Pre-Crohn’s Disease Stool Promotes Colitis in Germ-Free Mice Puls One

Posted on October 27, 2026 by gutsandgrowth

C Dang et al. Gastroenterology, 2026; 171, 489-503. Pre-Crohn’s Disease Stool From Discordant Siblings Promotes the Development of Colitis in Germ-Free Mice

Methods: This study was conducted as part of The GEM Project, a prospective cohort study of healthy first-degree relatives of CD patients. Germ-free mice were colonized with fecal samples from 12 pairs of discordant siblings, where one sibling later developed CD (pre-CD), and the other remained a healthy matched control (HMC). The microbiome collected wa ~2.6 years before CD diagnosis.

Key findings:

Mice receiving pre-CD stool exhibited increased weight loss, fecal lipocalin-2, and intestinal histologic damage compared with mice receiving HMC stool. Thus, mice colonized with stool from individuals who later developed Crohn’s disease showed significantly faster and more severe intestinal inflammation compared with mice colonized with stool from the siblings who remained healthy.
Fecal metabolomic analysis revealed differences in 40 metabolites between pre-CD and HMC colonized mice.

My take:

Silly take: It’s a good idea not to eat someone else poop — it might make you sick!
Serious take (borrowed in part from the authors): “The stool microbiome of individuals susceptible to CD is altered years before diagnosis, exhibiting greater inflammatory potential when transferred to susceptible mice.” These studies about the microbiome are remniscent of studies 15-20 years ago indicating that manipulation of the microbiome may play a role in the developement of obesity and Kwashiokor. (Related posts: Could antibiotics make you fat? gutsandgrowth, Microbiome and the risk of Kwashiokor | gutsandgrowth, Microbial transfer for metabolic syndrome? | gutsandgrowth)

Related article: M Xue, C McShane, J Kim et al. Gastroenterol 2026; 171: 641-655. Open access! β-Glucan and Inulin Estimated Intake Are Associated With Reduced Risk of Crohn’s Disease, Improved Gut Barrier and Systemic Inflammation Markers, and Multi-Omic Signatures in a High-Risk Cohort

Methods: The Genetic, Environmental, Microbial (GEM) Project prospectively followed asymptomatic first-degree relatives of individuals with CD. Habitual intake of total fiber and select fiber subtypes was estimated from baseline food frequency questionnaires and biologic samples were collected.

Key findings:

During a median follow-up of 8.5 years of 3314 first-degree relatives, 94 developed CD. Higher β-glucan (HR, 0.70) and inulin (HR, 0.68 intake were associated with lower CD risk.
Higher β-glucan and inulin intake were associated with lower lactulose–mannitol ratio, lower abundance of pathobionts (Ruminococcus torques and Lachnoclostridium), and lower concentrations of inflammation- and barrier-related proteins.
Increased β-glucan found in oats, barley and grains. Increased inulin found in garlic, onions, leeks and asparagus

Related blog posts:

NASPGHAN Paper: Dietary Management in Pediatric Aerodigestive and GI Dysmotility

Posted on October 26, 2026 by gutsandgrowth

K El-Chammas et al. J Pediatr Gastroenterol Nutr. 2026; 83: 748-760. Dietary management and feeding considerations of pediatric aerodigestive and upper gastrointestinal motility disorders.

Oropharyngeal dysphagia (OPD):

“Untreated OPD (either penetration and/or aspiration) is associated with persistent symptoms, recurrent respiratory infections, elevations in pulmonary inﬂammatory markers, and even bronchiectasis”
“Because >80% of pediatric aspiration is silent, the presence of symptoms at the time of an aspiration event should not be the determining factor when considering thickening”
“Most infants with OPD and aspiration experience improvements in swallow function over time, and thickeners/delivery vehicles can be weaned or changed as swallow function, palate, and caloric needs change. Antegrade aspiration is unlikely to be seen in neurodevelopmentally normal children older than 2 years of age exhibiting persistent lower respiratory tract infections”
Table 2 lists common thickeners and key differences. In infants, cereals and gelmix (if >37 weeks gestational age) are recommended. In older age groups, xanthan gum (SimplyThick®), Corn starch (Thick-It®), Tapioca starch, and Tara gum (PuraThick®) are options.
“Thickening gastrostomy tube feeds either with commercial thickeners or food improves GI and pulmonary outcomes and reduces the number of gastroesophageal reflux events without prolonging gastric emptying”
Table 3 provides specific recommendations including the following: ‘The recommended thickener for formula-fed infants younger than 1 year of age is cereal or purées. Commercial thickeners may be an option for some expressed breast milk- or formula-fed infants under the age of 1 year without comorbidities, depending on institutional practices.”

