Cryptosporidium parvum competes with the intestinal epithelial cells for glucose and impairs systemic glucose supply in neonatal calves

• Published in: Veterinary research (Paris) Vol. 54; no. 1; pp. 1 - 16
• Main Authors: Dengler, Franziska, Hammon, Harald M., Liermann, Wendy, Görs, Solvig, Bachmann, Lisa, Helm, Christiane, Ulrich, Reiner, Delling, Cora
• Format: Journal Article
• Language: English
• Published: London BioMed Central 03.05.2023; BMC
• Subjects: Animals; Autopsies; Cryptosporidiosis; Diarrhea; Experiments; Feces; Glucose; GLUT2; Histopathology; in vivo; Infections; Metabolism; Parasites; Pathophysiology; SGLT1; Small intestine; Ussing chamber; United States > US; Japan; Germany
• ISSN: 1297-9716; 0928-4249; 1297-9716
• DOI: 10.1186/s13567-023-01172-y

Abstract Cryptosporidiosis is one of the main causes of diarrhea in children and young livestock. The interaction of the parasite with the intestinal host cells has not been characterized thoroughly yet but may be affected by the nutritional demand of the parasite. Hence, we aimed to investigate the impact of C. parvum infection on glucose metabolism in neonatal calves. Therefore, N  = 5 neonatal calves were infected with C. parvum on the first day of life, whereas a control group was not ( N  = 5). The calves were monitored clinically for one week, and glucose absorption, turnover and oxidation were assessed using stable isotope labelled glucose. The transepithelial transport of glucose was measured using the Ussing chamber technique. Glucose transporters were quantified on gene and protein expression level using RT-qPCR and Western blot in the jejunum epithelium and brush border membrane preparations. Plasma glucose concentration and oral glucose absorption were decreased despite an increased electrogenic phlorizin sensitive transepithelial transport of glucose in infected calves. No difference in the gene or protein abundance of glucose transporters, but an enrichment of glucose transporter 2 in the brush border was observed in the infected calves. Furthermore, the mRNA for enzymes of the glycolysis pathway was increased indicating enhanced glucose oxidation in the infected gut. In summary, C. parvum infection modulates intestinal epithelial glucose absorption and metabolism. We assume that the metabolic competition of the parasite for glucose causes the host cells to upregulate their uptake mechanisms and metabolic machinery to compensate for the energy losses.