Key Advances in 2024: An Overview from GutsandGrowth (Part 4)

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This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Key Advances in 2024: An Overview from GutsandGrowth (Part 3)

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This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Key Advances in 2024: An Overview from GutsandGrowth (Part 2)

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This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Key Advances in 2024: An Overview from GutsandGrowth (Part 1)

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This year I had the opportunity to give a lecture to our group that reviewed much of the important advances that happened in 2024. Here are some of the slides (if you have any trouble reading the slides, you can search for the original blog post using author name).

Fecal Microbiota Transplantation for Severe Constipation in Children

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Methods: The efficacy of retrograde colonic enema (RCE) with fecal microbiota transplantation (FMT) was studied in a randomized, double-blind, controlled trial with 110 children. The initial cohort recruited was 576 patients; however, 466 were excluded for not meeting inclusion criteria. All participants received a daily RCE, followed by a 4-week FMT treatment (twice a week) and a 12-week follow-up period. 

Key findings:

  • At the end of the follow-up period, 22 patients (40.0%) in the FMT with RCE group and 10 patients (18.2%) in the placebo with RCE group had ≥ 3 spontaneous bowel movements per week

There was a low response to RCE alone which the authors attributed in part to the severity of constipation in the cohort. It is unclear the degree of compliance with the treatment protocol which was done in the home setting. There was a prior open-label study with NJ FMT which improved constipation in half of participants.

My take: Modulating the microbiome can have beneficial effects on stool frequency. This can be through diet and possibly FMT in severe cases of constipation. The availability of capsules could make this type of therapy easier but perhaps less palatable. Even if FMT proves to be a useful treatment, the optimal treatment regimen is not clear.

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Understanding Alcohol’s Cancer Risks and Warnings

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NY Times and USAToday both reported on this topic earlier this month:

An excerpt from USAToday report:

According to the Centers for Disease Control and Prevention, alcohol consumption is the third-leading preventable cause of cancer in the United States, after tobacco and obesity. And according to the report released by Murthy’s office, it increases the risk for at least seven types of cancer…

In a post on X, Murthy said alcohol contributes to about 100,000 cancer cases and 20,000 cancer deaths annually in the U.S., a number greater than the 13,500 alcohol-related traffic accidents each year.

Murthy is calling on Congress to act to update the labels to include an increased risk of the following cancers linked to alcohol consumption:

  • Breast
  • Colon
  • Throat
  • Liver
  • Voice box
  • Esophagus
  • Mouth

From NY Times:

While most cancer deaths occur at drinking levels that exceed the current recommended dietary guidelines, the risk for cancers of the breast, the mouth and the throat may rise with consumption of as little as one drink a day, or even less, Dr. Murthy said on Friday.

Overall, one of every six breast cancer cases is attributable to alcohol consumption, Dr. Murthy said. …

The World Health Organization says there is no safe limit for alcohol consumption…The most widely accepted theory is that inside the body, alcohol breaks down into acetaldehyde, a metabolite that binds to DNA and damages it, allowing a cell to start growing uncontrollably and creating a malignant tumor.

My take: It is surprising that alcohol is attributed to causing more deaths due to cancer than due to motor vehicle accidents.

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Atlanta Botanical Gardens

Efficacy of Anthocyanin-Rich Extract in Ulcerative Colitis

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L Beidermann et al. Nutrients. 2024;16(23):4197. Open Access! Efficacy and Safety of Anthocyanin-Rich Extract in Patients with Ulcerative Colitis: A Randomized Controlled Trial

First of all: Bilberries are similar to blueberries, but have red inner flesh rather than white flesh.

Background: The authors note that some small studies have shown that anthocyanin-rich extract (ACRE), the bioactive ingredient of bilberries, has been effective for ulcerative colitis (UC)

“ACs have been associated with many protective biological effects, including anti-oxidative, anti-carcinogenic, antimicrobial, and anti-inflammatory properties [17,20,21]. Due to their phenolic structure, ACs exhibit an anti-oxidative capacity in vivo as they scavenge reactive oxygen species (ROS) [20,22], also a classical effect of 5-ASA [23]. After ingestion, ACs largely bypass absorption in the upper gastrointestinal tract, reaching the colon intact, where they are metabolized by microbiota through deglycosylation and further degraded into vanillic, protocatechuic, p-coumaric, gallic, and syringic acids (i.e., phenolic acids) [24]. ACs interrupt the pro-inflammatory signaling and are inhibitors of 5-lipoxygenase, a key enzyme implicated in the arachidonic acid pathway for the biosynthesis of active leukotrienes.”

Methods: A multi-center, randomized, placebo-controlled, double-blind study with a parallel group was conducted. Due to COVID-19’s effect on study enrollment, only 34 patients were randomized and only Eighteen ACRE and eight placebo patients could be analyzed (per protocol set)

Key finding:

  • Half (9/18) of ACRE patients and 3/8 of placebo patients responded clinically (p = 0.278). An improvement in the Mayo score was observed in the ACRE arm (77.8% vs. 62.5% placebo).
  • Fecal calprotectin (FC) dropped from 1049 ± 1139 to 557 ± 756 μg/g for ACRE but not for the placebo group (947 ± 1039 to 1040 ± 1179; p = 0.035).

The authors state that the placebo group had an unusually high response and that improved FC with ACRE patients indicates efficacy in UC.

Figure 2
Figure 3

My take: This is a negative study (despite the secondary finding of improved FC at some timepoints). Importantly, the study did not demonstrate any harms in the ACRE group. It did help me understand more about bilberries!

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Weird Xray and Successful Treatment for Water Bead Ingestion

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C Hoffman et al. J Pediatr Gastroenterol Nutr. 2024;78:448–449. Open Access! Orbeez ingestion: Successful medical management of1000 absorbent bead ingestion in a 3‐year‐old patient

An excerpt:

“There is no consensus regarding optimal management in instances of Orbeez™ ingestion. However, a review of reported cases from 2021 indicated that of 43 cases of bowel obstruction secondary to water bead ingestions, two patients required endoscopic removal and the remaining 41 required surgical enterotomy or intestinal resection. We report a case of successful medical management following ingestion of over 1000 water beads…The patient was placed on a clear liquid diet and received a mineral oil enema with minimal passage of beads. She was then started on sennosides and erythromycin ethylsuccinate to help stimulate expulsion. Stools were closely monitored and revealed passage of greater than 1000 beads over the next 24 h.”

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More Data Indicating GLP-1 Efficacy for MASH

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GI and Hepatology News, Open Access: Watershed Moment’: Semaglutide Shown to Be Effective in MASH (November 2024): “At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.”

“ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.” Cohort: N=1200, biopsy-defined MASH and fibrosis, stages F2 and F3…”After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.”

Key findings:

  • 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. 
  • 37% of those in the semaglutide group and 22.5% of those in the placebo group had improvement in liver fibrosis with no worsening of steatohepatitis
  • Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group
  • No new safety signals were identified
  • Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.
  • 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.

My take: This expected finding indicates that more GLP-1 agents are likely to be approved for MASH treatment. Survodutide received “U.S. FDA Breakthrough Therapy” in October 2024.

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Manuel Antonio National Park, Costa Rica