Cellular Respiration and Amino Acid Metabolism Is Altered by Dietary Oligosaccharides inSalmonellaDuring Epithelial Association

• DOI: 10.1101/2025.03.09.642302
• Publication Date: 2025-03-13T16:53:47Z
• Authors: Claire Shaw; Poyin Chen; Narine Arabyan; Bart C. Weimer

AbstractDietary prebiotic oligosaccharides are common in people’s diets; however, little is known about how different prebiotics alter the enteric epithelium and microbiome. Here we show two structurally different prebiotic oligosaccharides, human milk oligosaccharides (HMO) and mannanoligosaccharides (MOS), alter the metabolism of colonic epithelial cells and Salmonella enterica sv. Typhimurium in ways specific to each prebiotic. Initially, HMO and MOS addition decreased S. Typhimurium association with epithelial cells. However, gene expression analysis revealed significantly induced expression of Specific Pathogenicity Island (SPI) 1 and 2 with HMO treatment opposed to increased fimbriae expression with MOS treatment. MOS treatment induced the expression of genes for amino acid metabolism in both the host cells and in S. Typhimurium, a metabolic shift that was not observed in the HMO treated cells. MOS treatment also altered respiration metabolism in S. Typhimurium to be more closely aligned to those observed in vivo during gut inflammation, which is opposed to colonization-type expression with HMO. Alteration of virulence observed was found to be prebiotic specific and dose dependent, indicating that some dietary substrates likely alter specific pathogens to change their virulence potential in unanticipated ways that lead to multiple outcomes to potentiate or attenuate enteric infections.