Hemochromatosis drives acute lethal intestinal responses to hyperyersiniabactin-producing Yersinia pseudotuberculosis.

Hemachromatosis (iron-overload) increases host susceptibility to siderophilic bacterial infections that cause serious complications, but the underlying mechanisms remain elusive. The present study demonstrates that oral infection with hyperyersiniabactin (Ybt) producing Yersinia pseudotuberculosis Δfur mutant (termed Δfur) results in severe systemic infection and acute mortality to hemochromatotic mice due to rapid disruption of the intestinal barrier. Transcriptome analysis of Δfur-infected intestine revealed up-regulation in cytokine-cytokine receptor interactions, the complement and coagulation cascade, the NF-κB signaling pathway, and chemokine signaling pathways, and down-regulation in cell-adhesion molecules and Toll-like receptor signaling pathways. Further studies indicate that dysregulated interleukin (IL)-1ß signaling triggered in hemachromatotic mice infected with Δfur damages the intestinal barrier by activation of myosin light-chain kinases (MLCK) and excessive neutrophilia. Inhibiting MLCK activity or depleting neutrophil infiltration reduces barrier disruption, largely ameliorates immunopathology, and substantially rescues hemochromatotic mice from lethal Δfur infection. Moreover, early intervention of IL-1ß overproduction can completely rescue hemochromatotic mice from the lethal infection.

Oral microbiota analyses of paediatric Saudi population reveals signatures of dental caries.

BACKGROUND: Oral microbiome sequencing has revealed key links between microbiome dysfunction and dental caries. However, these efforts have largely focused on Western populations, with few studies on the Middle Eastern communities. The current study aimed to identify the composition and abundance of the oral microbiota in saliva samples of children with different caries levels using machine learning approaches. METHODS: Oral microbiota composition and abundance were identified in 250 Saudi participants with high dental caries and 150 with low dental caries using 16 S rRNA sequencing on a NextSeq 2000 SP flow cell (Illumina, CA) using 250 bp paired-end reads, and attempted to build a classifier using random forest models to assist in the early detection of caries. RESULTS: The ADONIS test results indicate that there was no significant association between sex and Bray-Curtis dissimilarity (p ~ 0.93), but there was a significant association with dental caries status (p ~ 0.001). Using an alpha level of 0.05, five differentially abundant operational taxonomic units (OTUs) were identified between males and females as the main effect along with four differentially abundant OTUs between high and low dental caries. The mean metrics for the optimal hyperparameter combination using the model with only differentially abundant OTUs were: Accuracy (0.701); Matthew's correlation coefficient (0.0509); AUC (0.517) and F1 score (0.821) while the mean metrics for random forest model using all OTUs were:0.675; 0.054; 0.611 and 0.796 respectively. CONCLUSION: The assessment of oral microbiota samples in a representative Saudi Arabian population for high and low metrics of dental caries yields signatures of abundances and diversity.