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Dr. Carlo DiLorenzo: Advice for Managing DGBIs (Part 2)

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Recently Dr. DiLorenzo gave our group a brilliant lecture. I have taken some notes and shared some slides. There may be inadvertent omissions and mistakes in my notes. This is part 2 of my summary.

Key points (intermixed with slides):

  • Improving Physical activity, Diet and Sleep Often Helps DGBI symptoms
  • Excess use of smartphones can be detrimental. There are issues with FOMO (fear of missing out), cyberbullying, effects on sleep, and effects on interpersonal skills
  • Displacement, or replacing important activities (including physical activity) with time spent on social media, is a significant concern
  • Working with pain psychologists is an important part of treatment for many children and adolescents
  • Lots of celebrities have been open about their mental health challenges: Lady Gaga, Ariana Grande, Kristen Bell, Selena Gomez, Ryan Reynolds, and Dwayne “The Rock” Johnson
  • For more serious mental health concerns, referral to psychiatry is more appropriate
  • Gut-Brain neuromodulators can be effective.
  • Despite their good safety profile, they are underutilized
  • Dr. DiLorenzo uses more citalopram than omeprazole
  • Amitriptyline is often used for abdominal pain in the absence of anxiety. Variable results have been published
  • Psychotropic medications: Amitriptyline is useful for pain predominant IBS, Citalopram often is effective for FAP/IBS with anxiety, Buspirone is helpful in dyspepsia with anxiety, and Mirtazapine is a good choice in the setting of dyspepsia with with weight loss. Generally, start with a low dose and slowly titrate with each medication
  • Safety: Despite black box warning, recent studies have suggested SSRIs may lower the risk of suicidality overall
  • Don’t be the doctor who only tells patients things they want to hear. (Don’t be afraid of online rating)

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

Dr. Carlo DiLorenzo: Advice for Managing DGBIs (Part 1)

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Recently Dr. DiLorenzo gave our group a brilliant lecture. I have taken some notes and shared some slides. There may be inadvertent omissions and mistakes in my notes. Dr. DiLorenzo gave our group a lecture in 2021 as part of the William Meyers Lectureship. This talk extended those observations he conveyed at that visit (Carlo DiLorenzo: Lessons Learnt Over 30 Years).  I highly recommend his upcoming NED talk at NASPGHAN.

Key points (intermixed with slides):

  • Diagnostic testing in the setting of DGBIs is mainly for confirmation that an adequate workup has been completed
  • Schedule enough time for each patient. In evaluations of visits, one of the most negative feelings for patients is when they feel rushed
  • Make sure the patient is allowed to speak. Parents may embellish (or underreport) symptoms
  • Families feel that when clinicians are sitting down that they spend more time with them
  • This extends into the hospital. A recent controlled study showed that having a chair within 3 ft of the bed increased the likelihood that physicians would sit when rounding and increased patient satisfaction (Effect of chair placement on physicians’ behavior and patients’ satisfaction: randomized deception trial. Iyer R, et al.BMJ. 2023 Dec 15;383:e076309). Study conclusion: “Chair placement is a simple, no cost, low tech intervention that increases a physician’s likelihood of sitting during a bedside consultation and resulted in higher patients’ scores for both satisfaction and communication.”
  • Dr. DiLorenzo rarely uses computers when he is in the room with families
  • Don’t belittle or get upset over an “easy” or “stupid” consult. All of us need help and hardly anyone wants to manage only highly-complex patients
  • Don’t speak poorly of other physicians in front of the patient
  • The problem with too much testing –>it can result in ‘Munchausen by Doctor’ and the discovery of incidental problems (that may not necessitate treatment). Further testing has been associated with intensification of symptoms
  • Identification of eosinophilic esophagitis is not helpful in resolving stomach pain
  • Newest “epidemics” associated with stomach pains include alpha gal and multiple vascular compression syndrome
  • While unusual disorders can occur, Dr. DiLorenzo mainly looks for unusual diagnoses when patients have unusual symptoms (like weight loss​, pain with exercise)
  • While guidelines often emphasize the use of treatments based on double-blind, placebo-controlled (DBPC) studies, “there has never been a DBPC for the effectiveness of a parachute.” Some treatments are worthwhile even in the absence of DBPC studies
  • Many of the medicines used for DGBIs and related symptoms have approval for other uses
  • Fundoplication which was commonplace is used rarely these days. Yet, it is still a good treatment for reflux
  • Antegrade enemas can be very effective for constipation
  • “All patients with chronic pseudo-obstruction necessitating parenteral nutrition should have a G-tube and an ileostomy.” It may help them come off parenteral nutrition
  • Don’t order AXR to diagnose constipation. AXRs ordered in ER to diagnose constipation are associated with a slightly higher likelihood of a missed diagnosis.
  • Though, “no need to be holier than the pope.” Using AXR in specific circumstances can be helpful with treatment (like determining success of a cleanout)
  • Treating the Brain is important in patients with DGBIs
  • Anxiety, which is increased in patients with DGBIs, has reached epidemic levels

