Meeting NewsPerspective

Patients with sucrase-isomaltase deficiency less likely to respond to low-FODMAP diet for IBS-D

SAN DIEGO — Roughly half of patients who go on a low-FODMAP diet to treat diarrhea predominant irritable bowel syndrome do not respond to the change in diet. According to data presented at Digestive Disease Week, many of those patients could have a genetic variant that causes a deficiency of the sucrase-isomaltase enzyme.

Shanti L. Eswaran, MD, of the University of Michigan, said patients with this deficiency, known as SID, have trouble breaking down complex carbohydrates, including sucrose.

“Given that patients with IBS may utilize an elimination diet in order to mitigate their food-related GI symptoms, this increased risk of [sucrase-isomaltase (SI)] activity in patients with IBS-like symptoms is particularly relevant as the low-FODMAP diet does not generally exclude starch or sucrose,” she said in her presentation. “This can hold potential for the phenotyping of IBS patients and allowing for the targeting of specific dietary therapy.”

Using salivary samples taken from patients with IBS-D in a previously published trial of the low-FODMAP diet, researchers looked for SI genotype and stratified patients into groups of carriers and non-carriers of the genes. Of 46 patients who had been randomly assigned the low-FODMAP diet in the previous trial, investigators found one common and four rare hypomorphic SI variants.

In the original study, 52% of patients experienced adequate relief after switching to the low-FODMAP diet. After stratifying patients by SI variant, however, researchers found that 61% of non-carriers achieved adequate relief compared with 44% of carriers (P = .031). Patients who were not carriers of an SI variant were also more likely to experience improvement in abdominal pain compared with carriers, but the difference was not significant.

Eswaran said that their findings show that SI hypomorphic variants are associated with a significant reduction in the likelihood of responding to the low-FODMAP diet.

“Given that our current dietary treatment strategies do not take SID into account, these results may bear implications for the development of treatment stratification in IBS, getting us closer to, hopefully, precision medicine in this patient population.” - by Alex Young

Reference:

Eswaran S, et al. Abstract 347. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosures: Eswaran reports no relevant financial disclosures. Please see the meeting disclosure index for all other authors’ relevant financial disclosures.

SAN DIEGO — Roughly half of patients who go on a low-FODMAP diet to treat diarrhea predominant irritable bowel syndrome do not respond to the change in diet. According to data presented at Digestive Disease Week, many of those patients could have a genetic variant that causes a deficiency of the sucrase-isomaltase enzyme.

Shanti L. Eswaran, MD, of the University of Michigan, said patients with this deficiency, known as SID, have trouble breaking down complex carbohydrates, including sucrose.

“Given that patients with IBS may utilize an elimination diet in order to mitigate their food-related GI symptoms, this increased risk of [sucrase-isomaltase (SI)] activity in patients with IBS-like symptoms is particularly relevant as the low-FODMAP diet does not generally exclude starch or sucrose,” she said in her presentation. “This can hold potential for the phenotyping of IBS patients and allowing for the targeting of specific dietary therapy.”

Using salivary samples taken from patients with IBS-D in a previously published trial of the low-FODMAP diet, researchers looked for SI genotype and stratified patients into groups of carriers and non-carriers of the genes. Of 46 patients who had been randomly assigned the low-FODMAP diet in the previous trial, investigators found one common and four rare hypomorphic SI variants.

In the original study, 52% of patients experienced adequate relief after switching to the low-FODMAP diet. After stratifying patients by SI variant, however, researchers found that 61% of non-carriers achieved adequate relief compared with 44% of carriers (P = .031). Patients who were not carriers of an SI variant were also more likely to experience improvement in abdominal pain compared with carriers, but the difference was not significant.

Eswaran said that their findings show that SI hypomorphic variants are associated with a significant reduction in the likelihood of responding to the low-FODMAP diet.

“Given that our current dietary treatment strategies do not take SID into account, these results may bear implications for the development of treatment stratification in IBS, getting us closer to, hopefully, precision medicine in this patient population.” - by Alex Young

Reference:

Eswaran S, et al. Abstract 347. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosures: Eswaran reports no relevant financial disclosures. Please see the meeting disclosure index for all other authors’ relevant financial disclosures.

    Perspective
    William D. Chey

    William D. Chey

    Most patients with irritable bowel syndrome relate the onset or worsening of their gut symptoms to eating a meal. Given this fact, it should come as no surprise that diet therapies are growing increasingly popular as a treatment for IBS. Currently, the low FODMAP diet is the most evidence-based diet intervention for IBS patients. Randomized controlled trials (RCT) report that 50% to 80% of patients with IBS experience significant clinical improvement with the low FODMAP diet.

    FODMAPs are short chain carbohydrates that are difficult or impossible for the human small intestine to digest or absorb. Because they are not absorbed, they are available for fermentation by the microbiota in the distal small bowel and colon producing short chain fatty acids and gases that can trigger symptoms in IBS patients who have underlying abnormalities in motility and visceral sensation.

    In patients with intestinal brush border lactase deficiency, lactose cannot be digested and thus cannot be absorbed. Thus, in patients with lactase deficiency, lactose becomes a FODMAP. On the other hand, in patients with normal levels of intestinal lactase, lactose can be digested and the resultant monosaccharides, glucose and galactose are normally absorbed. The other main intestinal disaccharidase in the intestinal brush border epithelium is sucrase isomaltase (SI). SI is responsible for the digestion of sucrose to glucose and fructose and starch to glucose monomers. A number of SI gene variants associated with decreased SI function have been found to be more prevalent in patients with IBS. In patients with SI deficiency, sucrose and starch become FODMAPs. This is potentially important as current teaching of the LFD does not account for patients with SI deficiency.

    The study from the University of Michigan by Eswaran et al, found that the presence of mutations in the SI gene were associated with a lower likelihood of clinical response to the low FODMAP diet in patients with IBS-D. This provocative, post-hoc analysis requires validation in a larger, prospective trial. If confirmed, it may be useful to test for SI deficiency either before initiating the low FODMAP diet or in patients who fail to respond to the low FODMAP diet. 

    References

    Dionne J, et al. Am J Gastroenterol. 2018;113:1290-1300.

    Garcia-Etxebarria K, et al. Clin Gastroenterol Hepatol. 2018;16:1673-1676.

    Zheng T, et al. Gut. 2019; in press.

    • William D. Chey, MD
    • Professor of medicine
      Director of the GI Physiology Laboratory
      University of Michigan Health System

    Disclosures: Chey reports financial ties to Allergan, Conti, IM Health, Ironwood, MyGiHealth, Nestle, QOL Medical, Ritter, Salix, Shire, True Self Foods, Volcant and Zespori.

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