Elegant Study: Childhood Exposure to a Sibling with Crohn’s Disease and Disease Susceptibility

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R Chen et al. Gut. Epub ahead of print, August 31, 2026. doi:10.1136/
gutjnl-2026-339257. Childhood exposure to a sibling with Crohn’s disease alters gut microbiome and Crohn’s disease susceptibility

Thanks to Mike Hart for sharing this reference. This study is worth reading in its entirety due to the combination of experiments. This is a fairly long post to summarize the most important findings.

Background:

“In a study of 2756 Dutch families, gut microbiome composition and function were more alike between siblings than between parent-offspring pairs or spouses…These findings suggest that increased disease susceptibility among siblings of individuals with CD may be mediated by their shared gut microbiome.”

Methods:

  1. The authors used the prospective Genetic Environmental Microbial (GEM) Project and the nationwide South Korean database to assess the association between childhood exposure to affected siblings and CD onset (n=3126). This was validated in the South Korean dataset.
  2. A T-cell transfer model of colitis in germ-free mice was conducted to investigate the effects of stool from childhood-exposed (n=4) versus adult-exposed (n=4) siblings.
  3. An integrative risk model combining faecal calprotectin (FCP) and microbial enterotypes was trained and internally validated within the GEM cohort.

Key findings:

  • “In the GEM cohort, childhood exposure to an affected sibling was associated with a fourfold higher risk of developing CD compared with adult exposure (adjusted HR (aHR) 4.00; p=5.3×10−4), which was validated in the South Korean dataset (aHR 2.54; p=6.0×10−6).”
  • “Childhood exposure was associated with reduced abundances of Lachnospira,
    Roseburia     and Colidextribacter, reductions that mediation analysis identified as partially mediating CD risk.”
  • “In vivo, transplantation of childhood exposure-associated microbiota into germ-free recipient mice exacerbated colitis and elevated mucosal interleukin-22 expression, supporting a potential mechanistic role.”
  • This “model identified siblings with elevated FCP and Blautia-enriched or
    Prevotella-enriched enterotypes as highest risk, with a 10-year cumulative incidence of 22.5%.”
Figure 1b. Childhood exposure to CD was demonstrated to associate with increased disease susceptibility in the GEM cohort, and confirmed in an independent nationwide dataset.
Figure 1d. Among siblings with childhood exposure to CD, the authors developed and validated a risk stratification based on gut inflammation and enterotypes to identify individuals at high risk of CD onset
Figure 3a. Bar chart presenting the proportion of individuals with gut barrier dysfunction and gut inflammation among those exposed to CD during childhood (blue) or adulthood (orange).
Figure 5d. Kaplan-Meier curves showing the cumulative CD-free probability for individuals classified as having non-inflammation (blue), gut inflammation with Bact2 (green) and gut inflammation with Blau/Prev (orange) in the GEM cohort.

Discussion

  • This “study demonstrates that the timing of exposure to a sibling with CD, specifically childhood versus adult exposure, plays a critical role in disease susceptibility. Childhood exposure was associated with a fourfold higher risk of CD, potentially mediated by alterations in the gut microbiome.”
  • “Genetic predisposition has traditionally been considered the primary explanation for the elevated disease risk among siblings of persons with CD. However, genetic factors account for only about 10% of the variance in CD risk…childhood exposure to a sibling
    with CD, compared with adulthood exposure, was associated with a fourfold increased risk of disease onset, independent of the CD-PRS [CD – polygenic risk score].”
  • This study adds to “a growing body of evidence [that] implicates early-life exposures in CD pathogenesis. A recent meta-analysis reported that prenatal exposure to antibiotics and cigarette smoking increased the risk of CD, while breastfeeding was protective. Similarly, a large population-based study found that rural residence during childhood, but not adulthood, was associated with a lower risk of CD.”

Limitations:

  • Participants were from high-income countries.
  • Study did not include dietary intake.
  • These findings do not prove causation. There may be additional unrecognized genetic factors between the groups with exposure before and after 18 years of age.

My take: The increasing prevalence of Crohn’s disease, particularly over the last few decades, must be related to environmental factors; population genetics and genetic predisposition are unlikely to rapidly change. This is a very important study supporting the notion that exposure to siblings with Crohn’s disease and alteration of the gut microbiome increases the risk of Crohn’s disease. By identifying a microbiome group with a higher risk, this study may facilitate research to determine whether manipulation of the gut microbiome could reduce the likelihood of developing Crohn’s disease. If we can reduce Crohn’s disease in a high risk population, it may allow broader use of the same treatment principles to lower risk groups as well.

