Bovine immunoglobulin protein isolates for the nutritional management of enteropathy

Table 1 Weight gain and growth following dietary supplementation with plasma protein concentrates

Animal Model (age)	Impact of dietary supplementation with SBI	Ref.
Piglets: 14-21 d	Superior growth and feed intakes during the first week in 4 of 5 experiments	Pierce et al[28]
	Growth performance improved by the IgG-rich fraction
Piglets: Varying age groups	Consistent improvement in growth, feed intake and sometimes feed conversion; similar results with spray dried plasma from porcine, bovine, and mixed origin	Torrallardona et al[30]
Piglets: Weaned at 14 d	Significantly increased mean daily body weight gains and food conversion efficiencies; no difference in protein intake	Jiang et al[37]
	Significantly greater lean body mass and total carcass mass (P < 0.05)
	Significantly lower circulating urea concentrations (P < 0.05), indicating greater retention of nitrogen and reduced amino acid catabolism
Piglets: Weaned at 21 d, infected with ETEC K88	Increased average daily weight gain and food intake	Bosi et al[44]
	Protected against E. coli-induced inflammation

SBI: Serum-derived immunoglobulin/protein isolates; E. coli: Escherichia coli; ETEC K88: Enterotoxigenic E. coli, K88 strain.

Table 2 Effects of plasma-derived protein concentrates on intestinal function in animal models

Species	Model/indication	Impact of dietary supplementation with SBI	Ref.
Pig	Postweaning	Reduced colonic paracellular permeability	Peace et al[46]
		Reduced ileal permeability
		Fewer lamina propria cells in ileum and colon
		Reduced transepithelial electrical resistance in the colon - improved tight junction
		Significantly improved fecal scores
	Rotavirus infection	Significantly reduced clinical signs of diarrhea	Corl et al[43]
		Significantly greater intestinal mucosal protein and lactase activity
	Infection by ETEC K88	Decreased inflammatory cell infiltration and mucosal damage	Bosi et al[44]
		Increased crypt depth, reduced intestinal expression of proinflammatory TNF-α and IL-8
Rat	Exposure to SEB	Improved ion transport function, as measured by reductions in the potential difference across the jejunum and Na-K-ATPase activity	Pérez-Bosque et al[47]
		Improved mucosal permeability (dextran flux and HRP paracellular flux)

SBI: Serum-derived immunoglobulin/protein isolates; ETEC K88: Enterotoxigenic Escherichia coli, K88 strain; TNF-α: Tumor necrosis factor alpha; IL-8: Interleukin 8; SEB: Staphylococcus aureus enterotoxin B; Na-K-ATPase: Sodium-potassium adenosine triphosphatase; HRP: Horse radish peroxidase.

Table 3 Human studies with serum-derived immunoglobulin/protein isolates to evaluate intestinal benefits and quality of life

Species	Model/indication	Impact of dietary supplementation with SBI	Ref.
Human n = 8, HIV positive adults	HIV-associated enteropathy	Significant reduction in mean bowel movements/day and improvement in stool consistency scores after 8 wk (P = 0.008)	Asmuth et al[31]
		Significant reduction in GI questionnaire scores from 17 at baseline to 8.0 at 8 wk (P =0.008)
		No change in gut permeability (disaccharide absorption); increase in D-xylose absorption in 7/8 subjects
		Maintained stool frequency and consistency for an additional 9 mo (n = 5)
Human n = 66 adults	IBS-D	10 g/d showed significant decrease in # symptom days with abdominal pain, flatulence, bloating, loose stools, urgency or any symptom over 6 wk (P < 0.05)	Wilson et al[32]
		5 g/d showed significant improvements in loose stools, hard stools, flatulence and incomplete evacuation (P < 0.05)
Human n = 10 infants or children (9-25 mo)	Malnutrition	Significant reductions in fecal wet and dry weights, and lower fecal fat and energy losses compared with the control diet (P < 0.05) in relation to the amount of SBI in the diet during three randomly ordered 7-d periods	Lembcke et al[41]
Human n = 259 infants (6-7 mo)	Malnutrition	Trends toward weight gain and upper arm circumference (a measure of lean body mass) increases were found in the SBI + micronutrient group vs SBI alone	Bégin et al[42]

HIV: Human immunodeficiency virus; IBS-D: Irritable bowel syndrome, diarrhea predominant.

Table 4 Effects of serum-derived immunoglobulin/protein isolates administration on immune and inflammatory markers

Species	Model/indication	Impact of dietary supplementation with SBI	Ref.
Pig	ETEC K88	Reduced expression of TNF-α and IL-8 in the gut	Bosi et al[44]
	Postweaning	Reduced TNF-α in the colon	Peace et al[46]
		Reduced IFNγ levels in the ileum and colon day 7, but not day 14 post weaning
Rat	SEB	Prevented the SEB-induced increase in IFN-γ, IL-6, and LTB4 in Peyer's patches and in the mucosa	Pérez-Bosque et al[69]
		Increased anti-inflammatory cytokines (IL-10 and mature TGF-β) in intestinal mucosa	Pérez-Bosque et al[68]
		Reduced SEB-induced increase in cytotoxic lymphocyte populations of γδ-T cells, natural killer cells, and the number of activated T lymphocytes in lamina propria.
Mouse	Mdr1-/- knockout mouse model of spontaneous colitis	Reduced the percentage of activated Th lymphocytes	Moretó et al[48]
		Reduced INF-γ and TNF-α expression in the colon
		Significantly reduced the expression of cytokines IL-2 and IL-17, chemokines MCP-1 and MIP-1b, and iNOS in the mucosa
Mouse	2% DSS-induced IBD model	Reduced elevation of IL-1α, IL-4, IL-6, IL-10, MCP-1, and KC	Jiang et al[67]
Human (HIV+ adults)	HIV enteropathy	I-FABP fell below baseline in 4/5 patients who continued receiving SBI (P < 0.12) out to 48 wk	Asmuth et al[31]
		MMP-9/TIMP-1 ratios in subjects were significantly lower than controls at baseline (P < 0.007)
		MCP-1 levels decreased in 5/5 patients who continued receiving SBI (P < 0.06) out to 48 wk

ETEC K88: Enterotoxigenic Escherichia coli, K88 strain; TNF-α: Tumor necrosis factor α; IL: Interleukin; SEB: Staphylococcus aureus enterotoxin B; IFNγ: Interferon-γ; LTB4: Leukotriene B4; TGF-β: Transforming growth factor β; MCP 1: Monocyte chemotactic protein 1; MIP-1b: Macrophage inflammatory protein; iNOS: Inducible nitric oxide synthase; KC: Keratinocyte-derived cytokine; HIV: Human immunodeficiency virus; I-FABP: Intestinal-fatty acid binding protein; MMP-9: Matrix metalloproteinas-9; TIMP: Tissue inhibitor of metalloproteinase.