Tag Archives: irritable bowel syndrome

Rome V: Lower GI Tract and Biliary Disorders of Gut-Brain Interaction in Pediatrics (Part 1)

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C DiLorenzo, M Saps et al. Gastroenterol 2026; 170: 1367-1387. Open Access! Lower and Biliary Disorders of Gut–Brain Interaction: Child and Adolescent

Before reviewing this article, I wanted to point out that Dr. DiLorenzo, who was the 2025 ANMS Lifetime Achievement Award recipient, overcame great hardship to become a leader in neurogastroenterology. Elsewhere in this same issue, Wong et al (Gastroenterol 2026; 170: 1190-1204) point out that in Italy (& Spain) there is not even a word for bloating!

Key points:

  • For the Rome V recommendations, the Pediatric Committees decided to depart from the age-based divisions used in Rome IV

Irritable Bowel Syndrome:

  • “In Rome IV, for those children with constipation, there was an attempt to differentiate functional constipation (FC) from IBS by first attempting to treat constipation.7 …the Rome V Committee proposes a shift akin to that described in the adult IBS criteria, with a focus on the predominant symptom of abdominal pain as the differentiating factor between IBS-C and FC.”
  • Pathophysiology of IBS includes early life events, heightened nerve sensitivity, and increased gut permeability. Also, “more than 90% of children and adolescents with IBS identify at least 1 food that exacerbates their GI symptoms.34,35“
  • Evaluation: “testing for celiac disease is recommended in those with IBS-D” and possibly testing for parasites and fecal calprotectin
  • Psycholological features: “studies have reported the association between abdominal pain–related DGBI and clinically evident as well as subclinical anxiety and depression.43–47 Anxiety and depression are as likely to follow as to precede pain48 and are not the main factors influencing pain outcomes.49–51…hildren with IBS may have increased school absenteeism, sleep disturbances, multisite pain, and functional disability.54,55“
  • Treatments: Hyponotherapy, cognitive behavioral therapy, percutaneous nerve field stimulation, dietary interventions, probiotics, peppermint oil, psyllium, and pharmacologic interventions (lack of RCT evidence with most medications). Dietary intevertions: “The majority of lactose challenge RCTs in children with abdominal pain–predominant DGBI do not support the role of lactose as the trigger of the child’s symptoms.60…Given concerns for abnormal eating behaviors and the potential occurrence of avoidant and restrictive food intake disorders, it is strongly recommended that a dietitian be involved in any restriction diet and that liberalization of the restriction be instrumented when possible.65” Related blog post: Treatment Guidelines for Pediatric Irritable Bowel Syndrome

Abdominal Pain Syndrome–Not Otherwise Specified

  • “The committee revised the criteria to differentiate intermittent pain (APS-NOS) from constant pain (CAPS) and specified that pain in APS-NOS should not be exclusively associated with meals, menses, or bowel movements.”

Biliary Pain Sydrome

  • “A key difference is the requirement for pain to be in the right upper quadrant with or without epigastric pain, helping distinguish it from functional dyspepsia.99“
  • “Biliary dyskinesia may resolve spontaneously, with conservative treatment often showing equivalent or better outcomes than cholecystectomy in long-term follow-up.104 Therefore, cholecystectomy should be considered only when other nonsurgical treatments have been appropriately trialed and have failed to improve symptoms…surgery may not alleviate symptoms or may exacerbate symptoms or result in complications.”

Abdominal migraine

  • “In cases of overlapping symptoms with cyclic vomiting syndrome, the predominant and most bothersome symptom will guide the primary diagnosis.”
  • “There are no US Food and Drug Administration–approved medications or evidence-based guidelines for treating AM in children…Treatment should be individualized…Children with frequent and debilitating episodes may benefit from prophylactic therapy, as some evidence suggests that antimigraine medications.”

Centrally Mediated Abdominal Pain Syndrome

  • “Continuous pain as in the case of CAPS is much less frequent. There is no specific epidemiologic data for this diagnosis, as CAPS was not part of previous pediatric Rome Criteria.”
  • “Some of the treatment strategies listed in the ESPGHAN-NAPGHAN guidelines related to IBS and FAP-NOS may apply to this condition as well.68 Brain–gut therapies are strongly recommended,122,123 given the central sensitization that is likely present in these patients.”

