Category Archives: Gastroenterology

Clostridioides difficile Treatment in 2026

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P Feuerstadt et al. AJG 2025; 120: 2468-2470. Treatment of Clostridioides difficile: The Times They Are Changing

This article summarizes the recent changes in the treatment options for Clostridioides difficile (C diff).

Key points:

  • Fidaxomicin targets C diff with limited collateral microbiome disruption. This leads to significantly lower recurrence rates compared to vancomycin. Thus, it is preferred 1st line therapy for initial and recurrent C diff. In “the coming years, fidaxomicin is expected to come off patents” which will improve access and affordability.
  • Bexlotoxumab which lowered recurrence rate is no longer being produced
  • FMT via Openbiome is no longer available. In those in which FMT was used, options include the following:
  1. live-jslm (REBYOTA), a broad consortium enema-based formulation
  2. live-brpk (VOWST), a narrow consortium of Firmicutes in an encapsulated form. This treatment in adults: four capsules daily for three days
  3. Both treatments are not recommended for patients who are severely immunocompromised. In these patients, prolonged vancomycin course with taper or using every other day therapy with fidaxomicin for days 7-25 could be considered

My take: I have been seeing less C diff cases recently. This may be due to better antibiotic stewardship, changes in C diff strains, or improved testing approaches.. My observation is supported by recent reports:

AY Guh et al. Infect Dis Clin North Am. 2025. 39:567-580. Changes in the Epidemiology of Clostridioides difficile Infection

Annual number of hospitalized community-onset and hospital-onset CDI events reported to the National Healthcare Safety Network, 2015 to 2023. (From CDC’s Antibiotic Resistance & Patient Safety Portal (Available at https://arpsp.cdc.gov/profile/nhsn/cdi).)

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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.

The Risks and Absolute Risks of GLP-1 RAs and Gastrointestinal Adverse Events

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C-H Chiang et al. Gastroenterol 2025; 169: 1268-1281. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis

With the widespread adoption of GLP-1 RAs, there have been increasing reports of adverse effects. This systematic review/meta-analysis (with 55 randomized controlled trials involving 106,395 participants) more fully describes the likelihood of GI adverse events.

Key findings:

  • GLP-1RAs increased the risk of cholelithiasis (risk ratio [RR], 1.46; 95% CI, 1.09–1.97; 2 more cases per 1000) and probably increased the risk of GERD (RR, 2.19; 95% CI, 1.48–3.25; 4 more cases per 1000) compared with placebo
  • GLP-1RAs probably have little or no effect on the risk of other gastrointestinal or biliary events

Figures 2 & 3 use a Forest plot to look at a large number of potential adverse gastrointestinal/biliary events. For example, cholecystitis and cholangitis had increased RR at 1.17 and 1.54 respectively. However neither reached statistical significance.

My take: GLP-1 RAs definitely cause adverse gastrointestinal effects, especially nausea, vomiting, diarrhea, bloating and reduced appetite. More severe adverse effects are quite uncommon and are unlikely to influence the decision to use these medications.

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Postoperative Outcomes with Tofacitinib Following Colectomy for ASUC and Real-World Outcomes for Upadacitinib in Crohn’s Disease

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C Larson et al. Clin Gastroenterol Hepatol 2025; 23: 2263-2271. Postoperative Outcomes in Tofacitinib-Treated Patients With Acute Severe Ulcerative Colitis Undergoing Colectomy

This  was a multicenter, retrospective, case-control study of patients hospitalized with ASUC who underwent colectomy, comparing patients treated with tofacitinib (n=41) prior to colectomy with infliximab-treated controls (n=68).

Key findings:

  • Compared with tofacitinib-treated patients, infliximab-treated patients had higher overall rates of overall (44 [64.7%] vs 13 [31.7%]; P = .002) and serious (19 [27.9%] vs 3 [12%]; P = .019) postoperative complications

My take: This study supports the safety of JAK inhibitor therapy for ASUC. It showed a significantly lower rate of overall postoperative complications in ASUC patients treated with tofacitinib compared with infliximab; the authors note that “these findings can likely be extrapolated to upadacitinib, a selective JAK inhibitor, given its similar mechanism of action.”

