Enterochromaffin Cells: Sentinels to Gut Microbiota in Hyperalgesia?

Xu, Xiaolin; Chen, Rongmin; Zhan, Gaofeng; Wang, Danning; Tan, Xi; Xu, Hui

doi:10.3389/fcimb.2021.760076

Cited by 23 publications

(15 citation statements)

References 162 publications

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“…Nowadays, it is possible to better understand these latter findings as described in Section 2.1 for EECs and as indicated in these references [ 42 , 43 , 44 ].…”

Section: Ultrastructural Features Of Enterochromaffin Cells and Their...mentioning

confidence: 91%

“…The above findings suggest a very useful role of 5-HT release from ECs, but it has been found that the proliferation of these cells and high presence of 5-HT in their vesicles are involved in visceral sensitization and hyperalgesia in irritable bowel syndrome [ 43 ]. If some receptors on duodenal mucosa ECs such as free fatty acid receptors are activated, ECs protect the small intestine mucosa regulating 5-HT biosynthesis and release, but if the stimulation of the receptors is excessive can induce the abnormal release of 5-HT.…”

Section: Heterogeneity Of Enterochromaffin Cellsmentioning

confidence: 99%

“…Excessive release of 5-HT can cause mucosal damage and a reduction in blood flow [ 73 ]. In this case, ECs are sentinels for sensing the variations in gut mechanisms and their functions are not yet well known; Xu et al, (2021) and Bi et al, (2021) demonstrated that knockout mice for 5-HT transporters showed visceral sensitization, GI disorders and an increased the relative proportion of ECs and colon 5-HT concentration [ 43 , 74 ]. This mechanism has been explained by suggesting that the release of 5-HT from ECs is related to adenosine triphosphate; this can activate the pain network to the brain through afferent nerve fibers and enteric nerve reflex [ 74 ].…”

Section: Heterogeneity Of Enterochromaffin Cellsmentioning

confidence: 99%

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A Focus on Enterochromaffin Cells among the Enteroendocrine Cells: Localization, Morphology, and Role

Rezzani

Franco

Franceschetti

et al. 2022

IJMS

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The intestinal epithelium plays a key role in managing the relationship with the environment, the internal and external inputs, and their changes. One percent of the gut epithelium is represented by the enteroendocrine cells. Among the enteroendocrine cells, a group of specific cells characterized by the presence of yellow granules, the enterochromaffin cells, has been identified. These granules contain many secretion products. Studies showed that these cells are involved in gastrointestinal inflammatory conditions and hyperalgesia; their number increases in these conditions both in affected and not-affected zones of the gut. Moreover, they are involved in the preservation and modulation of the intestinal function and motility, and they sense metabolic–nutritional alterations. Sometimes, they are confused or mixed with other enteroendocrine cells, and it is difficult to define their activity. However, it is known that they change their functions during diseases; they increased in number, but their involvement is related mainly to some secretion products (serotonin, melatonin, substance P). The mechanisms linked to these alterations are not well investigated. Herein, we provide an up-to-date highlight of the main findings about these cells, from their discovery to today. We emphasized their origin, morphology, and their link with diet to better evaluate their role for preventing or treating metabolic disorders considering that these diseases are currently a public health burden.

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“…Nowadays, it is possible to better understand these latter findings as described in Section 2.1 for EECs and as indicated in these references [ 42 , 43 , 44 ].…”

Section: Ultrastructural Features Of Enterochromaffin Cells and Their...mentioning

confidence: 91%

Section: Heterogeneity Of Enterochromaffin Cellsmentioning

confidence: 99%

Section: Heterogeneity Of Enterochromaffin Cellsmentioning

confidence: 99%

See 1 more Smart Citation

A Focus on Enterochromaffin Cells among the Enteroendocrine Cells: Localization, Morphology, and Role

Rezzani

Franco

Franceschetti

et al. 2022

IJMS

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“…Several GI-derived peptides are also synthesized within the brain, where they act as neuromodulators and/or neurotransmitters [ 4 ]. In this context, another important player has more recently emerged, the gut microbiota, whose interaction with GI hormones seems to have a key role in the effects of diets and improving the treatment of some intestinal disorders [ 7 , 8 ]. This adds a layer of complexity in terms of characterizing the physiologic role of GI-derived peptides.…”

