|Stress||Dysregulation of the brain–gut axis can influence the main pathophysiological features of IBS, including visceral hypersensitivity, colonic motility and alterations in the gut microbiota.||Clinical symptom severity. |
Salivary diurnal and/or waking cortisol.
Serum neuropeptide Y.
Serotonin transporter gene variants.
Catechol-O-methyltransferase Val158Met gene variants.
Cognitive behavioral therapy.
|Circadian disruption||Circadian rhythm disruption can affect several aspects of gastrointestinal function including gastrointestinal motility, visceral sensitivity, immunological function, and barrier integrity.||Questioning around sleep patterns and electric light-at-night exposure.|
|Extending the dark period.|
Regular sleep patterns.
|Physical inactivity||Clinical studies have found that increasing physical activity can improve gastric emptying, intestinal gas transit and reduce abdominal distension.||Tracking physical activity levels.|
Activity tracker step count.
|Carbohydrate intolerance||Fermentable carbohydrates may increase osmotic load and gas production in the distal small bowel and the proximal colon.||Breath testing for lactose and fructose intolerance.|
Breath testing for small intestinal bacterial overgrowth.
Genetic testing for sucrase-isomaltase gene variants.
|Reduce intake of refined sugar and carbohydrates.|
Low FODMAP diet.
|Lactose intolerance||Unabsorbed lactose in the intestine can increase osmotic load and intestinal water content in addition to undergoing fermentation to produce short chain fatty acids and gas including hydrogen and methane, which may cause or aggravate symptoms in susceptible individuals. ||Positive test of lactose malabsorption (genetic, biopsy, or H2-breath test) and subsequent open-label lactose challenge.||Lactase enzyme therapy.|
Low-lactose or lactose-free diet.
|Food hypersensitivity||Immunologically mediated food hypersensitivity may play a role in the development of gastrointestinal symptoms via a local and limited IgE-mediated reaction in the intestinal mucosa and/or IgE-independent mechanisms.||Dietary elimination and re-challenge.|
IgG antibodies to foods.
|Elimination and re-challenge diet.|
IgG antibody-guided exclusion diet.
|Non-celiac gluten sensitivity||People with NCGS have evidence of immune activation (measured with increased serum levels of soluble CD14), leaky gut (lipopolysaccharide-binding protein and antibody reactivity to bacterial LPS and flagellin) and intestinal damage (fatty acid-binding protein 2).||Clinical rating scale, response to a gluten-free diet, and double-placebo controlled gluten challenge.|
HLA-DQ2/8 gene variants.
|Nickel-related intestinal mucositis||In nickel sensitive people, exposure results in elevated levels of IFNy, IL-5, and IL-13 in the supernatants of peripheral blood mononuclear cell cultures stimulated with nickel, suggesting a pro-inflammatory effect.||Positive nickel patch test.||Low nickel diet.|
|Vitamin D deficiency||Vitamin D deficiency could contribute to mucosal inflammation, impaired epithelial cell integrity, and the alterations in the composition of the gut microbiome.||Serum 25-hydroxy vitamin D.||Sunlight exposure.|
Vitamin D3 supplementation.
|Exocrine pancreatic insufficiency||Impaired digestion of food may increase antigenic load and/or contribute to postprandial osmotic diarrhoea.||Clinical symptoms of postprandial osmotic diarrhoea, or galacto-oligosaccharide intolerance.|
Fecal elastase-1 (FE-1).
|Digestive enzyme therapy.|
|Low-grade inflammation||Low-grade intestinal inflammation contributes to altered permeability, hypersensitivity of enteric nerves and changes in serotonin signaling.||Fecal calprotectin.||Low antigenic/elimination diet. |
Anti-inflammatory herbal medicines, such as Boswellia serrata.
|Intestinal permeability||Intestinal permeability contributes to low-grade intestinal inflammation and increased visceral and pain sensitivity.||Intestinal permeability (lactulose/mannitol).|
Serum lipopolysaccharide binding protein.
|Bile acid malabsorption||An increase in the fecal excretion and change in the proportion of the various bile acids in stool contributes to intestinal permeability, water and electrolyte secretion, and increased colonic transit.||Therapeutic trial of bile acid binders.|
Selenium homotaurocholic acid test.
KLB rs17618244 and GPBAR1rs11554825 gene variants.
|Bile acid binders.|
Pancreatic enzyme therapy.
Diet that minimizes bile acid production and/or excretion.
|Chronic constipation||Functional constipation is associated with visceral sensitivity and alterations in serotonin signaling.||The Bristol Stool Scale.||Laxatives.|
|Dysbiosis||Alterations in the gastrointestinal microbiota activate mucosal innate immune responses which increase epithelial permeability, initiate nociceptive sensory pathways and dysregulate the enteric nervous system.||Comprehensive stool microbiology.|
Breath testing for small intestinal bacterial overgrowth.
|Gut-microbiota-targeted dietary interventions.|
|Small intestinal bacterial overgrowth||Colonic gram-negative aerobes and anaerobic species overgrow in the small intestine where they ferment carbohydrate and contribute to digestive symptoms.||Breath testing for small intestinal bacterial overgrowth.||Antibiotics.|
Medical food-based elemental diet.
|Parasitic infection or overgrowth||Specific subtypes of Blastocystis species may contribute to dysbiosis, upregulate pro-inflammatory cytokines, and degrade tight junction proteins and increase intestinal permeability. D. fragilis-infection may result in inflammatory changes and intestinal permeability in the gut mucosa.||Comprehensive stool parasitology, including Blastocystis species and D. fragilis.||Antibiotic therapy.|
Emulsified oil of Oregano. Saccharomyces boulardii.