Summary: This study aims to provide an in-depth view of current knowledge concerning the effect of bovine immunoglobulins on the human immune system. The stability and functional effects of oral ingestion of bovine immunoglobulins in dairy products have been described, and the potential mechanisms of action were also discussed. Bovine IgG orally ingestion can be rebuilt from excrement, reaching up to 50% of digested IgG that has passed through the digestive tract. In the case of infants, recovery levels are higher than for adults, probably mainly due to differences in the abdomen and intestinal conditions such as pH levels. This indicates that bovine IgG may be functionally active through the gastrointestinal tract. In fact, a significant number of studies on infants and adults have shown that bovine IgG (or Colostrum as a rich source) can prevent infections of the digestive tract, upper respiratory tract, and lipolisaccharide-induced inflammation (LPS). These studies differ significantly in terms of the study group, study design, bovine IgG source, dosage, and measured endpoints making it difficult to draw general conclusions concerning the effectiveness of rich bovine immunoglobulins. Typical sources of bovine IgG in human studies are obtained from serum IgG, Colostrum, obtained from Colostrum IgG, or immunoglobulins obtained from milk. Additionally, many studies have used IgG of vaccinated cows, but studies that have used IgG of unvaccinated animals have also been reported to be effective. Bovine IgG bonds in terms of many human pathogens and allergens in a mechanical manner, and may neutralize experimental infection of human cells and reduce gastrointestinal inflammation. Furthermore, bovine IgG bonds with Fc receptors, which strengthens phagocytes, killing bacteria and the occurrence of antigens, as well as supports the functioning of the protective barrier of the digestive system for in vitro models. These mechanisms are increasingly established and explained concerning why bovine IgG may have an immunological effect in vivo. Including oral consumption of bovine immunoglobulins in specialized dairy products and the nutrition of infants may constitute a promising method in supporting functions concerning vulnerable groups such as infants, children, the elderly, and patients with impaired immunity.

Summary: Maternal milk is often absent or in limited supply just after preterm birth. Many preterm infants are therefore fed infant formula as their first enteral feed despite an increased risk of feeding intolerance, necrotizing enterocolitis (NEC), and infection. Using preterm pigs as a model for preterm infants, we hypothesized that bovine colostrum given before or after formula feeding would alleviate formula-induced detrimental effects during the first days after preterm birth.

A total of 74 preterm pigs received gradually increasing volumes of formula (F) or bovine colostrum (C) until day 5, when they were euthanized or transitioned to either C or F for another 4 days, resulting in six groups: C or F until day 5 (C5, F5, n = 11 each), C or F until day 9 (CC, FF n = 12–13 each), C followed by F (CF, n = 14), and F followed by C (FC, n = 13).

Systemically, colostrum feeding stimulated circulating neutrophil recruitment on day 5 (C5 vs. F5, P < 0.05). Relative to initial formula feeding, initial colostrum feeding promoted the development of systemic immune protection as indicated by a decreased T-helper cell population and an increased regulatory T-cell population (CC + CF vs. FC + FF, P < 0.01). In the gut, colostrum feeding improved intestinal parameters such as villus heights, enzymes, hexose absorption, colonic goblet cell density, and decreased the incidence of severe NEC (27 vs. 64%), diarrhea (16 vs. 49%), and gut permeability on day 5, coupled with lowered expression of LBP, MYD88, IL8, HIF1A, and CASP3 (C5 vs. F5, all P < 0.05). On day 9, the incidence of severe NEC was similarly low across groups (15–21%), but diarrhea resistance and intestinal parameters were further improved by colostrum feeding, relative to exclusive formula feeding (CC, CF, or FC vs. FF, respectively, all P < 0.05). The expression of MYD88 and CASP3 remained downregulated by exclusive colostrum feeding (CC vs. FF, P < 0.01) and colostrum before or after formula feeding down regulated HIF1A and CASP3 expression marginally.

Colostrum feeding ameliorated detrimental effects of formula feeding on systemic immunity and gut health in preterm newborns, especially when given immediately after birth.

In conclusion, our study underlines the importance of initial enteral feeding and how initial feeding shapes the developmental trajectory of intestinal health and systemic immunity in preterm neonates. Although colostrum also had some therapeutic effects to repair the detrimental effects induced by formula feeding, it was more restricted in the digestive system with less strength. Thus, bovine colostrum is suggested to be used as the initial feeding to prepare the digestive and immune systems in very preterm infants for the later consumption of formula in resource-limited hospitals, when MM is not available immediately after birth.

Summary: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Currently, several vaccine candidates against SARS-CoV-2 are in clinical trials but approval of these vaccines is likely to take a long time before they are available for public use. In a previous report, the importance of passive immunity and how immunoglobulin (Ig)G collected from recovered coronavirus patients could help in the protection against COVID-19 and boost the immune system of new patients was reported. Passive immunity by immunoglobulin transfer is a concept employed by most mammals and bovine IgG has a role to play in human therapy. IgG is one of the major components of the immunological activity found in cow's milk and colostrum. Heterologous transfer of passive immunity associated with the consumption of bovine immune milk by humans has been investigated for decades for its immunological activity against infections. This short review focuses on passive immunity and how microfiltered raw immune milk or colostrum collected from cows vaccinated against SARS-CoV-2 could provide short-term protection against SARS-CoV-2 infection in humans and could be used as an option until a vaccine becomes commercially available. In conclusion, after the emergence of SARS-CoV-1 in November 2002, several vaccine candidates were developed and tested in animal models and in some clinical trials in humans. However, effective and safe vaccines are not yet commercially available for public use. Nevertheless, the different approaches used in these studies will help to optimize the efficiency of current vaccine candidates against SARS-CoV-2 by inducing a protective immune response and not causing disease. One effective approach has been the passive transfer of immune sera collected from animals immunized with SARS-CoV-1 to naïve animals, conferring protection against subsequent SARS-CoV-1 infection. Based on passive immunity, the vaccination of cows against SARS-CoV-2 before collecting their milk or colostrum may increase the specificity of IgG in the milk or colostrum against this new coronavirus and offer short-term protection to individuals who consume this hyperimmune cow's colostrum or immune milk. In the clinical trial, healthy subjects received human polyclonal IgG antibody (SAB-301) produced from cattle immunized with a MERS coronavirus vaccine and single infusions of this IgG antibody, up to 50 mg/kg, appeared to be safe and well-tolerated in healthy participants (39, 40). In line with this clinical observation, the company SAb Biotherapeutics in South Dakota has genetically modified cows to provide human IgG antibodies against SARS-CoV-2. Currently, this company is planning to start clinical trials of this human IgG against SARS-CoV-2 this summer (2020).

