Функциональные расстройства желудочно-кишечного тракта: факторы риска и современные классификации.

Functional gastrointestinal disorders (FGID), also known as disorders of gut–brain interaction, include a number of separate idiopathic disorders which affect different parts of the gastrointestinal tract and involve visceral hypersensitivity and motility disturbances.

Using the Delphi method, the Rome Foundation and its board of directors, chairs and co chairs of the ROME IV committees developed the current definition for disorders of gut brain interaction. A group of disorders classified by GI symptoms related to any combination of: Successively, the Rome I, Rome II, Rome III and Rome IV proposed consensual classification system and terminology, as recommended by the Rome Coordinating Committee. These now include classifications appropriate for adults, children and neonates/toddlers. These factors affect how FGID manifest in terms of symptoms but also affect the clinical outcome. These factors are interconnected and the influences on these factors are bidirectional and mutually interactive.

Early life factors include genetic factors, psychophysiological and sociocultural factors, and environmental exposures. Genetics – Several polymorphisms and candidate genes may predispose individuals to develop FGID. These include alpha 2 adrenergic and 5 HT receptors; serotonin and norepinephrine transporters (SERT, NET); inflammatory markers interleukin (IL)10, tumor necrosis factor (TNF) alpha, and TNF super family member 15 (TNF SF15); intracellular cell signaling (G proteins); and ion channels (SCN5A). However, the expression of a FGID requires the influence of additional environmental exposures such as infection, illness modeling and other factors. Psychophysiological factors may affect the expression of these genes, thus leading to symptoms production associated with FGID. Sociocultural factors and family interactions have been shown to shape later reporting of symptoms, the development of FGIDs, and health care seeking. The expression of pain varies across cultures as well including denial of symptoms to dramatic expression. Environmental exposures  – Prior studies have shown the effect of environmental exposures in relation to the development of FGIDs. Environmental exposures such as childhood salmonella infection can be a risk factor for IBS in adulthood.

There is a strong link between FGIDs and psychosocial factors. Psychosocial factors influence the functioning of the GI tract through the brain gut axis, including the GI tract's motility, sensitivity, and barrier function. Psychosocial factors also affect experience and behavior, treatment selection, and clinical outcome. Psychological stress or one's emotional response to stress exacerbates gastrointestinal symptoms and may contribute to FGID development and maintenance. Specifically in children and adolescents, anxiety and depression may present as FGID associated somatic complaints, such as nausea, vomiting, and abdominal pain. Similarly, anxiety in individuals with FGIDs is linked to greater pain severity, frequency, duration, chronicity, and disabling effects. This is because psychological stress can impact the gut's mucosal barrier functions, allowing bacteria and bacterial products to migrate and cause pain, diarrhea, and other GI symptoms. Conversely, since the brain gut axis is bidirectional, GI inflammation and injury can amplify pain signals to the brain and contribute to worsened mental status, including anxiety and depression symptoms. In addition, children with FGIDs are more likely to experience bullying. As such, stressful situations which influence socialization (seen as either a lack thereof or negative experiences) may lead to an impaired functioning in patients with FGIDs. Family interactions may also play a role in the development of FGIDs through their effects on the physical and psychosocial functioning of an individual. Family factors which may influence the development of an FGID include child attachment style, maladaptive parenting behaviors (paternal rejection and hostility), and even the parents' health status, as children of chronically ill parents experience increased somatization, insecure attachment, and worsened biopsychosocial functioning. Each of these factors leads to the accumulation of stressors, which can ultimately lead to the development of an FGID. In addition, family units which have a member with an FGIDs diagnosis are more likely to face family functioning difficulties, including challenges to familial roles, communication, affective involvement, organization, and cohesion. These challenges arise due to the nature of the disease, and ultimately worsen symptoms for the FGID patient.

