Category Archives: Gastroenterology

Helicobacter pylori Treatment 2026

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T Rokkas, DY Graham. Gastroenterol 2026; 171: 271-284. The Unfinished Agenda in Helicobacter pylori Treatment: Resistance, Microbiome Effects, and Future Directions

This was a narrative review aimed at synthesizing contemporary evidence.

Background: Globally, approximately half of the population is infected. Prevalence surpasses 70% in many low- and middle-income countries (LMICs) where crowded living conditions, poor sanitation, and limited access to clean water enhance transmission. 

Key points:

  • Global resistance to clarithromycin, metronidazole, and fluoroquinolones significantly undermines the performance of traditionally effective antimicrobial therapies. The corner stone of successful antimicrobial therapy is susceptibility-guided therapy but remains of limited use with H pylori because of lack of infrastructure.
  • Clarithromycin should no longer be prescribed as an empiric therapy (ie, it should be restricted to susceptibly based therapy)…Despite the poor cure rates with clarithromycin achieved with vonoprazan in the United States, the American College of Gastroenterology H pylori guideline still recommended vonoprazan triple therapy.17 (With clarithromycin-susceptible infections, vonoprazan is not more effective than PPIs.) The discordance between guideline recommendations and clinical effectiveness contributes to treatment failures.
  • Bismuth quadruple therapy (BQT), which combines metronidazole with tetracycline and bismuth, can partially overcome moderate metronidazole resistance through antimicrobial synergy and higher effective dosing.
  • Next-generation sequencing (NGS) is now available at a fraction of the cost of an endoscopy in the United States using stools, fresh, frozen, or paraffin-embedded gastric biopsies37 (American Molecular). Economic analyses indicate that susceptibility-guided therapy is cost-effective.
  • When BQT fails or is unavailable, several alternative regimens can be considered.4–6 Rifabutin-based triple therapy can achieve eradication rates of 70% to 90% even in heavily pretreated patients.40
  • When designing rescue therapy, antibiotics previously associated with failure should not be reused unless susceptibility has been clearly established.
  • Optimizing H pylori treatment requires evidence-based regimen selection, precision-guided strategies, antimicrobial stewardship, and equitable access to essential medications

My take: This is a helpful review of H pylori issues and management.

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Should the Gluten Threshold Dose in Celiac Disease Change Based on Immune Activation?

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Background: Interleukin 2 (IL2) rises acutely after gluten ingestion, allowing the definition of threshold doses that trigger immune activation.

Methods: This was a randomized double-blind, placebo-controlled adaptive dose–response trial in adults with biopsy-proven celiac disease on a gluten-free diet for >2 years. Participants (n = 51; median age, 52 years; 69% were female) underwent 3 oral gluten (1–1000 mg) or placebo challenges at 4-week intervals. Eliciting dose (EDp, ie, the dose at which p% of people respond) was estimated by interval-censored survival analysis.

Key findings:

  • Gluten induced dose-dependent IL2 elevations, with ≥2-fold increases in 83% at 1000 mg, 83% at 610 mg, 36% at 90 mg, 17% at 13 mg, 27% at 8 mg, and 17% at 3 mg; none responded to 5 mg, 2 mg, 1 mg, or placebo.  
  • Estimated ED50 was 111 mg, ED10 was 2.4 mg, ED05 was 0.8 mg, and ED01 was 0.1 mg

From the editorial:

“To date, the few investigators who addressed this question defined tolerance in relation to quantifiable histologic damage (intestinal morphometry)…Bearing in mind that the typical Western diet contains 10–15 g of gluten per day, these studies found that the protracted, daily ingestion of 1000, 200, or 50 mg of gluten elicits significant damage at the mucosal level.2,3 A daily dose of 10 mg was also associated with minimal architectural changes in some patients…

In 2007, the Food and Agricultural Organization/World Health Organization Codex Alimentarius Commission4 applied these findings to establish that commercially available gluten-free food must not contain more than 20 mg/kg gluten (20 part per million [ppm]), as this would ensure that daily gluten intake does not exceed 10 mg…Not a single case of proven intolerance to 20 ppm gluten-free food has been described…in some 20-ppm countries, most labeled gluten-free products already contain much less than 20 ppm of gluten, usually <10 ppm5…

The authors concluded that the daily gluten threshold should be decreased because acute IL2 release occurred at 3 mg, which is less than is allowed by current food-labeling rules for gluten-free products…

Because symptoms did not correlate with the result of the IL2 test for gluten doses <1 g, further prolonged microchallenge studies remain the only reliable strategy to investigate the correlation between the IL2 test and the gold standard of CeD activity—histologic damage of the small intestinal mucosa.10,11“

My take: This study is intriguing that there is evidence of immune activation at lower gluten exposures; however, it does not prove that changing the gluten threshold is beneficial.

