Oral Serum-Derived Bovine Immunoglobulin/Protein Isolate Has Immunomodulatory Effects on the Colon of Mice that Spontaneously Develop Colitis

Dietary immunoglobulin concentrates prepared from animal plasma can modulate the immune response of gut-associated lymphoid tissue (GALT). Previous studies have revealed that supplementation with serum-derived bovine immunoglobulin/protein isolate (SBI) ameliorates colonic barrier alterations in the mdr1a-/- genetic mouse model of IBD. Here, we examine the effects of SBI on mucosal inflammation in mdr1a-/- mice that spontaneously develop colitis. Wild type (WT) mice and mice lacking the mdr1a gene (KO) were fed diets supplemented with either SBI (2% w/w) or milk proteins (Control diet), from day 21 (weaning) until day 56. Leucocytes in mesenteric lymph nodes (MLN) and in lamina propria were determined, as was mucosal cytokine production. Neutrophil recruitment and activation in MLN and lamina propria of KO mice were increased, but were significantly reduced in both by SBI supplementation (p < 0.05). The increased neutrophil recruitment and activation observed in KO mice correlated with increased colon oxidative stress (p < 0.05) and SBI supplementation reduced this variable (p < 0.05). The Tact/Treg lymphocyte ratios in MLN and lamina propria were also increased in KO animals, but SBI prevented these changes (both p < 0.05). In the colon of KO mice, there was an increased production of mucosal proinflammatory cytokines such as IL-2 (2-fold), IL-6 (26-fold) and IL-17 (19-fold), and of chemokines MIP-1β (4.5-fold) and MCP-1 (7.2-fold). These effects were significantly prevented by SBI (p < 0.05). SBI also significantly increased TGF-β secretion in the colon mucosa, suggesting a role of this anti-inflammatory cytokine in the modulation of GALT and the reduction of the severity of the inflammatory response during the onset of colitis

Impact of serum-derived bovine immunoglobulin/protein isolate therapy on irritable bowel syndrome and inflammatory bowel disease: a survey of patient perspective

Audrey L Shaw,1 Adam Tomanelli,2 Timothy P Bradshaw,1 Bryon W Petschow,1 Bruce P Burnett3 1Clinical Research, Entera Health, Inc., Cary, NC, 2Market Research, Praxis Research Partners, Fairfield, CT, 3Medical Affairs, Entera Health, Inc., Cary, NC, USA Background: Patients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) commonly experience diarrhea, abdominal pain, bloating, and urgency. These symptoms significantly compromise the patient&rsquo;s quality of life (QoL) by limiting participation in normal daily activities and adversely affect work productivity and performance.Purpose: The aim of this study was to understand from the patient&rsquo;s perspective how oral serum-derived bovine immunoglobulin/protein isolate (SBI) impacts bowel habits, management of condition, and basic QoL.Methods: A 1-page questionnaire was distributed randomly to &gt;14,000 patients who were prescribed SBI (EnteraGam&reg;) for relevant intended uses. The survey was designed to collect data related to the influence of IBS or IBD on daily life activities and the impact of SBI usage on daily stool frequency, management of their condition, and QoL. Patient-reported responses were analyzed using a paired t-test to compare mean change in daily stool output and descriptive statistics for continuous variables.Results: A total of 1,377 patients returned the surveys. Results from 595 surveys were analyzed with a focus on patients with IBS or IBD who had provided numeric responses regarding daily stool frequency. Respondents with IBS who reported having a normal stool frequency (&le;4 stools per day) increased from 35% prior to using SBI to 91% while using SBI. A similar change toward normal stool frequency was reported by IBD respondents. Mean daily stool numbers decreased for respondents in the combined IBS and IBD groups (P=0.0001) from 6.5&plusmn;4.3 before SBI to 2.6&plusmn;1.9 following SBI use. The majority of respondents agreed strongly or very strongly that SBI helped them manage their condition (66.9%) and helped them return to the activities they enjoyed (59.1%).Conclusion: Results from this patient survey suggest that SBI use can lead to clinically relevant decreases in daily stool frequency in patients with IBS or IBD along with improvements in the overall management of their condition and aspects of QoL. Keywords: IBD, IBS, patient satisfaction, stool frequency, quality of lif

Absorption and safety of serum-derived bovine immunoglobulin/protein isolate in healthy adults

Audrey L Shaw,1 David W Mathews,1 John E Hinkle,2 Bryon W Petschow,1 Eric M Weaver,3 Christopher J Detzel,1 Gerald L Klein,4 Timothy P Bradshaw1 1Clinical Development, Entera Health, Inc., 2Life Sciences Consulting and Analytics, EarlyPhase Sciences, Inc., Cary, 3Executive Management, Prairie Pharms, LLC, Nora Springs, 4Executive Management, MedSurgPI, LLC, Raleigh, NC, USA Purpose: Previous studies have shown that oral administration of bovine immunoglobulin protein preparations is safe and provides nutritional and intestinal health benefits. The purpose of this study was to evaluate the plasma amino acid response following a single dose of serum-derived bovine immunoglobulin/protein isolate (SBI) and whether bovine immunoglobulin G (IgG) is present in stool or in blood following multiple doses of SBI in healthy volunteers.Methods: A total of 42 healthy adults were administered a single dose of placebo or SBI at one of three doses (5 g, 10 g, or 20 g) in blinded fashion and then continued on SBI (2.5 g, 5 g, or 10 g) twice daily (BID) for an additional 2&nbsp;weeks. Serial blood samples were collected for amino acid analysis following a single dose of placebo or SBI. Stool and blood samples were collected to assess bovine IgG levels.Results: The area under the curve from time 0&nbsp;minute to 180 minutes for essential and total amino acids as well as tryptophan increased following ingestion of 5&nbsp;g, 10&nbsp;g, or 20&nbsp;g of SBI, with a significant difference between placebo and all doses of SBI (p&lt;0.05) for essential amino acids and tryptophan but only the 10&nbsp;g and 20&nbsp;g doses for total amino acids. Bovine IgG was detected in the stool following multiple doses of SBI. No quantifiable levels of bovine IgG were determined in plasma samples 90&nbsp;minutes following administration of a single dose or multiple doses of SBI.Conclusion: Oral administration of SBI leads to increases in plasma essential amino acids during transit through the gastrointestinal tract and is safe at levels as high as 20&nbsp;g/day. Keywords: bovine immunoglobulin, intestinal absorption, plasma amino acid