Summary: Bovine colostrum has been advocated as a source of immunity against external environmental microorganisms. Recurrent upper respiratory tract infections present a critical public health concern in the developing countries. The present case report was performed to assess the influence of bovine colostrum in preventing recurrent upper respiratory tract infections caused by respiratory viruses in an adult in Jordan in addition to its effect on respiratory microbiome. In conclusion, bovine colostrum was successful in the prevention of upper respiratory tract infections and significantly affected the nasal swab microbiome. This is the first case report investigating the influence of bovine colostrum on the nasal swab microbiome. In this case report, there was no URTI episodes over the one-year following initiation of BC regimen compared to 5 episodes past BC regimen over the previous year (p < 0.05). The results of this case report indicate that BC was effective in preventing URTIs. These results match those observed in earlier studies . In contrast to earlier findings which found that significantly less participants taking BC stated symptoms of URTI within only 7 weeks following termination of BC compared with those taking placebo. In a previous study, BC had no impact on symptoms once they had developed, however, our finding suggest a possible reduction in the viral load and symptoms. These findings cannot be extrapolated to all patients unless a larger study confirms. BC was effective in the prevention of URTI and we suggest that BC could be recommended as a treatment option for individuals with recurrent URTI. BC significantly affected the nasal swab microbiome. Moreover, this knowledge is necessary to implement the precision medicine.

Summary: Enteral nutrition seems to play a significant role in the treatment of both adults and children with active Crohn’s disease, and to a lesser degree in the treatment of patients with active ulcerative colitis. The inclusion of some special factors in the enteral nutrition formulas might increase the rate of the efficacy. Actually, enteral nutrition enriched in Transforming Growth Factor-β reduced the activity index and maintained remission in patients with Crohn’s disease. In addition, a number of experimental animal studies have shown that colostrum exerts a significantly positive result. Probiotics of a special type and a certain dosage could also reduce the inflammatory process in patients with active ulcerative colitis. Therefore, the addition of these factors in an enteral nutrition formula might increase its effectiveness. Although the use of these formulas is not supported by large clinical trials, it could be argued that their administration in selected cases as an exclusive diet or in combination with the drugs used in patients with inflammatory bowel disease could benefit the patient. In this review, the authors provide an update on the role of enteral nutrition, supplemented with Transforming Growth Factor-β, colostrum, and probiotics in patients with inflammatory bowel disease.

The available data indicate that EN enriched in TGFβ, apart from restoring the impaired nutritional status, could also modulate intestinal immune responses, thus positively affecting the inflammatory bowel processes. This type of EN could be characterized as a supporting and/or primary therapy aiming to induce and/or maintain remission. These formulas enriched with colostrum and probiotics of a special amount and consistency might be proved of benefit in patients with IBD in the near future. In our opinion, it is important not to underestimate the role of nutrition as supportive care in patients with CD. Further well-designed large trials with enteral formulas containing TGFβ, colostrum, probiotics and other nutritional compounds are necessary in order to improve the results of EN.

Summary: Lactoferrin (Lf) is an iron-binding glycoprotein protein known to have immune-modulatory role and recently, its anticancerous effect against different cancer cell types was emphasized. In the present investigation, a comparative evaluation of anticancer potential of colostrum-derived lactoferrin from Indian native zebu cow (Sahiwal, SAC), crossbred (Karan Fries, KFC) and commercially available (C-Lf) lactoferrin from exotic cow using cellular models was made. A protocol was standardized successfully to purify Lf protein from colostrum of both breeds using HPLC and purity was confirmed by LC–MS. A standardized dose of 750 µg/mL Lf was used to treat two cell types MDA-MB-231 and MCF-7 with Lf from three different sources; SAC-Lf, KFC-Lf and C-Lf for 48 h and 72 h. Different cellular parameters including cytotoxicity, viability, apoptosis and cell proliferation were determined. Comparatively, Lf from commercial source (C-Lf) had maximum effect in both cell types followed by SAC-Lf and KFC-Lf. Further, transcriptional changes in genes associated with apoptosis (Bax and Bcl-2), tumor progression (p53, p21, CD44 and NF-κβ) and survival (survivin) were evaluated in Lf treatment. The overall results strongly emphasized to the fact that Lf purified from cow colostrum has the capacity to inhibit the in vitro growth of cancerous cell lines albeit to a varied extent.

The overall results strongly emphasized to the fact that Lf purified from cow colostrum had the capacity to inhibit the growth of cancerous cells. Though, the anti-cancer potential of C-Lf, SAC-Lf and KFC-Lf against two breast cancer cells was established; the difference in their anti-cancer efficacy might be attributed to the difference in structural conformation or iron saturation level. Still, the colostrum purified Lfs, especially of SAC (native cows) has shown encouraging results and in future could be further evaluated for its therapeutic potential.