The physiology of FGID is characterized by abnormal motility, visceral hypersensitivity as well as dysregulation of the immune system and barrier function of the GI tract as well as inflammatory changes. Abnormal motility Studies have shown altered muscle contractility and tone, bowel compliance, and transit may contribute to many of the gastrointestinal symptoms of FGID which may include diarrhea, constipation, and vomiting. Visceral hypersensitivity In FGID there is poor association of pain with GI motility in many functional GI disorders. These patient often have a lower pain threshold with balloon distension of the bowel (visceral hyperalgesia), or they have increased sensitivity even to normal intestinal function; Visceral hypersensitivity may be amplified in patients with FGIDs. Immune dysregulation, inflammation, and barrier dysfunction Studies on postinfectious IBS have shown that factors such as mucosal membrane permeability, the intestinal flora, and altered mucosal immune function. Ultimately leading to visceral hypersensitivity. Factors contributing to this occurrence include genetics, psychological stress, and altered receptor sensitivity at the gut mucosa and myenteric plexus, which are enabled by mucosal immune dysfunction. Microbiome There has been increased attention to the role of bacteria and the microbiome in overall health and disease. There is evidence for a group of microorganisms which play a role in the brain gut axis. Studies have revealed that the bacterial composition of the gastrointestinal tract in IBS patient differs from healthy individuals (e. g., increased Firmicutes and reduced Bacteroidetes and Bifidobacteria) However, further research is needed to determine the role of the microbiome in FGIDs. Food and diet The types of food consumed and diet consumed plays a role in the manifestation of FGID and also their relationship to intestinal microbiota. Studies have shown that specific changes in diet (e. g., low FODMAP—fermentable oligo , di , and monosaccharides and polyols, or gluten restriction in some patients) may help and reduce the symptom burden in FGID. However, no one diet has been shown to be recommended for all people.

The brain gut axis is a bidirectional mechanism in which psychosocial factors influence the GI tract and vice versa. Specifically, the emotional and cognitive centers of the brain influence GI activity and immune cell function, and the microbes within the gut regulate mood, cognition, and mental health. These two systems interact through several mechanisms. There are direct, physical connections between the central nervous system and nerve plexuses to the visceral muscles. In addition, neurotransmitters send signals related to thoughts, feelings, and pain regulation from the brain to the GI tract. The brain gut axis influences the entire body through a variety of pathways; it regulates sensory, motor, endocrine, autonomic, immune, and inflammatory reactions. Within the physical and psychological interactions of FGIDs specifically, psychiatric disorders such as anxiety, depression, and even autism are well linked to GI dysfunction. Conversely, functional GI diseases are linked to several comorbid psychiatric diseases. Each of these therapies aims to alter an individual's thought patterns and behaviors while improving self efficacy, which all work together to improve health outcomes. Cognitive behavioral therapy is a treatment based on the theory that thinking affects one's feelings and behaviors. As such, alterations in one's thought process can have a positive or negative affect on actions and perceptions. Through the lens of FGIDs, a negative thought pattern may be associated with a negative physical experience of abdominal pain, discomfort, and general sickness. In theory, retraining the patient's thought patterns can alleviate these symptoms and improve quality of life. In patients with FGIDs, CBT is an effective treatment option; one study found 87.5% of participants to be completely pain free following treatment. Hypnotherapy, another method for reducing symptoms of FGIDs, teaches users how to alter their perception of uncomfortable sensations in the body. Gut directed hypnotherapy specifically gives greater improvements in symptoms than standard treatment of the disease. For patients with irritable bowel syndrome (IBS) and functional abdominal pain (FAP), hypnotherapy reduces pain intensity and frequency. The visual, real time feedback given through BART empowers the patient to see the difference that the therapy is making, thus giving the patient control over the physiological components of the disease. This allows the patient to maximize their mind body connection and eventually optimize symptom management and quality of life. BART allows the patient to break the positive feedback loop of anxiety and pain, thus reducing disease exacerbations.

Antidepressants have been thoroughly studied as a potential treatment for FGIDs. Tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and selective norepinephrine reuptake inhibitors (SNRIs) show the most promise in treating some of the symptoms of FGIDs. TCAs, specifically amitriptyline, show promising results when examining common FGIDs symptoms such as pain and poor quality of life. SNRIs also demonstrate pain relieving qualities.

There is considerable research into the causes, diagnosis and treatments for FGIDs. Diet, microbiome, genetics, neuromuscular function and immunological response all interact.