A Genomic Research of Environmental Enteric Dysfunction
On 29 January, 2021, professor Lee A Denson from Cincinnati Children’s Hospital Medical Center，Syed Asad Ali from Aga Khan University and Sean R Moore from University of Virginia published a paper on Gastroenterology. The paper titled Mucosal Genomics Implicate Lymphocyte Activation and Lipid Metabolism in Refractory Environmental Enteric Dysfunction.
Background & Aims: Environmental enteric dysfunction (EED) limits the Sustainable Development Goals of improved childhood growth and survival. We applied mucosal genomics to advance our understanding of EED.
Methods: The Study of Environmental Enteropathy and Malnutrition (SEEM) followed 416 children from birth to 24 months in a rural district in Pakistan. Biomarkers were measured at 9 months and tested for association with growth at 24 months. The duodenal methylome and transcriptome was determined in 52 undernourished SEEM participants and 42 North American controls and celiac disease patients.
Results: After accounting for growth at study entry, circulating IGF-1 and ferritin predicted linear growth, whereas leptin correlated with future weight gain. The EED transcriptome exhibited suppression of antioxidant, detoxifification, and lipid metabolism genes, and induction of anti-microbial response, interferon, and lymphocyte activation genes. Relative to celiac disease, suppression of antioxidant and detoxifification genes and induction of anti-microbial response genes were EED-specifific. At the epigenetic level, EED showed hyper-methylation of epithelial metabolism and barrier function genes, and hypo-methylation of immune response and cell proliferation genes. Duodenal co-expression modules showed association between lymphocyte proliferation and epithelial metabolic genes and histologic severity, fecal energy loss, and wasting (weight-for-length/height Z<-2.0). Leptin was associated with expression of epithelial carbohydrate metabolism and stem cell renewal genes. Immune response genes were attenuated by giardia colonization.
Conclusions: Children with reduced circulating IGF-1 are more likely to experience stunting. Leptin and a gene signature for lymphocyte activation and dysregulated lipid metabolism are implicated in wasting, suggesting new approaches for EED refractory to nutritional intervention.
Gastroenterology
Gastrointestinal diseases mainly refer to general inflflammatory gastrointestinal diseases, peptic ulcer, gastric cancer, esophageal cancer, colorectal cancer and irritable bowel syndrome.Generally, inflflammatory gastroenteritis is mainly caused by an external inflflammatory reaction, which destroys the inner epidermal cells of the digestive tract, causing damage to the epidermis and internal stroma in the digestive tract, and exhibits gastrointestinal problems. At the same time, with the damage of endothelial cells and stromal cells, the proteins in the cell matrix can also appear in feces or serum. It is only necessary to detect the content of the marker proteins in these samples, and it is easy to judge the development and severity of the disease. For example, gastric mucosal damage: the levels of pepsin (PP) and gastrin releasing peptide precursor (ProGRP) in feces and serum have increased.The current research results show that the occurrence of gastrointestinal cancer is closely related to long-term inflflammation and genetic factors. During the process of growth, division and migration, cancer cells secrete specifific substances or stimulate the host cells to produce unique substances. These substances become TM (Tumor markers), and the detection of these substances can reflflect cancer.
