Is There a Way to Prove Which Dietary Factors Trigger Irritable Bowel Syndrome?

In a recent study (A Fritscher-Ravens et al. Gastroenterol 2019; 157: 109-18) uses confocal laser endomicroscopy (CLE) for “real-time detection and quantification of changes in intestinal tissues” related to food challenges. The authors previously had used this technique in a feasibility study (Gastroenterol 2014; 147: 1012-20). In this study, two-thirds of patients with CLE+ IBS showed improvement of IBS symptoms after a 12-month exclusion diet.

In the current study, the authors prospectively examined patients (n=108 completed study) who had irritable bowel syndrome and were convinced that this was triggered by foods (with negative IgE food allergy testing).  The CLE testing evaluated four food components

Key findings:

  • 76 of 108 (70%) had abnormal CLE; 46 of these reactions were to wheat
  • In those with CLE+ reactions, intraepithelial lymphocytes were significantly higher compared to those with CLE-negative (normal evaluations).
  • Other biomarkers associated with CLE+ included increased claudin-2 expression from crypt to villous tip, lower levels of occludin, and higher eosinophilic cationic protein.

Abnormal CLE indicated abnormal mucosal appearance including formation of epithelial leaks/gaps and widening of the intervillous spaces after food challenge.

My take: This study shows that in individuals with a strong suspicion of food-triggered IBS, immediate reactions in the mucosa can be detected with CLE in more than 50%. Whether this type of approach could/should be developed for wider use in targeting a specific diet is unclear.  More studies are needed.

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Sagrada Familia, Barcelona

 

 

FDA News: FDA Warning for FMT, IB-Stim Device Approval, Teduglutide Approval

1.From John Pohl Twitter Feed:  FDA Warns of One Death Linked to Fecal Transplants (6/13/19)

An excerpt:

The consent should include, at a minimum, a statement that the use of FMT to treat C. difficile is investigational and a discussion of its potential risks.

“Two immunocompromised adults who received investigational FMT developed invasive infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (E.coli). One of the individuals died,” the agency said Thursday…

Openbiome, a nonprofit stool bank based in Cambridge, MA, told Focus: “We are saddened to hear of the recent patient death due to an infection from a multi-drug resistant organism (MDRO) transmitted through a fecal transplant. OpenBiome material was not involved. OpenBiome screens its donors and fecal transplant material for MDROs and related risk factors, and this serious event further highlights the importance of rigorous screening and clinical oversight for all fecal transplant procedures.”

 2. FDA approval for IB-stim (a.k.a. Neuro-stim) device.

Link:: FDA permits marketing of first medical device for relief of pain associated with irritable bowel syndrome in patients 11-18 years of age

An excerpt:

IB-Stim treatment resulted in at least a 30% decrease in usual pain at the end of three weeks in 52% of treated patients compared to 30% of patients who received the placebo, and at least a 30% decrease in worst pain in 59% of treated patients compared with 26% of patients who received the placebo.

:Kovacic K1Hainsworth K2Sood M1Chelimsky G1Unteutsch R1Nugent M3Simpson P3Miranda A4. 2017 Oct;2(10):727-737. doi: 10.1016/S2468-1253(17)30253-4. Epub 2017 Aug 18.

Link to abstract of relevant study:  Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial.

3. FDA Approves Gattex (Teduglutide) for Pediatric SBS

From CenterWatch: Gattex New FDA Drug Approval

Pediatric SBS: “In a 24-week pediatric study 59 pediatric patients with SBS aged 1 year through 17 years chose whether to receive Gattex or standard of care (SOC)…Based on patient-diary data, patients who received Gattex 0.05 mg/kg/day experienced a 42% mean reduction in PS volume (mL/kg/day) from baseline (-23 mL/kg/day from baseline). At week 24, 38% of patients (10/26) were able to reduce PS infusion by at least 1 day per week. Patients reduced their PS infusion time by 3 hours per day on average compared to baseline.”

