The Role of Lactoferrin in Intestinal Health

Abstract

The intestine represents one of the first barriers where microorganisms and environmental antigens come into tight contact with the host immune system. A healthy intestine is essential for the well-being of humans and animals. The period after birth is a very important phase of development, as the infant moves from a protected environment in the uterus to one with many of unknown antigens and pathogens. In that period, mother's milk plays an important role, as it contains an abundance of biologically active components. Among these components, the iron-binding glycoprotein, lactoferrin (LF), has demonstrated a variety of important benefits in infants and adults, including the promotion of intestinal health. This review article aims to provide a compilation of all the information related to LF and intestinal health, in infants and adults.

Keywords: antimicrobial activity; immune system; intestinal damage repair; intestinal growth; intestinal health; intestinal maturation; iron absorption; lactoferrin; microbiota.

Figure 1

Outline of the potential benefits of LF at the intestinal level. LF can fullfil different roles in the intestine including iron absorption, intestinal cell proliferation and maturation, intestinal barrier enhancement, immunomodulatory activity, antimicrobial activity, and modulation of gut microbiota. Increase (↑).

Figure 2

Mechanisms of iron absorption in the enterocyte. Heme Fe²⁺ ions (from meat) enter into enterocyte by the heme carrier protein 1 (HCP-1). Non-heme Fe³⁺ ions need to be reduced to Fe²⁺ ions by Dcytb, prior to being transported into cells by the DMT-1 transporter. Other pathways that may contribute to iron absorption include the LF/LF receptor-mediated iron uptake. Once inside the cell, Fe6²⁺ ions can be stored in the iron-binding ferritin or released into circulation by the ferroportin transporter (FPN). Then, Fe²⁺ ions can be oxidized to Fe³⁺ ions by hephaestin or serum ceruloplasmin, and iron can be transported to tissues by transferrin. The hepatic, hepcidin, as a master regulator of iron, inhibits the activity of FPN and iron release into circulation.

Figure 3

Schematic representation of the effects of human LF (hLF) on small intestinal proliferation and differentiation in early life stages in children. High concentrations of LF, achieved at the first period of lactation in colostrum, enhance intestinal cell proliferation with an increase in thymidine incorporation, whereas low concentrations of LF in mature milk stimulate intestinal differentiation, increasing the sucrase and lactase activities, as well as their mRNA. Increase (↑).