Tag Archives: irritable bowel syndrome

Course of Functional Abdominal Pain Before and During Pandemic

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C Strisciuglio et al. JPGN 2021; 73: 689-694. Overall Impact of Coronavirus Disease 2019 Outbreak in Children With Functional Abdominal Pain Disorders: Results From the First Pandemic Phase

In this multicenter, observational, international study conducted between April and July 2020 at six different referral centers, the authors studied two groups:

  1. Children diagnosed with FAPDs between October 2019 and February 2020 were enrolled and prospectively interviewed at 4 months of follow-up during the first pandemic phase (Quarantine group, n=180, mean age 14 yrs)
  2. A cohort of children diagnosed with FAPDs between October 2018 and February 2019 was used as a Control group, n=176, mean age 13 yrs)

Key findings:

  • At 4 months of follow-up, both groups had a significant reduction of children reporting >5 episodes of abdominal pain per month when compared to baseline. Quarantine group: 63.9% vs 42.2%, P < 0.001; Control group: 83.5% vs 50%, P < 0.001.
  • Overall, 57% of the Quarantine group and 63.5% of the Control group had improvement of all symptoms.

My take: This study shows that the majority of patients with functional abdominal pain have improvement (at least temporarily) and reinforce the benefit of reassurance/conservative approach for many even during the pandemic. It is possible that school closures and additional parental attention mitigated some of the improvement in the Quarantine group.

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Siesta Key, FL

Gluten-Free Diet –Role in IBS?

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MI Pinto-Sanchez et al. Clin Gastroenterol Hepatol 2021; 19: 2343-2352. Open Access: Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG

In this prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) were studied before and after 4 weeks of a GFD. Celiac disease (CD) was ruled out in patients and controls by negative tissue transglutaminase (tTG) IgA antibody and deamidated gliadin IgA or IgG antibodies and by the absence of mucosal atrophy in a duodenal biopsy specimen (Marsh 0 or 1). At least 4 and 2 biopsy specimens were obtained from the second and the first part of the duodenum, respectively.

Key findings:

  • Compared with baseline, IBS symptoms improved in 18 of 24 patients (75%) with antigliadin IgG and IgA and in 8 of 21 patients (38%) without the antibodies
(A) Improvement in IBS symptoms (>4.5 points in the total Birmingham score) in antigliadin antibody (AGA)+ and AGA– patients after GFD. (B) Change in IBS symptoms after a gluten-free diet (GFD) compared with baseline in AGA+ and AGA– patients.

The associated editorial (A Rej et al. Open Access: Personalizing Dietary Therapies For Irritable Bowel Syndrome: What Is Gluten’s Role?) provides some useful points:

  • “A key trigger for symptom generation in IBS is diet, with more than 80% reporting food-related symptoms…It seems that wheat is a key component for symptom generation in IBS, as demonstrated by a study in 920 patients by Carroccio et al,8 which identified wheat sensitivity in 30% of patients”
  • The authors note that the Pinto-Sanchez population had a higher-than-expected rate of AGA positivity of 50% when previous studies have found rates of 7-18%.

My take: This prospective study indicates that a GFD is associated with clinical improvement in a significant number of individuals with IBS (with and without antigliadin antibodies) who did not report any gluten sensitivity or were not on a gluten-restricted diet before study entry. Based on a number of other studies, however, it seems that a low FODMAPs diet is likely to have a higher efficacy for patients with IBS.

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“How to Approach a Patient with Difficult-to-Treat IBS”

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L Chang. Gastroenterol 2021; 163: 1092-1098. How to Approach a Patient with Difficult-to-Treat IBS

For a short article, this review provides a lot of practical advice. Challenges with IBS include the lack of objective biomarkers and “patients are often dissatisfied with a positive diagnostic approach or even after multiple negative tests.” The author recommends the following:

  • Confidently communicate the diagnosis of IBS
  • Explain visceral hypersensitivity and its associated with pain, and bloating and why central neuromodulators and behavioral therapy are often used. Explain that IBS can be associated with high-amplitude propagating contractures which can cause pain/diarrhea
  • Treatment focused on ‘RESET’ =Relationship with patient-provider, Education/reassurance, Symptom assessment, Exacerbating/alleviating factors, and Targeting treatment (see Table 1)

