Evaluation of serum-derived bovine immunoglobulin protein isolate in subjects with diarrhea-predominant irritable bowel syndrome

Dale Wilson, Malkanthi Evans, Eric Weaver, Audrey L Shaw, Gerald L Klein, Dale Wilson, Malkanthi Evans, Eric Weaver, Audrey L Shaw, Gerald L Klein

Abstract

Background: There is increased interest in combining nutritional modalities with pharmacological therapies for managing patients with diarrhea-predominant IBS (IBS-D).

Aim: A randomized, double-blind, placebo-controlled study to evaluate the impact of oral serum-derived bovine immunoglobulin/protein isolate (SBI) on gastrointestinal symptom scores and quality of life (QoL) in subjects with IBS-D.

Methods: Study subjects previously diagnosed with IBS-D according to ROME II criteria were recruited from London, Ontario, Canada and assigned to receive 5 g/day SBI, 10 g/day SBI, or placebo for 6 weeks. Daily symptom frequency and severity scores and a modified IBS-36 questionnaire assessed the impact of nutritional intervention. Laboratory assessments were performed at screening and end of treatment (EOT) to evaluate safety. Within-group comparisons of changes in number of days per week with symptoms and symptom severity were conducted on the per-protocol population of subjects using a t-test.

Results: Subjects who received SBI at 10 g/day (N = 15) had statistically significant within-group reductions in abdominal pain (p < 0.01), loose stools (p < 0.01), bloating (p < 0.05), flatulence (p < 0.01), urgency (p < 0.05) and any symptom (p < 0.01) at EOT vs. baseline. Subjects receiving 5 g/day of SBI (N = 15) realized statistically significant within-group reductions in days with flatulence (p < 0.035), incomplete evacuation (p < 0.05), and any symptom (p < 0.01). There were no significant changes in QoL scores or in hematology or clinical chemistry among treatment groups.

Conclusions: This pilot study showed that nutritional therapy with either 10 g/day or 5 g/day of SBI in 30 patients was well tolerated and resulted in statistically significant within group improvements in both symptom days and in daily symptom scores in subjects with IBS-D. Additional studies are underway with larger numbers of subjects to validate these findings.

Keywords: bovine serum immunoglobulin; diarrhea-predominant; irritable bowel syndrome.

Figures

Figure 1
Figure 1
Study design.
Figure 2
Figure 2
Subject disposition.

