Survival and digestibility of orally-administered immunoglobulin preparations containing IgG through the gastrointestinal tract in humans.

Victoria S Jasion,Bruce P Burnett

doi:10.1186/s12937-015-0010-7

Abstract

Oral immunoglobulin (Ig) preparations are prime examples of medicinal nutrition from natural sources. Plasma products containing Ig have been used for decades in animal feed for intestinal disorders to mitigate the damaging effects of early weaning. These preparations reduce overall mortality and increase feed utilization in various animal species leading to improved growth. Oral administration of Ig preparations from human serum as well as bovine colostrum and serum have been tested and proven to be safe as well as effective in human clinical trials for a variety of enteric microbial infections and other conditions which cause diarrhea. In infants, children, and adults, the amount of intact IgG recovered in stool ranges from trace amounts up to 25% of the original amount ingested. It is generally understood that IgG can only bind to antigens within the GI tract if the Fab structure is intact and has not been completely denatured through acidic pH or digestive proteolytic enzymes. This is a comprehensive review of human studies regarding the survivability of orally-administered Ig preparations, with a focus on IgG. This review also highlights various biochemical studies on IgG which potentially explain which structural elements are responsible for increased stability against digestion.

Highlights

The biological role of immunoglobulins (Ig) in the protection of the gastrointestinal (GI) tract is wellestablished, the role of Ig in colostrum and breast milk [1,2]
This review summarizes in vitro biochemical studies that have assessed structural features of Immunoglobulin G (IgG) which contribute to their overall stability and discusses for the first time the proposed structural basis for resistance to digestion in the GI tract
Twelve of the 15 human studies in infants, children and adults that clearly demonstrate that orally-administered Ig ( IgGs), from human and bovine serum as well as from bovine colostrum and milk, survive gastric exposure and resist proteolytic digestion in the stomach and intestinal tract (Table 1) [4,5,6,9,10,11,12,13,14,16,17,18]

Summary

Introduction

The biological role of immunoglobulins (Ig) in the protection of the gastrointestinal (GI) tract is wellestablished, the role of Ig in colostrum and breast milk [1,2]. Due to the need for pasteurization, Ig preparations from these sources will have inconsistent amounts of IgG since the amount of IgG denaturation depends upon both the quality of the colostrum and exact method of pasteurization [3] Efficacy of these formulations in various enteropathies in humans depends upon the Ig surviving past the stomach into the small and large bowels. With the introduction to the market of the first nutritional therapy in the form of a physician supervised medical food containing high levels of IgG from bovine sera, it is important to understand the pharmacokinetics of these molecules This understanding is necessary for the usefulness of any Ig-containing formulation

Objectives

Findings

Conclusion