Functional gastrointestinal disorders (FGIDs) definition in children has changed over the years trying to facilitate clinicians, because the diagnostic process is complicated by the interpretation variability of symptoms described by children or by their caregivers for newborns and toddlers. This review refers to the Rome IV classification system, drafted in 2016. FGIDs pathophysiology is multifactorial and still poor understood, with limitations for the therapeutic process, which results often in unnecessary and alternative treatments trying to reduce the relevant caregiver distress, but with increased costs for families and for the National Health Service. This study reports the most recent evidence-based treatments for FGIDs in newborns: though in most cases the first action is an educational and behavioral intervention, reassuring caregivers about the transient and self-limiting natural history of FGIDs, there is now more evidence to recommend probiotics in some infant FGIDs.

The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study

BackgroundsThe intestinal microbiota is considered as a potential common underpinning pathophysiology of Functional Gastrointestinal Disorders (FGIDs) and psychiatric disorders such as depression and anxiety. Fecal Microbiota Transplantation (FMT) has been reported to have therapeutic effects on diseases related to dysbiosis, but few studies have evaluated its effect on psychiatric symptoms. MethodsWe followed 17 patients with either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms. Changes in Hamilton Rating Scale for Depression (HAM-D) and subscale of sleep-related items, Hamilton Rating Scale for Anxiety (HAM-A) and Quick Inventory for Depressive Symptoms (QIDS) between baseline and 4 weeks after FMT, and relationship with the intestinal microbiota were measured. ResultsAt baseline, 12 out of 17 patients were rated with HAM-D ≥ 8. Significant improvement in HAM-D total and sleep subscale score, HAM-A and QIDS were observed (p = 0.007, p = 0.007, p = 0.01, p = 0.007, respectively). Baseline Shannon index indicated that microbiota showed lower diversity in patients with HAM-D ≥ 8 compared to those of healthy donors and patients with HAM-D < 8. There was a significant correlation between baseline Shannon index and HAM-D score, and a correlation between Shannon index change and HAM-D improvement after FMT. LimitationsThe small sample size with no control group. ConclusionsOur results suggest that depression and anxiety symptoms may be improved by FMT regardless of gastrointestinal symptom change in patients with IBS, FDr and FC, and the increase of microbiota diversity may help to improve patient's mood.

Pharmacogenetics and the treatment of functional gastrointestinal disorders.

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.

Tests, scans and investigations, 10. Hydrogen breath test

There are several procedures that are undertaken in order to help make a diagnosis or to assess a patient's response to treatment, or their disease progression. Hydrogen breath testing is one of these procedures. This test is used widely; it is a non-invasive way to assist with the diagnosis of a number of conditions. The test investigates the pathophysiology of functional gastrointestinal disorders. This article provides the reader with an overview of the hydrogen breath, with a focus on the procedure and a discussion of the role and function the healthcare assistant and the assistant practitioner (HCA and AP) play in relation to this procedure.

Learned Fear of Gastrointestinal Sensations in Healthy Adults.

Gastrointestinal symptom-specific fear and anxiety are important determinants of gastrointestinal symptom perception. We studied learning of fear toward innocuous gastrointestinal sensations as a putative mechanism in the development of gastrointestinal symptom-specific fear and anxiety. Fifty-two healthy subjects (26 women) received 2 types of esophageal balloon distention at a perceptible but nonpainful intensity (conditioned stimulus [CS], the innocuous sensation) and at a painful intensity (unconditioned stimulus [US]). Subjects were assigned randomly to 1 of 2 groups. During the learning phase, the innocuous CS preceded the painful US in the experimental group (n= 26). In the control group (n= 26), on the contrary, the US never followed the CS directly. During a subsequent extinction phase, both groups received only CS distention-the painful US was no longer administered. Indexes of fear learning toward the innocuous CS distention included the skin conductance response, fear-potentiated startle (measured by the eye-blink electromyogram), and self-reported expectancy of the US. During the learning phase, only the experimental group learned to fear the innocuous gastrointestinal CS, based on the increase in US expectancy (compared with the control group, P=.04), increased skin conductance response (compared with the control group, P= .03), and potentiated startle reflex (compared with the control group, P= .001) in response to the CS. The differences between the experimental and control groups in US expectancy and skin conductance, but not fear-potentiated startle, disappeared during the extinction phase. Fear toward innocuous gastrointestinal sensations can be established through associative learning in healthy human beings. This may be an important mechanism in the development of fear of gastrointestinal symptoms, implicated in the pathophysiology of functional gastrointestinal disorders.