Treatment may need to target gut, brain and/or both

  • Dietary treatments considered 1st line approach
  • Treatment pharmacology options for IBS-D include antidiarrheals, antispasmotics, rifaximin, eluxadoline, alosetron (rarely, can cause ischemic colitis), bile acid sequestrants
  • Treatment pharmacology options for IBS-C include polyethylene glycol, lubiprostone, linaclotide, plecanatide, and tegaserod (restricted to women <65 yrs w/o cardiovascular dz)
  • Treatment pharmacology options for all IBS include TCAs (start with low dose and can titrate upwards; amitriptyline for IBS-C, nortriptyline or desipramine for IBS-M or IBS-C), SNRI (eg. duloxetine (may be better than TCAs in patients with IBS-C and comorbidities like fibromyalgia and depression), mirtazapine (small studies demonstrated benefit for IBS-D and functional dyspepsia), SSRIs (“consider…in patients with predominant anxiety and/or depression…advise against its use as primary treatment for IBS w/o comorbid psychological disorder”), delta ligand agent (eg. pregabalin) (consider if refractory to other treatments), and brain-gut therapies (eg. CBT, GDH)

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It Hurts Here and Here and Here

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A recent study (below) reminded me of a joke. First the joke (better with the visual effect):

A guy goes to his doctor. The patient says, “Doctor when I touch here on my shoulder (with index finger) it hurts, when I touch here on my leg (with index finger) it hurts, and when I touch here on my stomach (with index finger) it hurts.”

The doctor says: “Your finger is broken.”

BP Chumpitazi et al. J Pediatr 2021; 236; 131-136. Multisite Pain Is Highly Prevalent in Children with Functional Abdominal Pain Disorders and Is Associated with Increased Morbidity

In this cross-sectional study of 7-17 year olds (n=406) with Rome III functional abdominal pain disorder (FAPD), the authors examined the frequency of pain outside GI tract over a 2 week study period. Patients were recruited from both a large academic pediatric GI practice and general pediatric offices in same hospital system.

Key findings:

  • In total, 295 (73%) children endorsed at least 1 co-occurring nonabdominal pain, thus, were categorized as having multisite pain with the following symptoms: 172 (42%) headaches, 143 (35%) chest pain, 134 (33%) muscle soreness, 110 (27%) back pain, 94 (23%) joint pain, and 87 (21%) extremity (arms and legs) pain
  • In addition, 200 children (49%) endorsed 2 or more nonabdominal pain symptoms
  • Participants with (vs without) multisite pain had significantly higher abdominal pain frequency (P < .001) and severity (P = .03), anxiety (P < .001), and depression (P < .001). Similarly, children with multisite pain (vs without) had significantly worse functional disability (P < .001) and health-related quality of life scores (P < .001).

The authors note that due to the design of their study, they cannot establish a causal association between pain symptoms and psychosocial functioning.

My take: A lot of kids with stomach pain have multisite pain as well as anxiety and depression. This study reminds us to ask about them.

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More Pictures From Atlanta Beltline West End

“An Allergic Basis for Abdominal Pain”

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A recent post (Mechanisms of Postinfectious IBS & Functional Pain) reviewed a study which described how food antigens during an infectious process can result in meal-induced pain.

A recent review of this study (M Rothenberg. NEJM 2021; 384:2156-2158. An Allergic Basis for Abdominal Pain) provides more insight.

Key points:

  • “A peripheral immune mechanism involving local mast cells stimulated by food-induced local IgE may underlie the symptoms associated with IBS and functional abdominal pain; these findings prompt consideration of new therapeutic strategies to target mast cells and allergies.”
  • The article reviews the experimental methods/results used in both mice and humans. Mice that were treated with agents that interfered with allergy “including anti-IgE, mast-cell stabilizers, and histamine H1 receptor antagonists, attenuated the pathologic and symptomatic responses…mice [that were] deficient in mast cells or in histamine H1 receptor were protected” as well.
  • The study shows that a “bacterial infection can break oral tolerance to a dietary antigen…which in turn can lead to increased gut permeability.”
  • The findings in human “showed no evidence of systemic IgE against common foods” but localized reactions were identified in every IBS patient after allergen injection into rectal mucosa.

My take: This study adds to the evidence that specific foods can lead to localized tissue-specific allergic responses. Nevetheless, it is still a futile effort to look for systemic allergic food reactions in patients with IBS and functional GI disorders.

