Beyond Infection: Risk Factors for IBS

Doctor treating patient for IBS

Development of irritable bowel syndrome (IBS) is now understood to a matter of epigenetics and environmental factors, and biomarkers can aid in creation of individualized dietary treatment strategies.1

As genetic analyses decrease in cost, personalized interventions become increasingly possible. Knowing the key genetic variations for chronic conditions enables more targeted treatments, as well as prevention, if tests are done early. A recent study in Caucasian individuals connected genetic variations (in ZMIZ1 and TL1A) associated with impaired disaccharide digestion to IBS symptomatology.2 This result suggests that a nutrigenomic approach for individuals with these variations, resulting in a personalized dietary plan, may greatly reduce symptoms. The identified genetic SNPs result in reduced enzyme activity for sucrase-isomaltase (SI) in the small intestine, leading to poor digestion of some carbohydrates (disaccharides like sugars and starches). This could result in the stomach pain, diarrhea, and bloating common to some IBS patients. The researchers identified this SNP first by analyzing seven patients with IBS with diarrhea (IBS-D), as well as one asymptomatic relative, from four families.2

Findings were confirmed with a cohort of 1031 IBS cases and over 850 controls. The study found that patients with rare congenital sucrase-isomaltase (SI) deficiency variations in the SI gene had a two-fold increase in IBS risk, as well as a significantly increased risk from a more common variation, 15Phe at SNP rs9290264. Thus, this one study found two genetic risk factors for IBS-D, both connected to disaccharide metabolism.2

For these patients, a low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet may help, but may also be unnecessarily restrictive if only disaccharides are the main problem. Since not all patients with IBS-D respond to the FODMAP diet,3 other underlying mechanisms are most certainly at work.

Among the interventions for managing IBS (pre-, pro-, and synbiotics; non-absorbable antibiotics; diets (FODMAP, gluten-free),4 low FODMAP diets are prominent. Difficulty in digesting carbohydrates, which are usually foods high in FODMAP, is common in IBS. An individualized approach is also necessary to address co-morbidities, food sensitivities, or other factors which prevent a “one size fits all” approach to nutritional interventions.

Fermentation of FODMAPs in the colon produces carbon dioxide, methane hydrogen, and other gases. It slows colonic transit and alters the microbiome, which may negatively impact tight junctions and activation of the mucosal immune system.5

A meta-analysis of multiple studies showed that, compared to those on a standard IBS diet, patients on a low FODMAP diet enjoyed a significantly greater improvement in symptoms 6  The authors conclude that a dietician-led low FODMAP diet could be a first-line approach to IBS management.7  Eliminating FODMAP foods and then slowly reintroducing them can help specify offending foods, leading to a less restrictive overall diet.8 Since not all patients with IBS respond favorably to a low FODMAP diet, the use of biomarkers can be used to identify those who would most benefit.9

Learn more about the many antecedents, triggers, and mediators for IBS at IFM’s GI Advanced Practice Module (APM).

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  1. Aleksandrova K, Romero-Mosquera B, Hernandez V. Diet, gut microbiome and epigenetics: emerging links with inflammatory bowel diseases and prospects for management and prevention. 2017;9(9):E962. doi:10.3390/nu9090962.
  2. Henström M, Diekmann L, Bonfiglio F, et al. Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome. 2018;67(2):263-270. doi:10.1136/gutjnl-2016-312456.
  3. Eswaran SL, Chey WD, Han-Markey T, Ball S, Jackson K. A randomized controlled trial comparing the low FODMAP diet vs. modified NICE guidelines in US adults with IBS-D. Am J Gastroenterol. 2016;111(12):1824-1832. doi:1038/ajg.2016.434.
  4. Lan X, Lan X, Chang Y, et al. Identification of two additional susceptibility loci for inflammatory bowel disease in a Chinese population. Cell Physiol Biochem. 2017;41(5):2077-2090. doi:1159/000475439.
  5. Rodiño-Janeiro BK, Vicario M, Alonso-Cotoner C, Pascua-García R, Santos J. A review of microbiota and irritable bowel syndrome: future in therapies. Adv Ther. 2018;35(3):289-310. doi:1007/s12325-018-0673-5.
  6. Eswaran S, Farida JP, Green J, Miller JD, Chey WD. Nutrition in the management of gastrointestinal diseases and disorders: the evidence for the low FODMAP diet. Curr Opin Pharmacol. 2017;37:151-157. doi:1016/j.coph.2017.10.008.
  7. Varjú P, Farkas N, Hegyi P, et al. Low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet improves symptoms in adults suffering from irritable bowel syndrome (IBS) compared to standard IBS diet: a meta-analysis of clinical studies. PLoS One. 2017;12(8):e0182942. doi:1371/journal.pone.0182942.
  8. Dolan R, Chey WD, Eswaran S. The role of diet in the management of irritable bowel syndrome: a focus on FODMAPs. Expert Rev Gastroenterol Hepatol. 2018:1-9. doi:1080/17474124.2018.1476138.
  9. Valeur J, Småstuen MC, Knudsen T, Lied GA, Røseth AG. Exploring gut microbiota composition as an indicator of clinical response to dietary FODMAP restriction in patients with irritable bowel syndrome. Dig Dis Sci. 2018;63(2):429-436. doi:1007/s10620-017-4893-3.

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