Rapid Gut Microbiome Recovery: Diet Outperforms Microbial Transplant

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Briefly noted: MS Kennedy et al. Nature (2025). https://doi.org/10.1038/s41586-025-08937-9. Diet outperforms microbial transplant to drive microbiome recovery in mice

Methods:  Here we characterize the trajectory by which the gut microbiome recovers its taxonomic and functional profile after antibiotic treatment in mice on regular chow (RC) or Western Diet (WD).

Key findings: “Only mice on RC undergo a rapid successional process of recovery. Metabolic modelling indicates that a RC diet promotes the development of syntrophic cross-feeding interactions, whereas in mice on WD, a dominant taxon monopolizes readily available resources without releasing syntrophic byproducts. Intervention experiments reveal that an appropriate dietary resource environment is both necessary and sufficient for rapid and robust microbiome recovery, whereas microbial transplant is neither.”

Conclusion (from authors): “Our data challenge widespread enthusiasm for faecal microbiota transplant (FMT) as a strategy to address dysbiosis, and demonstrate that specific dietary interventions are, at a minimum, an essential prerequisite for effective FMT, and may afford a safer, more natural and less invasive alternative.”

My take: This study suggests that the best way to get a “healthy” microbiome is to eat a healthy diet rather than to try to alter with FMT. This finding likely would be the same for probiotics as well.

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Andaman Sea (Thailand)

Increased Mortality in Pediatric Steatotic Liver Disease Plus One

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From UCSD 4/28/25: Children with Liver Disease Face Dramatically Higher Risk of Early Death (via Jeff Schwimmer’s X feed)

The findings, published April 22, 2025 in Hepatology, the scientific journal of the American Association for the Study of Liver Diseases, come from the Longitudinal InVestigation Evaluating Results of Steatosis (LIVERS) study, which followed 1,096 children over an average of 8.5 years. Nearly half of all deaths in the cohort were liver-related, and the overall mortality rate was 40 times higher than that of similar peers in the general U.S. population...

The retrospective cohort study used medical records and National Death Index data to follow children ages 2 to 18 who were diagnosed with MASLD between 2000 and 2017. Over an average of 8.5 years of follow-up, 3.4% of children had died…

In addition to the risk of early death, many children in the study developed serious health problems while still in their teens or twenties. These included high blood pressure (14%), obstructive sleep apnea (9.5%) and type 2 diabetes (7.3%). Problems with blood fats, such as high triglycerides or low HDL, were even more common — making dyslipidemia, the presence of abnormal levels of fats (lipids) in the blood, the most frequent complication overall.

Link to study: JB Scwimmer et al Hepatology ():10.1097/HEP.0000000000001357. Long-term mortality and extrahepatic outcomes in 1,096 children with MASLD: A retrospective cohort study

My take: Since this was a retrospective single center study, the severity of the findings may be different with a more-representative national cohort. Nevertheless, this study shows that MASLD has serious consequences including premature death and numerous comorbidities.

Related article: J Panganiban et al. Obesity Pillars 2025: 14. https://doi.org/10.1016/j.obpill.2025.100164. Open Access! Metabolic dysfunction-associated steatotic liver disease (MASLD) in children with obesity: An Obesity Medicine Association (OMA) and expert joint perspective 2025. This Obesity Medicine Association (OMA) Expert Joint Perspective is a comprehensive review (~28 pages) of steatotic liver disease (SLD), metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH) in children with obesity.

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Safe for Patients with Celiac Disease to Kiss after Partner’s Gluten Ingestion

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An excerpt from News Medical:

Researchers recruited 10 couples, each with one partner who has celiac disease, for a two-part study. In each session, the non-celiac partner ate 10 saltine crackers, and then the couple kissed for 10 seconds. In one session, the partners waited five minutes before the kiss, and in the other, they drank 4 ounces of water before kissing…

Although gluten was still found in saliva after kissing a partner who had consumed gluten and then had a glass of water, in all cases the amount was less than 20 parts per million, the level allowed in gluten-free products, which is considered safe.

“Patients with celiac disease can be more relaxed, knowing that the risk of gluten cross-contact through kissing a partner who has consumed gluten can be brought down to safe levels if food is followed by a small glass of water.”

From NBC article:

In the first scenario — waiting five minutes before kissing — two of the celiac participants had more than 20 parts per million of gluten in their saliva sample. 

In the scenario in which non-celiac partners drank 4 ounces of water before the kiss, everyone’s saliva tests contained fewer than 20 ppm of gluten. 

