Female serotonin transporter‐knockout rat: A potential model of irritable bowel syndrome

Bi, Zijuan; Zhang, Shisheng; Meng, Yangyang; Feng, Yanjun; Wang, Yinshu; Wang, Enkang; Pan, Xuran; Zhu, Rong; Fan, Haiting; Pang, Shuhua; Zhu, Lixin; Yuan, Judy Chia Chun

doi:10.1096/fj.202000007rrr

Cited by 14 publications

(12 citation statements)

References 72 publications

(133 reference statements)

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“…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%

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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Section: Heterogeneity Of Enterochromaffin Cellsmentioning

confidence: 99%

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

Rezzani

Franco

Franceschetti

et al. 2022

IJMS

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“…T. spiralis and Campylobacter jejuni reduce SERT expression in the gut [100,101], while L. rhamnosus upregulated gene expression and protein levels of SERT in a rat model of PI-IBS [100], and Lactobacillus acidophilus and Bifidobacterium longum supernatants to upregulate SERT expression in HT-29 and Caco-2 cells [102]. SERT deficiency is related to dysbiosis and changes in the metabolic function of the mouse enteric microbiome [94], and female SERT -/rats showed visceral hypersensitivity and accelerated GI motility [118]. In humans, reduced SERT expression was observed in the rectal tissue of patients with IBS [119].…”

Section: Akkermansia Muciniphilamentioning

confidence: 99%

Enteric Microbiota-Mediated Serotonergic Signaling in Pathogenesis of Irritable Bowel Syndrome

Mishima¹,

Ishihara²

2021

IJMS

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Irritable bowel syndrome (IBS) is a chronic functional disorder that affects the gastrointestinal tract. Details regarding the pathogenesis of IBS remain largely unknown, though the dysfunction of the brain-gut-microbiome (BGM) axis is a major etiological factor, in which neurotransmitters serve as a key communication tool between enteric microbiota and the brain. One of the most important neurotransmitters in the pathology of IBS is serotonin (5-HT), as it influences gastrointestinal motility, pain sensation, mucosal inflammation, immune responses, and brain activity, all of which shape IBS features. Genome-wide association studies discovered susceptible genes for IBS in serotonergic signaling pathways. In clinical practice, treatment strategies targeting 5-HT were effective for a certain portion of IBS cases. The synthesis of 5-HT in intestinal enterochromaffin cells and host serotonergic signaling is regulated by enteric resident microbiota. Dysbiosis can trigger IBS development, potentially through aberrant 5-HT signaling in the BGM axis; thus, the manipulation of the gut microbiota may be an alternative treatment strategy. However, precise information regarding the mechanisms underlying the microbiota-mediated intestinal serotonergic pathway related to the pathogenesis of IBS remains unclear. The present review summarizes current knowledge and recent progress in understanding microbiome–serotonin interaction in IBS cases.

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“…Some studies have found that IL-6, a pro-inflammatory cytokine, is significantly elevated in patients with IBS, which can regulate intestinal secretion and participate in the development of IBS ( O’Brien et al, 2021 ). Regarding the Tryptophan metabolism pathway, studies have found that the decreased serum tryptophan concentration exhibited by SERT –/– rats is associated with visceral hypersensitivity and abnormal gastrointestinal motility ( Bi et al, 2021 ). In addition, the tryptophan metabolic pathway is considered to be one of the main metabolic pathways in the WAS-induced IBS model rats, and the changes in the intestinal microbiota of the model rats are closely related to the changes in tryptophan metabolism ( Mishima and Ishihara, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Metagenomics and metabolomics analysis to investigate the effect of Shugan decoction on intestinal microbiota in irritable bowel syndrome rats

et al. 2022

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BackgroundThe effect of Shugan Decoction (SGD) on intestinal motility and visceral hypersensitivity in Water avoid stress (WAS)-induced diarrhea predominant irritable bowel syndrome (IBS-D) model rats has been confirmed. However, the mechanisms of its action involved in the treatment of IBS-D need to be further studied. Intestinal microbiota plays an important role in maintaining intestinal homeostasis and normal physiological function. Changes in the intestinal microbiota and its metabolites are thought to participate in the pathophysiological process of IBS.AimThis study aimed to analyze the influence of SGD on intestinal microbiota and fecal metabolites in IBS-D rats by multiple omics techniques, including metagenomic sequencing and metabolomics.MethodsWe measured the intestinal motility and visceral sensitivity of three groups of rats by fecal pellets output and colorectal distension (CRD) experiment. In addition, metagenome sequencing analysis was performed to explore the changes in the number and types of intestinal microbiota in IBS-D model rats after SGD treatment. Finally, we also used untargeted metabolomic sequencing to screen the metabolites and metabolic pathways closely related to the therapeutic effect of SGD.ResultsWe found that compared with the rats in the control group, the fecal pellets output of the rats in the WAS group increased and the visceral sensitivity threshold was decreased (P < 0.05). Compared with the rats in the WAS group, the fecal pellets output of the SGD group was significantly decreased, and the visceral sensitivity threshold increased (P < 0.05). Besides, compared with the rats in the WAS group, the relative abundance of Bacteroidetes increased in SGD group, while that of Firmicutes decreased at the phylum level, and at the species level, the relative abundance of Bacteroides sp. CAG:714, Lactobacillus reuteri and Bacteroides Barnesiae in SGD group increased, but that of bacterium D42-87 decreased. In addition, compared with the WAS group, several metabolic pathways were significantly changed in SGD group, including Taurine and hypotaurine metabolism, Purine metabolism, Sulfur metabolism, ABC transporters, Arginine and proline metabolism and Bile secretion.ConclusionSGD can regulate specific intestinal microbiota and some metabolic pathways, which may explain its effect of alleviating visceral hypersensitivity and abnormal intestinal motility in WAS-induced IBS-D rats.

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Female serotonin transporter‐knockout rat: A potential model of irritable bowel syndrome

Cited by 14 publications

References 72 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

Enteric Microbiota-Mediated Serotonergic Signaling in Pathogenesis of Irritable Bowel Syndrome

Metagenomics and metabolomics analysis to investigate the effect of Shugan decoction on intestinal microbiota in irritable bowel syndrome rats

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