Related blog post: Teduglutide for SBS

Jeppesen PB, Pertkiewicz M, Messing B, Iyer K, Seidner DL, O’keefe SJ, Forbes A, Heinze H, Joelsson B Teduglutide reduces need for parenteral support among patients with short bowel syndrome with intestinal failure. Gastroenterology 2012 Dec;143(6):1473-1481

Jeppesen PB, Gilroy R, Pertkiewicz M, Allard JP, Messing B, O’Keefe SJ Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome. Gut 2011 Jul;60(7):902-14.

Relooking at Medications for Constipation-Predominant Irritable Bowel Syndrome

A recent study (CJ Black et al. Gastroenterol 2018; 155: 1753-63) examined the effectiveness of secretagogues for constipation-predominant irritable bowel syndrome (IBS-C).  The authors conducted a systematic review and network meta-analysis with 15 eligible randomized controlled trials (8462 patients).

Key findings:

  • Linaclotide (290 mcg per day) was ranked first in efficacy using the end point recommended by the FDA for IBS-C trials
  • Tenapanor (50 mg twice a day) was ranked first for bloating
  • Plecanatide (6 mg per day) ranked first for safety
  • Diarrhea was significantly more common with all of the secretagogues except for lubiprostone; nausea was significantly more common with lubiprostone

The authors acknowledge the limitations in comparing medicines without direct head-to-head trials (which may never occur).  They state that linaclotide being superior to other treatments had a probability of 88%.

My take: This study indicates that linaclotide may be more likely to be effective than other IBS-C medications; all of these secretagogues have been shown to be superior to placebo.

In this same issue, pgs 1666-9 (J Ruddy), a patient describes her long journey with abdominal pain/GI symptoms.  She describes her initial experiences with physicians who were dismissive and not attentive. Ultimately, a physician listened to her and  helped her improve after explaining that she had a postinfectious IBS and provided treatment.

Related study: S Ishague et al. BMC Gastroenterol 2018; 18:71.  This randomized controlled trial which compared a multistrain probiotic (Bio-Kult, n=181) to placebo (n=179).  The probiotic group had a 69% decrease in abdominal pain compared to a 47% decrease in placebo group.

Sunrise, Death Valley

Evidence-Based IBS Treatment Recommendations from ACG

A recent  American College of Gastroenterology Task Force conducted a systematic review (AC Ford et al. The American Journal of Gastroenterology 2018;113:1–18 ) to update management recommendations for irritable bowel syndrome -Link:

American College of Gastroenterology Monograph on Management of Irritable Bowel Syndrome

The highlights of this report are summarized at Gastroenterology & Hepatoloy: Highlights of the Updated Evidence-Based IBS Treatment Monograph

A few excerpts:

“There have been numerous studies performed on the roles of diet and dietary manipulation in IBS. Three fairly firm conclusions were made following the review of these studies: (1) the low–fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet seems to be effective for overall IBS symptom improvement; (2) a gluten-free diet is not effective for symptom improvement; and (3) conducting tests to detect various types of allergies or intolerances in order to base a diet on those results does not appear to be effective. Of these 3 conclusions, the most impressive data that came out of the research was the evidence for the low-FODMAP diet. Not only were there more studies on this diet, but the results were fairly consistent and favorable, at least for the short-term management of IBS.”

” We did not find evidence supporting the idea that prebiotics and synbiotics were effective in IBS management… In ­contrast, studies demonstrated that probiotics did improve global gastrointestinal symptoms, as well as the individual symptoms of bloating and flatulence in patients with IBS. However, determining which probiotic is best was difficult”

“Three prosecretory agents are available: linaclotide (Linzess, Allergan/Ironwood Pharmaceuticals), lubiprostone (Amitiza, Takeda), and plecanatide (Trulance, Synergy Pharmaceuticals), with plecanatide being the most recently approved agent. All 3 of these agents had convincing data to support their use in patients with constipation-predominant IBS

My take: In IBS patients, if dietary therapy is recommended, current evidence favors a low FODMAP diet rather than a gluten-free diet.