Esophageal Dysmotility

This section reviews several disorders including achalasia, gastroesophageal reflux, and esophageal atresia.

Reflux: In infants with reflux, “thickening of feeds can reduce overt symptoms such as vomiting but does not decrease reflux events.” Also, in this population, “a trial of maternal cows’ milk elimination, extensively hydrolyzed or amino-acid based formulas (in more severe cases with intractable symptoms) may be appropriate”
Achalasia: “There are no clear guidelines on the management of feedings in pediatric or adult patients with achalasia…Patients should be encouraged to eat in an upright position and to minimize eating for several hours before bedtime. A liquid or purée may be required with the guidance of a dietitian to ensure adequate nutritional intake while waiting for the diagnosis and definitive management of achalasia”
Esophageal atresia: “Only 28% of children with EA are consuming age‐appropriate food textures within the ﬁrst 2 years of life, with that improving to 70% of children over 5 years of age…Many infants with EA require gastrostomy tube placement because they cannot safely tolerate oral feeding or meet caloric requirements”
Table 4 summarizes recommendations for esophageal dysmotility, including “children with esophageal dysmotility should avoid foods with a high risk for esophageal obstruction/irritation, eat in an upright position, and avoid eating several hours before bedtime”

Gastric Dysmotility

“Most pediatric cases are idiopathic or post-viral, with less common causes being drug-induced or post-surgical”
“While dietary modification is often considered first-line therapy in patients with mild gastroparesis, it often results in suboptimal improvement in symptoms in clinical practice. Small, frequent meals and maintaining a post-prandial upright position may be better tolerated.^{74, 75} Liquids typically empty from the stomach faster than solids⁷⁶; therefore, increasing liquid calories and switching from solid to liquid calories later in the day may help patients with their symptoms.”
“Fatty, acidic, spicy, and high-fiber foods can exacerbate symptoms in patients with gastroparesis as they delay gastric emptying, exacerbate pain, and promote release of cholecystokinin”
“Small-particle diets, consisting of puréed, blended, or finely ground foods, facilitate gastric emptying by reducing mechanical workload on the stomach”
“Caution is advised when initiating enteral or parenteral nutrition in patients with gastroparesis given the significant overlap with functional dyspepsia and increased prevalence of feeding intolerance in adolescents with disorders of gut–brain interaction”
“In aerodigestive patients with upper gut dysmotility and feeding intolerance, gastrostomy and/or post-pyloric tube placement may provide access to decompress as well as provide nutrition when oral feeding is inadequate to sustain appropriate growth and symptom control”
“Blenderized tube feeds may be considered over commercial formulas to help with symptoms, decrease healthcare utilization, and improve quality of life…The American Society for Parenteral and Enteral Nutrition recently published detailed practice recommendations (L Epp et al. Nutr Clin Pract. 2023; 38(6): 1190-1219) providing guidance to medical providers and family pertaining to the use of BTFs regardless of their indication”

My take: This is a useful article regarding potential dietary interventions across a wide range of pediatric GI disorders. Just like medications, dietary interventions can result in complications. As such, the involvement of experienced dietitians and careful follow-up are needed.

Related blog posts:

Dysphagia:

Esophageal dysmotility:

Blenderized Diets:

Gastroparesis:

Ethan Mollick on AI’s Exponential Rise and an Otter on a Plane

Posted on October 25, 2026 by gutsandgrowth

One of the substack authors that I follow is Ethan Mollick. He is a professor at the Wharton School of Business (University of Pennsylvania) and a leading researcher on the practical impacts of artificial intelligence. Link to substack: One Useful Thing

A recent newsletter, 30 Months on the Exponential (in Charts) on 10/20/26, summarized the exponential progress of AI over the last three years, though noting the progress is uneven across many fields. In addition, the newsletter promotes his new book, Co-Existence.