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

Celiac Studies: Lower Rates of Undiagnosed Celiac Disease in Norway, and Lower Rates of Celiac with Early Dietary Fiber

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P Lukina et al. Clin Gastroenterol Hepatol 2025; 23: 1143-1151. The Prevalence and Rate of Undiagnosed Celiac Disease in an Adult General Population, the Trøndelag Health Study, Norway

Methods: The study used the fourth Trøndelag Health Study (HUNT4), conducted in 2017–2019, where 56,042 adult (aged >20 years) residents of Nord-Trøndelag County, Norway, participated. Serum samples from 54,505 participants were analyzed for anti-transglutaminase 2 IgA and IgG.

Key findings:

  • The rate of CeD seropositivity was 2.0% (1107/54,505).  
  • The total biopsy-confirmed prevalence of CeD was 1.5% (853/56,042).
  • The study confirmed a new CeD diagnosis after participation in HUNT4 in 470 individuals and a known CeD diagnosis before participation in HUNT4 in 383 individuals.
  • The ratio of new, previously undiagnosed CeD cases (after HUNT4) to known, previously diagnosed CeD cases (before HUNT4) was 1.2:1 (470/383).

My take: This study showed that the ratio of undiagnosed cases to diagnosed case of CeD was improved from previously in Norway.

EM Hård af Segerstad, et al. Gastroenterol 2025; 168: 1185-1188. Open Access! Early Dietary Fiber Intake Reduces Celiac Disease Risk in Genetically Prone Children: Insights From the TEDDY Study

Methods: This study examined the quantity and timing of dietary fiber intake in children up to 5 years of age who were at genetic risk for celiac disease, assessing its relationship with their subsequent risk of developing the condition. The analysis included 6520 children carrying the HLA-DQ2 and/or DQ8 risk haplotypes who were prospectively followed for a total 61,669 person-years to age 13 years in The Environmental Determinants of Diabetes in the Young (TEDDY) study.

Key findings:

  • Dietary fiber intake from 6 months to 3 years of age was inversely associated with the subsequent risk of celiac disease in models unadjusted for the concurrent gluten intake and to 2 years of age in models adjusted for gluten intake (Figure 1A). In contrast, no association was observed between dietary fiber intake to 4 and 5 years of age and the risk of celiac disease regardless of whether models accounted for the gluten intake. 

My take: Higher dietary fiber intake during the first 2 years of life was associated with a lower risk of celiac disease in children at genetic risk. Although this effect was modest, it was independent of gluten intake and other components found in fiber-rich foods in the child’s diet.

Related blog posts:

Tailoring IBS Dietary Therapy Based on Proprietary IgG-Based Blood Test –Does It Work?

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Background (from editorial): “Biomarkers that correspond with the distinct pathophysiological disturbances that underlie food sensitivity, and that can be used to monitor and guide management or predict response to food elimination are lacking…Previous studies have suggested a role for IgG-mediated food sensitivities in driving IBS symptoms.12 However, the role of IgG testing and subsequent dietary elimination for the management of IBS symptoms remains a subject of debate. Elevated IgG levels have been observed in healthy individuals, indicating that these antibodies may reflect a physiological response to dietary exposure rather than intolerance or sensitivity to a specific food.”

In this study, the researchers used a proprietary IgG-based sensitivity testing (“inFoods IBS” ELISA) from the company sponsor, Biomerica.  This was a randomized, double-blind, sham-controlled trial enrolling subjects with IBS from 8 centers. Subjects positive for ≥1 food on an 18-food IgG assay. 223 were included in the modified intention-to-treat analysis. The primary outcome was a ≥30% decrease in abdominal pain intensity for ≥2 of the last 4 weeks of the treatment period.

