Serum-derived Bovine Immunoglobulin/protein Isolate Research Articles

Serum-Derived Bovine Immunoglobulin/Protein Isolate Bind Aflatoxins B2 and G1

Aflatoxins are highly toxic biproducts of mold growth which commonly contaminate agricultural commodities, including food and feed. The United States Centers for Disease Control and Prevention estimates approximately half of people worldwide are chronically exposed to aflatoxins through their regular food consumption. The gut serves as both the initial target of toxicity and the location of absorption, leading to systemic exposure. Serum-derived bovine immunoglobulin/protein isolate (SBI) is a purified protein powder enriched in immunoglobulins IgG (55%), IgM (5%), and IgA (1%) used to help manage gut enteropathy. SBI binds a variety of pro-inflammatory antigens and decreases inflammatory markers in the gut by neutralizing or preventing translocation of antigen across the intestinal barrier. The objective of this study is to determine if the immunoglobulins in SBI bind to aflatoxins. Due to the protective effects of SBI, we hypothesize SBI and a highly purified immunoglobulin fraction (>95%), b ovine gamma globulin (BGG), can bind to aflatoxin B2 (AFB2) and aflatoxin G1 (AFG1). Fluorescence spectroscopy was used to quantify the binding of aflatoxins to SBI. Previous work has shown the binding of aflatoxins to tryptophan containing proteins, such as bovine serum albumin, reduces the fluorescence of the protein’s tryptophan residue. The same principle works for SBI, upon excitation at 280 nm, the emission spectra of SBI exhibits a peak at 370 nm which is decreased upon aflatoxin binding. Either SBI (5 μM) or BGG (5 μM) was titrated with an increasing concentration of either AFB2 or AFG1 (0-40 μM). The protein solution was excited at 280 nm and the emission spectra was recorded at 350-450 nm with quenching quantified at 370 nm. The fluorescence from SBI or BGG was reduced in a concentration-dependent manner as the concentration of AFB2 or AFG1 increased. The quenching constant (Ksv) was calculated using the Stern-Volmer equation, while a derivative from the equation was used to calculate the binding constant (Kb). All protein-aflatoxin pairs tested showed binding with Ksv values ranging from 0.9–1.2 x 104 M−1 (R2=0.99) and Kb values ranging from 2.5 x 104 to 4.21 x 105, with SBI-AFB2 exhibiting the tightest binding. Further, the Gibbs free energy for each pair was -6.0 to -7.7 kcal/mol, indicating favorable binding. The quenching of both protein solutions indicates structural and conformational changes in the native structures of both SBI and BGG, likely caused by the interaction of the immunoglobulins with the aflatoxin. The quenching of BGG suggests immunoglobulins in SBI play a significant role for the observed phenomenon, though other serum proteins within SBI could contribute to the quenched fluorescence. Future work will examine if the binding of the aflatoxins by SBI can prevent or mitigate aflatoxin toxicity in the gut. Proliant Health and Biologicals. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Serum-derived bovine immunoglobulin/protein isolate binds to various opportunistic microbes along with associated virulence factors

The gut microbiome consists of a complex population of bacteria, fungi, and viruses that aid the host in various physiological functions. When the microbiota is imbalanced, known as dysbiosis, symbiotic microbes can become opportunistic and excrete virulence factors that decrease intestinal barrier function, causing chronic inflammation that leads to disease. Therefore, maintaining gut microbiome balance is critical to overall health. Endogenous immunoglobulins play a positive role in gut homeostasis and immunoglobulin supplements can assist the body with microbiome maintenance. Serum-derived bovine immunoglobulin/protein isolate (SBI), a spray-dried protein powder enriched in immunoglobulins (IgG, IgA, IgM), is clinically proven to help manage loose and frequent stools associated with gastrointestinal enteropathies. A previous study used an in vitro cell culture model to show that SBI binds and neutralizes pattern-associated molecular patterns by steric/immune exclusion mechanisms. The goal of our study is to expand the list of antigens to which SBI binds. We hypothesize the IgG in SBI binds additional opportunistic microbes found in the gut and their associated virulence factors. Heliobacter pylori ( H. pylori), Shigella dysenteriae, Escherichia coli ( E. coli), and Candida albicans ( C. albicans) are common microbes associated with human gastroenteropathies. Therefore, we initially tested the binding of SBI to H. pylori lysate, H. pylori cytotoxicity-associated immunodominant antigen (CagA), Shiga toxin type-1 (Stx1), E. coli cytolethal distending toxin (CDT), C. albicans lysate, and C. albicans agglutinin-like protein 3 (Als3) by a dot blot method. SBI demonstrated binding to all antigens except the H. pylori lysate. To validate specificity of IgG, further binding studies were completed using a modified ELISA. The absorbance of IgG bound to immobilized antigens increased proportionally to SBI concentration (CagA R 2 =0.98, Stx1 R 2 =0.97, CDT subunit A R 2 =0.99, CDT subunit C R 2 =0.99, C. albicans lysate R 2 =0.99, and Als3 R 2 =0.99). Control experiments verified effective blocking, non-specific binding, and functionality (denatured SBI), as no significant absorbance was measured for any antigen tested. Together, the dot blot and modified ELISA showed the IgG in SBI was found to bind to a variety of opportunistic microbes and their associated virulence factors, including CagA, Stx1, CDT subunit A, CDT subunit C, C. albicans lysate, and Als3. Future work will examine if IgG binding can promote gut microbiome balance. Proliant Health and Biologicals This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Potential use of serum‐derived bovine immunoglobulin/protein isolate for the management of COVID‐19