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Singing Therapy for Supragastric Belching

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H Shang H et al. Clinical Gastroenterology and Hepatology, 2026; Singing Therapy versus Diaphragmatic Breathing for Supragastric Belching: A Multicenter Randomized Controlled Trial

Background: “Supragastric belching (SGB) significantly impairs quality of life. Although diaphragmatic breathing is recommended as a first-line intervention in clinical guidelines, some patients perceive it as monotonous.”

Methods: “This randomized controlled trial, 72 adult patients with supragastric belching diagnosed according to Rome IV criteria were randomly assigned (1:1) to structured singing therapy (ST) or diaphragmatic breathing at 2 tertiary gastroenterology centers in China.  The primary outcome was the treatment response, defined as ≥50% reduction in belching visual analog scale scores.”

Singing Therapy:

“Patients with excessive belching episodes underwent structured ST sessions administered by gastroenterologists using 1 of 4 standardized Chinese folk songs (“The Sea,” “For Whom,” “Story of Spring,” or “The Most Dazzling National Style”), with each session lasting approximately 5 minutes.

Participants were required to:

  1. Perform vocalization with musical accompaniment.
  2. Sustain open-mouth phonation to promote diaphragmatic activation, with real-time feedback provided via ‌visual cues‌ (observation of abdominal expansion in a mirror during inhalation) and tactile cues (light hand placement on the abdomen to monitor respiratory motion and suppress thoracic dominance).
  3. Achieve a target vocal intensity of 80 dB, verified using calibrated smartphone decibel meter applications (Decibel Meter App).
  4. Patients were instructed to perform 5-minute vocal therapy sessions 3 times daily, with additional 5-minute sessions when symptomatic. This regimen was maintained continuously for 7 days.”

Key Findings:

  • “After 1 week, ST demonstrated a significantly higher response rate than diaphragmatic breathing both immediately postintervention (72.2% vs 38.9%; P = .004) and at 1-month follow-up (50.0% vs 30.6%; P = .032). “
  • “ST demonstrated greater and more sustained benefits in quality-of-life measures.”

Discussion:

  • “ST may ameliorate belching through mechanisms potentially shared with DB. First, both interventions likely reduce belching by attentional diversion, as distraction-based attentional modulation has been shown to alleviate belching.21“
  • “Existing literature indicates that both ST16,28 and DB29 possess anxiolytic effects.”

My take: It will be interesting to see if this therapy will be effective in different populations and in pediatric cohorts. Also, could this treatment lead to more American Idol auditions?

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Two pictures of the exterior and interior of the Harpa Opera house in Reykjavkik. The irregular, crystalline shapes mimic the geometric basalt columns found in volcanic rock across Iceland.

Discordant Clostridiodes difficile Testing In Patients with Inflammatory Bowel Disease

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P Ramakrishan et al. Inflamm Bowel Dis 2026; 32: 1313–1320. Discordant Clostridioides difficile testing as a predictor of inflammatory bowel disease therapy escalation

Background: “In the general population, individuals with discordant tests (PCR+/TOX−) have similar outcomes to PCR− individuals, suggesting that this group represents individuals colonized with C. difficile.[14]”

Methods: In this retrospective study (n=117), outcomes assessed included CDI-directed therapy or escalation of IBD treatment.

Key findings:

  • 79% (93/117) were PCR+/TOX− and 21% (24/117) were PCR+/TOX+
  • PCR+/TOX+ patients had significantly higher CRP (98 vs 6 mg/L, P = .005)
  • PCR+/TOX− patients had more severe underlying IBD and higher rates of steroid use (48% vs 21%, P = .02) and were significantly more likely to require IBD therapy escalation (54% vs 25%, P = .004). Multivariable analysis showed PCR+/TOX− status (odds ratio [OR], 3.2) was a significant predictor of IBD treatment escalation. Antibiotic use did not significantly alter the need for escalation among PCR+/TOX−  patients.