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Audio-Recorded Gut-Directed Hypnotherapy for Disorders of Gut-Brain Interaction Plus Measles Update

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L Barash et al. J Pediatr Gastroenterol Nutr. 2026; doi.org/10.1002/jpn3.70545. The role of audio‐recorded gut‐directed hypnotherapy onsleep and abdominal pain: A pilot and feasibility study.

Background: Gut-directed hypnotherapy (GDH) is an evidence-based treatment that improves abdominal pain and quality of life in pediatric DGBI both in the short- and long term.3, 4 Home-based audio-guided GDH has shown comparable efficacy to in-person treatment, while enhancing access to care for families with logistical or socioeconomic barriers.5, 6 

Methods: This was a non-blinded randomized controlled trial with partial crossover. Treatment includes three 25-min audio sessions every 2 weeks and daily 10–20-min sessions, with a goal of ≥5 sessions per week. Out of 25 participants who initiated GDH 16 (64%), completed treatment. Reasons for dropout included side effects (nausea, n = 2), lack of improvement (n = 1), resolution of symptom (n = 1), and unknown (n = 5).

Key findings:

  • Combined abdominal pain scores significantly improved post-treatment with GDH, with a 40.2% reduction from baseline (p < 0.001; d = 0.9), compared to a 16.6% reduction in the standard medical therapy (SMT) group
  • The SMT group had no improvements in sleep-related impairment (SRI) (p = 0.90) … whereas those who completed GDH demonstrated significant improvements in SRI at both 4 weeks (p = 0.01) and at the completion of treatment (p = 0.01)
  • Two participants in our study discontinued due to worsening nausea. Many of the audio recordings included motion-related imagery, which may have contributed to symptoms in susceptible participants.

In a separate study (n=230) (JTW Snijkers et al. Gut Published Online First: 25 July 2026. doi: 10.1136/gutjnl-2026-338385. Open Access! In-person therapist-delivered hypnotherapy versus smartphone-based self-guided hypnotherapy in IBS: a multicentre three-armed randomised controlled trial), a self-guided smartphone hypnotherapy program did not meet the prespecified threshold for noninferiority to in-person hypnotherapy for abdominal pain response in patients with irritable bowel syndrome (IBS). At weeks 13-16, Food and Drug Administration-defined abdominal pain response rates were 48.1% with in-person therapist-delivered hypnotherapy, 33.3% with smartphone-based self-guided hypnotherapy, and 21.8% with online psychoeducation. 

My take (borrowed in part from the JPGN authors): “Providers may consider GDH as a low-risk, home-based therapeutic option for children with DGBI, particularly when sleep is also a concern.”

Rigorous pharmacologic studies show that medications, to date, recommended for patients with DGBIs have difficulty outperforming placebo. With hypnotherapy, having an adequate control group is problematic. It would not be surprising, though, for GDH to have difficulty outperforming pharmacologic agents/placebo despite its good response in patients with DGBIs. In this setting, the use of GDH or medications with a low incidence of adverse effects and plausible beneficial effects continue to have a role in improving symptom control.

From AGA Today: US Measles Outbreak Tops 3,000 Cases Reaching 35-Year High

NBC News (9/4, Edwards) reports, “A 6-week-old baby girl is one of two people with measles who died in Pennsylvania, the Lancaster County coroner said Friday, as the nation’s measles tally hit a new 35-year record of 3,134 cases. … At least 115 more people in Pennsylvania, mostly in Lancaster County, have been diagnosed with measles in the last week, the health department said Friday, bringing the state’s outbreak to about 577 cases within the last few months.” Experts say there are likely many more across the country who have contracted measles but have not gotten tested. NBC adds, “The new milestone, the highest number of confirmed cases since 1991, is yet another indication that the highly contagious virus is taking over, particularly in areas of the country with plummeting vaccination rates.”

Related blog posts (for DGBIs):

Related blog posts (for Measles)

Blog Case Report: Eosinophilic Colitis

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This past month I helped diagnose a 2nd young child with eosinophilic colitis. This was an 8 month old who developed rectal bleeding over a 6 week period with subsequent anemia (Hgb 7.1). His colonoscopy showed patchy deep erythema in the right colon and transverse colon; his biopsies identified >100 eosinophils/hpf.

This prompted me to review a case of a child presenting with eosinophilic colitis at 13 months of age.

