Harnessing Gut Bacteria: Short- Chain Fatty Acids Against Diarrheagenic E. coli? Exploring the Impact of Bacterial Metabolites on Inflammation in Pediatric Intestinal Infections

This thesis states the effect that diarrheagenic E. coli (DEC) has on the gut microbiota in children, and the possible contribution of bacterial metabolites, such as SCFAs, in the outcome of the disease. Fecal samples analysis of children from Santiago, Chile, showed that DEC infections were associated with unique bacterial communities, highlighting the presence of the pathogens Citrobacter werkmanii and Escherichia albertii; this community was different compared to the one found in viral infections or healthy individuals. Additional experiments demonstrated that supernatants of these pathogens modulated gene expression in DEC bacteria and influenced IL-8 secretion induced by these bacteria.
Sequencing analysis of these children’s feces revealed shifts in gut bacterial composition, with significant implications for metabolic activity. Metabolite detection in stool samples showed higher levels of histamine and lower levels of ornithine in DEC diarrheal samples compared to healthy individuals. These findings were associated with specific resident microbiota and could contribute to inflammation during diarrhea. A metagenomic approach revealed associations between fecal gut microbiota and SCFAs, particularly acetate and propionate, with their levels being partially explained by the composition of the resident microbiota. To further investigate this, we cultivated bacterial consortia mimicking DEC and healthy microbiota and used their supernatants to investigate their effects on DEC virulence, which showed an increase of IL-8 secretion, indicative of inflammation.
Our findings emphasize the role of gut metabolites in bacterial infections, showing that a healthy microbiota may determine the severity of DEC diarrhea in children.