Briefly Noted: Kiwi for IBS-C

R Gearry et al. AJG 2022. DOI: 10.14309/ajg.0000000000002124.Open Access! Consumption of 2 Green Kiwifruits Daily Improves Constipation and Abdominal Comfort—Results of an International Multicenter Randomized Controlled Trial

Participants included healthy controls (n = 63), patients with functional constipation (FC, n = 60), and patients with constipation-predominant irritable bowel syndrome (IBS-C, n = 61). Mean age 35 years.

Key findings: Consumption of green kiwifruit was associated with a clinically relevant increase of ≥ 1.5 CSBM (complete spontaneous bowel movement) per week (Functional constipation; 1.53, P < 0.0001, IBS-C; 1.73, P = 0.0003) and significantly improved measures of GI comfort (GI symptom rating scale total score) in constipated participants (FC, P < 0.0001; IBS-C, P < 0.0001)

Related blog post: Small Study: Kiwi For Constipation

Which Diet is Best for Irritable Bowel Syndrome? A Randomized Trial

A Rej et al. Clin Gastroenterol Hepatol 2022; 20: 2876-2887. Open Access! Efficacy and Acceptability of Dietary Therapies in Non-Constipated Irritable Bowel Syndrome: A Randomized Trial of Traditional Dietary Advice, the Low FODMAP Diet, and the Gluten-Free Diet

Methods: In patients (n=99) with Rome IV–defined non-constipated IBS, outcomes after randomization to one of three diets were compared. The “traditional dietary advice” group: “Its principles include adopting healthy, sensible eating patterns such as having regular meals, never eating too little/too much, maintaining adequate hydration, and reducing the intake of (1) alcohol/caffeine/fizzy drinks, (2) fatty/spicy/processed foods, (3) fresh fruit to a maximum of 3 per day, (4) fiber and other commonly consumed gas-producing foods (eg, beans, bread, sweeteners, etc), and (5) addressing any perceived food intolerances (eg, dairy).” (Link: National Institute for Health and Care Excellence advice on IBS mgt). The Gluten-Free diet allowed for cross-contamination. All patients had specialist dietary counseling.

Key findings:

  • All three diets resulted in improvement. The primary end point of ≥50-point reduction in IBS-SSS was met by 42% (n = 14/33) undertaking TDA, 55% (n = 18/33) for LFD, and 58% (n = 19/33) for GFD (P = .43)
  • Alterations in stool dysbiosis index were similar across the diets, with 22%–29% showing reduced dysbiosis
  • “The pragmatic study design, whereby the responsibility was left on patients to undertake the diets following appropriate education, means our findings can be generalized”

My take: All three diet approaches would be appropriate to reduce IBS symptoms, thought the TDA is the easiest for patients.

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Is Fecal Transplantation Needed To Treat Irritable Bowel? Three Year Data

M El-Salhy et al. Gastroenterol 2022; 163: 982-994. Open Access! Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation

Background: “Fecal microbiota transplantation (FMT) might be a promising treatment for IBS, and this has been investigated in 7 randomized controlled trials (RCTs). 2 In 4 of these, FMT reduced symptoms and improved the quality of life of patients with IBS, whereas no effects were indicated in the other 3. 2 The difference in these results was likely because of differences in the protocols used, the selected donors, the cohort of treated patients, the fecal transplant dose, and the route by which the transplant was administrated.2

Methods: In this placebo-controlled trial with 125 patients, fecal microbiota transplantation (FMT) was administered into duodenum (30 g or 60 g). The donor was a healthy male aged 36 years with a normal body mass index who was born via vaginal delivery, breastfed, a nonsmoker, was not taking any medication, was only treated a few times with antibiotics, exercised regularly, and consumed a sport-specific diet that was richer in protein, fiber, minerals, and vitamins than the average diet.

Key findings:

  • Response rates were 26.3%, 69.1%, and 77.8% in the placebo, 30-g, and 60-g groups, respectively, at 2 years after FMT, and 27.0%, 64.9%, and 71.8%, respectively, at 3 years after FMT. 
  • Fluorescent signals of 10 bacteria had significant correlations with IBS symptoms and fatigue after FMT in the 30-g and 60-g groups.
  • No long-term adverse events were recorded. The authors note in the discussion rare serious safety issues with FMT but indicate in this population without systemic diseases or immune deficiency, that adverse effects were mild and self-limited gastrointestinal symptoms

The associated editorial (815–817, Treatment of Irritable Bowel Syndrome Using Fecal Microbiota Transplantation: A Step Forward?) noted that 25% of patients in the donor FMT continue to experience severe symptoms based on IBS-SSS>300; in addition, 50% (in 30 g) and 40% (in 60 g) had moderately severe IBS scores >175.