Functional Abdominal Bloating

  • “Functional abdominal bloating is a recent addition to the pediatric Rome Criteria.”
  • “Potential organic causes of both bloating and distention include small bowel bacterial overgrowth, celiac disease,199 congenital sucrase-isomaltase deficiency, and other malabsorption disorders.195“

Infant Distress Syndrome

  • “IDS is a new name proposed by the Rome V Committee in lieu of the term “infant colic.” The Rome V Committee agrees that this syndrome of excessive crying in infancy belongs to the DGBI group because there is evidence for a role of both brain and gut in its pathophysiology. However, the term “colic” suggests that the pain arises in the colon, which has not been proven to date. “
  • “The Rome V committee, however, agreed that this criterion of 3 hours was arbitrary and that many infants present to the pediatrician with excessive crying of a duration of less than 3 hours per day but with severe impact on at least 1 of the caregivers.”
  • Pathophysiology: “The pathophysiological mechanisms underlying IDS are still poorly understood, but IDS is likely to be a multifactorial disorder with GI, neurologic, and psychosocial disturbances.207 The pathogenesis of excessive crying may be closely related to the development of the GI microbiome.”
  • Maternal Psychology: “Maternal anxiety has been consistently found to be both a preceding and concurrent condition of excessive crying…However, depression seems to be a result of IDS, with excessive crying and maternal depression exacerbating simultaneously in a vicious cycle.214“
  • Treatment: “The cornerstone of helping infants with IDS is to validate the infant’s symptoms and the emotional burden of the parents, reassure the parents that their child is healthy, and educate them about the self-limited nature of IDS and the need for support by family members…Probiotics may reduce crying time in infants with IDS…Evidence for the effectiveness of dietary modifications to treat IDS is scarce and presents a significant risk of bias.222 However, removing cow’s milk from the infant’s diet or from the maternal diet in those who are breastfed may be beneficial..Tthe evidence for using …proton pump inhibitors is very weak.224“

My take: This is a very useful article and worth reading. I like the change in terminology from colic to infant distress syndrome and labeling IBS-C instead of FC when patient has predominantly abdominal pain.

How FODMAPS Contribute to Irritable Bowel Symptoms

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J Gao et al. Gastroenterology. 206; 170:132 – 147. Open Access! Low Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols Diet Improves Colonic Barrier Function and Mast Cell Activation in Patients With Diarrhea-Predominant Irritable Bowel Syndrome: A Mechanistic Trial

Background: “Mechanisms by which fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) drive pathophysiology of irritable bowel syndrome (IBS) are not well understood.”

Methods: 42 patients with “Rome IV diarrhea-predominant IBS (IBS-D) underwent barrier function evaluation pre- and post-LFD along with assessment of mast cell number and activation profile. Finally, fecal supernatants (FS) were administered intracolonically to wild-type mice with and without pharmacologic inhibition, toll-like receptor 4 (tlr4)–/– mice, and mast cell-deficient mice with/without mast cell reconstitution.”

Key findings:

This is a highly technical study and would recommend reviewing the findings directly (open access article).

To summarize:

  • “Patients with IBS-D had significant improvement in colonic barrier structure and function, mast cell number, and levels of mast cell mediators post-LFD (low FODMAP diet). The magnitude of physiological changes did not correlate with the magnitude of clinical response.”
  • “This study showed the complex interplay among food, microbiome, local immune activation, and epithelial physiology in IBS by demonstrating that FODMAPs increase fecal lipopolysaccharide levels, which activates colonic mast cells to causes barrier dysfunction in diarrhea-predominant IBS.”

    My take: By understanding the GI effects of a low FODMAP diet in patients with IBS-D more precisely, it may improve dietary approaches as well as other treatments like mast cell stabilizers.

    Related blog posts:

    New Study: Mediterranean Diet for IBS

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    JO Bamidele et al. Annals Int Med 2025; https://doi.org/10.7326/ANNALS-25-015. The Mediterranean Diet for Irritable Bowel Syndrome: A Randomized Clinical Trial

    Methods: Randomized noninferiority clinical trial (n=139 Adults from UK) — 6 weeks of the MD (Mediterranean diet) (n = 68) versus TDA (traditional diet advice) (n = 71).  Primary end point was the proportion achieving clinical response, defined as 50-point or greater reduction in IBS Symptom Severity Scale (IBS-SSS).

    Traditional dietary advice’s main elements are to “adopt sensible eating habits
    and avoid excess fatty foods, spicy foods, processed foods, caffeine, fizzy drinks, and alcohol. The principal components of the MD are a diet rich in fruit, vegetables,
    pulses (aka legumes), whole grains, nuts, fish, and olive oil.”

    Key findings:

    • The primary end point was met by 62% following a MD versus 42% following TDA (P = 0.017)
    • There was a greater reduction in the mean IBS-SSS after a MD than TDA (−101.2 vs. −64.5)

    My take: I agree with the authors: The Mediterranean diet “represents a viable first-line dietary intervention for IBS.”