Key findings:

  • A significantly greater proportion of subjects in the experimental diet group met the primary outcome than those in the sham diet group (59.6% vs 42.1%, P = .02).
  • Subgroup analysis revealed that a higher proportion of subjects with constipation-predominant IBS and IBS with mixed bowel habits in the experimental diet group met the primary endpoint vs the sham group (67.1% vs 35.8% and 66% vs 29.5%, respectively).

Discussion Points:

The authors claim the following: “Because IgG-based antibodies to foods can be elevated in healthy controls, it is important to develop disease-specific assays. The assay used in our study was developed specifically for patients with IBS and uses cutoff values derived from healthy controls.”

Limitations:

  1. “Adherence was poor. Of those who filled out the dietary diary as instructed, 35% were nonadherent in the intervention group and 42% nonadherent based on a yes to an adherence question on ≥80% of days over the 12-week trial.” Adherence was higher in the sham control.
  2.  “Second, in a per-protocol analysis that included only the adherent participants, the clinical outcomes are much less impressive for the IgG-based elimination diet, raising critical questions as to whether other factors were responsible for the improvement in symptoms in the full dataset.”
  3. Possible confounding bias: “2 of the 3 most commonly eliminated foods in the IgG-based elimination diet were high in FODMAPs (eg, milk, wheat), whereas all 3 most commonly eliminated foods in the sham diet were low in FODMAPs (poultry, rice, and goat cheese).”
  4. The authors noted that it was unexpected that the response was more robust in the IBS-C and IBS-M groups rather than the IBS-D groups.

The company sponsor has had good success in publicizing their results on ABC, CBS and NBC. Here is a link from their website direct to YouTube. It highlights a specific young woman reporting success with this approach and commentary by one of the lead authors: inFoods IBS Finding Trigger Foods Faster.

My take: While most patients are eager to pinpoint trigger foods, I remain skeptical about this “precision testing for IBS.” There is no data indicating that this IgG-based diet outperforms patients who limit dairy and wheat, two common triggers. I agree with the associated editorial: “The clinical efficacy of IgG-based elimination diets will need further evaluation before they are implemented in routine clinical practice.”

Related blog posts:

Andaman Sea (Thailand)

Jump in Knowledge Regarding Gut-Brain Axis

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Eric Topol has summarized some of the recent advances in the understanding of the Gut-Brain Axis. Open Access Link: The Gut-Brain Axis Takes Center Stage (6/22/25)

Here’s a lengthy excerpt:

We’ve known about the gut-brain axis for decades but there has recently been an unprecedented jump in our knowledge base that has transformed our expectations for its preeminence.

There are 2 types of neural pathways, the “second brain” referring to the enteric (gut) nervous system from the cells that line the intestine and communicate to the vagus nerve to the brain (and in the opposite direction, too). There are also connections via the sympathetic, parasympathetic nervous system (autonomic nervous system, ANS) branches and spinal cord innervation to the gut primarily through the ANS.

Cells in the gut produce hormones (enteroendocrine cells) such as glucagon-like peptide (GLP-1), gastric inhibitory peptide (GIP), peptide YY, secretin, gherlin, gastrin, and many others. Some of these regulate pancreatic hormones such as insulin, glucagon and amylin, which can be considered as gut hormones but derived from pancreatic cells rather than intestinal lining cells. The hormonal interaction between gut and brain also goes through the hypothalamus-pituitary-adrenal (HPA) axis.

The abundant and diverse bacteria in the gut microbiome of tens of trillion of cells of more than 3,000 species. These gut bacteria and their metabolites have an outsized impact by producing or stimulating different neurotransmitters (5HT, GABA) and metabolites (e.g. short chain fatty acids, SCFAs) that communicate with the brain and the immune system. For example, see my previous Ground Truths on how a gut bacteria and its metabolites can drive sugar cravings.

The interaction with the immune system is critical to maintain integrity of the gut lining (avoiding “leaky gut syndrome”) and the blood-brain-barrier…

The precise way by which the gut can induce inflammation in the brain has remained unclear. In the journal Nature this week it was shown that inflamed gut-derived CD4+ T cells can infiltrate the brain, leading to neuroinflammation and neurological damage in the experimental model…bacteria derived proteins (antigens) looking like host derived proteins, inciting an immune response.