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near Banff

Image above -Parker Ridge Trail

Low Quality Evidence for IBS Dietary Therapy

A recent systematic review and meta-analysis (J Dionne et al. Am J Gastroenterol 2018; 113: 1290-1300) throws some shade on the effectiveness of dietary therapies for irritable bowel syndrome. Thanks to Ben Gold for this reference. The authors reviewed 1726 citations -only 9 were eligible for systematic review; two RCTs (n=111 participants) with gluten-free diet (GFD) and 7 RCTs (n=397) with low FODMAPs diet.

Key findings:

  • A GFD was associated with reduced global symptoms compared with control interventions (RR=0.42, CI 0.11-1.55) which was not statistically significant.  Thus, there is “insufficient evidence to recommend a GFD to reduce IBS symptoms.”
  • A low FODMAP diet was associated with reduced global symptoms compared with control interventions (RR=0.69, CI 0.54-0.88). The three RCTs with rigorous control diets found the least magnitude of effect. Thus, the overall quality of the data was “very low” according to the GRADE criteria.

Given the limited data supporting dietary therapy for IBS, the authors caution that in those who are placed on a low FODMAPs diet, that after a 2-6 week trial, those who “fail to improve should not continue the diet. ”

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Differential Microbiome Effects of Prebiotics and low FODMAPs

A recent study (J-W Huaman et al. Gastroenterol 2018; 155: 1004-7) examined the effects of a prebiotic (Bimuno) and a low FODMAPs diet for the treatment of functional GI disorders and their effects on the microbiome.

This was a randomized controlled 4-week trial with a 2-week followup period.  Those who received the prebiotic (N=19) received a placebo diet (Mediterranean-type) and those who were randomized to a low FODMAP diet (n=21) were instructed to consume a placebo.  The prebiotic contained beat-galactooligosaccharide.

Key findings:

  • Both groups had significant reduction in GI symptoms, though low FODMAPs was the only treatment helpful for flatulence/borborygmi.
  • The symptom reduction persisted in the prebiotic group for the 2 -week follow-up period, whereas symptoms reappeared immediately in the low FODMAP group.
  • The two treatments had opposite effects on the intestinal microbiota –the prebiotic treatment led to an increase in bifidobacteria and a decrease in Bilophilia wadsworthia.

My take: (borrowed from editorial pg 960-2): This study “may indicate that the effect of the prebiotic is mediated through its effects on gut microbiota composition, whereas the effect of the low FODMAP diets is more related to the meal composition…than to its effects on gut microbiota composition.”

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From two of the missions in San Antonio

 

 

 

 

Chronic Fatigue and Irritable Bowel Syndrome -10 years after Giardia Infection!

A recent study (S Litleskare et al. Clin Gastroenterol Hepatol 2018; 16: 1064-72) involved prospective follow-up of 1252 laboratory-confirmed cases of giardiasis from a 2004 outbreak in Norway.

Key findings:

  • Prevalence of irritable bowel syndrome (IBS) was 43% 10 years after the outbreak among 576 exposed individuals compared with 14% among 685 controls. Thus, the odds ration of developing IBS was 4.74 following Giardia exposure.
  • Chronic fatigue at 10 years was higher as well, reported in 26% in the exposed group compared with 11% in the control group.
  • The authors note that the change in IBS between 6 years and 10 years following the infection was 40% and 43% respectively and the change in chronic fatigue was 31% at 6 years and 26% at 10 years.

My take: Don’t get Giardia!! It may cause chronic fatigue and IBS 10 years after acquisition of an infection.  This study reinforces other studies which have shown that numerous enteric pathogens can increase the risk of IBS.  These other studies reported lower rates of IBS following infections, between 7-36%.

Moraine Lake, Banff