Tag Archives: irritable bowel syndrome

Gluten sensitivity without celiac disease

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Gluten free is big business.  In a range of conditions, eliminating gluten has been advocated to improve symptoms.  The most frequent problem in which a gluten-free diet (GFD) may be beneficial is irritable bowel syndrome (IBS).  A selected summary in Gastroenterology discusses this topic (Gastroenterology 2012; 142: 664-73).

This review highlights an article that showed improvement in a double-blind randomized trial (Am J Gastroenterol 2011; 106: 508-14) & then reviews the topic more broadly.  The study is the first randomized controlled trial that suggests that nonceliac IBS patients may improve with a GFD.  The study looked at 34 patients with IBS who had improved with a GFD & had no evidence of celiac disease (either negative HLA-DQ2/DQ8 or duodenal biopsy).  Then 19 patients had 16g of gluten per day reintroduced; control patients were offered equivalent food that was gluten-free.  The gluten products in the study were free of fermentable oligo-, di-, monosaccharides and polyols to avoid confounders (What to make of FODMAPs).  The patients who continued a GFD had less reported pain, bloating and tiredness.  The GFD group reported good control of symptoms the previous week in 68% vs. 40% in the study group.

The commentary notes that ‘gluten sensitivity’ is big business, accounting for 1.3 billion in 2011 expenditures.  Companies like General Mills, Betty Crocker, PF Chang’s, and Subway are offering gluten-free choices.  Since immune activation and low-grade inflammation may be important for IBS, it is possible that some foods trigger these processes.  At the same time, individuals with reported gluten sensitivity have not been shown to have increased intestinal permeability; this is in contrast to celiac disease (BMC Med 2011; 9; 23).

There may be more patients with IBS who will benefit from a GFD due to gluten sensitivity than patients with celiac disease.

Additional references:

  • -Nutr Clin Pract. 2011;26:294-299.  A gluten-free diet (GFD) is commonly recognized as the treatment for celiac disease. It also has been investigated as a treatment option for other medical conditions, including dermatitis herpetiformis, irritable bowel syndrome, neurologic disorders, rheumatoid arthritis, diabetes mellitus, and HIV-associated enteropathy. The strength of the evidence for the use of a GFD in these nonceliac diseases varies.
  • -Clin Gastro & Hep 2007; 5: 844. GFD in IBS pts (w/o celiac)
  • -Am J Gastro 2009; 104: 1587. Gluten sensitivity in IBS (w celiac)
  • -Gastroenterology 2011; 141: 1187. Prevalence of celiac similar in IBS as general population though higher number (7%) with celiac antibodies (esp gliadin).
  • -Am J Gastro 2008; 103: S472 (abstract P687) Serology for Celiac in IBS patients same as in controls. n=566. n=555 controls.
  • -Clin Gastro & Hep 2007; 5: 844. d-IBS patients may respond to gluten-free diet, especially if positive HLA-DQ2 expression or positive celiac serology.
  • -Lancet 2001; 358: 1504-08. n=300 uninvestigated pts w IBS criteria & 300 controls. 66 w positive serology; 14 w biopsy-proven celiac dz, 43 w normal biopsies. Odds ratio of 7 to have celiac compared to control group (2 w biopsy-proven disease).

Rifaximin for Crohn’s disease?

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Rifaximin (Xifaxan®) shows promise as a new treatment for Crohn’s disease (Gastroenterology 2012; 142: 473-81).  Rifaximin is an oral medication with minimal systemic absorption; it has a good track record in a number of GI indications, including bacterial gastroenteritis (traveler’s diarrhea), bacterial overgrowth in irritable bowel disease, and hepatic encephalopathy.  There are a few reasons why rifaximin would be considered a good candidate treatment for Crohn’s disease:

  • The pathophysiology of Crohn’s disease involves interaction of adherent bacteria to the intestinal mucosa and with the immune system
  • Other antimicrobials have shown benefit for Crohn’s disease
  • Animal models do not manifest Crohn’s disease when in a bacteria-free environment

In this study of 402 patients with moderate-to-severe Crohn’s disease, a multicenter randomized double-blind trial examined efficacy and safety of rifaximin at doses of 400mg, 800mg, and 1200mg twice daily.  The primary end point was remission based on Crohn’s Disease Activity Index (CDAI).

At the end of the 12-week treatment period, 62% of the 800mg group were in remission compared to 43% of the placebo group.  This difference was maintained 12 weeks afterwards with 45% maintaining remission compared with 43% of patients receiving placebo.  When looking at the other dosing regimens, at 12 weeks, 54% of the 400mg group and 47% of the 1200mg group were in remission based on CDAI.

Clinical response, but not remission, occurred in 56% of placebo patients compared with 63% for 400mg patients, 72% for 800mg patients, and 57% of 1200mg patients.  This trial may have been hampered by patient selection in that the placebo response was high.  This may be due to the fact that ~50% of patients had a low CRP value at baseline.

Safety was good in all patient groups.  However, one rifaximin-treated patient developed C difficile infection.

The fact that a clear dose response was not evident suggests the need for more studies.

Additional Rifaximin References:

  • -NEJM 2011; 364: 22 (pg 81-editorial).  About 10% improvement over placebo in pts with IBS-D.  (see abstract below).  Effects lasted up to 3 months.
  • -JPGN 2009; 49: 400-04. helped symptoms in 61% of IBD pts. n=23 (12 w Crohn). dose 10-30mg/kg/day.
  • -Aliment Pharm Ther 2005; 22: 31-35. Use in SBBO. n=90; 1200mg/day x 7 days. NL glucose breath test in 60% (vs 17% in low dose group); no side effects.
  • -Ann Intern Med 2006; 145: 557-563. double-blind, randomized controlled trial, n=87 for IBS. 400mg tid x 10days. Rx resulted in greater IBS improvement, ~40% improvement vs 20% w placebo during 10 week study
  • -IBD 2006; 12: 335. open-label use of rifaximim (400mg BID) for 30 pts c UC flare on ASA products resulted in clinical remission in 23 of 30.
  • -J Infect 2011; 62: 34-38. Rx may lead to resistant staphylococci.
  • -Hepatology 2010; 52: 1484. Review.

