Intestinal disorders are common in metabolic syndrome. However, their pathogenesis is still not fully understood. Pig and human intestines are highly similar in terms of associated metabolic processes. Here, we successfully constructed a metabolic disease-susceptible transgenic (TG) Bama pig model by knocking in three humanized disease risk genes with the CRISPR/Cas9 technique to assess its potential as a model for human intestinal diseases and explore the possible pathological mechanisms involved. We found that jejunal barrier integrity was disrupted and that the infiltration of inflammatory cells increased in TG pigs after high-fat and high-sucrose diet (HFHSD) treatment. We revealed significant differences in the transcriptome, associated microbiome profiles and microbial metabolite short-chain fatty acid (SCFA) content of the jejunum of TG pigs. Notably, we found that SLC26A3 was significantly downregulated in TG pigs. Knockdown or overexpression of the SLC26A3 gene in IPEC-J2 cells significantly affected the expression of MUC2, MUC13 and occludin. Furthermore, in vitro experiments further verified that CDX2 directly regulated the expression of SLC26A3. Mechanistically, CDX2 mediated intestinal barrier function by enhancing the expression of SLC26A3 by binding to its promoter region between -1120 and - 1070 bp. TG pigs represent a promising model that provides new insights into preclinical research on human intestinal metabolic diseases associated with metabolic disorders and revealed that SLC26A3 may be a potential therapeutic target for intestinal metabolic diseases.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.ijbiomac.2024.136245 | DOI Listing |
Front Cell Infect Microbiol
December 2024
Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.
Introduction: is the most prevalent enteric protozoan parasite causing infectious diarrhea in neonatal calves worldwide with a direct negative impact on their health and welfare. This study utilized next-generation sequencing (NGS) to deepen our understanding of intestinal epithelial barriers and transport mechanisms in the pathophysiology of infectious diarrhea in neonatal calves, which could potentially unveil novel solutions for treatment.
Methods: At day 1 of life, male Holstein-Friesian calves were either orally infected (n = 5) or not (control group, n = 5) with oocysts (in-house strain LE-01-Cp-15).
Poult Sci
December 2024
Queensland Alliance for Agriculture and Food Innovation (QAAFI), The University of Queensland, Australia. Electronic address:
The early post-hatching phase remains to be one of the most vulnerable phases in broiler production. Some essential oils have been reported to improve gut health and growth in broiler chickens when applied to post-hatching diets. However, in-feed applications are unable to prevent the health challenges observed immediately after hatching.
View Article and Find Full Text PDFNutrients
November 2024
UMR-PNCA, Université Paris-Saclay, AgroParisTech, INRAE, 91120 Palaiseau, France.
Background/objectives: Injection of lipopolysaccharides (LPS) in experimental models induces a systemic inflammatory response that is associated with deleterious effects on intestinal morphology and physiology. In this study, we have studied in female mice the effects of dietary supplementation with bovine lactoferrin (bLF) given before intraperitoneal injection of LPS on jejunum and colon.
Methods: The first study evaluated the efficiency of different bLF and LPS concentrations to determine the optimal experimental conditions.
J Agric Food Chem
December 2024
PEGASE, INRAE, Institut Agro, Saint Gilles 35590, France.
Dietary fibers (DF) are important components of human and animal diets. However, they can decrease protein digestibility and absorption and thus the nutritional value of a food. The aim of this study was to investigate how the form of delivery of pea DF impacted the integrity of the intestinal barrier and, thereby, the potential absorption of molecules.
View Article and Find Full Text PDFPoult Sci
November 2024
Department of Poultry Science, University of Georgia, Athens, GA 30602-2772, USA. Electronic address:
Salmonella contamination in poultry products is a significant concern due to its potential to cause severe economic losses and public health problems. On the other side, coccidiosis is induced by Eimeria (E.) species.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!