References

    1. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480–1491.
    1. Saito YA, Schoenfeld P, Locke GR., 3rd The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol. 2002;97(8):1910–1915.
    1. Andrews EB, Eaton SC, Hollis KA, et al. Prevalence and demographics of irritable bowel syndrome: results from a large web-based survey. Aliment Pharmacol Ther. 2005;22(10):935–942.
    1. Gwee KA. Irritable bowel syndrome in developing countries—a disorder of civilization or colonization? Neurogastroenterol Motil. 2005;17(3):317–324.
    1. Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci. 1993;38(9):1569–1580.
    1. Drossman DA, Camilleri M, Mayer EA, Whitehead WE. AGA technical review on irritable bowel syndrome. Gastroenterology. 2002;123(6):2108–2131.
    1. Spiller R, Aziz Q, Creed F, et al. Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut. 2007;56(12):1770–1798.
    1. Gasbarrini A, Lauritano EC, Garcovich M, Sparano L, Gasbarrini G. New insights into the pathophysiology of IBS: intestinal microflora, gas production and gut motility. Eur Rev Med Pharmacol Sci. 2008;12(Suppl 1):111–117.
    1. Camilleri M, Lasch K, Zhou W. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012;303(7):G775–785.
    1. Camilleri M. Peripheral mechanisms in irritable bowel syndrome. N Engl J Med. 2012;367(17):1626–1635.
    1. Simren M, Barbara G, Flint HJ, et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013;62(1):159–176.
    1. Matricon J, Meleine M, Gelot A, et al. Review article: Associations between immune activation, intestinal permeability and the irritable bowel syndrome. Aliment Pharmacol Ther. 2012;36(11–12):1009–1031.
    1. Barbara G, Zecchi L, Barbaro R, et al. Mucosal permeability and immune activation as potential therapeutic targets of probiotics in irritable bowel syndrome. J Clin Gastroenterol. 2012;46(Suppl):S52–55.
    1. Thabane M, Kottachchi DT, Marshall JK. Systematic review and meta-analysis: The incidence and prognosis of post-infectious irritable bowel syndrome. Aliment Pharmacol Ther. 2007;26(4):535–544.
    1. Halvorson HA, Schlett CD, Riddle MS. Postinfectious irritable bowel syndrome—a meta-analysis. Am J Gastroenterol. 2006;101(8):1894–1899. quiz 1942.
    1. Asmuth DM, Ma ZM, Albanese A, et al. Oral Serum-Derived Bovine Immunoglobulin Improves Duodenal Immune Reconstitution and Absorption Function in Patients with HIV Enteropathy. AIDS. 2013;27:2207–2217.
    1. Wilson D, Weaver EM, Klein GL, Shaw AL, Evans M, Cohn J. Efficacy of Serum-Derived Bovine Immunoglobulin Protein Isolate (SBI) in Patients with Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Digestive Disease Week. 2013 May 18;
    1. Peace RM, Campbell J, Polo J, Crenshaw J, Russell L, Moeser A. Spray-dried porcine plasma influences intestinal barrier function, inflammation, and diarrhea in weaned pigs. J Nutr. 2011;141(7):1312–1317.
    1. Asmuth DM, Stombaugh J, Ma ZM. Changes in stool microbiota, bacterial translocation and mucosal immunity after oral serum-derived bovine immunoglobulin (SBI) administration; 20th Conference on Retroviruses and Opportunistic Infections; 2013 Mar 3; Atlanta, GA. 2013.
    1. Lembcke JL, Peerson JM, Brown KH. Acceptability, safety, and digestibility of spray-dried bovine serum added to diets of recovering malnourished children. J Pediatr Gastroenterol Nutr. 1997;25(4):381–384.
    1. Jiang R, Chang X, Stoll B, et al. Dietary plasma protein is used more efficiently than extruded soy protein for lean tissue growth in early-weaned pigs. J Nutr. 2000;130(8):2016–2019.
    1. Jiang R, Chang X, Stoll B, et al. Dietary plasma protein reduces small intestinal growth and lamina propria cell density in early weaned pigs. J Nutr. 2000;130(1):21–26.
    1. Bosi P, Casini L, Finamore A, et al. Spray-dried plasma improves growth performance and reduces inflammatory status of weaned pigs challenged with enterotoxigenic Escherichia coli K88. J Anim Sci. 2004;82(6):1764–1772.
    1. Thompson WG, Longstreth GF, Drossman DA, Heaton KW, Irvine EJ, Muller-Lissner SA. Functional bowel disorders and functional abdominal pain. Gut. 1999;45(Suppl 2):II43–47.
    1. Groll D, Vanner SJ, Depew WT, et al. The IBS-36: a new quality of life measure for irritable bowel syndrome. Am J Gastroenterol. 2002;97(4):962–971.
    1. Clarke G, Fitzgerald P, Cryan JF, Cassidy EM, Quigley EM, Dinan TG. Tryptophan degradation in irritable bowel syndrome: evidence of indoleamine 2,3-dioxygenase activation in a male cohort. BMC Gastroenterol. 2009;9:6.
    1. Keszthelyi D, Troost FJ, Masclee AA. Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function. Neurogastroenterol Motil. 2009;21(12):1239–1249.
    1. Peuhkuri K, Vapaatalo H, Korpela R. Even low-grade inflammation impacts on small intestinal function. World J Gastroenterol. 2010;16(9):1057–1062.