The editorial suggests that overall response is modest bust similar to FDA-approved medications for IBS. The number needed to treat (NNT) would be 4-5 patients to reduce the proportion with severe IBS-SSS based on per-protocol analysis (most IBS medications range from 6 to 10).

My take: This study strengthens the notion that alterations in our microbiome can the outcomes of patients suffering from IBS. Now, we have to identify which patients will benefit from this approach and how to optimally modify the microbiome. In addition, this study suggests that finding an optimal FMT donor will impact results given variability in prior trials.

Related blog posts:

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

AGA Guidelines for Pharmacologic Therapy of IBS-D and IBS-C

A Lembo, S Sultan et al. Gastroenterol 2022; 162: 137-151. Open access PDF: AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Diarrhea

LChang, S Sultan et al. Gastroenterol 2022; 162: 118-136. Open access: AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation

The associated 1-page summary (“Spotlight: IBS Treatment“) on pg 153 reviews society guidelines on testing in IBS. This includes for IBS-D celiac serology, calprotectin/lactoferrin, CRP, possilby Giardia antigen (if in endemic area) and possibly bile acid diarrhea testing. Not recommended include food allergy/sensitivity testing, colonoscopy if <45 years and lactulose or glucose hydrogen breath testing. This 1-page summary details therapeutic dosing and costs. Monthly costs of selected medications according to this report:

  • Lubiprostone (Amitiza): $374
  • Linaclotide (Linzess): $523
  • Pleacnatide (Trulance): $528
  • Tegaserod (Zelnorm): $480
  • Tenapanor (IBSRELA): $1680
  • Rifaximin (Xifaxan) $1544 (for 14 day course)
  • Eluxadoline (Viberzi): $1550
  • Alosetron (Lotronex): $1457-1929 (starting dose), $2915-3859 (max dose)

My take: These guideline publications provide comprehensive information regarding potential pharmacological therapies.

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Avoidant/Restrictive Food Intake Disorder (ARFID) with Irritable Bowel Syndrome and with Inflammatory Bowel Disease

Last week, this blog highlighted a study regarding the prevalence of ARFID in pediatric neurogastroenterology (Prevalence of Avoidant/Restrictive Food Intake Disorders in Pediatric Neurogastroenterology).

Today, this post reviews a study with 955 adult patients from 4 prospective studies who had completed the IBS Quality of Life Instrument (IBS-QOL). The 3 questions constituting the food domain were used to identify patients with reported severe food avoidance and restriction.

Key findings:

  • In total, 13.2 % of the patients reported severe food avoidance and restriction, and in these patients all aspects of quality of life were lower (P < .01) and psychological, GI, and somatic symptoms were more severe (P < .05). 

The associated editorial provides a lot of information on ARFID in this setting.

Key points:

  • “The sine qua non of ARFID is a reduction in food intake, in terms of volume and/or variety, not primarily motivated by body image disturbance”
  • “Motivations behind changes in eating in ARFID need to be 1 or more of 3 prototypical presentations: (1) fear of aversive consequences (eg, IBS symptoms), (2) a lack of interest in eating or low appetite, and (3) sensitivity to sensory characteristics of food (eg, taste, texture, smell)”
  • “Weight suppression has similar deleterious health effects as is seen in anorexia nervosa, including cardiac abnormalities and bone mineral density loss”
  • “Up to 90% of patients in IBS reporting avoidance of specific foods”
  • “To identify presence of problematic avoidant/restrictive eating, there are ARFID measures validated with cutoffs (eg, the 9-item ARFID Screen;22,23 the PARDI-ARFID questionnaire).24 Nevertheless, more research is needed on the utility of these screening measures in IBS populations”

My take: Patients with ARFID and IBS need much more careful dietary counseling. So, it is important to consider the possibility of ARFID in this patient population.

Related article: E Yelencich et al. Clin Gastroenterol Hepatol 2022; 20: 1282-1289. Open Access PDF: Avoidant Restrictive Food Intake Disorder Prevalent Among Patients With Inflammatory Bowel Disease In this cross-sectional study of adults with IBD, 28/161 (17%) had a positive ARFID risk score (>/=24). Most participants (92%) reported avoiding 1 or more foods while having active symptoms, and 74% continued to avoid 1 or more foods even in the absence of symptoms. Patients with a positive ARFID risk screen were significantly more likely to be at risk for malnutrition (60.7% vs 15.8%; P < .01)

Related blog post:

Afraid to Eat -Could be “Avoidant Restrictive Food Intake Disorder”

A (Virtual) Reality Without Pain?

NY Times Magazine, Helen Ouyang 5/22/22: Can Virtual Reality Help Ease Chronic Pain?

