Project description:Epithelial Barrier and Leaky Gut in Dyspepsia Running title: Epithelial Barrier and Leaky Gut in Dyspepsia Context: Some studies suggest that FD is associated with ex vivo duodenal epithelial micro-inflammation and barrier impairment; the pathogenesis of these findings is unclear. miRNAs reduce expression of epithelial barrier genes and have been postulated to increase epithelial permeability in irritable bowel syndrome. New findings: Compared to controls, there is reduced mRNA expression of several barrier proteins (zona occludin-1), increased expression of several miRNAs (eg, miR-142-3p) that suppress the genes for barrier proteins in FD. However, mucosal eosinophils, intraepithelial lymphocytes, and mast cells, ex- and in vivo permeability (urinary lactulose and mannitol excretion) were not significantly different in FD. Impact: Patients with FD do not have a leaky gut syndrome.
Project description:Epithelial Barrier and Leaky Gut in Dyspepsia Running title: Epithelial Barrier and Leaky Gut in Dyspepsia Context: Some studies suggest that FD is associated with ex vivo duodenal epithelial micro-inflammation and barrier impairment; the pathogenesis of these findings is unclear. miRNAs reduce expression of epithelial barrier genes and have been postulated to increase epithelial permeability in irritable bowel syndrome. New findings: Compared to controls, there is reduced mRNA expression of several barrier proteins (zona occludin-1), increased expression of several miRNAs (eg, miR-142-3p) that suppress the genes for barrier proteins in FD. However, mucosal eosinophils, intraepithelial lymphocytes, and mast cells, ex- and in vivo permeability (urinary lactulose and mannitol excretion) were not significantly different in FD. Impact: Patients with FD do not have a leaky gut syndrome.
Project description:Tissue lymphatics are crucial for fluid homeostasis and immunosurveillance. We asked whether the lymphatics are adapted to the organ in which they reside, such as along the gut. Duodenal lymphatic capillaries (lacteals) displayed the mot discontinuous tight junction composition versus lacteals at other sites, resulting in a dependence on duodenal lacteals for rapid dietary lipid uptake. Duodenal helminths abrogated these features. RNAseq of LECs and the mucosa along the intestine revealed that LEC transcriptomes matched the functional profile of the local mucosa. Helminth infection reverses key duodenal signatures like lipid metabolism and immune activation, instead triggering lymphangiogenic and mucosal antimicrobial responses. We identified a putative VEGFR2/3 signaling gradient that may explain differences in tight junction along the small intestine at homeostasis. Inflammation-induced lymphangiogenesis and decreased fat exposure likely underlie duodenal lymphatic impermeability upon helminth infection, while microbial depletion acted additively on lymphatic restructuring. Our study provides molecular insights into lymphatic function along the intestine and stages lymphatic permeability as subject to dynamic regulation by environmental queues.
Project description:Tissue lymphatics are crucial for fluid homeostasis and immunosurveillance. We asked whether the lymphatics are adapted to the organ in which they reside, such as along the gut. Duodenal lymphatic capillaries (lacteals) displayed the mot discontinuous tight junction composition versus lacteals at other sites, resulting in a dependence on duodenal lacteals for rapid dietary lipid uptake. Duodenal helminths abrogated these features. RNAseq of LECs and the mucosa along the intestine revealed that LEC transcriptomes matched the functional profile of the local mucosa. Helminth infection reverses key duodenal signatures like lipid metabolism and immune activation, instead triggering lymphangiogenic and mucosal antimicrobial responses. We identified a putative VEGFR2/3 signaling gradient that may explain differences in tight junction along the small intestine at homeostasis. Inflammation-induced lymphangiogenesis and decreased fat exposure likely underlie duodenal lymphatic impermeability upon helminth infection, while microbial depletion acted additively on lymphatic restructuring. Our study provides molecular insights into lymphatic function along the intestine and stages lymphatic permeability as subject to dynamic regulation by environmental queues.
Project description:Gene expression was detected using duodenal samples to identify the key regulatory genes for the treatment of dyspepsia with Jianwei Xiaoshi oral liquid
Project description:Proteomic analysis was conducted on gastric and duodenal tissues from rats with functional dyspepsia of spleen deficiency and normal rats, as well as rats with functional dyspepsia treated with Jianwei Xiaoshi tablets.
2023-11-29 | PXD047366 |
Project description:Multi-omics Analysis Reveals the Metabolic Regulators of Duodenal Low-grade Inflammation in Functional Dyspepsia
