FGIDs share in common any of several physiological features including increased reactivity of gastrointestinal movement, hypersensitivity, altered immune function, inflammatory function (associated with bacterial
dysbiosis), and altered central nervous system and
enteric nervous system (CNS-ENS) regulation. The pathophysiology of FGID has been best conceptualized using
biopsychosocial model help to explain the relationships between an individual factors in their early life that in turn can influence their psychosocial factor and physiological functioning. This model also shows the complex interactions between these factors through the
brain-gut axis. 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 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.
Psychosocial factors 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. 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 somatic symptoms, 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.
Physiology 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 can ultimately lead 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.
Brain-gut axis 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. Negative emotions such as fear, anxiety, anger, stress, and pain may delay gastric emptying, decrease intestinal and colonic transit time, and induce defecation and diarrhea. ==Treatments==