Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments

Ford, Alexander C.; Vanner, Stephen; Kashyap, Purna C.; Nasser, Yasmin

doi:10.1053/j.gastro.2024.01.045

Cited by 6 publications

(1 citation statement)

References 146 publications

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“…Together, these data indicate that ReFerm ® affects the levels of MCT in the tissue without reducing the number of mast cells present. Stabilizing mast cells as well as targeting their mediators, such as tryptase, histamine, vasoactive intestinal polypeptide, or serotonin, has been of interest for many years ( 38 , 39 ), demonstrating modestly promising results, corroborating the ground truth about the multifaceted etiology of the disease and the need for combination therapies. Our findings show decreased mast cell degranulation by ReFerm ® , which further emphasizes the importance of mast cell activation in IBS pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

ReFerm®: a postbiotic fermented oat gruel composition is reducing mast cell degranulation in the colon of patients with irritable bowel syndrome

Biskou,

Walter,

Israelsen

et al. 2024

Front. Med.

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BackgroundIrritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder that affects ~4% of the global population. ReFerm® is a postbiotic product derived from oat gruel fermented with Lactobacillus plantarum 299v, and it has been shown to have beneficial effects on intestinal permeability in patients with IBS. In this study, we investigated the effects of ReFerm® on regulators of intestinal permeability, namely mast cells and enteric glial cells.Materials and methodsA total of 30 patients with moderate to severe IBS were treated with an enema containing ReFerm® or a placebo twice daily. The patients underwent sigmoidoscopy with biopsies obtained from the distal colon at baseline and after 14 days of treatment. These biopsies were processed in two ways: some were fixed, embedded in paraffin, sectioned, and stained for mast cells and enteric glial cells; others were cryopreserved, lysed, and subjected to Western blotting to analyze the same markers.ResultsTreatment with ReFerm®, but not the placebo, significantly reduced mast cell tryptase protein levels in the biopsy lysates. Although the number of mast cells remained unchanged in colonic biopsies, ReFerm® treatment significantly reduced mast cell degranulation, a result not observed in the placebo group. Neither ReFerm® or placebo treatment had an impact on total protein levels or the number of enteric glial cells in the biopsies.ConclusionReFerm® treatment significantly reduced both total mast cell tryptase levels and the degranulation of mast cells in colonic biopsies from patients with IBS, suggesting a decrease in mast cell activity as a potential mechanism underlying the beneficial effects of ReFerm®. However, further research is required to assess the molecular mechanisms through which ReFerm® operates in the colons of patients with IBS.Clinical trial registrationhttps://clinicaltrials.gov, identifier: NCT05475314.

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Section: Discussionmentioning

confidence: 99%

ReFerm®: a postbiotic fermented oat gruel composition is reducing mast cell degranulation in the colon of patients with irritable bowel syndrome

Biskou,

Walter,

Israelsen

et al. 2024

Front. Med.

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Breaking Down the Pain Pathway: Bacterial Proteases Activate Nociceptors to Cause Pain

Altier

2024

Cellular and Molecular Gastroenterology and Hepatology

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The role of the gut microbiome in disorders of gut–brain interaction

Gawey,

Mars,

Kashyap

2024

The FEBS Journal

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Disorders of Gut‐Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large‐scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite‐host interactions, offering exciting possibilities for the future of treatment of DGBI.

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Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments

Cited by 6 publications

References 146 publications

ReFerm®: a postbiotic fermented oat gruel composition is reducing mast cell degranulation in the colon of patients with irritable bowel syndrome

ReFerm®: a postbiotic fermented oat gruel composition is reducing mast cell degranulation in the colon of patients with irritable bowel syndrome

Breaking Down the Pain Pathway: Bacterial Proteases Activate Nociceptors to Cause Pain

The role of the gut microbiome in disorders of gut–brain interaction

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