    Related blog posts:

    Treatment Guidelines for Pediatric Irritable Bowel Syndrome

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    J Green et al. JPGN 2025; Open Access! ESPGHAN/NASPGHAN guidelines for treatment of irritable bowel syndrome and functional abdominal pain-not otherwise specified in children aged 4–18 years

    Overall, this article notes that the evidence based for most treatments for pediatric irritable bowel (IBS) is often lacking.

    Specific recommendations:

    Executive summary of Best Practice Statements‐ The Guideline Development Group (GDG) notes that a crucial emphasis should be placed on education regarding the abdominal pain‐related disorders of gut–brain interaction.

    My take: This is a helpful guideline and likely to influence practice.

    Related blog posts:

    Increase in Irritable Bowel Syndrome During COVID Pandemic

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    CV Almario et al. Neurogastroenterology and Motility; https://doi.org/10.1111/nmo.70020. Trends in Prevalence of Rome IV Disorders of Gut-Brain Interaction During the COVID-19 Pandemic: Results From a Nationally Representative Sample of Over 160,000 People in the US

    Methods: From May 2020 to May 2022, the authors performed a series of cross-sectional online surveys among a representative sample of adults ≥ 18 years old in the US (n=160,154). We administered Rome IV gastroduodenal and bowel DGBI questionnaires.

    Key findings:

    •  During the COVID-19 pandemic, the prevalence of irritable bowel syndrome (IBS) increased from 6.1% [May 2020] to 11.0% [May 2022]
    • In addition, the prevalence of chronic idiopathic constipation (CIC) increased mildly from 6.0% [May 2020] to 6.4% [May 2022]
    • No changes in prevalence were seen for the other examined gastroduodenal and bowel disorders of gut-brain interaction (DGBI)

    My take: This study identified increases in the prevalence of IBS during COVID. Increases in IBS following other enteric infections (eg. norovirus, shigella, campylobacter) has been shown previously as well.

    Related blog posts:

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    Targeting Intestinal Epithelial Serotonin for Treating Disorders of Gut-Brain Interaction and Mood

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    Briefly noted: LY Hung et al. Gastroenterol 2025; 168: 754-768. Open Access! Intestinal Epithelial Serotonin as a Novel Target for Treating Disorders of Gut-Brain Interaction and Mood

    This study used transgenic, surgical, and pharmacological approaches to study the effects of intestinal epithelial serotonin reuptake transporter or serotonin on mood and gastrointestinal function, as well as relevant communication pathways.

    Key findings:

    • Serotonin reuptake transporter ablation targeted to the intestinal epithelium promoted anxiolytic and antidepressive-like effects without causing adverse effects on the gastrointestinal tract or brain; conversely, epithelial serotonin synthesis inhibition increased anxiety and depression-like behaviors. 
    • In utero SSRI exposure is a significant and specific risk factor for development of the DGBI, functional constipation, in the first year of life.

    My take: While this lengthy article presents data mainly from mice studies, it further supports the likelihood that SSRI selective targeting of the gut epithelium may improve anxiety, depression and comorbid DGBI. Selective targeting of the GI tract would reduce adverse effects of these medications.

    Related blog posts:

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    Does a Less Restrictive Low FODMAP Diet Work?

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    In the movie There’s Something About Mary, there is a scene (YouTube: 7-minute abs) where the main character picks up a hitchhiker. The hitchhiker reveals his brilliant idea for the 7-minute ab workout to replace the 8-minute ab workout. Of course, he becomes upset when the lead character suggests that someone else could invent the 6-minute ab workout.

    This is what I was thinking of when I read a recent article describing a simplified, less restrictive low FODMAP diet.

    P Singh et al. Clin Gastroenterol Hepatol 2025; 23: 362-364. Is a Simplified, Less Restrictive Low FODMAP Diet Possible? Results From a Double-Blind, Pilot Randomized Controlled Trial

    This pilot study with 35 subjects with IBS-D were randomized to a standard low FODMAP diet (LFD) or to a simplified FODMAP diet which eliminated solely fructans and galactooligosaccharides. The primary endpoint was the proportion of subjects meeting the FDA responder definition for abdominal pain intensity (ie. a >/= 30% reduction in weekly average of daily abdominal pain scores for 2 of the 4-week treatment period).

    Key findings:

    • There was a similar reduction in key symptoms (see below)
    • Fewer individuals in the simplified diet dropped out due to side effects or difficulty with adherence (12.5% vs 26.3%)
    Blue columns indicate response to traditional low FODMAP diet (n=19)
    and orange represents response to simplified low FODMAP diet (n=16)

    My take: Larger trials are needed. This study suggests that a simplified version of a low FODMAP diet would improve symptoms in most patients with IBS-D.