Case study: He was born at 36 week gestation with a prenatal diagnosis of proximal bowel obstruction due to type IIIb jejunal atresia, s/p ex-lap and tapering enteroplasty for long dilated jejunal segment and with subsequent short gut syndrome (~50 cm of small bowel). He required supplemental HAL dependency for his initial 9 months of life. At 13 months of age, he developed bloody diarrhea (up to 12/day) with associated anemia and peripheral eosinophilia (max elevation of AEC during his course was 23,000).

Initial endoscopy took place in January 2022. Images are noted below and histology confirmed eosinophilic colitis (>100 eos/hpf).

He underwent extensive testing and no monogenetic/immune dysregulation disorders were identified. After not improving with an elemental diet, his treatment ​consisted of prednisolone along with enteral antibiotics (vancomycin/gentamicin)​. His symptoms recurred with steroid taper and he was changed from antibiotic therapy to mesalamine. This was also ineffective. Subsequently, he started with vedolizumab therapy.

Due to ongoing symptoms, tacrolimus (along with PCP prophylaxis) was added two months later (this was 4 months after initial colonoscopy). The target level was between 8-10. He had a rapid and sustained response allowing him to stop corticosteroids which had been used intermittently for more than 6 months. His vedolizumab was stopped shortly thereafter.

After a followup panendoscopy demonstrated resolution of his colitis (see image below), his diet was gradually advanced (no restrictions) while continuing tacrolimus.

His tacrolimus was discontinued after 2.5 years and he has continued to do well off therapy for two years at this point. He still requires periodic vitamin-micronutrient monitoring for his short bowel syndrome.

My take: Eosinophilic colitis is a rare disorder in pediatrics with sparse data to guide management. In this young pediatric patient, tacrolimus was effective. It is possible that vedolizumab would have been effective if given for a longer duration prior to administration of tacrolimus. At the time of presentation, dupilumab had not been approved for eosinophilic esophagitis. There have been case reports of its use off-label for eosinophilic colitis (T Sia et al. Clin Transl Gastroenterol. 2025 Aug 26;16(10):e00908. Dupilumab for Adult and Adolescent Patients With Primary Eosinophilic Colitis).

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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.

Immune Mediated Enterocolitis with CAR-T Cell Therapy

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JA Damianos et al. Alimentary Pharmacology & Therapeutics, 2026; 0:1–12. Open Access! Review Article: Immune Effector Cell-Mediated Enterocolitis Following CAR-T Cell Therapy—Clinical Features, Pathophysiology and Management

Background: “Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, and its use is expanding rapidly into numerous other disease states including autoimmune diseases. However, CAR-T therapy is associated with a spectrum of immune-related toxicities…it has become apparent that rarely, CAR-T can cause gastrointestinal mucosal inflammation, termed immune effector cell-mediated enterocolitis (IEC-EC).”

Other treatments affecting the immune system can result in gastrointestinal inflammation. “Immune checkpoint inhibitors, including cytotoxic T lymphocyte associated anti-gen 4 (CTLA- 4) inhibitors, programmed death-1 (PD1) inhibitors, and PD-ligand 1 (PDL-1) inhibitors have been associated with colitis (with or without enteritis) in up to 54% of patients treated with these agents”

Key points:

  • “Occurring in up to approximately 6% of patients typically following B cell maturation antigen-targeted CAR-T therapy, IEC-EC presents with severe diarrhea and malabsorption, responds poorly to treatment, and portends a dire prognosis.”
  • “Step-up pharmacotherapy, often featuring biologics and small molecules drawn from the inflammatory bowel disease pharmacologic armamentarium.” Figure 6 presents an algorithm for evaluation and management.
  • “Patients typically present 1–3 months after CAR-T infusion with persistent watery, non-bloody diarrhea, often Grade 3 or higher [33]. Diarrhea is often severe and persistent, frequently accompanied by malnutrition and significant weight loss, and may necessitate prolonged parenteral nutritional support [25]. Diagnosis is often delayed due to the rarity and novelty of this condition, and the fact that patients receiving CAR-T have numerous other potential reasons to experience diarrhea.”

My take: There are a growing number of individuals needing CAR-T cell therapy. Recognizing this delayed complication quickly may help improve outcomes.