Discussion:

  • “Most IBD patients who are PCR+/TOX−  are colonized with C. difficile, and IBD treatment could be considered rather than delaying for CDI therapy.”

My take: In patients with IBD, PCR-positivity for C diff is frequently a false positive due to high rates of colonization in this population. Patients who have their infection confirmed with an immunoassay are much more likely to respond to C diff therapy.

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Resources:

National Civil Rights Museum in Atlanta, GA. One of the powerful exhibits is a Woolworth lunch counter replica with headphones.  With your eyes closed, the exhibit challenges you to keep your hands on the counter as one receives menacing threats like ‘Boy, I’m going to kill you.’ 

Dupilumab for Eosinophilic Gastritis: DEGAS study

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N Gonsalves, E Dellon E, K Kliewer K et al. The Lancet Gastroenterology & Hepatology, 2026; DOI: 10.1016/S2468-1253(26)00116-0. Open Access! Dupilumab versus placebo in adults and adolescents with eosinophilic gastritis (DEGAS): a double-blind, placebo-controlled, phase 2, multicentre, randomised controlled trial

Methods: This was a phase 2b trial with a 12-week, double-blind, placebo-controlled period, followed by a 24-week open-label extension period. Patients aged 12–70 years from 11 hospitals in the USA with histologically active eosinophilic gastritis (≥30 eosinophils per high-power field [HPF] in at least five HPFs in the gastric antrum and/or body) and moderate-to-severe symptoms. Eligible patients were individually randomised (1:1) to parallel groups and received six injections over 12 weeks: subcutaneous dupilumab (n=21) (600 mg once followed by 300 mg every 2 weeks) or subcutaneous placebo (n=20).  The primary endpoint of relative change from baseline in mean gastric eosinophil count.

Key findings:

  • At week 12, the relative reduction in the primary endpoint was greater with dupilumab (estimated mean change –50%) than with placebo (–4%)
  • Reduction from baseline in EoG-REFS (Eosinophilic Gastritis Endoscopic Reference Score) at week 12 was greater with dupilumab (estimated mean change –3·47 points than with placebo (–0·06 points)

 

 

Discussion Points:

“Currently, there are no FDA-approved therapies for patients with eosinophilic gastritis…this first prospective trial of dupilumab for eosinophilic gastritis show a greater reduction in mean gastric eosinophil count from the five most eosinophil-dense HPFs (the primary endpoint) with dupilumab compared with placebo.”

My take: Dupilumab improved eosinophilic gastritis histology and endoscopic appearance. This study suggests that there may be overlapping pathophysiology between eosinophilic gastritis and eosinophilic esophagits as dupilumab appers to be effective in both disorders.

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How Effective is Ustekinumab Dose Intensification in Crohn’s Disease: REScUE Trial

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Methods: This was an investigator-initiated, multicenter, randomized, placebo-controlled trial conducted at 15 hospitals in Belgium. Eligible patients were adults (n=108) with CD treated with ustekinumab on maintenance dosing of 90 mg subcutaneous every 8 weeks and experiencing a secondary loss of response. Patients were randomized 1:1 to receiving a single intravenous reinduction with ustekinumab ≈6 mg/kg followed by either subcutaneous ustekinumab 90 mg every 4 weeks or every 8 weeks until week 48. 

Key findings:

  • Steroid-free clinical remission at week 48 was reached in 15% vs 19% of patients in the every 4 weeks vs the every 8 weeks group 

Discussion Points:

  • “Remarkably, the overall steroid-free clinical remission rates at week 48 were low in both arms: 15% and 19% for ustekinumab Q4W and Q8W, respectively. Most of the patients achieved clinical remission in the first 24 weeks after IV reinduction though, suggesting that the IV reinduction is the main driver of the effectiveness, rather than the subsequent SC dose intensification.”
  • “Our results are in contrast with several retrospective and observational nonrandomized and open-label cohort studies suggesting a clinical response rate after dose intensification up to 60% and clinical remission rates up to 50% after 1 year of treatment.4,13–17“

The associated editorial notes that the modest remission rate could be partly due to a more refractory patient poulation. “The cohort was indeed difficult to treat: median disease duration exceeded a decade, and more than 90% of patients had prior anti–tumor necrosis factor exposure.” Despite this caveat, “the trial avoids overestimating therapeutic success and aligns outcomes with contemporary treat-to-target principles.4 From this perspective, REScUE provides a realistic benchmark for what ustekinumab intensification can and cannot achieve in routine clinical practice.”