One particularly fascinating tool for the past few years is an AI prompt to create an image of an ‘otter on a plane using wifi.’ It is worth reading this recent newsletter and if you are in a hurry scroll down to the ~2 minute video which is the latest iteration of an otter on a plane.

Congratulations!

Posted on October 23, 2026 by gutsandgrowth

Outcomes in Pediatric “Potential” Celiac Disease Plus One

Posted on October 23, 2026 by gutsandgrowth

B Laxer et al. J Pediatr Gastroenterol Nutr. 2026; 83: 717-722. Open Access! Heterogeneous outcomes in pediatric potential celiac disease: a multicenter longitudinal study.

Background: Potential celiac disease (PCD) is defined by positive celiac serology without villous atrophy.

Methods: This was a multicenter retrospective study with 88 children with mean follow-up of 3.3 years (with a range up to 6 years). Indications for repeat endoscopic evaluation while on a GCD included—a rise in tTG titers to >10× ULN, persistent tTG elevation >10× ULN for over 24 months and the emergence of clinical symptoms necessitating reassessment. During follow-up, only 23 patients (26.1%) underwent a repeat upper endoscopy, as per the clinician’s decision, after a median period of 29 (IQR 11.5–36.5) months from the initial PCD diagnosis.

Key findings:

17/88 (19.3%) patients progressed to Celiac Disease (CeD).
33/88 (37.5%) had normalization of anti-tissue transglutaminase antibodies (tTG), while continuing a diet containing gluten
38/88 (43.2%) continue to have PCD
Among 16 patients with high tTG levels (>×10 upper limit of normal) at PCD diagnosis, the results were similar: three (18.8%) progressed to CeD and six (37.5%) normalized tTG
Asymptomatic patients were significantly more likely to achieve serological normalization compared to their symptomatic counterparts (61.9% vs. 35.8%, p = 0.011)

Discussion Points:

“A recent meta-analysis⁹ of 1010 patients reported a progression rate of approximately 33% to CeD, while another third achieved serological normalization.”

Limitations:

Follow-up period of up to 6 years may not capture late-onset progression.
Only a small subset had a follow-up endoscopy; if all patients had had a repeat endoscopy, there would have been a higher rate of CeD diagnosis

My take: This study found about one-fifth of patients progressed from potential celiac disease to celiac disease during a mean follow-up of 3.3 years. However, 70% of patients did not undergo repeat endoscopy.

Related blog posts:

Also, in same issue:

MC Pacheco et al. J Pediatr Gastroenterol Nutr. 2026; 83: 723-727. Does diagnosis by biopsy versus serology-only affect follow-up in celiac disease? In this retrospective study wiht 54 children, there was no significant difference in frequency of clinical follow-up or decrease in TTG IgA levels between patients who were diagnosed with biopsy versus serology alone.

Bruarfoss (Iceland) is often called “Iceland’s Bluest Waterfall”

Micro-Computed Tomographic Imaging Shows the Blurry Line Between Potential Celiac Disease and Celiac Disease

Posted on October 22, 2026 by gutsandgrowth

A Reunamo et al. Gastroenterology, 2026; 171, 553-555. Open Access! Three-Dimensional Micro-Computed Tomographic Imaging Reveals Early Mucosal Remodeling in Individuals With Potential Celiac Disease

Background: “A subset of individuals, characterized as having potential CeD (PCeD), present with positive transglutaminase 2 or endomysial antibodies, or both, but lack histologic findings that meet the diagnostic criteria.¹ Importantly, only a subgroup of individuals with PCeD progress to CeD during follow-up.¹“

Methods: The authors “recently developed a 3-dimensional (3D) x-ray micro-computed tomographic (micro-CT) imaging and analysis procedure for duodenal biopsy specimens.⁶^,⁷ The method enables the precise histomorphometric quantification, including measurements of villus height–to–crypt depth ratio (VH:CrD) and mucosal surface area, with excellent reproducibility.⁷” This study used micro-CT imaging to investigate the early-stage mucosal changes in individuals initially diagnosed with PCeD. This study enrolled 20 patients with PCeD who progressed to CeD, 5 patients who continued with PCeD, and 16 control individuals.

