Lactobacillus reuteri in Its Biofilm State Improves Protection from Experimental Necrotizing Enterocolitis

Abstract

Necrotizing enterocolitis (NEC) is a devastating disease predominately found in premature infants that is associated with significant morbidity and mortality. Despite decades of research, medical management with broad spectrum antibiotics and bowel rest has remained relatively unchanged, with no significant improvement in patient outcomes. The etiology of NEC is multi-factorial; however, gastrointestinal dysbiosis plays a prominent role in a neonate's vulnerability to and development of NEC. Probiotics have recently emerged as a new avenue for NEC therapy. However, current delivery methods are associated with potential limitations, including the need for at least daily administration in order to obtain any improvement in outcomes. We present a novel formulation of enterally delivered probiotics that addresses the current limitations. A single enteral dose of Lactobacillus reuteri delivered in a biofilm formulation increases probiotic survival in acidic gastric conditions, increases probiotic adherence to gastrointestinal epithelial cells, and reduces the incidence, severity, and neurocognitive sequelae of NEC in experimental models.

Keywords: Lactobacillus reuteri; dextranomer microspheres; necrotizing enterocolitis; prematurity; probiotics.

Figure 1

Adherence of L. reuteri to dextranomer microspheres. (A) scanning electron microscopy (SEM) image demonstrating the adherence of L. reuteri to the surface of a biocompatible dextranomer microsphere (DM; red); (B) magnified SEM image demonstrating the production of biofilm (green) by L. reuteri adhered to a sucrose-loaded DM.