New concepts of microbial translocation in the neonatal intestine: mechanisms and prevention

Abstract

Bacterial translocation from the gastrointestinal tract is an important pathway initiating late-onset sepsis and necrotizing enterocolitis in very low-birth-weight infants. The emerging intestinal microbiota, nascent intestinal epithelia, naive immunity, and suboptimal nutrition (lack of breast milk) have roles in facilitating bacterial translocation. Feeding lactoferrin, probiotics, or prebiotics has presented exciting possibilities to prevent bacterial translocation in preterm infants, and clinical trials will identify the most safe and efficacious prevention and treatment strategies.

Figure 1. Mechanisms of Bacterial Translocation [BT] in the Small Intestine

Multiple pathways, receptors and cells are involved in BT from the intestinal lumen. Toxins such as flagellin, endotoxins, exotoxins, and other bacterial products can disrupt tight junctions and facilitate paracellular translocation of bacteria between intestinal epithelial cells. Transcellular translocation of bacteria can occur via receptors including Intelectin [also lactoferrin receptor], type III secretory system, Toll-like receptors, LFA-1 [lectin] receptor, β1 integrin, and IgA displayed on M cells. Bacterial uptake through these cells can result in systemic dissemination of the microbe.

Figure 2. Commensal Bacteria and Paneth Cells Participate in the Development, Maintenance and Repair of an Intestinal Villus

Stem cells at the base of the crypts give rise to 4 cell lineages (enterocytes, goblet cells, Paneth cells, and intestinal neuroendocrine epithelia. These cells participate in host defense against bacterial translocation (50,63). The role of neuroendocrine epithelia in host defense of the intestinal villus is undefined.