This was the second of 2 recent discoveries centered around gut-derived immune cells that get into the brain. Newly identified specialized CD4+ T cells from the gut and white adipose tissue establish residence in the brain’s subfornical organ and regulate feeding behavior…

It turns out the H. pylori can do good things too! As in blocking the formation of amyloid protein formation. This week in Science Advances it was demonstrated that H. pylori releases the protein CagA (cytotoxin-associated gene A) which potently inhibits pathogenic amyloid assemblies..for formation in Alzheimer’s disease, Parkinson’s disease and type 2 diabetes…

Several new gut hormone clinical trials, beyond the ones that are widely used—semaglutide (Ozempic) and tirzepatide (Zepbound, Mounjaro), were unveiled…Through randomized trials, their broad impact has been unequivocally proven for diabetes, obesity, and for treating related conditions of heart failure (with preserved ejection fraction), kidney disease, liver disease, sleep apnea, along with unexpected suppression of addiction to alcohol, cigarette smoking, nail biting and gambling. Add a surprising impact that we’re starting to see for autoimmune diseases. Even before there is weight loss with these drugs, there is evidence from experimental models of reduced systemic (body-wide) and brain inflammation. What is surprising is that drugs like semaglutide have little direct penetrance to the brain, but exert their effect chiefly through the gut-brain axis. New molecules in this class will have enhanced brain penetrance…

Will They Work For Alzheimer’s Disease?

[In a Liraglutide trial with 200 participants with Alzheimer’s,] after 1 year of treatment there was a reported 18% less cognitive decline and 50% reduced brain shrinkage compared to placebo…[There are also two studies] pending EVOKE and EVOKE Plus trials of daily oral semaglutide participants aged 55–85 years with mild cognitive impairment or mild dementia due to Alzheimer’s…About 12% of American adults are already taking GLP-1 drugs

Sulfasalazine vs 5-ASA: Treatment Outcomes in Pediatric UC

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I Mansuri et al. J Pediatr Gastroenterol Nutr. 2025;80:988–997. Clinical outcomes of maintenance therapy with sulfasalazine compared to 5-aminosalicylates in children with ulcerative colitis

Methods: This was a retrospective review of children diagnosed with UC between June 1999 and December 2019 at Boston Children’s Hospital. 124 started on sulfasalazine (SZ) and 309 on 5-aminosalicylates (5-ASA). Most patients had mild to moderate disease based on PUCAI score; ~12% had severe disease.

Key findings:

  • At 1 year, 54%, 44.3%, and 36.6% of patients on SZ, 5-ASA, and those who switched, respectively, were in steroid-free remission (p = 0.13)
  • All medication switches due to adverse reactions (24) were from SZ to 5-ASA. No patient was switched from 5-ASA to SZ because of adverse reactions. The non-severe adverse reactions noted were nausea, vomiting, abdominal pain, non-severe skin rash, headache, mild leucopenia, and lymphadenitis. Three patients had serious skin reactions, and one had pancreatitis.
  • SZ tended to have more minor adverse reactions. Except for countering adverse reactions, switching between SZ and 5-ASA did not offer therapeutic benefits. Disease severity at diagnosis predicted early treatment escalation

Discussion Points:

  • SZ offers advantages such as lower cost and availability in suspension form; the suspension form is particularly beneficial for young children and those unable to swallow the solid form of medication.
  • 5-ASA formulations can be almost 10–50 times more expensive than SZ. For example, the wholesale acquisition cost of monthly generic SZ is $30 compared to $274 for generic Lialda, $1131 for generic Pentasa, and $1890 for generic Asacol HD

My take: About 20% of patients had to switch from Sz to 5-ASA due to adverse reactions; though, Sz had a mildly higher response rate (not statistically-significant). Switching between SZ and 5-ASA or vice versa is unlikely to provide much therapeutic benefit; patients who switched agents for medical reasons (rather than reactions) were more likely to require escalation to either a biologic or immune modulator.