My take: Sounds like a fun study. Best to drink water before kissing your partner who has celiac disease.

Reference: Anne Lee. DDW Abstract Mo1242, 5/5/25: “Assessing gluten transfer via kissing; a prospective study of celiac-discordant couples”

When an Inflammatory Bowel Disease Diagnosis is Far Away

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JF McLaughin et al. Clin Gastroenterol Hepatol 2025; 23: 825-834. Travel Time to Treating Center Is Associated With Diagnostic Delay in Pediatric Inflammatory Bowel Disease

This was a cross-sectional study of newly diagnosed pediatric patients (n=869) with IBD at 22 United States sites from 2019 to 2022. 57% were diagnosed with CD, 34% with UC, and 4% with IBD-U.

Key findings:

  • Overall, the mean time from symptom onset to diagnosis was 265.9 days
  • Factors associated with longer diagnosis time included CD vs UC (odds ratio [OR], 2.6), and longer travel time to clinic (>1 hour [OR, 1.7], >2 hours [OR, 1.8] each vs <30 minutes)
  • There was no association with race, ethnicity, birth country, gender, parent education, household income, insurance type, health literacy, and health system distrust

The finding that there is a longer diagnostic delay with CD than UC is consistent with prior studies. The longer travel time has not been widely recognized as a factor associated with delayed diagnosis, though it has been associated with other negative outcomes like higher mortality with chronic liver disease.

Regarding the lack of a negative impact from factors like race/ethnicity and income, my suspicion is that this is probably related to several factors:

  • Overall, the pediatric age group has a very high rate of being insured as most children without commercial insurance currently qualify for Medicaid. This helps improve access to needed/timely health care
  • A recent study showed that pediatric GI specialists do not have disparities in treatment compared to pediatric GI providers with an IBD focus; thus, pediatric specialists are more likely to minimize treatment delay (Treatment Disparities in Adult vs. Pediatric IBD Care Related to Provider Specialization)
  • Parents help limit diagnostic delay in their children

My take: There are many places that are far away from pediatric specialists. This results in diagnostic delays.

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Mai Khao Beach, Phuket, Thailand

Triple Therapy for Cystic Fibrosis May Improve Liver Damage

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S Diemer et al. JPGN 2025; DOI: 10.1002/jpn3.70050. Open Access! The effect of elexacaftor–tezacaftor–ivacaftor on liver stiffness in children with cystic fibrosis

In this retrospective study, 12 of 21 patients had cystic fibrosis hepato-biliary involvement (CFHBI). The authors examined the liver stiffness after administration of the new and highly potent CF transmembrane conductance regulator modulator therapy, elexacaftor–tezacaftor–ivacaftor (ETI). All of the patients in this cohort had normal liver enzymes.

Key findings:

  • Analyzing liver stiffness in CwCF with CFHBI showed a decline to 5.7 kPa median (IQR: 3.9–7.1) during ETI treatment, and this decline was statistically significant (W = −60, n = 12, p = 0.0161) (Figure 3B) (after at least 3 months of ETI treatment)
Liver stiffness over time in patients with CFHBI

Discussion Points:

“Our findings of a clear improvement of liver stiffness in CwCF and CFHBI during ETI treatment is in line with the recently published study by Terlizzi et al.28  Calvo et al. prospectively investigated liver stiffness and liver enzyme development in a single-centre cohort with a starting point before ETI and a follow-up at 1, 3 and 6 months on ETI…A significant overall reduction in mean liver stiffness was found at 6 months, and already after 1 month of ETI, a decline in liver stiffness was observed in those with values ≥5 kPa.29“

My take: Liver stiffness is a biomarker for chronic liver damage. Longer term studies will be needed to determine how important triple therapy is for liver health in persons with cystic fibrosis. Thus far, there has not been improvement in the number of patients with CF needing a liver transplant; however, there has been a marked improvement in the need for lung transplantation.

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Impact of Disease Severity on Eosinophilic Esophagitis Treatment Responses

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CC Reed et al. Clinical Gastroenterology and Hepatology 2025; Worsening Disease Severity as Measured by I-SEE Associates With Decreased Treatment Response to Topical Steroids in Eosinophilic Esophagitis Patients

This was a retrospective study with children and adults with eosinophilic esophagitis (EoE). Among 1312 patients, there were 657 (50%), 461 (35%), and 194 (15%) with mild, moderate, and severe disease by I-SEE, respectively. Disease activity was categorized as mild (I-SEE 1–6), moderate (I-SEE 7–14), or severe (I-SEE ≥15).

