Bovine immunoglobulin protein isolates for the nutritional management of enteropathy

Abstract

The gastrointestinal tract is responsible for a multitude of digestive and immune functions which depend upon the balanced interaction of the intestinal microbiota, diet, gut barrier function, and mucosal immune response. Disruptions in one or more of these factors can lead to intestinal disorders or enteropathies which are characterized by intestinal inflammation, increased gut permeability, and reduced capacity to absorb nutrients. Enteropathy is frequently associated with human immunodeficiency virus (HIV) infection, inflammatory bowel disease, autoimmune enteropathy, radiation enteritis, and irritable bowel syndrome (IBS), where pathologic changes in the intestinal tract lead to abdominal discomfort, bloating, abnormal bowel function (e.g., diarrhea, urgency, constipation and malabsorption). Unfortunately, effective therapies for the management of enteropathy and restoring intestinal health are still not available. An accumulating body of preclinical studies has demonstrated that oral administration of plasma- or serum-derived protein concentrates containing high levels of immunoglobulins can improve weight, normalize gut barrier function, and reduce the severity of enteropathy in animal models. Recent studies in humans, using serum-derived bovine immunoglobulin/protein isolate, demonstrate that such protein preparations are safe and improve symptoms, nutritional status, and various biomarkers associated with enteropathy. Benefits have been shown in patients with HIV infection or diarrhea-predominant IBS. This review summarizes preclinical and clinical studies with plasma/serum protein concentrates and describes the effects on host nutrition, intestinal function, and markers of intestinal inflammation. It supports the concept that immunoglobulin-containing protein preparations may offer a new strategy for restoring functional homeostasis in the intestinal tract of patients with enteropathy.

Keywords: Diarrhea; Gut barrier; Immunoglobulins; Inflammation; Malabsorption; Nutrition; Plasma proteins; Treatment.

Figure 1

Factors involved in the pathogenesis of enteropathy associated with certain human disease states or conditions (e.g., diarrhea-predominant irritable bowel syndrome or human immunodeficiency virus infections).

Figure 2

Proposed mode of action for serum-derived bovine immunoglobulin protein isolates to aid management of enteropathy.

Figure 3

Summary of the postulated mode of action for serum-derived immunoglobulin/protein isolates. Immunoglobulins in SBI support intestinal homeostasis by binding MAMPs (endotoxins, etc.), toxins or other antigens in the lumen of the intestinal tract. Immunoglobulin binding interferes with downstream antigen detection by cell surface receptors on IELs or APCs such as DCs and macrophages that influence T cell activation, cytokine production, and barrier fortification. Additionally, biologically active compounds in immunoglobulin isolates may interact directly with mucosal immune cells in the lamina propria to influence mucosal inflammatory responses and epithelial cells to influence barrier function. SBI: Serum-derived immunoglobulin/protein isolates; MAMP: Microbe-associated molecular patterns; IEL: Intraepithelial lymphocytes; APC: Antigen presenting cells; DC: Dendritic cells; T-reg: Regulator T-lymphocytes; Th1: T helper type 1; Th2: T helper type 2. Reprinted with permission from Moretó et al[48].