Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome

Hasler, William L.; Grabauskas, Gintautas; Singh, Prashant; Owyang, Chung

doi:10.1111/nmo.14339

Cited by 49 publications

(34 citation statements)

References 150 publications

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“…However, we found little or no response, which may suggest that MSG signals through receptors on intermediary pathways such as mast cells or enterochromaffin cells or enterocytes, which in turn release pronociceptive mediators such as histamine and 5-HT, respectively. [37][38][39] In keeping with this reasoning, we did not observe visceral hypersensitivity in the chronic WAS + MSG mice that were exposed to vehicle alone in the lumen. This argues against hypersensitivity intrinsic to the nerves following WAS + MSG and could imply heightened signaling in an intermediary pathway situated between the acute luminal exposure to MSG and the nerves (see graphical abstract).…”

Section: Discussionsupporting

confidence: 78%

“…Together this suggested that tissue glutamate concentration would be greater in these mice, and we therefore tested whether MSG signals directly to small intestinal afferents by superfusing MSG directly into the bath (rather than through the lumen). However, we found little or no response, which may suggest that MSG signals through receptors on intermediary pathways such as mast cells or enterochromaffin cells or enterocytes, which in turn release pronociceptive mediators such as histamine and 5‐HT, respectively 37–39 . In keeping with this reasoning, we did not observe visceral hypersensitivity in the chronic WAS + MSG mice that were exposed to vehicle alone in the lumen.…”

Section: Discussionsupporting

confidence: 71%

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Dietary monosodium glutamate increases visceral hypersensitivity in a mouse model of visceral pain

Brant

Omar

et al. 2023

Neurogastroenterology Motil

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BackgroundMonosodium glutamate (MSG) has been identified as a trigger of abdominal pain in irritable bowel syndrome (IBS), but the mechanism is unknown. This study examined whether MSG causes visceral hypersensitivity using a water‐avoidance stress (WAS) mouse model of visceral pain.MethodsMice were divided into four groups receiving treatment for 6 days: WAS + MSG gavage, WAS + saline gavage, sham‐WAS + MSG gavage, and sham‐WAS + saline gavage. The acute effects of intraluminal administration of 10 μM MSG on jejunal extrinsic afferent nerve sensitivity to distension (0–60 mmHg) were examined using ex vivo extracellular recordings. MSG was also applied directly to jejunal afferents from untreated mice. Glutamate concentration was measured in serum, and in the serosal compartment of Ussing chambers following apical administration.Key ResultsAcute intraluminal MSG application increased distension responses of jejunal afferent nerves from mice exposed to WAS + MSG. This effect was mediated by wide dynamic range and high‐threshold units at both physiologic and noxious pressures (10–60 mmHg, p < 0.05). No effect of MSG was observed in the other groups, or when applied directly to the jejunal afferent nerves. Serum glutamate was increased in mice exposed to WAS + MSG compared to sham‐WAS + saline, and serosal glutamate increased using WAS tissue (p = 0.0433).Conclusions and InferencesThese findings demonstrate that repeated exposure to MSG in mice leads to sensitization of jejunal afferent nerves to acute ex vivo exposure to MSG. This may contribute to visceral hypersensitivity reported in response to MSG in patients with IBS.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 71%

Dietary monosodium glutamate increases visceral hypersensitivity in a mouse model of visceral pain

Brant

Omar

et al. 2023

Neurogastroenterology Motil

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“…They also directly affect the gut microbiota and enteric nervous system [ 2 ]. Low-grade inflammation and related impaired intestinal permeability, specific conditions linked to IBS pathophysiology, at least in a subgroup of patients, can contribute to heightened visceral sensation and its onset along with pain [ 42 ]. Lastly, changes in gut microbiota could contribute to inducing such symptoms [ 43 ], even if attempts to modify intestinal bacterial populations by administering probiotics or antibiotics have produced conflicting or no results [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