Key findings:

  • Patients with severe disease were less likely to have histologic response (49% (severe) vs 55% (moderate) vs 64% (mild); P = .03 for <15 eosinophils per high-power field) 
  • Patients with severe EoE also had lower global symptom response rates (53% vs 79% vs 83%, respectively) and higher post-treatment EoE Endoscopic Reference Scores (EREFS; 3.6 ± 2.3 vs 2.4 ± 1.8 vs 1.6 ± 1.6, respectively)

My take: More severe disease is harder to treat with EoE (and most everything else too).

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Link: I-SEE Tool Scoring Table

Crazy wiring in Chiang Mai, Thailand (but prevalent in many areas of Thailand)

How Gut Bacteria Might Increase Colon Cancer Risk in Young Adults

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Will Stone, NPR 4/25/25: Damage from gut bacteria may play a role in the rise in colon cancer in young adults

An excerpt:

It’s unclear why colon cancer cases have doubled in people under 55 over the past two decades, a staggering rise that has alarmed doctors and cancer researchers.

But part of the story could be colibactin, a toxin made by certain strains of E. coli and other bacteria. In a study out this week, researchers have identified a strong link between this DNA-damaging toxin and colon cancer among younger patients.

The team, based at the University of California, San Diego, analyzed tissue samples from close to 1,000 colorectal cancer patients across four continents. They found the majority had cancers bearing mutations that signaled a past encounter with colibactin.

“You can think of it as the weapon system of a bacteria to fight other bacteria and to defend themselves,” says Ludmil Alexandrov, the lead author of the study, which was published in Nature this week.

Strikingly, those under the age of 40 with early-onset colon cancer were three to five times more likely to have these mutations than those in their 70s and older.

The thinking goes that in some people, this bacterial weaponry — technically called a “genotoxin” — can get directed at their gut cells, seeding mutations that put them at increased risk of developing colorectal cancer.

According to their data, this exposure isn’t ongoing when the cancer is diagnosed. Instead, it appears to have happened during childhood.

“Our estimate is that it happens within the first 10 years of life,” Alexandrov says. “So if you get that mutation at age 5, that puts you 20 to 30 years ahead of schedule for getting colorectal cancer.”

While the study shows a strong association, the data can’t prove colibactin caused these patients to develop cancer at a younger age. And researchers in the field don’t expect E. coli, or any single microbe for that matter, to be the skeleton key for the surge in colorectal cancer.

Related article: M Diaz-Gay, et al. Nature https://doi.org/10.1038/s41586-025-09025-8 (2025). Geographic and age variations in mutational processes in colorectal cancer

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View from plane over Thailand

“A Good Doctor Knows When to Bend The Rules”

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Yesterday’s post, Cholangiocarcinoma Risk in Pediatric PSC-IBD Plus one, was updated with the following caveats:

At the same time, the authors acknowledge limitations including a highly-selected patient population (selection bias) and relatively small number of patients. The absolute increase in risk for cholangiocarcinoma is not known. This study did not provide an estimate of the number of patients with IBD-PSC who develop cholangiocarcinoma; it only provides data on those with cholangiocarcinoma (thus no denominator to establish risk).

Daniela Lamas, NY Times 4/20/25 (likely has a paywall): A Good Doctor Knows When to Bend The Rules

An excerpt:

“My patient had been intubated with Covid-19 for weeks, her lungs growing stiffer each day. Her sons held vigil at the bedside, pausing only to critique the nurses and health care team. They didn’t like the way the nurse turned their mother. They demanded yet another course of antiviral treatment for Covid-19…The son pulled a pill bottle from his backpack. It was a mixture of herbs that he had ordered off the internet. He wanted me give the supplement to his mother through her feeding tube, along with her other medications…

Doctors may agree to give their patients probiotics because they are harmless, even though the evidence for their effectiveness is weak in most cases. They might prescribe an unnecessary antibiotic. They might even agree to spread out the timing of pediatric vaccinations at a family’s insistence...

For Dr. Brown…he could justify prescribing the drug to build rapport…Dr. Van Scoy sees acceding to requests for unproven medicines as a “slippery slope.” When doctors prescribe medications that they don’t believe in, even ones that pose little risk to the patient, it can cost them the trust of their colleagues…

But when distrust is so entrenched, as is the case in the United States now, that ideal might not be achievable — especially in our conventional clinical practices where doctors have some 15 minutes with each patient…

We ask our patients to trust us implicitly, to believe our diagnoses and to undergo courses of treatment they might not understand. This doesn’t mean that we need to give patients whatever they want just to level the playing field. But we can take their requests seriously, even if we wouldn’t have considered them otherwise.”