This lengthy article describes the emerging therapy of virtual reality to help with chronic pain. Some of the article focuses on chronic abdominal pain.

Here are some excerpts:

  • Brennan Spiegel, a gastroenterologist and researcher at Cedars-Sinai .. runs one of the largest academic medical initiatives studying virtual reality as a health therapy…
  • As Daniel Clauw, who runs the Chronic Pain and Fatigue Research Center at the University of Michigan, put it in a 2019 lecture, there isn’t “any drug in any chronic-pain state that works in better than one out of three people.” He went on to say that nonpharmacological therapy should instead be “front and center in managing chronic pain — rather than opioids, or for that matter, any of our drugs…”
  • In November, the Food and Drug Administration gave authorization for the first V.R. product to be marketed for the treatment of chronic pain.
  • [In one] virtual environment … built specifically for patients with chronic gastrointestinal symptoms…[the patient] used hand controls. Inside a virtual clinic, a robot named Maia — short for “mixed-reality artificial-intelligence assistant” — guided her to a young blond woman, who expressed frustration with abdominal symptoms. [The patient] examined the [virtual] patient with her virtual hands, placing a stethoscope on her stomach to listen to the sounds of digestion. Maia explained how the brain and the gut work together. As she spoke, an image of a brain popped up, connected to intestines by a yellow flashing line. When the brain became stressed, it turned fuchsia in color, and the yellow line to the gut metamorphosed into a stream of fire...
  • Scientists knew that the brain has some control over pain, but that insight was mostly confined to the situations described by Patrick Wall’s and Ronald Melzack’s gate-control theory, which helps explain why, say, a person running from a house on fire may not realize that she sprained her ankle until she is a safe distance away. The brain, so intent on escaping the fire, shuts the gate, blocking pain signals coming up the spinal cord from the ankle. “You could close the gate,” says Clifford Woolf, a neurobiology professor at Harvard Medical School who worked in Wall’s lab, but “essentially there was nothing about the opposite possibility — which is that the brain, independent of the periphery, could be a generator of pain.”
  • “Woolf was conducting his own experiment in Wall’s lab, applying painful stimuli to rats’ hind legs. The animals developed large “fields” of pain that could easily be activated months later with a light tap or gentle warmth, even in spots that weren’t being touched directly. “I was changing the function of the nervous system, such that its properties were altered,” Woolf says. “Pain was not simply a measure of some peripheral pathology,” he concluded; it “could also be the consequence of abnormal amplification within the nervous system — this was the phenomenon of central sensitization.”
  • V.R.’s “unique ability to convey a sense of just ‘being there,’ wherever there happens to be,” as he [Spiegel] puts it in his book “VRx: How Virtual Therapeutics Will Revolutionize Medicine.” “All of its revolutionary potential tumbles out of its ability to compel a person’s brain and body to react to a different reality.” 
  • RelieVRx also has modules that prompt patients to redirect their attention through game play or by allowing scenes — waves washing onto a sunny coast, say — to soothe their nervous systems. The average session lasts seven minutes, and patients are directed to do just one a day for eight weeks
  • A recently published study by researchers affiliated with the company [AppliedVR], for which they recruited subjects during the pandemic through Facebook ads and pain organizations, reported an average drop in chronic back pain by nearly 43 percent for the RelieVRx group compared with 25 percent for the control group. For those who used RelieVRx, pain also interfered less with their activity and sleep. Three months after the last V.R. session, these gains were mostly found to endure
  • In chronic pain, the body part that hurts may be undamaged and even seem healthy; what’s altered is the area of the brain that corresponds to its anatomical location...
  • If doctors do start prescribing V.R., there’s another hurdle to clear: Who will pay for it? 

My take: I am looking forward to the pediatric studies which will be needed before this technology can be promoted. I would think pediatric patients with chronic pain may respond even more favorably than adults. If this technology were in our clinic, I am certain that are “no show” rate would be lower.

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This could be me in a virtual reality. Picture taken at Connie’s Photo Park in Madrid, NM.

Good Study, Bad Practice: Placebo for IBS and Functional Abdominal Pain

Have a great day (Mt Yonah, Cleveland GA)

S Nurko et al. JAMA Pediatr. 2022;176(4):349-356. doi:10.1001/jamapediatrics.2021.5750. Adolescents With Functional Abdominal Pain or Irritable Bowel Syndrome

Design: Patients completed 1 week of observation prior to randomization to 1 of 2 counterbalanced groups: OLP for 3 weeks followed by a 3-week control period or control period for 3 weeks followed by OLP for 3 weeks. During the OLP period, participants took 1.5 mL of an inert liquid placebo twice a day.

