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EnteraGam® Addresses Distinct Nutritional Requirements

Serum-derived bovine immunoglobulin/protein Isolate (SBI) addresses the distinct nutritional requirements in patients with chronic diarrhea and loose stools due to specific intestinal disorders

Chronic diarrhea is frequently associated with several human disease conditions, including diarrhea-predominant irritable bowel syndrome (IBS-D) and HIV infection, and are caused by changes in the lining of the intestinal tract. Such changes disrupt the normal balance of the GI tract, which leads to symptoms of abdominal discomfort, bloating, and abnormal bowel function (e.g., urgency, diarrhea, constipation).

While the causes of intestinal disorders are not well understood, there is evidence to suggest the involvement of heredity, diet, stress, and exposure to foreign substances, toxins, or other environmental insults (including infection). There are dozens of mutated genes, for example, which have been implicated in IBS, a specific enteropathy which affects 10%-20% of the population.1 These mutations can negatively affect the barrier function of the intestine, change the ability to metabolize tryptophan,2 an essential amino acid needed by the body to produce certain chemicals which effect pain perception, and the synthesis and metabolism of bile acids3 which can increase bowel movements.

Modifications in tryptophan, serotonin, and bile acid metabolism, as well as alterations in the intestinal microbiota (bacteria), have been implicated in causing or making symptoms worse in patients with IBS-D. Besides the potential hereditary involvement, changes of the intestinal microbiota (microbes which live in the gut) and gut permeability can limit or impair digestive and absorptive function leading to changes in fluid balance and vitamin production and absorption, and adversely affect digestion of carbohydrates and fats. Poor absorption of key nutrients such as vitamins, minerals, protein, carbohydrates, and fat during chronic diarrhea can lead to malnutrition or chronic under-nutrition and play a central role in patients with intestinal problems. A simple dietary change does not correct these issues in patients with a variety of intestinal disorders.

Role of Immunoglobulins

It is widely recognized that breast milk, the sole source of nutrition for the premature infant, contains a number of proteins (including immunoglobulins). These proteins, along with early exposure to external antigens and bacteria, are critical for establishing the intestinal microbiota, normal immune function, integrity of the gut barrier, and digestive processes in the GI tract.4-7 Studies evaluating specially formulated bovine immunoglobulin preparations have revealed a similar need for immunoglobulins in maintaining gut homeostasis in enteropathy.8-14

Study Data (clinical and nonclinical)

A clinical study supplementing a formulation similar to serum-derived bovine immunoglobulin/protein isolate (SBI), a specially formulated bovine IgG-containing preparation, replacing 25% and 50% of the milk protein of the control diet, provided distinct nutritional support which promoted trends in better carbohydrate and nitrogen absorption, as well as nitrogen retention. Additionally, there was a statistically significant decrease in fat and energy loss in the feces which resulted in a significantly greater absorption of fat and energy in infants who were malnourished,12 a condition that contributes to enteropathy.

In another clinical study comparing a formulation similar to SBI to soy protein at the same level, only SBI demonstrated within group statistically significant management of IBS-D,14 another type of enteropathy. Finally, SBI administered daily to patients with HIV-associated enteropathy provided nutritional support as evidenced by an increase in D-xylose absorption, a marker for nutrient uptake.13 These results appear to demonstrate that SBI, a specially formulated bovine-IgG preparation, provides for a distinct nutritional requirement induced by enteropathies in different clinical populations.

Nonclinical studies corroborate the clinical findings with regard to addressing a distinct dietary requirement for immunoglobulin-containing preparations for restoring a normal homeostasis to the gut. In a review of data from 75 studies in 43 publications involving over 12,000 piglets (which are prone to developing intestinal disorders during the critical weaning period)15 the addition of plasma protein concentrates to normal feed provided high levels of immunoglobulins similar to levels found in SBI. Nutritional status improved only in piglets fed immunoglobulin-containing protein formulations which increased nutrient ingestion, digestion, absorption, and metabolism of feed and certain nutrients when compared to a range of other proteins added to feed (i.e., from dairy, fish, soy, and other vegetable sources).8 Other models of environmental stress, including viral infection and GI toxin exposure, demonstrated that only bovine plasma containing high levels of immunoglobulin managed enteropathy in weanling pigs compared to soy protein at the same level, as well as in rats when added and compared to normal feed, respectively.16-18

Conclusion

Taken together, results from clinical and nonclinical studies appear to reveal a distinct dietary requirement for immunoglobulins for the purpose of nutritional support in maintaining homeostasis to the disrupted gut environment.

