Examination of the mechanism of Piezo ion channel in 5-HT synthesis in the enterochromaffin cell and its association with gut motility.

In the gastrointestinal tract, serotonin (5-hydroxytryptamine, 5-HT) is an important monoamine that regulates intestinal dynamics. QGP-1 cells are human-derived enterochromaffin cells that secrete 5-HT and functionally express Piezo ion channels associated with cellular mechanosensation. Piezo ion channels can be blocked by Grammostola spatulata mechanotoxin 4 (GsMTx4), a spider venom peptide that inhibits cationic mechanosensitive channels. The primary aim of this study was to explore the effects of GsMTx4 on 5-HT secretion in QGP-1 cells in vitro. We investigated the transcript and protein levels of the Piezo1/2 ion channel, tryptophan hydroxylase 1 (TPH1), and mitogen-activated protein kinase signaling pathways. In addition, we observed that GsMTx4 affected mouse intestinal motility in vivo. Furthermore, GsMTx4 blocked the response of QGP-1 cells to ultrasound, a mechanical stimulus.The prolonged presence of GsMTx4 increased the 5-HT levels in the QGP-1 cell culture system, whereas Piezo1/2 expression decreased, and TPH1 expression increased. This effect was accompanied by the increased phosphorylation of the p38 protein. GsMTx4 increased the entire intestinal passage time of carmine without altering intestinal inflammation. Taken together, inhibition of Piezo1/2 can mediate an increase in 5-HT, which is associated with TPH1, a key enzyme for 5-HT synthesis. It is also accompanied by the activation of the p38 signaling pathway. Inhibitors of Piezo1/2 can modulate 5-HT secretion and influence intestinal motility.

Early life stress induces irritable bowel syndrome from childhood to adulthood in mice.

Background: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorder. Traditionally, early life stress (ELS) is predisposed to IBS in adult. However, whether ELS induces IBS in early life remains unclear. Methods: Separated cohort studies were conducted in neonatal male pups of C57BL/6 mice by maternal separation (MS) model. MS and non-separation mice were scheduled to be evaluated for prime IBS-phenotypes, including visceral hypersensitivity, intestinal motility, intestinal permeability, and anxiety-like behavior. Ileal contents and fecal samples were collected and analyzed by 16S rRNA gene sequencing and bacterial community analyses. Subcellular structures of intestinal epithelial, such as epithelial tight junctions and mitochondria, were observed under transmission electron microscopy. Results: MS induced visceral hypersensitivity and decreased total intestinal transit time from childhood to adulthood. In addition, MS induced intestinal hyperpermeability and anxiety-like behavior from adolescence to adulthood. Besides, MS affected intestinal microbial composition from childhood to adulthood. Moreover, MS disrupted intestinal mitochondrial structure from childhood to adulthood. Conclusion: The study showed for the first time that MS induced IBS from early life to adulthood in mice. The disrupted intestinal mitochondrial structure and the significant dysbiosis of intestinal microbiota in early life may contribute to the initiation and progress of IBS from early life to adulthood.

Alterations in the Fecal Microbiota Composition in Pediatric Acute Diarrhea: A Cross-Sectional and Comparative Study of Viral and Bacterial Enteritis.

Objective: To examine the association between the fecal microbiota of acute diarrhea in children and provide gut microbiota information related the acute diarrhea with rotavirus. Patients and Methods: Children with acute diarrhea aged 3-60 months were selected for the study. Routine stool examination was performed, and stool samples were collected and stored at -80 °C until further analysis. Fecal microbial DNA was extracted, and DNA concentration and quality were detected. PCR amplification and 16S rDNA high-throughput sequencing analysis using the Illumina MiSeq platform were performed, and intestinal flora was statistically analyzed. Results: Children with acute diarrhea exhibited gut microbial dysbiosis. Lower microbial diversity and richness were observed in the viral enteritis and bacterial enteritis groups than in the control group. Composition of the microbiota in acute diarrhea differed from that in the control group. The Bacteroidetes/Firmicutes dramatically decreased in the viral enteritis and bacterial enteritis groups. However, the relative abundance of Proteobacteria and Fusobacteria increased, especially in the bacterial enteritis group. In addition, the relative abundance of Actinobacteria had dramatically increased in the viral enteritis group. According to the Kyoto Encyclopedia of Genes and Genomes map analysis, the membrane transport dysfunction was caused by rotavirus infection, while the membrane transport dysfunction was more evident in bacterial infection. Conclusion: Acute diarrhea infections cause fecal microbiota dysbiosis in children. Changes in fecal microflora in children suggest that the regulation of intestinal flora in children with acute diarrhea should be strengthened.

Vitamin D improves irritable bowel syndrome symptoms: A meta-analysis.