Key findings:

  • The mean (SD) pain scores were significantly lower during open label placebo (OLP) treatment compared with the control period (39.9 [18.9] vs 45.0 [14.7]; difference, 5.2; 95% CI, 0.2-10.1; P = .03)
  • Patients took nearly twice as many hyoscyamine pills during the control period compared with during the OLP period (mean [SD] number, 3.8 [5.1] pills vs 2.0 [3.0] pills; difference, 1.8 pills; 95% CI, 0.5-3.1 pills)

My take: It is a mistake to consider placebo as a treatment for functional abdominal pain. In many children, pain fluctuates and may improve with reassurance, distraction, healthier diets, and physical activity. However, we also need more effective therapies including pain psychology, dietary approaches and medications. The idea that placebo helps is misleading and undermines the fact that patients with functional disorders need effective treatment.

Related blog posts:

Auricular Stimulation Associated with Less Pain, Less Disability, and Better Sleep

N Santucci et al. Neurogastroenterology & Motility. 2022;00:e14358. Effect of percutaneous electrical nerve field stimulation on mechanosensitivity, sleep, and psychological comorbidities in adolescents with functional abdominal pain disorders

This study evaluated the effects of IB-stim® (Innovative Health Solutions, Versailles, IN, USA) in 20 patients (11-19 years old) with functional pain. This external auricular device with a battery powered generator that creates percutaneous electrical nerve field stimulation (PENFS), targeting cranial nerves V, VII, IX, and X. This device which has been associated with improvement in functional abdominal pain previously was evaluated for its effects on resting and evoked pain and nausea, sleep and psychological functioning, and long-term outcomes.

Key Findings:

  • During pain evoked by Water Load Symptom Provocation Task (WL-SPT), visual analog scale (VAS) pain intensity and nausea were lower following PENFS compared with baseline (p = 0.004 and p = 0.02, respectively)
  • After PENFS, resting VAS pain unpleasantness (p = 0.03), abdominal pain (p < 0.0001), pain catastrophizing (p = 0.0004), somatic complaints (0.01), functional disability (p = 0.04), and anxiety (p = 0.02) exhibited significant improvements, and some were sustained long-term.
  • Self-reported sleep improved after PENFS (p’s < 0.05) as well as actigraphy-derived sleep onset latency (p = 0.03). The authors note that, paradoxically, patients receiving neuromodulators had more trouble with sleep at baseline. “It is hard to tease out if these differences are due to the medications themselves or if the patients on these medications have more severe symptoms that may have a bigger impact on their life”
  • In assessing predictors of response to PENFS therapy, those with higher pain catastrophizing and somatization had lesser reduction in VAS pain scores, while those with high anxiety had lesser improvements in functioning.
  • Study limitations: small sample size and lack of control/sham group

In this limited study, PENFS was associated with improvements in pain intensity and nausea through visual analog scales and validated questionnaires. Disability, pain catastrophizing, somatization, and anxiety reduced after four weeks of PENFS and effects were sustained at 6–12 months post-treatment.

My take: Auricular stimulation if feasible (in terms of cost) is a good alternative to pharmacologic therapy. It would be of interest to study outcomes of patients who received this treatment modality compared with those who were treated by well-qualified pain psychologists.

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Osprey on The Hunley Bridge, Isle of Palms, SC

Functional Abdominal Pain in Children with Celiac Disease

F Cristofori et al. Clin Gastroenterol Hepatol 2021; 19: 2551-2558. Functional Abdominal Pain Disorders and Constipation in Children on Gluten-Free Diet

This prospective cohort (2016-2018, n=417, mean age 13.7 y) examined the frequency of functional disorders (based on questionnaire) in children with celiac disease (CD) who were receiving a strict gluten free diet (GFD) for at least one year.

Key findings:

  • Functional abdominal pain disorders (FAPDs) had a higher prevalence s among patients with CD (11.5%) than controls (6.7%)  (P < .05)
  • Irritable bowel syndrome (IBS) and functional constipation (FC) defined by the Rome IV criteria were more prevalent in patients with CD (7.2% for IBS and 19.9% for FC) than controls (3.2% for IBS and 10.5% for FC) (P < .05 and P < .001, respectively)
  • Younger age (P < .05) and a higher level of anti–transglutaminase IgA at diagnosis (P < .04) were associated with FAPDs (in particular for IBS) irrespective of GFD duration
  • A GFD did help with abdominal pain: After starting a GFD, 80% of children with celiac disease had resolution of stomach pain, whereas 9% started to complain of symptoms after starting a GFD

In the discussion, the authors speculate on the reasons for ongoing pain including inadvertent gluten exposure, intestinal inflammation/visceral hyperalgesia, altered microbiome, and refractory CD.

My take: Persistent stomach pain in CD is a common occurrence, even in those trying to adhere to a strict GFD.

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Chattahoochee River, Atlanta