J Devi et al. Clin Gastroenterol Hepatol 2025; 23: 2281-2291. Open Access! Real-World Effectiveness and Safety of Upadacitinib in Crohn’s Disease: A Multicenter Study

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Spotlight: AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease

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Yesterday’s post (AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease) summarized the following article:

The associated “Spotlight” provides useful a graphic summary. Here is most of the information:

AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease

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FI Scott et al. Gastroenterology, Volume 169, Issue 7, 1397 – 1448; Open Access! AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease

The guideline panel agreed on 16 recommendations. This highly-detailed report provides a comprehensive, patient-centered, evidence-based approach to the pharmacologic management of adult patients with moderate-to-severely active CD. Table 1 summarizes this lengthy 53-page report. Tomorrow’s post will be the “spotlight” summary which presents the recommendations in easier to read graphic.

Key Points:

The guidelines are overall very helpful. They identify higher efficacy medications and recommend them. In addition, they support the use of combination therapy with thiopurines (which are less frequently used in pediatrics). It is interesting that the sixteenth recommendation clashes with prior expert recommendations. The sixteenth recommendation in this report makes no recommendation on using endoscopic surveillance compared to symptomatic clinical remission. Most experts advise “treat-to-target” therapy approaches.

In the discussion of this, the authors state the followiing:

“Recent position statements from an international consortium of experts have advised that longitudinal targets for the management of IBD should include not only clinical remission but also endoscopic resolution of inflammation.31 Several studies have demonstrated that patients who achieve endoscopic remission (vs those with ongoing endoscopic activity) have favorable long-term outcomes…

There are limited RCTs assessing whether there is actual benefit in systematically treating toward endoscopic remission target vs symptomatic remission targets (ie, testing whether the target has been achieved, followed by algorithmic treatment adjustment, including escalating index therapy, adding an immunomodulator, followed by switching to an alternative advanced therapy and surgery). There was significant heterogeneity among the 2 reviewed studies, both in terms of the advanced therapy used, algorithms for therapy modification, and the cadence and frequency of endoscopic monitoring that challenge interpretation. Based on the significant uncertainty of evidence with regard to improving maintenance of remission or reducing the risks of adverse events, the guideline panel could not make a recommendation in relation to selecting endoscopic targets over clinical targets.

It is worth emphasizing that in both of the included trials, the majority of individuals in the endoscopic healing arms were not able to meet the goal of endoscopic healing despite an algorithmic approach. For example, in STARDUST, only 11% of individuals achieved endoscopic remission.149…There are specific patient populations, such as those who have recently undergone intestinal resection,155 in which endoscopic evaluation may be particularly valuable in clinical decision making...

The benefit of a monitoring strategy incorporating biochemical monitoring over clinical monitoring alone was demonstrated in the CALM trial,152 and has been addressed in previous AGA guidelines on the role of biomarkers in patients with CD.12“

My take: These “living” guidelines are likely to be quite influential in selecting Crohn’s disease therapy. In pediatrics, ImproveCareNow provides a similar role of guiding treatment.

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Guidelines for UC:

Crohn’s Disease:

How to Best Use Steroids for Inflammatory Bowel Disease

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JD Feuerstein et al. Clin Gastroenterol Hepatol 2025; 23: 2068-2082. Open Access! Appropriate Use and Complications of Corticosteroids in Inflammatory Bowel Disease: A Comprehensive Review

Steroids are commonly used and misused for inflammatory bowel disease. This article reviews best practices, steroid formulations/dosing, and potential complications.

  • For moderate to severe ulcerative colitis (in adults), the authors recommend treatment with 40 mg of prednisone daily. Patients with ASUC (acute severe ulcerative colitis) should be treated with 60 mg of IV methylprednisolone for 3 to 5 days, after which rescue therapy should be initiated
  • Use of budesonide is recommended as an option for many clinical situations to minimize steroid adverse effects. These situations include mild-moderate UC failing to respond to mesalamine, ileal CD and older patients
  • Postoperative complications: “In the postoperative period, patients treated with CS had a higher risk of both infectious complications (aOR, 3.69; 95% CI, 1.24–10.97) and major infectious complications (aOR, 5.54; 95% CI, 1.12–27.26) [Abrerra et al].135  Subramanian pooled data from 7 studies showing that preoperative CS use is associated with increased postoperative complications (OR, 1.41; 95% CI, 1.07–1.87) as well as infectious complications.

The authors note that corticosteroids “remain widely available and are an effective short-term option for induction of remission in patients with active UC or inflammatory CD. However, their well-described and significant safety profile warrants proactive strategies to limit their use through non-systemic formulations, short-term exposures, steroid-sparing maintenance options, and most recently, complete steroid avoidance strategies.”

My take: Continuing steroids when they are not effective prior to potential surgery (eg. ASUC) remains a frequent problem. Sometimes, it is difficult to know it they are helping some.