    1. Al-Sadi R, Boivin M, Ma T. Mechanism of cytokine modulation of epithelial tight junction barrier. Front Biosci. 2009;14:2765–2778.
    1. Martin GR, Wallace JL. Gastrointestinal inflammation: a central component of mucosal defense and repair. Exp Biol Med (Maywood) 2006;231(2):130–137.
    1. Cummins PM. Occludin: one protein, many forms. Mol Cell Biol. 2012;32(2):242–250.
    1. Spiller R, Garsed K. Infection, inflammation, and the irritable bowel syndrome. Dig Liver Dis. 2009;41(12):844–849.
    1. Spiller RC. Role of infection in irritable bowel syndrome. J Gastroenterol. 2007;42(Suppl 17):41–47.
    1. Barbara G, Cremon C, Carini G, et al. The immune system in irritable bowel syndrome. J Neurogastroenterol Motil. 2011;17(4):349–359.
    1. Ohman L, Simren M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nature Reviews Gastroenterology & Hepatology. 2010;7(3):163–173.
    1. Martinez C, Vicario M, Ramos L, et al. The jejunum of diarrhea-predominant irritable bowel syndrome shows molecular alterations in the tight junction signaling pathway that are associated with mucosal pathobiology and clinical manifestations. Am J Gastroenterol. 2012;107(5):736–746.
    1. Martinez C, Lobo B, Pigrau M, et al. Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut. 2013;62(8):1160–1168.
    1. Perez-Bosque A, Miro L, Polo J, et al. Dietary plasma proteins modulate the immune response of diffuse gut-associated lymphoid tissue in rats challenged with Staphylococcus aureus enterotoxin B. J Nutr. 2008;138(3):533–537.
    1. Perez-Bosque A, Miro L, Polo J, et al. Dietary plasma protein supplements prevent the release of mucosal proinflammatory mediators in intestinal inflammation in rats. J Nutr. 2010;140(1):25–30.
    1. Moretó M, Lluïsa MM, Polo J, et al. Dietary supplementation with porcine plasma proteins reduce lymphocyte recruitment and cytokine and chemokine expression in a mouse model of spontaneous colitis. Gastroenterology. 2010
    1. Jiang H, Becker C, Przybyszewski J, MacDonald RS. Dietary immunoglobulins affect colon cytokines in mouse model of inflammatory bowel disease. FASEB J. 2010;24(720):1.
    1. Maijo M, Miro L, Polo J, et al. Dietary plasma proteins attenuate the innate immunity response in a mouse model of acute lung injury. Br J Nutr. 2012;107(6):867–875.
    1. Corl BA, Harrell RJ, Moon HK, et al. Effect of animal plasma proteins on intestinal damage and recovery of neonatal pigs infected with rotavirus. The Journal of Nutritional Biochemistry. 2007;18(12):778–784.
    1. Perez-Bosque A, Amat C, Polo J, et al. Spray-dried animal plasma prevents the effects of Staphylococcus aureus enterotoxin B on intestinal barrier function in weaned rats. J Nutr. 2006;136(11):2838–2843.
    1. Nofrarias M, Manzanilla E, Pujols J, et al. Effects of spray-dried porcine plasma and plant extracts on intestinal morphology and on leukocyte cell subsets of weaned pigs. J Anim Sci. 2006;84(10):2735–2742.
    1. Weaver EM, GL K, DeVries BK, et al. Endotoxin neutralization activity (ENA) of bovine plasma and bovine Immunoglobulin (IgG)-rich fractions as compared to human plasma. FASEB J. 2013;27(1079):58.
    1. Jian ZM, Cao JD, Zhu XG, et al. The impact of alanyl-glutamine on clinical safety, nitrogen balance, intestinal permeability, and clinical outcome in postoperative patients: a randomized, double-blind, controlled study of 120 patients. JPEN J Parenter Enteral Nutr. 1999;23(5 Suppl):S62–66.
    1. Hanning RM, Drew M. Bovine Immunoglobulin Feeding Trial. (data on file)
    1. Shi X, Gisolfi CV. Paracellular transport of water and carbohydrates during intestinal perfusion of protamine in the rat. Am J Med Sci. 1996;311(3):107–112.
    1. Visser JT, Lammers K, Hoogendijk A, et al. Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat. Diabetologia. 2010;53(12):2621–2628.
    1. Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nature Reviews Genetics. 2012;13(4):260–270.
    1. Romano-Keeler J, Weitkamp JH, Moore DJ. Regulatory properties of the intestinal microbiome effecting the development and treatment of diabetes. Curr Opin Endocrinol Diabetes Obes. 2012;19(2):73–80.
    1. Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220–230.
    1. Kassinen A, Krogius-Kurikka L, Makivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology. 2007;133(1):24–33.
    1. Saulnier DM, Riehle K, Mistretta TA, et al. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome. Gastroenterology. 2011;141(5):1782–1791.
    1. Pimentel M, Constantino T, Kong Y, Bajwa M, Rezaei A, Park S. A 14-day elemental diet is highly effective in normalizing the lactulose breath test. Dig Dis Sci. 2004;49(1):73–77.

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