Key findings:

Micro-CT imaging revealed a significantly reduced VH:CrD at both the PCeD and CeD stages compared with the controls, but the difference between PCeD and CeD did not reach significance
Only 7/20 with PCeD had normal biopsy VH:CrD values >2.0 across all sites

A) VH:CrD (left) and relative mucosal surface area (right) across PCeD (orange), CeD (blue), and nonCeD control (non-CeD) groups. Box and whisker plot: The boxes indicate the 25th percentile (bottom border), median (center line), and 75th percentile (top border), the whiskers show the maximum and minimum ranges, and the circles indicate outliers

Discussion:

“Most of the PCeD cases were already below the commonly used VH:CrD cutoff when assessed using micro-CT cross-sections, implying that histologic thresholds may lack sufficient sensitivity to capture signs of early CeD.”

My take (borrowed in part from the authors): This study strengthens the “concept that enteropathy in CeD represents a progressive continuum.⁵ In fact, pinpointing the exact moment when the condition becomes “CeD” is difficult, especially because what is considered normal can vary individually and depending on the biopsy site.” This study may help explain why many symptomatic patients with PCeD respond to a gluten-free diet.

Related blog posts:

Icotrokinra for Patients with Ulcerative Colitis (ANTHEM-UC Phase 2 Trial)

Posted on October 21, 2026 by gutsandgrowth

MT Abreu et al. N Engl J Med 2026;395:1495-1504. Phase 2 Trial of Icotrokinra for Patients with Ulcerative Colitis

Background: “Icotrokinra (JNJ-77242113) is a first-in-class targeted oral peptide that precisely blocks the interleukin-23 receptor. The development of oral peptide therapeutics has historically been limited by poor epithelial membrane permeability, susceptibility to enzymatic degradation in the gastrointestinal tract, and low intestinal absorption.⁷ The cyclic peptide technology used in icotrokinra enables high stability and epithelial permeability.⁷ These features, in combination with high selectivity and potent binding of the interleukin-23 receptor, result in an orally administered peptide that effectively inhibits the interleukin-23 pathway.^8,9“

Methods: This was a “phase 2b, double-blind, randomized trial of oral icotrokinra, a peptide that blocks the interleukin-23 receptor, in adults with moderately to severely active ulcerative colitis. Participants were assigned to receive icotrokinra at a once-daily dose of 400 mg, 200 mg, or 100 mg or placebo. The primary end point was clinical response at week 12.” A total of 252 participants underwent randomization.

Key findings:

All the doses of icotrokinra were superior to placebo with respect to a clinical response at week 12, which occurred in 63% of the participants in the 400-mg group, 58% in the 200-mg group, and 55% in the 100-mg group, as compared with 27% in the placebo group (P<0.001)
The percentage of participants with clinical remission at week 12 was also significantly higher in the 400-mg group than in the placebo group (30% vs. 11%, P=0.006), as were…the percentage of participants with endoscopic improvement (37% vs. 14%, P=0.002)

Clinical response was defined as a decrease from baseline in the modified Mayo score by at least 30% and at least 2 points, with either a decrease of at least 1 point from baseline in the rectal bleeding
subscore or a rectal bleeding subscore of 0 or 1

Clinical remission was defined by a stool frequency subscore of 0 or 1,
a rectal bleeding subscore of 0, and an endoscopic subscore of 0 or 1.

Symptomatic remission was defined by a stool frequency subscore of 0 or 1
and a rectal bleeding subscore of 0

Endoscopic improvement was defined by an endoscopic subscore of 0 or 1.

Discussion:

“The benefits of treatment with once-daily icotrokinra appeared to be generally sustained or improved through week 28 for all outcomes and doses tested.”
“Although all the tested doses of icotrokinra appeared to attenuate systemic inflammation, the 400-mg and 200-mg doses appeared to result in greater reduction of the inflammatory burden than the 100-mg dose.”
“The incidence of adverse events with icotrokinra was similar to that with placebo, and no dose–response relationship for adverse events was observed. Among the 212 participants treated with icotrokinra in this trial, no deaths, serious infections, or adverse events of special interest were reported through 28 weeks of treatment.”