Worrisome Report: PPI Use and Early Onset Colorectal Cancer

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C Strong, ACG 10/28/25: Long-Term PPI Treatment Linked to Higher Risk for Early-Onset CRC Before Age 50

An excerpt:

“Long-term treatment with proton pump inhibitors (PPIs) is independently associated with an increased risk for early-onset colorectal cancer (EOCRC) among individuals aged younger than 50 years, according to study results presented at the American College of Gastroenterology (ACG) 2025 conference…”

“Researchers reviewed data from the National Inpatient Sample from 2016 to 2020. Individuals were aged 18 to 49 years and had a main diagnosis of colorectal cancer (CRC)…Investigators identified PPI exposure through diagnostic codes indicating long-term use (Z79.891) or adverse effects (T45.4X5A/D)….

“Of the 7140 hospitalizations for patients with EOCRC aged younger than 50 years, 1056 (14.8%) reported long-term PPI treatment. After multivariable adjustment, PPI users had a 41% increased risk for EOCRC vs individuals without PPI use (adjusted odds ratio [aOR], 1.41…”

My take: More studies will be needed to determine if this link between PPI use and early onset CRC is truly significant. Many prior associations between PPI and other health conditions on observational studies have not held up with well-controlled studies. There was no increased risk of cancer in a previous randomized control trial (see below).

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Amicalola Falls State Park

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.”

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ACupuncTure for Irritable bOwel syNdrome (ACTION)

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J-W Yang et al. Gastroenterology, Volume 169, Issue 5, 958 – 969.e5. Open Acces! Efficacy of ACupuncTure in Irritable bOwel syNdrome (ACTION): A Multicenter Randomized Controlled Trial

This ACTION study enrolled 280 patients (18-75 yrs) with IBS-D in a multicenter randomized controlled trial in 6 hospitals in China. “For the sham acupuncture group, blunt-tipped placebo needles with a similar appearance to real needles were used over the adhesive pads with no skin penetration. Five fixed pairs of non-acupoints (10 stimulation points in total) away from meridians or conventional acupoints were used.”

Key finding:

  • The primary outcome (see below) was reached by 71 (57.9%) patients in the acupuncture group compared with 47 (41.4%) patients in the sham acupuncture group (risk ratio 1.40; P = .008)
  • The effects of acupuncture in symptomatic improvements of IBS-D persisted 3 months after treatment with minimal to no side effects
  • Limitations including the difficulty of acupuncture blinding (despite the identical treatment setups)

My take: Acupuncture, especially given its safety, is a reasonable therapy for IBS-D; though, it is not recommended in recent pediatric guidelines. “The rub” in many locations is finding qualified practitioners.

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Proximal Ileal Crohn’s Disease is Harder to Treat

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K Takenaka et al. Clin Gastroenterol Hepatol 2025; 23: 1991-2000. Open Access! Inadequate Efficacy of Biologics for Treating Proximal Ileal Lesions in Crohn’s Disease: A Prospective Multicenter Study

This multicenter prospective study (n=253) examined efficacy of treatment in patients with proximal ileal disease using balloon-assisted enteroscopy (BAE). The recruited patients had a mean disease duration of 4 years. 52% were naive to biologic treatment at baseline.

Key findings:

  • At baseline, 74 patients (29.2%) had proximal ileal ulcerations without terminal ileal ulcerations
  • At week 26, after treatment with anti-TNF therapy (n=103), ustekinumab (n=99) or vedolizumab (n=51), endoscopic remission was achieved in 91 patients (36.0%). Of the patients with complete ulcer healing of the terminal ileum, 28.6% (22/77) had residual ulcers in the proximal ileum
  • The rate of endoscopic remission in the proximal ileum (50.9%) was relatively lower compared with the colon (63.4%) and terminal ileum (56.7%)
  • After a median follow-up of 134 weeks, residual ulcerations in the proximal ileum were associated with a poorer prognosis (P = .0126 for hospitalization and P = .0014 for surgery). In contrast, there was no significant differences in hospitalization and surgery associated with endoscopic activity vs remission in the colon or terminal ileum.

Discussion: Residual “proximal ileal ulcerations … are associated with a poorer prognosis…Additionally, we confirmed that proximal ileal inflammation is less responsive to biologic therapies compared with colonic inflammation. Although the reasons for this disparity remain unclear”

My take: Balloon-assisted enteroscopy is not frequently used in the setting of inflammatory bowel disease, particularly in pediatrics. MRE is typically used to follow proximal small bowel disease, though it has less sensitivity for luminal mucosal disease.

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