Effects of Bovine Immunoglobulins on Immune Function, Allergy, and Infection

Abstract

This review aims to provide an in depth overview of the current knowledge of the effects of bovine immunoglobulins on the human immune system. The stability and functional effects of orally ingested bovine immunoglobulins in milk products are described and potential mechanisms of action are discussed. Orally ingested bovine IgG (bovine IgG) can be recovered from feces, ranging from very low levels up to 50% of the ingested IgG that has passed through the gastrointestinal tract. In infants the recovered levels are higher than in adults most likely due to differences in stomach and intestinal conditions such as pH. This indicates that bovine IgG can be functionally active throughout the gastrointestinal tract. Indeed, a large number of studies in infants and adults have shown that bovine IgG (or colostrum as a rich source thereof) can prevent gastrointestinal tract infections, upper respiratory tract infections, and LPS-induced inflammation. These studies vary considerably in target group, design, source of bovine IgG, dosage, and endpoints measured making it hard to draw general conclusions on effectiveness of bovine immunoglobulin rich preparations. Typical sources of bovine IgG used in human studies are serum-derived IgG, colostrum, colostrum-derived IgG, or milk-derived immunoglobulins. In addition, many studies have used IgG from vaccinated cows, but studies using IgG from nonimmunized animals have also been reported to be effective. Mechanistically, bovine IgG binds to many human pathogens and allergens, can neutralize experimental infection of human cells, and limits gastrointestinal inflammation. Furthermore, bovine IgG binds to human Fc receptors which, enhances phagocytosis, killing of bacteria and antigen presentation and bovine IgG supports gastrointestinal barrier function in in vitro models. These mechanisms are becoming more and more established and explain why bovine IgG can have immunological effects in vivo. The inclusion of oral bovine immunoglobulins in specialized dairy products and infant nutrition may therefore be a promising approach to support immune function in vulnerable groups such as infants, children, elderly and immunocompromised patients.

Enriched bovine IgG fraction prevents infections with Enterohaemorrhagic Escherichia coli O157:H7, Salmonella enterica serovar Enteritidis, and Mycobacterium avium

“…Bovine IgG‐enriched preparations protect bacterial infections on several levels via enhancing clearance of pathogens, preventing colonization, and modulating immune functions (Funatogawa et al, ; Ulfman et al, ). Our previous in vitro study using sections made from the cecum wall demonstrated that 5% solution of immunoglobulin‐enriched bovine colostrum significantly blocked the attachment of EHEC O157 to mucous membrane and inhibits the colonization of the bacteria (Funatogawa et al, ).…”

Impact of oral immunoglobulins on animal health—A review

“…The bovine Ig was also found to prevent the replication of human rotaviruses in in vitro tissue culture experiments. This protective effect of bovine Ig has not only been shown for rotavirus in in vivo animal models but also for other pathogens such as enteropathogenic E. coli bacteria (Funatogawa et al, ; Ulfman et al, ) and Helicobacter pylori (Casswall et al, ; Ulfman et al, ). The strongest evidence on protective effects of bovine Ig from non‐immunized cows come from studies in HIV patients with recurrent diarrhoea (Asmuth et al, ; Ulfman et al, ).…”

“…This protective effect of bovine Ig has not only been shown for rotavirus in in vivo animal models but also for other pathogens such as enteropathogenic E. coli bacteria (Funatogawa et al, ; Ulfman et al, ) and Helicobacter pylori (Casswall et al, ; Ulfman et al, ). The strongest evidence on protective effects of bovine Ig from non‐immunized cows come from studies in HIV patients with recurrent diarrhoea (Asmuth et al, ; Ulfman et al, ). As HIV patients are severely immunosuppressed as a result of the depletion of CD4 + T cells, they have reduced capacity to resist infections and are highly susceptible to diarrhoea, especially induced by Cryptosporidium, Amoeba and Campylobacter .…”

“…Moreover, animals fed the FDOI diet had greater amounts of secretory IgA and IgG (only in jejunal) in both jejunal and ileal digesta which would likely play a vital role in protecting the gut from invading pathogens and in doing so it may suppress inflammatory processes (Parlesak, Schäfer, & Bode, ). Reports have shown oral administration of bovine colostrum stimulated non‐specific immunity of the host by up‐regulating the systemic immune response or by modulating immunocompetent cell function (Sugisawa, Itou, & Sakai, ; Ulfman, Leusen, Savelkoul, Warner, & van Neerven, ). Based on the study of Balan et al (), feeding rats with ovine Ig could have enhanced their innate immunity by improving phagocytic activity of PBLs and also enhanced T‐cell function by increasing IFNγ secretion in the presence of mitogens.…”

“…Number of studies have now shown efficacy of bovine Ig in preventing natural infection in humans as well as in animal infection models (Hammarström & Weiner, ; Ulfman et al, ). The bovine Ig was also found to prevent the replication of human rotaviruses in in vitro tissue culture experiments.…”