Background & aims: Approximately 5%-10% of the population in most geographical regions suffer from irritable bowel syndrome (IBS), which creates a significant burden on individual patients, their families, and society. Recent advances in IBS therapies have indicated that vitamin D supplementation is potential to relieve its symptoms, but evidence of this is lacking. This meta-analysis aimed to estimate the effect of vitamin D on gastrointestinal (GI) symptoms in IBS patients. Methods: The PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched from their inception to March 2022. Statistical analyses were performed with Stata 12.0 and Review Manager 5.4, and statistical significance was defined as P < 0.05. The pooled results are presented as weighted mean differences (WMD) and 95% confidence intervals (CI). Results: The meta-analysis including 6 randomized controlled trials (RCT) with 572 patients found a significant difference in IBS symptom severity score (WMD, -34.88; 95% CI, -62.48 to -7.27; P = 0.013; random-effects model) but no significant difference in IBS quality of life score (WMD, 3.33; 95% CI, -5.12 to -11.77; P = 0.440; random-effects model). Conclusions: Overall, IBS patients may benefit from vitamin D supplementation to reduce the GI symptoms.

Maternal separation leads to dynamic changes of visceral hypersensitivity and fecal metabolomics from childhood to adulthood.

We assessed dynamic changes in visceral hypersensitivity and fecal metabolomics through a mouse model of irritable bowel syndrome (IBS) from childhood to adulthood. A mouse model of IBS was constructed with maternal separation (MS) in early life. Male mice aged 25, 40, and 70 days were used. Visceral sensitivity was assessed by recording the reaction between the abdominal withdrawal reflex and colorectal distension. Metabolomics was identified and quantified by liquid chromatography-tandem mass spectrometry. The visceral sensitivity of the MS group was significantly higher than that of the non-separation (NS) group in the three age groups. The top four fecal differential metabolites in the different age groups were lipids, lipid molecules, organic heterocyclic compounds, organic acids and derivatives, and benzenoids. Five identical differential metabolites were detected in the feces and ileal contents of the MS and NS groups at different ages, namely, benzamide, taurine, acetyl-L-carnitine, indole, and ethylbenzene. Taurine and hypotaurine metabolism were the most relevant pathways at P25, whereas histidine metabolism was the most relevant pathway at P40 and P70. Visceral hypersensitivity in the MS group lasted from childhood to adulthood. The different metabolites and metabolic pathways detected in MS groups of different ages provide a theoretical basis for IBS pathogenesis.

Low FODMAP Diet Relieves Visceral Hypersensitivity and Is Associated with Changes in Colonic Microcirculation in Water Avoidance Mice Model.

(1) Background: Irritable bowel syndrome (IBS) is a global public health problem, the pathogenesis of which has not been fully explored. Limiting fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) can relieve symptoms in some patients with IBS. Studies have shown that normal microcirculation perfusion is necessary to maintain the primary function of the gastrointestinal system. Here, we hypothesized that IBS pathogenesis might be related to abnormalities in colonic microcirculation. A low-FODMAP diet could alleviate visceral hypersensitivity (VH) by improving colonic microcirculation; (2) Methods: C57BL/6 mice were raised to establish an IBS-like rodent model using water avoidance (WA) stress or SHAM-WA as a control, one hour per day for ten days. The mice in the WA group were administered different levels of the FODMAP diet: 2.1% regular FODMAP (WA-RF), 10% high FODMAP diet (WA-HF), 5% medium FODMAP diet (WA-MF), and 0% low FODMAP diet (WA-LF) for the following 14 days. The body weight and food consumption of the mice were recorded. Visceral sensitivity was measured as colorectal distention (CRD) using the abdominal withdrawal reflex (AWR) score. Colonic microcirculation was assessed using laser speckle contrast imaging (LCSI). Vascular endothelial-derived growth factor (VEGF) was detected using immunofluorescence staining; (3) Results: The threshold values of CRD pressure in the WA-RF, WA-HF, and WA-MF groups were significantly lower than those in the SHAM-WA group. Moreover, we observed that colonic microcirculation perfusion decreased, and the expression of VEGF protein increased in these three groups of mice. Interestingly, a low-FODMAP dietary intervention could reverse this situation. Specifically, a low-FODMAP diet increased colonic microcirculation perfusion, reduced VEGF protein expression in mice, and increased the threshold of VH. There was a significant positive correlation between colonic microcirculation and threshold for VH; (4) Conclusions: These results demonstrate that a low-FODMAP diet can alter VH by affecting colonic microcirculation. Changes in intestinal microcirculation may be related to VEGF expression.

Alarming antibiotics resistance of Helicobacter pylori from children in Southeast China over 6 years.