My take: This is an important study indicating that an oral IL-23 can be effective for ulcerative colitis which is not surprising based on its previous effectiveness with plaque psoriasis, another immune-mediated disease. It would be helpful to determine the efficacy of this oral agent compared to the IV/SC IL-23 biologic medications (eg. risankizumab, guselkumab, and mirikizumab).

Related blog posts:

Enteral Rifaximin May Reduce Central Line Infections in Children with Short Bowel Syndrome

Posted on October 20, 2026 by gutsandgrowth

Johnson E, Konicek C, Lamb N, Fishbein J, Jhaveri R, Cohran V. J Pediatr Gastroenterol Nutr. 2026; 83: 675-680. Effectiveness of rifaximin in reducing central line-associated bloodstream infections in pediatric intestinal failure

Methods: This was a retrospective cohort study of patients (n=33) with IF managed at a single pediatric center between January 2010 and December 2022. Patients in the cohort had at least 1 CLABSI prior to initiation of rifaximin. Rifaximin was prescribed one to two times a day for 2 weeks a month, every month; median dose was 22 mg/kg/day. Rifaximin was not administered concurrently with other antimicrobials.

Key findings:

The observed incidence of CLABSI for all patient, before and after rifaximin initiation, was 10.2 (8.2, 12.7) and 7.3 (5.8, 9.2) per 1000 central line days, respectively, p = 0.03.
Subgroup analysis showed patients who received rifaximin without ethanol lock therapy had significant reduction in CLABSIs, 8.3 versus 3.0 (p < 0.001).
There were no statistically significant differences in the proportion of gram-positive or gram-negative bacteria or yeast isolated before and after rifaximin.

Discussion:

“Cole et al. showed a correlation between SIBO, intestinal permeability, bacterial translocation,and an increase in bloodstream infections. Patients with IF and SIBO had seven-fold higher odds of having a bloodstream infection than those with IF without SIBO.” However, this was a very small study with only 10 patients with SBS; 5 of the 10 were determined to have SIBO. In addition, there may have been a selection bias as there was a high rate of CLABSI in this study (80%). Ref: Cole CR, et al. The rate of bloodstream infection is high in infants with short bowel syndrome: relationship with small bowel bacterial overgrowth, enteral feeding, and inﬂammatory and immune responses. J Pediatr. 2010;156(6):941‐947.e1.
An important limitation of this retrospective study was the lack of correlation with the presence of SIBO. While studies have shown correlation of CLABSI with SIBO, presumably related to intestinal translocation, the exact mechanisms for how CLABSI occur in children with intestinal failure remain speculative. Intestinal translocation has been shown in animals but not proven to cause CLABSI in humans.

My take: The degree of CLABSI reduction seen in this rifaximin study indicates it is a reasonable option when central locks are unavailable. However, it may be difficult to get covered. In addition, a liquid preparation requires compounding of crushed pills. For most patients, meticulous line care is likely more important than SIBO treatment in preventing CLABSI.

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.

Real-World Outcomes of Risankizumab in Children With Crohn’s Disease

Posted on October 19, 2026 by gutsandgrowth

Briefly noted:

EA Spencer et al. Journal of Crohn’s and Colitis. 2026; 20: jjag134. https://doi.org/10.1093/ecco-jcc/jjag134 Real-world effectiveness and safety of risankizumab induction and maintenance therapy in pediatric patients with Crohn’s disease: a multicenter retrospective analysis.

Methods: This was a retrospective, global multicenter cohort of patients <18 years initiating risankizumab monotherapy (2022-2025). Among the 96 study participants, 38% had prior ustekinumab exposure.

Key findings:

Post-induction corticosteroid-free clinical remission (CFR) was achieved in 28/68 (41%), clinical response in 37/68 (54%), and combined CFR + CRP remission in 22/68 (32%).
Week 30 and 54 CFR were attained in 34/68 (50%) and 34/68 (50%), respectively.
No serious safety events occurred.