My take: In the pediatric GI realm, I am often asked to do low yield procedures (eg. esophagogastroduodneoscopy, colonoscopy), low yield imaging (eg. MRI, CT scans), allergy testing as well as numerous dubious treatments.

One measure of how likely physicians in our group are at ‘bending’ to patient wishes is evident in study that we did looking at the yield from colonoscopy. Among 16 physicians, the diagnostic yield ranged as low as 22% to as high as 86% with an overall diagnostic yield of 48% for colonoscopy. Thus, it is clear that physicians have widely different approaches in accommodating family pressures.

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Phuket, Thailand
Floating flowers in large vase

Cholangiocarcinoma Risk in Pediatric PSC-IBD Plus one

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B Kaj‐Carbaidwala et al. J Pediatr Gastroenterol Nutr. 2025; 80:450–454. Determining the time to cholangiocarcinoma in pediatric‐onset PSC‐IBD

Background: “Cholangiocarcinoma is a devastating disease, with up to 80% mortality and limited treatment options…A large retrospective cohort study reported that cholangiocarcinoma occurred in 1000 per 100,000 (1%) of children with PSC, with all occurring in children over 15 years of age and at a median of 6 years after the PSC diagnosis…Primary sclerosing cholangitis (PSC) is associated with a 400× increased risk of cholangiocarcinoma.”

Methods: Review of n = 175 studies resulted in a cohort of n = 21 patients with pediatric‐onset PSC‐IBD‐cholangiocarcinoma

Key findings:

  • The earliest diagnosis of cholangiocarcinoma was made at 14 years of age.
  • 14% of of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 6 months of the second diagnosis
  • 23% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first year of the second diagnosis
  • 38% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 2 years.
  • 50% of patients with pediatric‐onset PSC/IBD developed cholangiocarcinoma within the first 7 years
  • 50% of patients were between 14 and 25 years old when diagnosed with cholangiocarcinoma

Based on these data, the authors recommend screening for cholangiocarcinoma in this population of pediatric patients with IBD-PSC. Screening would include ultrasound or magnetic resonance cholangiopancreatography along with serum cancer antigen 19‐9 screening every 6–12 months. At the same time, the authors acknowledge limitations including a highly-selected patient population (selection bias) and relatively small number of patients. The absolute increase in risk for cholangiocarcinoma is not known. This study did not provide an estimate of the number of patients with IBD-PSC who develop cholangiocarcinoma; it only provides data on those with cholangiocarcinoma (thus no denominator to establish risk).

My take: Children, particularly adolescents, with IBD-PSC are at increased risk for both cholangiocarcinoma and colorectal cancer. The optimal surveillance strategy is still unclear. However, particularly in adolescents, I would favor yearly ultrasound and CA 19-9 for cholangiocarcinoma along with a low threshold for frequent colonoscopy (see ESPGHAN guidelines below).

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In the news: AP 5/4/25: Cuts have eliminated more than a dozen US government health-tracking programs “U.S. Health Secretary Robert F. Kennedy Jr.’s motto is “ Make America Healthy Again,” but government cuts could make it harder to know if that’s happening…..Among those terminated at the Centers for Disease Control and Prevention were experts tracking abortions, pregnancies, job-related injuries, lead poisonings, sexual violence and youth smoking, the AP found.”

Anantara Resort, Mai Khao Phuket

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.

Infection Risks with Biologic Switches: Findings from Recent Study

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Briefly noted: AJ Kruger et al. Clinical Gastroenterology and Hepatology 2025. Biologic switch timing and risk of infection in patients with ulcerative colitis/Crohn’s disease: a retrospective study

Methods: This was a “real-world practice” retrospective study (2017-2022) with 11,992 adult patients who were newly initiating a biologic therapy for UC/CD. 1,293 patients underwent a biologic switch, 64.2% of which were considered an overlapping switch (OS).

Key findings:

  • Adjusted incidence ratio IR) per 1,000 person years, for any infection, were comparable across switching groups. No significant differences in aHR of infections were found between OS and NOS [any infection aHR: 1.40, P=.17; serious infection aHR: 0.95, P=.93].

My take (borrowed from authors): “Overlapping switches were common and not associated with an increased risk of serious infection versus non-overlapping biologics.” Thus, shortened washout periods appear to pose minimal safety risks to patients while improving UC/CD therapy management.

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Bohicket Creek near Charleston, SC

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..