Understanding how bacterial products from the microbiota enter the host, determining where they aggregate, and their influence over immune cells at these sites

The microbiota is crucial for gut homeostasis by aiding in nutrient uptake, and protecting against pathogens. Recent evidence suggests the benefits provided by the microbiota are not restricted to the intestine but also extend to systemic sites. Systemic benefits are hypothesized to be mediated by bacterial products, derived from the microbiota, such as peptidoglycan and lipopolysaccharide, entering the bloodstream and acting as novel signalling molecules at distal sites. However the precise way in which these microbial products enter the bloodstream remains largely unclear. Our data suggest bacterial products can cross the intestinal epithelium, and that routes across may vary between different bacterial products. Using in vitro and in vivo models, we find that host processing of cell wall molecules, by host antimicrobial lysozyme, promotes their translocation across the epithelium. Once they have traversed the intestinal barrier our preliminary data provide support that the liver plays a role in clearing bacterial products from the blood, as here we see a reservoir of peptidoglycan. This increased dissemination of cell wall molecules additionally enhances resistance to pulmonary infection. Therefore lysozyme treatment enhances bacterial product migration and increases host protection against systemic pathogens. Our work provides mechanistic insight into how the gut microbiota exerts systemic effects. Furthermore it provides a basis on which to launch further investigations, including examining the influence these aggregated cell wall proteins have over innate immune cells at these sites. Giving us greater insight into how the host controls microbial signalling and the benefits provided to our innate immune system.