EnteraGam® Mechanism of Action (MOA)

Onset of Action

EnteraGam® works differently than products that provide short-term relief of symptoms. While EnteraGam® immediately begins targeting the factors that contribute to chronic loose or frequent stools, it may take 2 to 4 weeks for a patient to see noticeable results.

When taken, the concentrated immunoglobulins in EnteraGam® begin to bind inflammatory antigens in the gut that may contribute to diarrhea and loose stools. Research has shown that the epithelial lining of the gut regenerates every few weeks, and the binding and neutralization of inflammatory antigens by the immunoglobulins in EnteraGam® may help manage inflammation, allowing for normal regeneration and repair of the lining of the digestive tract.

In a study of patients with diarrhea-predominant IBS (IBS-D), EnteraGam®significantly reduced the number of days that patients had GI-related symptoms, including loose stools, abdominal pain, urgency, and bloating with the onset of action being around 2 to 4 weeks.

MOA

To best explain how EnteraGam® works, we start with a review of the factors that can cause chronic diarrhea and loose stools in patients with specific intestinal disorders.

Watch the animation below or click on the expand arrow on any of the sections below to learn more.

Altered Gut Microbiota: An Important Underlying Etiology of Chronic Loose and Frequent Stools

Chronic diarrhea and loose stools due to specific intestinal disorders, such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), often result from alterations to the gut microbiome.

The involvement of genetic predispositions, diet, stress, and exposure to external antigens, toxins, or environmental insults (including infection) may combine to trigger a continuing cycle of altered gut microbiota, immune activation (resulting in inflammation), gut barrier dysfunction with permeability changes, and impaired nutrient absorption which serves to further amplify and prolong this cycle of events. (See figure below)

 

A microscopic depiction of the pathological changes in the lining of the intestine that disrupt GI homeostasis

Alterations to gut microbiota — Foreign antigens/toxins challenge the epithelial barrier of the small intestine. Toxins invade the epithelial cell layer and antigens penetrate the lamina propria.

Immune activation — Dendritic cells present antigens to the lymphocytes. Mast cells increase, and pro-inflammatory cytokines are produced. Inflammation results.

Gut barrier dysfunction — Epithelial cell damage takes place, a breakdown of tight junction proteins occurs, and epithelial permeability results.

Impaired nutrient absorption — Digestion and absorption of nutrients is compromised due to alterations to the gut microbiota and increased gut permeability
EnteraGam® has a multifaceted MOA

Nonclinical1 and clinical studies2,3 suggest that immunoglobulin-containing protein preparations, such as that found in EnteraGam®, fulfill a distinct nutritional requirement for patients with chronic diarrhea and loose stools due to specific intestinal disorders that cannot be provided by other dietary protein sources or by a simple dietary change.

A growing body of evidence suggests that the specially formulated distinct nutrition of the immunoglobulins found in EnteraGam® plays a key role in providing nutrients to the appropriate areas of the GI tract to help maintain homeostasis of normal intestinal processes in patients with chronic diarrhea and loose stools due to specific intestinal disorders, such as IBS-D2 and IBD.4-7 Specifically, these immunoglobulins and other plasma proteins may help maintain normal intestinal digestion, absorption, and metabolism of ordinary foodstuffs and certain nutrients. EnteraGam® has been shown to: bind microbial components, maintain GI immune balance, manage gut barrier function, and improve nutrient utilization (see figure below).8-15

EnteraGam® binds to microbial components – Immunoglobulins bind to foreign toxins/antigens preventing them from passing through the epithelial cell layer. Decreased number of antigens penetrate (translocation) into lamina propria.

EnteraGam® maintains GI immune balance – Fewer foreign antigens penetrate the lamina propria to activate an immune response. Increase in anti-inflammatory cytokine (TGF-β) expression occurs.

EnteraGam® manages gut barrier function – Tight junction protein expression restored. Reduces permeability of the intestinal barrier.

EnteraGam® improves nutrient utilization – Improved intestinal absorption. Increases in lean body mass. Increased utilization and decreased catabolism of protein. Decreased fecal fat and energy loss.