References
  1. Saito YA. The role of genetics in IBS. Gastroenterol Clin North Am. 2011;40(1):45-67.
  2. Keszthelyi D, Troost FJ, Masclee AA. Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function. Neurogastroenterol Motil. 2009;21(12):1239-1249.
  3. Wong BS, Camilleri M, Carlson P, et al. Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol. 2012;10(9):1009-15 e3.
  4. Petherick A. Development: Mother’s milk: A rich opportunity. Nature. 2010;468(7327):S5-S7.
  5. Stockinger S, Hornef MW, Chassin C. Establishment of intestinal homeostasis during the neonatal period. Cell Mol Life Sci; 2011;68(22):3699-3712.
  6. Martin R, Jiménez E, Heilig H, et al. Isolation of bifidobacteria from breast milk and assessment of the bifidobacterial population by PCR-denaturing gradient gel electrophoresis and quantitative real-time PCR. Appl Environ Microbiol. 2009;75(4):965-969.
  7. Aaltonen J, Ojala T, Laitinen K, Poussa T, Ozanne S, Isolauri E. Impact of maternal diet during pregnancy and breastfeeding on infant metabolic programming: a prospective randomized controlled study. Eur J Clin Nutr. 2011;65(1):10-19.
  8. Torrallardona D. Spray dried animal plasma as an alternative to antibiotics in weanling pigs—a review. Asian-Aust. J. Anim. Sci. 2010;23(1):131-148.
  9. Moretó M, Pérez-Bosque A. Dietary plasma proteins, the intestinal immune system, and the barrier functions of the intestinal mucosa. J Anim Sci. 2009;87(14 Suppl):E92-100.
  10. Campbell JM, Polo J, Russell LE, J.D. Review of spray-dried plasma’s impact on intestinal barrier function. Livestock Sci. 2010;133:239-41.
  11. Bégin F, Santizo MC, Peerson JM, Torún B, Brown KH. Effects of bovine serum concentrate, with or without supplemental micronutrients, on the growth, morbidity, and micronutrient status of young children in a low-income, peri-urban Guatemalan community. Eur J Clin Nutr. 2008;62(1):39-50.
  12. 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.
  13. 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(14):2207-2217.
  14. Wilson D, Evans M, Weaver E, Shaw AL, Klein GL. Evaluation of serum-derived bovine immunoglobulin protein isolate in subjects with diarrhea-predominant irritable bowel syndrome. Clin Med Insights Gastroenterol. 2013;6:49-60.
  15. van Beers-Schreurs HM, Nabuurs MJ, Vellenga L, Kalsbeek-van der Valk HJ, Wensing T, Breukink HJ. Weaning and the weanling diet influence the villous height and crypt depth in the small intestine of pigs and alter the concentrations of short-chain fatty acids in the large intestine and blood. J Nutr. 1998;128(6):947-953.
  16. Corl BA, Harrell RJ, Moon HK, et al. Effect of animal plasma proteins on intestinal damage and recovery of neonatal pigs infected with rotavirus. J Nutr Biochem. 2007;18(12):778-784.
  17. Pérez-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.
  18. Moretó M, Miró L, Polo J, et al. Oral porcine plasma proteins prevent the release of mucosal pro-inflammatory cytokines in rats challenged with S. aureus enterotoxin B. Gastroenterol. 2008;134(Suppl 1)A-524.

Intended Use

EnteraGam® is a medical food product intended for the dietary management of chronic diarrhea and loose stools. EnteraGam® must be administered under medical supervision.

Important Safety Information:

EnteraGam® contains beef protein: therefore, patients who have an allergy to beef or any other component of EnteraGam® should not take this product. EnteraGam® has not been studied in pregnant women, in women during labor and delivery, or in nursing mothers. The choice to administer EnteraGam® during pregnancy, labor and delivery, or to nursing mothers is at the clinical discretion of the prescribing physician.

EnteraGam® does not contain any milk-derived ingredients such as lactose, casein, or whey. EnteraGam® is gluten-free, dye-free, and soy-free.

Please see full Product Information

To report suspected adverse reactions, contact Entera Health, Inc. at 1-855-4ENTERA (1-855-436-8372), or the FDA at 1-800-FDA-1088 (1-800-332-1088) or www.fda.gov/medwatch.