The editorial also notes that the “STARDUST trial [which] evaluated a treat-to-target, endoscopy-guided escalation algorithm vs standard of care in ustekinumab-treated CD and did not demonstrate a clear advantage for the intensive, endoscopy-driven strategy at 1 year.7“

My take (borrowed from editorial): “In carefully selected patients who previously responded well to ustekinumab, a short and closely monitored trial of IV reinduction may be considered. However, the threshold for switching to another advanced therapy should remain low if treatment targets are not achieved.”

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This year’s Peachtree Road Race. It didn’t look like I would be finishing first this year!

Extending Benjamin Franklin’s Observations: Chart Your Fart Study

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E Brindal et al. JAMA Netw Open. 2026;9;5):e2615637. doi:10.1001/jamanetworkopen.2026. 15637. Open Access! Regular Flatulence Patterns Among Community-Dwelling Individuals in Australia. Thanks to Stan Cohen for sharing this study.

Methods: Cross-sectional study with 6416 participants  Data were recorded into a purpose-designed mobile phone application (Chart Your Fart) by participants who logged their flatus passages in real time, consistent with experience sampling methods.3

Key findings:

  • See Table below – Mean flatus per day was 5.0

Discussion:

  • “In terms of range, observed data suggest good consistency with other methods, including retrospective frequency reports in a large US sample of individuals experiencing gas or bloating (n = 16 537),6 a small laboratory study that collected a median of 8 emissions throughout 24 hours,7 and even Benjamin Franklin’s personal account of “discharging wind from bowels” 7 times a day.8“
  • “Limitations of this study include failing to quantify emissions made while asleep due to reliance on self-report.”

My take: Looks like another good study to discuss at the GI dinner table. Also, lots of jokes that would be apropos. Here’s one:

An elderly patient goes to her doctor and at the end of her exam she tells him there is one other matter that she would like to discuss. “It seems that I have frequent gas but fortunately it is silent and does not smell. I have even passed some gas while I’ve been here.” The physician says, “Hmmm… take these pills for one week and then come back.”

When she returns, she complains, “I don’t know what was in those pills. The gas now smells terrible but thank goodness it is silent.” The doctor replies, “Well, it looks like the antibiotics have improved your ability to smell. Now we need to get your hearing evaluated.”

Related blog post: Somewhat Funny Flatulent Research

Island Ford, Sandy Springs at sunrise

Safety Data Up to Seven Years with Vedolizumab

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E Louis et al. Clin Gastroenterol Hepatol 2026; 24: 1654-1665. Open Access! Long-Term Safety of Vedolizumab in Patients With Ulcerative Colitis/Crohn’s Disease: A Prospective Observational Study

Methods: This was a prospective, observational, multicenter cohort study in adult patients (n=5208) with UC or CD starting treatment with vedolizumab or other biologics. The primary safety outcome was serious infections compared between cohorts using a Cox proportional hazards model adjusted by propensity score. Clinical effectiveness was a secondary outcome. Mean follow-up duration was 37.4 months. The vedolizumab group had greater age, duration of disease, and concomitant medication use at baseline, indicating more advanced disease.

Key findings:

  • In patients with UC, the incidence rate per 100 person-years of serious infections was 5.5 (vedolizumab) and 7.0 (other biologic), with an adjusted hazard ratio of 0.89 (P = .38).
  • In patients with CD, corresponding findings were 7.9 (vedolizumab) and 6.5 (other biologic) with adjusted hazard ratio of 1.15 (P = .16).
  • Rates of clinical response and clinical remission were similar in patients treated with vedolizumab compared with other biologics for both UC and CD.
Time to treatment failure in (A) biologic-naïve. Treatment failure included discontinuation of biologic treatment, IBD nonsurgical hospitalization, primary IBD surgery, and corticosteroid initiation.
Time to treatment failure in (B) biologic-experienced CD patients. 

My take: This large prospective study showed no new safety signals with mean followup of more than 3 years. There were no new trends or changes of clinical importance for infections (serious and opportunistic infections, gastrointestinal infections, respiratory tract infections, other infections), malignancies, infusion-related reactions, hepatotoxicity, and pregnancies. No cases of PML were reported. Efficacy was similar between vedolizumab and other biologics.