Section: Introductionmentioning

confidence: 99%

Adrenomedullin: Not Just Another Gastrointestinal Peptide

Martínez-Herrero

Martı́nez

2022

Biomolecules

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Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are two bioactive peptides derived from the same precursor with several biological functions including vasodilation, angiogenesis, or anti-inflammation, among others. AM and PAMP are widely expressed throughout the gastrointestinal (GI) tract where they behave as GI hormones, regulating numerous physiological processes such as gastric emptying, gastric acid release, insulin secretion, bowel movements, or intestinal barrier function. Furthermore, it has been recently demonstrated that AM/PAMP have an impact on gut microbiome composition, inhibiting the growth of bacteria related with disease and increasing the number of beneficial bacteria such as Lactobacillus or Bifidobacterium. Due to their wide functions in the GI tract, AM and PAMP are involved in several digestive pathologies such as peptic ulcer, diabetes, colon cancer, or inflammatory bowel disease (IBD). AM is a key protective factor in IBD onset and development, as it regulates cytokine production in the intestinal mucosa, improves vascular and lymphatic regeneration and function and mucosal epithelial repair, and promotes a beneficial gut microbiome composition. AM and PAMP are relevant GI hormones that can be targeted to develop novel therapeutic agents for IBD, other GI disorders, or microbiome-related pathologies.

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“…The proliferation of enterochromaffin (EC) cells and increased release of 5-hydroxytryptamine (5-HT) have been shown to contribute to the development of visceral sensitization and peripheral mechanical hyperalgesia in IBS (6)(7)(8)(9). It has been estimated that only 5% of the body's 5-HT is stored in the central nervous system and 95% is stored in the gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture Attenuates Post-Inflammatory IBS-Associated Visceral and Somatic Hypersensitivity and Correlates With the Regulatory Mechanism of Epac1–Piezo2 Axis

Guo

Chen²,

Wang³

et al. 2022

Front. Endocrinol.

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Electroacupuncture (EA) is considered to have a therapeutic effect in the relief of irritable bowel syndrome (IBS)-associated visceral hypersensitivity via the reduction of the level of 5‐hydroxytryptamine (5‐HT) and 5-HT3 receptors (5-HT3R). However, whether Epac1/Piezo2, as the upstream of 5-HT, is involved in this process remains unclear. We investigated whether EA at the ST36 and ST37 acupoints alleviated visceral and somatic hypersensitivity in a post-inflammatory IBS (PI-IBS) model mice via the Epac1-Piezo2 axis. In this study, we used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS as a mouse model. Visceral sensitivity was assessed by the abdominal withdrawal reflex test. Somatic sensitivity was evaluated by the hind paw withdrawal threshold. Quantitative real-time PCR, immunofluorescence staining, ELISA, and Western blotting were performed to examine the expressions of Epac1, Piezo2, 5-HT, and 5-HT3R from the mouse distal colon/L5–S2 dorsal root ganglia (DRG). Our results showed that EA improved the increased visceral sensation and peripheral mechanical hyperalgesia in PI-IBS model mice, and the effects of EA were superior to the sham EA. EA significantly decreased the protein and mRNA levels of Epac1 and Piezo2, and reduced 5-HT and 5-HT3R expressions in the distal colon. Knockdown of colonic Piezo2 eliminated the effect of EA on somatic hypersensitivity. Combined knockdown of colonic Epac1 and Piezo2 synergized with EA in relieving visceral hypersensitivity and blocked the effect of EA on somatic hypersensitivity. Additionally, protein levels of Epac1 and Piezo2 were also found to be decreased in the L5–S2 DRGs after EA treatment. Taken together, our study suggested that EA at ST36 and ST37 can alleviate visceral and somatic hypersensitivity in PI-IBS model mice, which is closely related to the regulation of the Epac1–Piezo2 axis.

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Enterochromaffin Cells: Sentinels to Gut Microbiota in Hyperalgesia?

Cited by 23 publications

References 162 publications

A Focus on Enterochromaffin Cells among the Enteroendocrine Cells: Localization, Morphology, and Role

A Focus on Enterochromaffin Cells among the Enteroendocrine Cells: Localization, Morphology, and Role

Adrenomedullin: Not Just Another Gastrointestinal Peptide

Electroacupuncture Attenuates Post-Inflammatory IBS-Associated Visceral and Somatic Hypersensitivity and Correlates With the Regulatory Mechanism of Epac1–Piezo2 Axis

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