Related blog posts:

Puffins on the Edge of a Cliff Overlooking a Black Sand Beach

Federal Policies Changing Medical Standards

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BA Barsky et al. N Engl J Med 2026;395:419-421. Medical Standards by Federal Fiat

An excerpt:

“Historically, the federal–state division of authority over medical practice has been strict. This division is evident in health care financing and medical product regulation, for example. States license physicians and set standards for medical care, often incorporating standards established by the medical profession while allowing broad discretion for physician judgment.1…

The Trump administration has attempted to alter the balance of federal–state authority in the area of gender-affirming care in two important ways. First, in June 2025, the U.S. Department of Justice (DOJ) issued administrative subpoenas to more than 20 health systems and clinics providing gender-affirming care, demanding unusually broad information related to off-label prescribing of puberty blockers and hormones…The DOJ’s subpoenas, however, demanded information at the heart of physician judgment and the patient–doctor relationship, including physicians’ case-specific clinical assessments justifying off-label prescriptions and information that could be used to identify patients, including children, by name…

The second federal disruption came in December 2025, when Secretary of Health and Human Services Robert F. Kennedy, Jr., issued a declaration stating that gender-affirming care for children and adolescents is unsafe and does not meet professionally recognized standards of care…

Much of the authority and discretion now held by medical professionals and the states would move upward to a federal government that would exert expanded control over the health care that patients receive. Such a shift would potentially force all states to accept a single federal standard of care in various areas of medicine while concentrating immense medical power in the hands of political appointees. Federal authority over health care standards is appropriate in some instances. But this authority should be established using a proper legal process — Congress acting within its enumerated constitutional powers, or the executive branch acting under properly delegated authority — not by fiat.”

Established Roles for Setting the Medical Standard of Care
and Changes Implied by Trump Administration Actions.

My take: While this issue primarily affects a narrow area currently, it is not difficult to imagine that other administratioins could similarly impose policies affecting other sensitive decisions like abortion (expanding or limiting options), contraceptive availability, discussions about guns, and viability decisions.

Dr. Michael Wilsey: Endoscopy Pearls and Ergonomics (Part 2)

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Dr. Michael Wilsey gave our group an excellent update on Endoscopy Pearls and Ergonomics. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of his slides.

Yesterday’s post focused on endoscopy pearls. Today’s post focuses on ergonomics. Most of the attendees realized that we could use a lot of improvement in this area after listening to this presentation. This issue is likely of even greater importance in those with a high endoscopy case load.

  • A high percentage of gastroenterologists/pediatric gastroenterologists develop injuries related to repetitive endoscopy procedures.  These can be mitigated using proper ergonomics.  Although this advice is pretty straight forward, a lot of endoscopists could benefit from careful attention to this.
Areas included neck/upper back (44.0%), thumb (42.0%), hand/finger (38.0%), lower back (36.0%).
  • Keep Monitor near eye level and in front of you (don’t torque your neck)
  • Maintain good posture. Can start by standing upright against a wall
  • Position bed so elbows can be in a fairly neutral position with bed not more than 10 cm below elbows
  • Two-piece lead aprons helpful to distribute weight better
  • Handle endoscope more like holding a pencil than using a firm grip
  • Cushioned mat and cushioned soles can help with standing posture/fatigue

Dr. Michael Wilsey: Endoscopy Pearls and Ergonomics (Part 1)

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Dr. Michael Wilsey gave our group an excellent update on Endoscopy Pearls and Ergonomics. My notes below may contain errors in transcription and in omission. Along with my notes, I have included many of his slides.

Endoscopy Pearls:

  • Video Link to show techniques:
    • YouTube (~6 minute): How to Perform a Water-aided colonoscopy. Sergio Cadoni, Sauid Ishaq, VideoGIE, Volume 3, Issue 5, 2018; Pages 169-170.
    • Residue can be suctioned while infusing more water, which helps to clean the colon, but if there is too much residue, it is very difficult to see clearly enough to insert the colonoscope properly.
    • The water immersion technique starts with the patient in the left lateral position so that the progressive irrigation of water eases down the sigmoid by gravity on the left abdominal quadrant. Instead of syringes, the use of water flushing pumps allows one to better adjust the quantity of water needed according to the morphology of the sigmoid and does not delay the maneuvers of scope progression.
  • Anatomy: sigmoid and transverse colon are more mobile. They are suspended by mesenteries (the transverse mesocolon and sigmoid mesocolon), which allow them to swing or shift freely in the abdomen, unlike the other fixed parts of the colon.