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How Does Remission in Crohn’s Disease Affect the Abnormal Microbiome/Gut Signature?

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T Braun et al. Gastroenterol 2026; 170: 971-984. Open Access! Perturbations of Diet and Gut Signatures Persist During Remission in Crohn’s Disease Despite Effective Immune Suppression

Methods: The authors analyzed diet, ileal transcriptomics, microbiomics, and metabolomics across patients with CD in remission, patients with active CD, and non–inflammatory bowel disease (IBD) controls as the reference for healthy signals.

Key findings:

  • Immune signals: Ileal transcriptomics revealed a significant decrease in genes and pathways associated with adaptive T cells and innate granulocytes during remission, which was even deeper than observed in non-IBD controls.
  • Antimicrobial gene expression: Patients in remission showed an increase in the expression of epithelial antimicrobial pathways and related genes, including DUOX2, along with an increase in genes associated with goblet cells and mucin glycosylation.
  • Microbiome and diet: In patients in remission, there was persistent pathogenic gut microbial composition, metabolic alterations, and less healthy dietary habits, which were characterized by a higher intake of ultraprocessed foods and lower consumption of fiber, folate, vitamin C, and vegetables
Purple = control (n=64), Yellow = CD remission (n=56), Red = CD active disease (n=24). Fecal signals persist during remission and substantially correlate with dietary exposures. (A) Boxplots of Faith’s phylogenetic alpha diversity, our previously defined health index,23 the previously defined Gevers IBD dysbiosis index21, and our IBD-specific index23 between controls, CD patients in remission, and CD with active disease.

Fecal signals persist during remission and substantially correlate with dietary exposures. (A) Boxplots of Faith’s phylogenetic alpha diversity, our previously defined health index,23 the previously defined Gevers IBD dysbiosis index21, and our IBD-specific index23 between controls, CD patients in remission, and CD with active disease.

My take (borrowed from the authors): This study shows that, during remission with advanced therapies, “disturbances in antibacterial epithelial signals, along with unhealthy dietary patterns, altered microbiome, and perturbed metabolome, continue and are partly linked to the risk of flare 6 months later.”

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NSAIDs and IBD Flares (2026)

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AS Mayer,et al. Arthritis Care Res. https://doi.org/10.1002/acr.80067. Open Access! Safety of Prescription Nonsteroidal Anti-inflammatory Drugs in Adults With Inflammatory Bowel Disease: Data From a Large Administrative Claims Cohort.

Methods:

  • “This retrospective cohort study included patients with IBD aged at least 18 years from Optum’s deidentified Clinformatics Data Mart Database (2000–2022). Patients with a new NSAID prescription fill were matched to those without an NSAID fill during the study period…Propensity score-based inverse probability of treatment-weighted Cox proportional hazards models evaluated the association between NSAID exposure and time to IBD-related hospitalization across IBD subtypes.”

Key findings:

Unweighted Kaplan-Meier curve for IBD-related hospitalization in patients
with Crohn disease (B).
Unweighted Kaplan-Meier curve for IBD-related hospitalization in patients
with ulcerative colitis (C).

Discussion:

  • “The use of IPTW [inverse probability of treatment weighting] to balance an extensive number of confounders associated with NSAID use optimizes the assessment of the association of NSAID exposure with IBD-related hospitalization and helps address recent concern of residual confounding in observational studies of NSAID risk in IBD.”
  • Besides the potential risk of an IBD flare, “NSAID use is associated with risk of hospitalization from several non-IBD–related entities such as acute kidney injury and adverse cardiac events…a large prospective multicenter observational study of more than 18,000 admitted patients in England found that NSAIDs were responsible for 29.6% of admissions related to adverse drug reactions, including gastrointestinal bleeding, stroke, and renal impairment.34“

My take: This study shows an association of increased hospitalization in patients with CD but not UC based on NSAID exposure. The absolute risk of this appears low and could be in fact related to residual confounders (despite use of IPTW) as this was not a prospective study. The risk of NSAIDs outside the GI tract are likely more significant for most patients. Nevertheless, there are limited options for pain management and NSAID benefits have to be weighed against other approaches.

Related blog post: Rethinking the Link between NSAIDs and IBD Flares