P205 - ALGINATE OLIGOMERS, A POTENTIAL ADJUVANT IN THE TREATMENT OF FISTULIZING CROHN’S DISEASE
(Room Poster Hall)
19 Jan 18
5:30 PM
-
7:00 PM
Background: OligoG is a low mol. wt. alginate oligosaccharide (Mn 3200g/mol) that disrupts bacterial biofilm, potentiates antibiotics, reconditions mucus and facilitates re-epithelialization and wound closure. These combined features suggest a potential role for alginate oligomers in the treatment of Fistulizing Crohn’s Disease (FCD), where infection and mucosal epithelial healing remain key clinical challenges. Methods: A mouse intestinal obstruction model was used to test OligoG on intestinal dysregulation and small intestinal bacterial overgrowth (SIBO). Two cohorts of mice were treated for 3 weeks with 2% OligoG. Total bacterial load in the small intestine was measured by qPCR using universal bacterial 16S rRNA-specific primers (Nadkarni et al., Microbiology 148:257-266, 2002). In addition, bacterial growth and inhibition studies were performed on genitourinary pathogens (C. difficile, P. aeruginosa, E. coli and G. vaginalis). Cultures were grown at 37oC in 96-well plates for 24hrs in appropriate medium. C. difficile was grown under anaerobic conditions. MIC assays were performed in 384-plates using a robotic high throughput screening protocol. Results: Mice treated with OligoG showed a mean decrease in total microbial load (Fig 1) suggesting a reduction of SIBO. Growth studies showed pathogen reduction in a dose dependent manner, and MIC data showed potentiation. Furthermore, OligoG inhibited the biofilm stress response at sub-lethal antibiotic concentrations (Fig 2) indicating a possible mechanism whereby alginate oligomers potentiate a wide range of antibiotic classes. Conclusions: Results indicate that treatment with OligoG restores mucosal function, reduces microbial burden and potentiates antibiotic activity. These findings complement previously documented wound healing and anti-inflammatory observations for OligoG. These combined properties suggest a potential role for alginate oligomers to treat infection and restore mucosal epithelial healing in FCD.