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Optimizing PPI Therapy for Eosinophilic Esophagitis with CYP2C19 Genotyping

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P Bose et al. American Journal of Gastroenterology. DOI: 10.14309/ajg.0000000000004117 Dose May Matter: CYP2C19 Genotype and Proton-Pump Inhibitor Response in Pediatric Eosinophilic Esophagitis

Methods: A cohort study of pooled data from 2 tertiary-care pediatric centers (Riley Children’s Health,Indianapolis, IN, and Children’s Hospital of Philadelphia, Philadelphia, PA) was conducted. N=131, mean age 8.5 yrs. Individuals with certain CYP2C19 polymorphisms were classified as normal (NMs), intermediate/slow(IMs), and rapid metabolizers (RMs) of PPIs based on the presence of normal function (*1), loss-of-function (*2), or gain-of-function (*17) alleles. PPI choice and dosing:

Key findings:

  • PPI response occurred in 22.1% of subjects (29/131)
  • Overall, IMs had the highest proportion of PPI response at 33.3% (10/30), followed by NM of 21.7% (13/60) and RM of 14.6% (6/41) (P 5 0.205).
  • No ultra-rapid metabolizers had a response.

Discussion: “Atypical dosing for PPI use in EoE may be related to mechanisms of action apart from gastric acid suppression, such as inhibiting eosinophil migration or restoring esophageal mucosal barrier integrity, which have been previously proposed.”

There may have been a selection bias in this population. The methods section does not detail these cohorts precisely. It is unclear if all patients in these centers undergo CYP2C19 genotype testing. In most centers, CYP2C19 genotype testing is uncommon and may be more likely in those who have not responded to therapy.

My take:

  1. CYP2C19 genotype testing may help determine whether PPI therapy is likely to work for a patient with EoE and influence the dosage selected. This is not a new concept. It was noted at a NASPGHAN meeting in 2017.
  2. In those with unfavorable CYP2C19 genotype, either an alternative therapy or a PPI that is not metabolized with CYP2C19 (eg. rabeprazole) should be considered.

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AI Diagnosis of Achalasia on Plain Chest X-ray

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T Ochaiai et al. Clin Gastroenterol Hepatol 2026; 24: 2308-2310. Open Access! Artificial Intelligence-Based Detection of Achalasia on Plain Chest Radiography

Methods: This retrospective study collected posteroanterior plain chest radiographs of
patients with and without achalasia. The training and validation datasets comprised 447
chest radiographs taken between January 2017 and March 2023.

Key findings:

  • In the validation dataset, the area under the curve for identifying achalasia was 0.971, and using Youden’s index, the sensitivity, specificity, accuracy, and positive and negative predictive values were 0.950, 0.917, 0.932, 0.905, and 0.957, respectively
  • In the temporal test dataset, the area under the curve for detecting achalasia was 0.964, and using Youden’s index, the sensitivity, specificity, accuracy, and positive and negative predictive values were 0.941, 0.891 , 0.901, 0.696 , and 0.983, respectively.
In Figure F, the CXR corresponds to the findings in the barium esophagogram in G

Discussion:

  • It may help detect patients with early achalasia with mild symptoms who are unlikely to undergo EGD. However, the rarity of the condition may result in many false positives.

My take: In this cohort, AI was developed and validated to detect achalasia on chest radiographs. This is yet another example of how AI can yield additional information from routine testing. Previously, AI has been shown to potentially identify diabetes from routine CXR (Emory News 2023: AI model enables earlier detection of diabetes through chest x-rays).

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Complimentary, Alternative, and Integrative Medical Therapie Use in a Pediatric DGBI Cohort

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A VonAxelson et al. J Pediatr Gastroenterol Nutr. 2026;83:282–284. Patterns in integrative medicine usage among pediatric patients in a disorders of gut–brain interaction clinic

In a retrospective cohort (n=331, mean age 15 years) from a DGBI clinic, the patterns of integrative medicine usage were evaluated. The most common comorbidities in the sample were anxiety (61%), sleep disturbance (36%), and depression (32%). The most common DGBI diagnoses in the study were FD (58%) and IBS (57.4%), with FAP-NOS being third most frequent 10.6%).

Key findings:

  • In total, 59% of patients were receiving some form of integrative treatment
  • Peppermint oil, caraway oil, and acupuncture were the most used in this practice. 

Limitations: “While this study does identify trends in IM strategies for management of DGBI, it is limited by retrospective design, so identifying use of many IM techniques may be underrepresented (ginger, L-glutamine, aloe vera, etc). These might have been used but were not reported or recorded in charts.”

My take: Whatever you want to call it, complementary, alternative or integrative, it is clear that many patients are using non-traditional therapies trying to improve their symptoms. This cohort may have higher use as they are from a specialty multidisciplinary DGBI clinic rather than a general pediatric gastroenterology or general pediatric cohort.

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