Related blog posts:

Chatttahoochee River (Sandy Springs)

Retrospective Study on Botulinum Toxin for Refractory Constipation in Children

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D Patel et al. J Pediatr Gastroenterol Nutr. 2025;80:956–962. Efficacy of anal botulinum toxin injection in children with functional constipation

Methods: This was a retrospective, multicenter study including pediatric patients (n=63) who received anal botulinum toxin (BTX) for functional constipation (FC) refractory to medical therapy.  Response to therapy was assessed based on improvement in weekly frequency of BM (bowel movements) to 3 or more per week and/or resolution of functional incontinence (FI)

Key findings:

  • There was a a response rate of 10% in group 1 (FC +FI), 50% in group 2 (only FC) and 14% in group 3 (only FI); the an overall symptom resolution in 21% of patients
  • Fecal incontinence was the most common side effect, reported in 11% of all patients 

My take: In this highly-selected refractory population, there was a poor response to BTX in those with fecal incontinence (groups 1 and 3). The results should be interpreted with caution due to the retrospective nature of the study and the a lack of a control group.

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.

Liver Transplantation for PSC: Long-term Outcomes and Complications

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M Mouchli et al. Liver Transplantation 2025; 31: 781-792. Long-term (15 y) complications and outcomes after liver transplantation for primary sclerosing cholangitis: Impact of donor and recipient factors

Methods: Using Mayo clinic prospectively maintained transplant database, 293 adult patients (>18 y, mean age 47 yrs) with PSC who underwent LT from 1984-2012 were identified. Patients with cholangiocarcinoma were excluded. One hundred and thirty-four patients received LT before 1995, and 159 were transplanted after 1995.

Key findings:

  • The 1-, 5-, 10-, and 15-year cumulative incidence of recurrent PSC was 1.0%, 8.0%, 23.5%, and 34.3%, respectively.
  • Vascular and biliary complications are frequent: hepatic artery thrombosis (N = 30), portal vein stenosis/thrombosis (N = 48), biliary leak (N = 47), biliary strictures (N = 87)
  • Graft failure occurred in 70 patients
  • Donor age >60 years was associated with an increased risk of recurrent PSC. 

My take: Overall, there was a good survival rate despite the increased frequency of vascular and biliary complications. Also, 2/3rds of patients did NOT have recurrent PSC. Older donor age was associated with higher graft failure in this cohort.

Related blog posts:

The VEO-IBD Foundation -Developing Resource for Families

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Link: Family reflections: research gives back childhood: a family’s experience with very early onset inflammatory bowel disease Pediatric Research; https://doi.org/10.1038/s41390-024-03506-8

An excerpt:

Very Early Onset Inflammatory Bowel Disease is so rare and individualized that no standard of care yet exists, and almost none of the interventions are approved for infants. After eliminating all dairy, prematurely ending breastfeeding, and moving exclusively to a prescription formula, we tried and failed multiple classes of medications, hoping each time that this medication would be the one that would ease our son’s suffering. Doctors are only now building a history of successful interventions to draw from, so treatment options come from very small studies from Very Early Onset Inflammatory Bowel Disease researchers and educated guesses. Treatment options generally ramp up in aggressiveness, which is hard enough for parents of a miserably sick infant to process and decide. Once these interventions fail, drug costs and insurance approval become major hurdles. This process of trial-and-error in treating Very Early Onset Inflammatory Bowel Disease patients is a nightmare. On a weekly or monthly basis, parents must make life-altering decisions with very little data for a patient too young to advocate for themselves.

Link: The VEO-IBD Foundation This foundation is still in its early stages, but anticipate it will be a resource for families with VEO-IBD.

Related blog posts:

Navigating Celiac Disease: Tips for Pediatric to Adult Transition

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L Kievela et al. Clinical Gastroenterology and Hepatology,2025; 23: 908 – 911. Transition of Care in Celiac Disease: A Chance to Advance

This clinical practice article offers some useful advice in transitioning patients with Celiac disease into adult provider care. Some of their recommendations for adult provider care:

  • Regular visits
  • Assessment of gluten-free diet adherence with low thresholf for dietician referral
  • Checking serum tissue transglutaminase antibody levels
  • Screening for other autoimmune conditions
  • Consider additional lab tests (eg. CMP, CBC, Ferritin, ALT, Albumin, Folate, Zinc, Vit D, Vit B12, and TSH) and DEXA scan based on clinical situation
  • Recommend screening family members
  • Check vaccination status
Figure 1 provides suggestions for a transition report

Related information that is not in the article:

College/school resources: