Researcher(s)
- Mackenzie Keichline, Pre-Veterinary Medicine and Animal Biosciences, University of Delaware
Faculty Mentor(s)
- Shafeekh Muyyarikkandy, College of Agriculture and Natural Resources, University of Delaware
Abstract
Iron deficiency is the most common extraintestinal complication of inflammatory bowel disease, yet oral repletion aggravates mucosal injury because unabsorbed luminal iron feeds pathobionts. Whether host iron handling also constrains efficacy of lactic acid bacteria–derived metabolites is unknown. Caenorhabditis elegans, which carries orthologs of mammalian iron transport machinery, was used to test whether iron homeostasis modifies susceptibility to dextran sodium sulfate (DSS)–induced barrier injury and responsiveness to cell-free supernatants (CFS) from three cottage cheese–derived lactic acid bacteria. L4 larvae of N2 wild type and iron homeostasis mutants smf-3(ok1035) and ftn-1(ok3625) were exposed to 1% (w/v) DSS with or without 25% (v/v) unneutralized CFS from Leuconostoc pseudomesenteroides, Lactococcus lactis, or Leuconostoc lactis, alongside untreated and 25% MRS vehicle controls (n = 60 worms per group across 3 independent replicates). Survival scored at 0, 2, 4, and 6 h and analyzed by two-way ANOVA with Šídák correction. Results showed survival was governed by isolate identity and host genotype. The ftn-1 matched or was relative to wild type throughout, whereas smf-3 was lowest in every group at every time point. The survivability changed from 71% at 0 h to 40% at 6 h against 88% and 71% for N2 (p < 0.001). This points out the role of divalent metal uptake for viability. Further, Leuconostoc lactis raised smf-3 survival to 54% at 2 h against 30% for DSS. By 6 h, Lactococcus lactis supported highest survival of any supernatant, 28% in N2 and 24% in ftn-1, against 7% and 14% for the 25% MRS carrier, whereas Leuconostoc lactis and Leuconostoc pseudomesenteroides did not exceed the carrier in N2. Therefore, Leuconostoc lactis was protective in the smf-3 challenge strain, and Lactococcus lactis was the most active isolate in N2 and ftn-1. These findings demonstrate that probiotic metabolites can partially mitigate the effects of intestinal injury in C. elegans, and suggest that iron regulation relates to probiotic efficacy as well as intestinal injury.