 

EnteraGam® is a medical food* product intended for the dietary management of chronic diarrhea and loose stools.

EnteraGam® must be administered under medical supervision.

*Medical foods are regulated by the FDA under the Orphan Drug Act16; specially formulated to be consumed or administered orally or enterally; to be used under physician supervision as part of ongoing care to ensure proper, safe use; specifically for management of distinctive nutrient needs, resulting from a specific chronic condition or disease; and specially formulated and processed, as results are not achievable by normal dietary intake.
References
  1. 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.
  2. 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.
  3. Lembcke JL, Peerson JM, Brown 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.
  4. Good L, Panas R. Case Series Investigating the Clinical Practice Experience of Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI) in the Clinical Management of Patients with Inflammatory Bowel Disease. J Gastrointest Syst. 2015;5(2)1-5.
  5. Shafran I, Burgunder P, Wei D, Young HE, Klein G, Burnett BP. Management of inflammatory bowel disease with oral serum-derived bovine immunoglobulin. Therap Adv Gastroenterol. 2015;8(6):331-339.
  6. Awad A, Jasion VS. Use of a Nutritional Therapy, Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI), to Achieve Improvement in Two Different Cases of Colitis. J Gastrointest Syst. 2015;5(2)1-5.
  7. Beauerle B, Burnett B, Dryden G. Successful management of refractory ulcerative colitis with orally administered serum-derived bovine immunoglobulin therapy. Clin Case Rep Rev. 2015;1(4): 90-92.
  8. Horgan A, Maas K, Henderson A, Detzel C, Weaver E. Serum-derived bovine immunoglobulin/protein isolate binds to microbe-associated molecular patterns. Poster presented at: Federation of American Societies for Experimental Biology; 2014; Washington, DC.
  9. Asmuth D, Netanya S. Utay NS, Somsouk M, et al. Oral bovine immunoglobulin reduces immune activation in HIV+ immune nonresponders. Poster presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 22-25, 2016; Boston, MA.
  10. Petschow BW, Burnett B, Shaw AL, Weaver EM, Klein Serum-derived bovine immunoglobulin/protein isolate: postulated mechanism of action for management of enteropathy. Clin Exp Gastroenterol. 2014;7:181-190.
  11. Henderson AL, Brand MW, Darling RJ, et al. Attenuation of colitis by serum-derived bovine immunoglobulin/protein isolate in a defined microbiota mouse model. Dig Dis Sci. 2015;60(11):3293-3303.
  12. Pérez-Bosque A, Miró L, Maijó M, et al. Dietary intervention with serum-derived bovine immunoglobulins protects barrier function in a mouse model of colitis. Am J Physiol Gastrointest Liver Physiol. 2015;308(12):G1012-G1018.
  13. Pérez-Bosque A, Miró L, Maijó M, et al. Oral serum-derived bovine immunoglobulin/protein isolate has immunomodulatory effects on the colon of mice that spontaneously develop colitis. PLoS One. 2016;11(5):e0154823.
  14. Detzel CJ, Horgan A, Henderson AL, Petschow BW, Warner CD, Maas KJ, Weaver EM. Bovine immunoglobulin/protein isolate binds pro-inflammatory bacterial compounds and prevents immune activation in an intestinal co-culture model. PLoS One. 2015;10(4):e0120278.
  15. EnteraGam® [product information]. Ankeny, IA: Entera Health, Inc.; October 2020.
  16. FDA Website. Orphan Drug Act. http://www.fda.gov/food/guidanceregulation/guidancedocumentsregulatoryinformation/medicalfoods/default.htm. Updated May 12, 2016. Accessed February 4, 2017.

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 supervising 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 .

To report suspected adverse reactions, contact Entera Health, LLC 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.

The product information provided in this site is intended for residents of the United States.

EnteraGam® is manufactured and
distributed by Proliant Health & Biologicals, LLC
©2021 Proliant Health & Biologicals, LLC
Ankeny, IA 50021
ENT100H0121 01/21

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