A Tritordeum-Based Diet for Female Patients with Diarrhea-Predominant Irritable Bowel Syndrome: Effects on Abdominal Bloating and Psychological Symptoms

et al. 2023

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Most female patients with irritable bowel syndrome (IBS) complain of abdominal bloating rather than abdominal pain and diarrhea. The higher incidence in women could be due to the so-called dysfunctional gas handling. Since diet seems the most effective and durable strategy for managing IBS symptoms, we aimed to evaluate the effects of a 12 week diet based on a relatively new cereal, Tritordeum (TBD), on gastrointestinal (GI) symptoms, anthropometric and bioelectrical impedance parameters, and psychological profiles in 18 diarrhea-predominant IBS (IBS-D) female patients with abdominal bloating as the dominant symptom. The IBS Severity Scoring System (IBS-SSS), the Symptom Checklist-90 Revised, the Italian version of the 36-Item Short-Form Health Survey, and the IBS-Quality of Life questionnaire were administered. The TBD reduces the IBS-SSS “Intensity of abdominal bloating” with a concomitant improvement in the anthropometric profile. No correlation was found between “Intensity of abdominal bloating” and “Abdominal circumference”. Anxiety, depression, somatization, interpersonal sensitivity, and phobic and avoidance manifestations were significantly reduced after TBD. Lastly, anxiety was correlated with “Intensity of abdominal bloating”. Overall, these results suggest the possibility of lowering abdominal bloating and improving the psychological profile of female IBS-D patients using a diet based on an alternative grain such as Tritordeum.

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“…Mast cells release potent mediators that alter enteric nerve and smooth muscle function and may play a vital role in the pathogenesis of IBS (36). The close proximity of the mast cells to the enteric nerves offers important potential for inducing changes in nerve function and the development of heightened visceral sensitivity (37). This may be one of the reasons causing higher incidence and more serious symptoms in female patients with IBS.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers functioning in the lipid-induced IBS symptoms

Ran

et al. 2023

Preprint

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Background: Fat intake is one of the most important triggers for symptom development in patients with irritable bowel syndrome (IBS). But long-term restriction in fatty foods ingestion may lead to nutritional inadequacies. In this study, we aim to identify the vital genes that function in lipid-induced gastrointestinal symptoms, contributing to precise management of fat control for IBS patients. Methods: The clinical characteristics of the subjects were collected by questionnaire investigation and analyzed using multivariate logistic regression. Differentially expressed genes (DEG) and signaling pathways were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The infiltrated immune cells in the small intestinal mucosa were analyzed using ImmuInfiltration and CIBERSORT packages. Random forest and SVM-RFE algorithms were used to select hub genes. A receiver operating characteristic curve (ROC) was performed to evaluate the diagnostic significance of each hub gene. Gene Set Enrichment Analysis (GSEA) was conducted to clarify the possible molecular mechanisms of hub genes in the pathogenesis of IBS after lipid infusion. Results: Fat intake was positively associated with the risk, severity, and quality of life (QOL) of IBS patients. A total of 116 robust DEGs were identified in patients with IBS after lipid infusion using the GSE166869 dataset and were mainly clustered in the immune and inflammatory pathways. The infiltration levels of Neutrophils, CD4+T cells and M1 Macrophages were significantly higher in IBS patients compared to the healthy controls. Furthermore, infiltration levels of Neutrophils and resting memory CD4+ T cells were inversely related to the expression of hub genes (IGKV1D-43, IGKV1-12, APOD, FCGR2A and IGKV2-29). GSEA results of each hub gene suggested the importance of pro-inflammatory pathways in IBS pathogenesis after lipid infusion. After verification, only APOD and FCGR2A were stably down-regulated in both small intestinal mucosa and plasma of IBS patients. The area under the curve of APOD combined with FCGR2A expression was 0.9. Conclusions: APOD and FCGR2A may act as promising biomarkers for discriminating lipid-sensitive IBS patients and IBS diagnosis. Their potential roles in the immune microenvironment of the small intestinal mucosa may provide a vital clue to IBS precision therapy.

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Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome

Cited by 49 publications

References 150 publications

Dietary monosodium glutamate increases visceral hypersensitivity in a mouse model of visceral pain

Dietary monosodium glutamate increases visceral hypersensitivity in a mouse model of visceral pain

A Tritordeum-Based Diet for Female Patients with Diarrhea-Predominant Irritable Bowel Syndrome: Effects on Abdominal Bloating and Psychological Symptoms

Identification of biomarkers functioning in the lipid-induced IBS symptoms

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