    Related blog posts:

    Key Advances in 2024: An Overview from GutsandGrowth (Part 3)

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    This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

    New Study: Leaky Gut and Irritable Bowel Syndrome

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    MR Barbaro et al. Gastroenterol 2024; 167: 1152-1166. Molecular Mechanisms Underlying Loss of Vascular and Epithelial Integrity in Irritable Bowel Syndrome

    This study examined markers of the epithelial and vascular barriers in 223 patients with irritable bowel syndrome in comparison to 78 healthy subjects. In actuality, this lengthy report was a composite of about 8 different experiments.

    Key findings:

    • Figure 2 summarizes in vivo and in vitro epithelial permeability testing using orally-administered sugars and using Caco-2 cell incubation of control/IBS supernatants. In all of these experiments, there was a significant mean increase in IBS-D permeability compared to controls.
    • Figures 3 and 4 report on significant changes the gut vascular barrier and specific mediators, respectively, in IBS compared to controls
    • One novel finding was correlation of epithelial barrier markers with gastrointestinal symptoms and gut vascular dysfunction with systemic systems including anxiety and depression (see heat map below)
    Relationships between epithelial and endothelial permeability markers and symptoms. The asterisks on the heatmap indicate significances in the Spearman’s correlation.

    My take: The term ‘leaky gut’ has a negative connotation among many gastroenterologists as it has been associated with misleading diagnostic and therapeutic claims. However, this study shows a correlation between epithelial and vascular barrier disruptions and symptoms in irritable bowel. This is useful information; nevertheless, there are not simple tests to identify these findings and there are not therapeutics with demonstrated efficacy.

    Related blog posts:

    Brave New World of Neuromodulators (2024) for Disorders of Brain-Gut Interaction

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    I Hanna-Jairala, DA Drossman AJG 2024; DOI: 10.14309/ajg.0000000000002800. Open Access! Central Neuromodulators in Irritable Bowel Syndrome: Why, How, and When

    This is a terrific review article. The authors detail the rationale for neuromodulators, strategies for selecting among them, side effects, and dosing.

    Background: “IBS is frequently associated with neuropsychiatric disorders such as depression and anxiety, which are considered triggers for the onset of symptoms or occur in response to having them (3). In the Rome Foundation global study that included 54,127 participants, subjects with psychological distress or clinically relevant somatic symptoms were 4.45 times more likely to have 1 or more DGBI than those without psychological distress. The same study reported that those who met specific criteria for bowel disorders presented clinically relevant psychological distress or somatic symptoms in 55.5% of cases (4). In addition, in a meta-analysis that included 7,095 subjects with IBS exclusively, the global prevalence of depression was 36%…Anxiety was present in 44% of patients with IBS….Central neuromodulators act on receptors along the brain-gut axis, so they are useful in treating psychiatric comorbidities, modifying gut motility, improving central downregulation of visceral signals, and enhancing neurogenesis in patients with IBS… Neuromodulator treatment is still considered off-label, many of the recommendations herein are based on expert consensus (6)”

    Key points:

    • “The first-line treatment for pain management in IBS is using tricyclic antidepressants.” Nortriptyline and desipramine are less likely to cause constipation.
    • “Selective serotonin reuptake inhibitors (SSRIs) are useful when symptoms of anxiety and hypervigilance are dominant but are not helpful for treating abdominal pain….The SSRIs include fluoxetine, fluvoxamine, sertraline, paroxetine, citalopram, and escitalopram. …Sertraline, citalopram, and escitalopram tend to have the fewest pharmacokinetic drug interactions”
    • “SSRIs are first-line pharmacologic agents for treating anxiety disorders, but they have the potential to induce restlessness and exacerbate anxiety when the drug is initiated. They are typically initiated at half of the usual starting dose to minimize these potential anxiogenic adverse effects. The dose may gradually increase to the regular starting dose after about 1 week… SSRIs should be considered when a significant component of anxiety without pain is present.”
    • SNRIs: “In addition to showing benefits with depression and painful disorders, SNRIs have shown significant improvement in anxiety.” Thus, they may be useful as monotherapy for patients with pain and anxiety.
    • Tetracyclics: “The most representative agent of this class is nirtazapine (Table 5). However, their effects seem to be mainly on anxiety, early satiety, nausea, and other symptoms associated with esophageal and gastroduodenal disorders, so their use in IBS is limited.”
    • “It is important to explain to the patients, …neuromodulators are not necessarily used for the treatment of depression but are a therapeutic alternative in the management of DGBI. It helps to use the term “neuromodulator” instead of “antidepressant” (6,8) It also helps to clarify that these medications can treat pain and other GI symptoms independent of treating depression, and the dosages are often lower than those used for treating major depression. This will preclude any patient concerns that their symptoms are being underestimated or considered to be in their head (6,8).”
    • Using central neuromodulators for IBS requires long-term treatment. From our experience, 6–12 months of treatment or more are needed to increase the likelihood of remission.

    Related blog posts:

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