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Identifying BAD (bile acid diarrhea) in IBS-D

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BC Beinvogl et al. JPGN 2021; 72: 859-865. Markers of Bile Acid Metabolism in Pediatric Diarrhea Predominant Irritable Bowel Syndrome and Healthy Controls

Background: Up to ~30% of adults with IBS-D may have bile acid diarrhea (BAD); however, identification has been hampered by cumbersome testing. In the U.S., the most reliable test has been a 48-hr fecal bile acid (FBA) level of >2337 micromol/48 h. Alternatively, blood tests have been used:

  1. 7alpha-hydroxy-4-cholesten-3-one (C4)–a direct measure of BA production
  2. Fibroblast growth factor-19 (FGF-19)–an indirect measure of ileal BA resorption

This prospective cross-sectional study of adolescents (n=26 and 56 healthy controls) examined these blood tests and 48-h FBA . Key findings:

  • 20% of IBS-D patients had elevated C4 levels based on 90% of serum C4 in healthy controls (HC). Mean value in HC was 12 and mean value in IBS-D was 16; 90th% was 22 in HC.
  • 28% had decreased fasting serum FGF-19 based on 10% of HC. Mean value in HC was 128 pg/mL compared with 93 in IBS-D; 10th% was 45 in HC.
  • There was good correlation between C4 and 48-h FBA and there was an inverse relationship between serum C4 and FGF-19. Mean value for 48-h FBA in HC was 490 micromol/48 h compared with 824 in IBS-D; 90th% was 972 in HC.

The authors argue that a definitive diagnosis of BAD is beneficial compared to empiric use of bile acid sequestrants. They point to studies showing that treatment is more effective in those with known BAD, up to 75% response rate. In addition, the use of empiric treatment “has not been validated as a diagnostic test for BAD.” Furthermore, definitive diagnosis would help with adherence to long-term treatment and avoid drug interactions/side effects in those who are unlikely to respond to treatment.

My take: This study shows that C4 could help identify BAD in IBS-D in adolescents and is in agreement with studies in adults (Mayo Clinic labs does run this test: Mayo Clinic: 7AC4, Bile Acid Synthesis, Serum).

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Below is a sign from the broadwalk in Hollywood, FL. Watch out if you are eating something!

Prospective Pediatric Study of the Persistence and Progression of Recurrent Abdominal Pain

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J Sjolund et al. Clin Gastroenterol Hepatol 2021; 19: 930-938. Prevalence and Progression of Recurrent Abdominal Pain, From Early Childhood to Adolescence

Using a prospective, population-based Swedish cohort (1994-1996) (BAMSE project), the authors analyzed data from 2455 children with complete follow-up evaluation at ages 1, 2, 12, and 16 years.

Key findings:

  • RAP was reported by 26.2% of children on at least 1 of 3 assessment points, of which 11.3% reported symptoms more than once
  • Children with RAP at 12 years had persistent symptoms at 16 years in 45% of cases and increased risks for RAP (relative risk, 2.2; 95% CI, 1.7–2.8), any AP-FGID (relative risk, 2.6; 95% CI, 1.9–3.6), and IBS (relative risk, 3.2; 95% CI, 2.0–5.1) at 16 years
  • Figure 3 summarizes the overlap of RAP at different time points:
  • **In early childhood (1-2 years of age), 149 (6%) had RAP per parental reports. Only 27 in this group, had RAP noted at 16 years of age which accounted for 7% of the total 16 year old cohort with RAP
  • **At 12 years of age, 98 (4%) had RAP. 44 (45%) of this group continued with pain at 16 years which accounted for 11% of the total 16 year old cohort with RAP

My take: Most children (84%) with RAP at 16 years of age did NOT report RAP at younger ages; however, in children with RAP at 12 years of age, 45% continued to have RAP at 16 years of age.

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Patient Information on Irritable Bowel Syndrome From Rome Foundation

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More information from Rome Foundation:

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Related humor: YouTube Link: SNL IBS Ad (4/10/21) Very funny!

Does Irritable Bowel Syndrome Occur More Commonly in the Setting of Endometriosis?

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According to a recent study (AD DiVasta et al. Clin Gastroenterol Hepatol 2021; 19: 528-537. Overlap Between Irritable Bowel Syndrome Diagnosis and Endometriosis in Adolescents), adolescents with surgically-confirmed endometriosis are at increased risk for irritable bowel syndrome.