The increasing rates of antibiotic resistance in Helicobacter pylori (H. pylori) are a major concern of the decreasing eradication rate. Large-scale and long-period studies on antimicrobial susceptibility of H. pylori in children are limited. This study aimed to describe the temporal changes of antibiotic resistance among children in southeast China. Gastric biopsies obtained from children were cultured for H. pylori from 2015 to 2020. Susceptibility to clarithromycin (CLA), amoxicillin (AML), metronidazole (MTZ), furazolidone (FZD), tetracycline (TET) and levofloxacin (LEV) was tested. Data from 2012 to 2014 reported previously were obtained for comparing the change in temporal trends of antibiotic resistance. A total of 1638 (52.7%) H. pylori strains were isolated from 3111 children recruited. The resistance rates to CLA, MTZ and LEV were 32.8%, 81.7% and 22.8%, respectively. There were 52.9% strains resistant to single resistance, 28.7% to double resistance, and 9.0% to triple resistance. The total resistance rate and resistance rates to CLA, MTZ, LEV, CLA + LEV and CLA + MTZ + LEV increased annually in a linear manner. All resistant patterns except single resistance increased obviously from 2015 to 2017 and 2018 to 2020 compared to that from 2012 to 2014. Double resistance to CLA + MTZ increased significantly with age. The resistance rate to CLA and triple resistance to CLA, MTZ and LEV increased in children with prior H. pylori treatment than that from children without prior treatment. The antibiotic resistance rates of H. pylori were high in a large pediatric population in southeast China from 2015 to 2020. Individual treatment based on susceptibility test is imperative and optimal regimens should be chosen in H. pylori eradication therapy.

Potential Roles of Enterochromaffin Cells in Early Life Stress-Induced Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, also known as disorders of the gut-brain interaction; however, the pathophysiology of IBS remains unclear. Early life stress (ELS) is one of the most common risk factors for IBS development. However, the molecular mechanisms by which ELS induces IBS remain unclear. Enterochromaffin cells (ECs), as a prime source of peripheral serotonin (5-HT), play a pivotal role in intestinal motility, secretion, proinflammatory and anti-inflammatory effects, and visceral sensation. ECs can sense various stimuli and microbiota metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids. ECs can sense the luminal environment and transmit signals to the brain via exogenous vagal and spinal nerve afferents. Increasing evidence suggests that an ECs-5-HT signaling imbalance plays a crucial role in the pathogenesis of ELS-induced IBS. A recent study using a maternal separation (MS) animal model mimicking ELS showed that MS induced expansion of intestinal stem cells and their differentiation toward secretory lineages, including ECs, leading to ECs hyperplasia, increased 5-HT production, and visceral hyperalgesia. This suggests that ELS-induced IBS may be associated with increased ECs-5-HT signaling. Furthermore, ECs are closely related to corticotropin-releasing hormone, mast cells, neuron growth factor, bile acids, and SCFAs, all of which contribute to the pathogenesis of IBS. Collectively, ECs may play a role in the pathogenesis of ELS-induced IBS. Therefore, this review summarizes the physiological function of ECs and focuses on their potential role in the pathogenesis of IBS based on clinical and pre-clinical evidence.

A case of rectal ulcers during aspirin therapy in acute Kawasaki disease.

Kawasaki disease (KD) is an acute febrile multisystem vasculitis and has been recognized to be one of the most common causes of acquired heart disease in children. Although gastrointestinal symptoms including vomiting, diarrhea, and abdominal pain are not uncommon in KD patients, KD with lower gastrointestinal bleeding is quite rare. Here, we describe a 3-year-old boy with typical KD who had lower gastrointestinal bleeding caused by rectal ulcers on the third day of aspirin therapy.

Gastrointestinal hemorrhage before anticoagulant therapy in Kawasaki disease: a case report.

BACKGROUND: Kawasaki disease (KD) is an acute febrile multisystem vasculitis and has been recognized to be the most common cause of acquired heart disease in children. Owing to its propensity to involve vessels throughout the entire body, KD often mimics other disease processes. The diagnosis might be delayed if other prominent symptoms appear before the characteristic clinical features of KD. Although gastrointestinal symptoms including vomiting, diarrhea, and abdominal pain are not uncommon in KD patients, KD with gastrointestinal bleeding is quite rare. CASE PRESENTATION: A previously healthy 4-year-old boy initially presented with abdominal pain, followed by fever, rash, and gastrointestinal hemorrhage, eventually diagnosed as complete KD. The patient recovered smoothly after appropriate management and no subsequent complications occurred in the following months. CONCLUSION: The diagnosis of KD should be considered in children presenting with abdominal symptoms and fever without definable cause. Pediatricians should be aware of the risk of gastrointestinal bleeding in patients with KD, especially in those with prominent abdominal symptoms.