Additional Crohn’s Antibiotic/Probiotic References:

  • -IBD 2009; 15; 17. 40% response to Cipro in treatment of peranal fistulas. n=25. No response to metronidazole.
  • -IBD 2008; 14: 1597, 1585. No proven role for probiotics and IBD except pouchitis (after Abx)
  • -Clin Gastro & Hep 2008; 6: 145. Pouch problems reviewed -excellent review.
  • -IBD 2006; 12: 335. open-label use of rifaximim (400mg BID) for 30 pts c UC flare on ASA products resulted in clinical remission in 23 of 30.
  • -Curr Med Res Opinion 2005; 8: 1165-70. Rx for traveler’s diarrhea.  May be useful for Crohn’s as well.
  • -Gastroenterology 2005; 128: 856. Use of ornidazole prophylaxis reduced recurrence p-op from 37.5% to 8%.
  • -IBD 2004; 10: 318-325. antibiotics & IBD review.
  • -Gastroenterology 2004; 127: 412-21. adherent-invasive E. coli associated with ileal mucosa in 22% of Crohn’s (n=63) ileal mucosa vs. 6% of controls (n=16); higher colonization noted in neo-terminal ileums (36%).

What to make of FODMAPs

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Consumption of FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) may trigger irritable bowel syndrome (IBS) symptoms.  Some research indicates that a diet low on FODMAPs may be beneficial (J Hum Nutr Diet 2011; 24: 487-95).  This study tried to assess whether a low FODMAPs diet which had been reported from a single center in Australia would be effective for IBS.

In this study, consecutive patients with IBS were divided into two groups.  39 received standard dietary advice based on UK National Institute for Health and Clinical Excellence (NICE) guidelines.  43 patients were placed on a low FODMAP dietary advice.  Patients were selected into each group consecutively (not randomized). This study reported a 76% satisfactory symptom response in the FODMAP group vs a 54% response in the control group (p=0.038).  Overall, 86% of FODMAP group had improved composite score compared with 49% of standard treatment group. Specific improvements were noted in bloating, abdominal pain, and flatulence.  The average age of the study population was 38 and 71% were females.  60% had diarrhea-predominant IBS.

NICE guidelines for IBS:

  • Healthy eating principles: regular eating, taking time to eat
  • Limit high fat foods and fizzy drinks
  • Limit insoluble fiber for diarrhea and gradually increase for constipation
  • Limit sugar-free sweets and foods with sorbitol
  • Limit fruit to 3 portions/day
  • Avoiding ‘resistant’ starch may be useful (eg. sweetcorn, green bananas, part-baked and reheated bread)
  • Addition of oats and linseeds may be helpful

Low FODMAP diet

  • Reduce high fructan foods (eg wheat and onion)
  • Reduction in high galactooligosaccharide foods (eg chickpeas, lentils)
  • Reduce high polyol foods and polyol-sweetened sources.  Replace with suitable fruits and vegetables
  • In patients with lactose malabsorption, reduce high lactose foods (eg milk, yoghurt) to smaller volumes or substitute lactose-free products
  • In those with fructose malabsorption, decrease excess fructose

Of course, reading the author’s description of a low FODMAP diet is confusing.  Translation:

Include more bananas, blueberries, lettuce, potatoes, gluten-free breads or cereals, rice, oats, hard cheeses, lactose-free milk, sugar, molasses, and artificial sweeteners that do not end in “ol.”

Avoid/eliminate apples, pears, canned fruits in natural juices, high-fructose corn syrup, cows’ milk (due to lactose), soft cheese, broccoli, cabbage, pasta, bread, baked goods from wheat/rye, mushrooms, and sweeteners like sorbitol or others that end in “ol.”

Since this diet has attracted more widespread attention, basic familiarity is important for all physicians who treat IBS.  A useful resource to explain this diet is the Wall Street Journal:

http://online.wsj.com/article/SB10001424052970204554204577023880581820726.html

This link has a good table illustrating the recommended dietary choices.

Whether FODMAPs will be superior to other dietary advice for IBS is still uncertain.  Though, given the limited number of effective treatments for IBS, this small study is a promising development.

Additional references:

  • -Clin Gastro & Hep 2009; 7: 706. n=17. 13 responded to very low carb diet (<20g/day)
  • -Clin Gastro & Hep 2008; 6: 765. Dietary triggers for IBS include fructose/fructans: honey, high fructose corn syrup, wheat, fruits.
  • -IBD 2006; 13: 91. Dietary guidelines for IBS.
  • -Clin Gastro Hepatol 2005; 10: 992-996. Obesity increases IBS symptoms; diet with low fat, high fruit/fiber have fewer symptoms
  • -Gut 2004; 53: 1459-1464. Food elimination based on IgG antibodies. Patients did better on diet with implicated foods than with control diet (diet was blinded/randomized).
  • -Am J Gastro 2011; 106: 508-514. randomized, double-blind trial showing efficacy of GFD for non-celiacs.  60% vs 32& placebo response.
  • -Nutr Clin Pract. 2011;26:294-299.  GFD for non-celiacs.
  • -Gastroenterology 2011; 141: 1941./Am J Gastro 2011; 106: 915.  Exercise improves IBS symptoms.