This study derived data from a longitudinal cohort; the sample for this study followed women with and without endometriosis who completed extensive surveys (n=323) and excluded women with celiac disease or inflammatory bowel disease. Cases of IBS were based on patient reports of Rome IV criteria, though 81% were confirmed via medical record review.

Key findings:

  • “More adolescents with endometriosis (54 of 224; 24%) had comorbid IBS compared with adolescents without endometriosis (7 of 99; 7.1%). The odds of IBS was 5.26-fold higher among participants with endometriosis than without (95% CI, 2.13–13.0).”
  • “For participants with endometriosis, each 1-point increase in acyclic pain severity increased the odds of IBS by 31% (adjusted odds ratio, 1.31; 95% CI, 1.18–1.47).”

The association of endometriosis with IBS was based on Rome IV criteria, as such, the authors assert that this is “not merely a diagnostic bias” However, some of the increase may be related to referral patterns.

Useful points:

  • “In the adult literature, pain in the pelvis, menstrual-related symptoms, symptoms related to sexual intercourse, ovarian cysts, and subfertility seem to distinguish women with endometriosis from other GI conditions.”
  • “Chronic pain syndromes were more prevalent in girls with endometriosis and IBS. Rates of migraine headaches, sleep disturbance, and urinary symptoms were higher…[and] had higher prevalence rates of mood disturbance.”

Why is there overlap between these disorders?

  • The authors speculate that “the inflammatory process likely plays a role…and central pain sensitization may play a crucial role in the two diseases”

My take: Adolescents with endometriosis have a higher likelihood of IBS. Acyclic pain is a strong predictor of IBS.

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Related humor: YouTube Link: SNL IBS Ad (4/10/21) Very funny!

FMT Research & The Shawshank Redemption

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In The Shawshank Redemption, Andy Dufresne (Tim Robbins) manages to escape prison by crawling through 500 yards of a filthy sewage pipe. It seems like a similar effort will be needed to find out how to benefit from fecal transplantation when given for problems like irritable bowel syndrome and metabolic disease/obesity. Some recent studies and associated editorials are noted below.

T Holvoet et al. Gastroenterol 2021; 160: 145-157. Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial

  • Key finding: At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P = .03).
  • Commentary: PW O’Toole, F Flanahan. Gastroenterol 2021; 160: 15-17. Full Text: Transplanting Microbes for Irritable Bowels or Irritated Microbes or Both?
    • This editorial stresses that trials of FMT in IBS have had inconsistent results and risks are unclear. “How many clinicians inform patients receiving FMT that the donor microbiota might include components that increase (or decrease) one’s risk of colorectal cancer?” Part of the problem is “due, in part, because a normal microbiome has not been defined.”

E Rinott et al. Gastroenterol 2021; 160: 158-173. Full text Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain

Key findings:

  • In this randomized controlled trial with 90 participants, autologous FMT (aFMT) significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P = .02) and improved insulin resistance: insulin rebound (aFMT, –1.46 ± 3.6 μIU/mL vs placebo, 1.64 ± 4.7 μIU/mL; P = .04) (Graphical abstract below)
  • In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet–induced regain phase (all, P < .05).

Commentary: M Nieurdorp, K Madsen. Gastroenterol 2021; 160: 17-19. Full text The Promise of Maintaining Diet-Induced Weight Loss by Swallowing One’s Own Feces: Time to Provide a Do-It-Yourself Manual?

  • “These findings add support to the current body of evidence that the gut microbiota have a role in weight gain and metabolism. However, many questions remain. Indeed, although studies have shown varying degrees of effectiveness of FMT in the improvement of metabolic parameters in human participants, there has been no evidence yet that FMT can induce weight loss in obese patients.”
  • “The finding that maintenance of weight loss was only seen in the one dietary group consuming the Mediterranean diet plus green tea and Mankai supplement who received autologous FMT, would suggest that specific microbial profiles may be involved and that weight loss per se may not result in the required microbial profiles.”
Figure 1 from editorial: Challenges associated with the use of fecal microbial transplantation (FMT) as treatment

My take: Both of these studies show that modulation of the fecal microbiome may be helpful under the right set of circumstances to help with both irritable bowel syndrome and metabolic syndrome. However, ‘hundreds of yards’ of more research is needed to determine if this is really feasible and to assure that the benefits outweigh the potential risks.

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