COVID‐19 manifests as a mild disease in most people but can progress to severe disease in nearly 20% of individuals. Disease progression is likely driven by a cytokine storm, either directly stimulated by SARS‐CoV‐2 or by increased systemic inflammation in which the gut might play an integral role. SARS‐CoV‐2 replication in the gut may cause increased intestinal permeability, alterations to the fecal microbiome, and increased inflammatory cytokines. Each effect may lead to increased systemic inflammation and the transport of cytokines and inflammatory antigens from the gut to the lung. Few interventions are being studied to treat people with mild disease and prevent the cytokine storm. Serumderived bovine immunoglobulin/protein isolate (SBI) may prevent progression by (1) binding and neutralizing inflammatory antigens, (2) decreasing gut permeability, (3) interfering with ACE2 binding by viral proteins, and (4) improving the fecal microbiome. SBI is therefore a promising intervention to prevent disease progression in COVID‐19 patients.

Oral Supplementation with Serum-derived Bovine Immunoglobulin Protein Isolate is Associated with a Reduction in the Incidence of Dietary Endotoxemia

Describe a method for identifying dietary endotoxemia and demonstrate how they could incorporate serum-derived bovine immunoglobulin protein isolate into the treatment of a variety of digestive disorders.

Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART.

Background:Systemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived bovine immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease.Methods:In this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis.Results:One hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/μL, P=0.002) and zonulin (-4.90 ng/μL, P=0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/μL, P=0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/μL), CD4+ T-cell counts increased significantly (26 cells/μL; P=0.002).Conclusions:Oral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART.

Evaluation of oral serum-derived bovine immunoglobulins in HIV-infected patients with chronic idiopathic diarrhea

ObjectivesTo evaluate serum-derived bovine immunoglobulin/protein isolate (SBI) for safety and impact on gastrointestinal (GI) symptoms in HIV patients with chronic idiopathic diarrhea.MethodsA multi-center trial comprised of a double-blind, placebo (PBO)-controlled lead-in phase, (participants received PBO or SBI at 2.5 or 5.0 g BID for 4 weeks) followed by a 20-week, PBO-free phase (SBI at either 2.5 or 5.0 g BID). Participants included HIV-infected patients who were virologically suppressed with a history of chronic idiopathic diarrhea, defined as > 3 loose stools per day for ≥ 3 months without an identifiable cause. Safety was evaluated by monitoring adverse events (AEs) and clinical laboratory testing. Health status and changes in GI symptoms were assessed using validated questionnaires.ResultsSBI was well tolerated by the 103 participants with only 2 withdrawals due to AEs potentially associated with SBI. Mean number of daily unformed stools decreased from about 4 at baseline to less than 2 by week 4 for all study groups. Improvements in several other GI symptoms were also reported. Comparison of the PBO group to SBI groups showed no significant differences, although both SBI cohorts reported significantly improved health status scores. GI symptom improvements were maintained throughout the 20-week PBO-free phase.ConclusionsOral SBI is safe and well tolerated at the doses studied in HIV patients with chronic diarrhea. No conclusions could be drawn regarding impact on GI symptoms. Additional studies are ongoing to examine the biological and immunologic effects of SBI in virologically suppressed HIV-infected patients.

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

BackgroundPatients with irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD) commonly experience diarrhea, abdominal pain, bloating, and urgency. These symptoms significantly compromise the patient’s quality of life (QoL) by limiting participation in normal daily activities and adversely affect work productivity and performance.PurposeThe aim of this study was to understand from the patient’s perspective how oral serum-derived bovine immunoglobulin/protein isolate (SBI) impacts bowel habits, management of condition, and basic QoL.MethodsA 1-page questionnaire was distributed randomly to >14,000 patients who were prescribed SBI (EnteraGam®) 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.ResultsA 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 (≤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±4.3 before SBI to 2.6±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%).ConclusionResults 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.

Potential mechanisms of effects of serum-derived bovine immunoglobulin/protein isolate therapy in patients with diarrhea-predominant irritable bowel syndrome.

Serum‐derived bovine immunoglobulin/protein isolate (SBI), an oral nutritional therapy, is efficacious in diverse diarrheal diseases. In an open‐label study in 15 patients with irritable bowel syndrome‐diarrhea (IBS‐D), we evaluated effects of SBI (5.0 g, twice a day) for 8 weeks on safety, on bowel function and abdominal pain, tryptophan metabolism (K:T ratio), intestinal permeability (13C‐mannitol and lactulose excretion), bile acid synthesis (fasting serum FGF‐19 and C4), duodenal and stool microbiome, and the expression of 90 genes related to inflammation, immune function, and tight junctions in duodenal mucosa. Statistical analysis (paired tests, baseline vs. treatment) was based on intention to treat (ITT) principles. One of 15 Caucasian patients (13F, 2M, age 40.3 ± 2.3y, BMI 34.3 ± 3.0 kg/m2) withdrew without completing studies. There were improvements in stools/day (decrease, P < 0.001), ease of passage (P = 0.035), and evacuation (P = 0.004) with SBI therapy. Worst pain severity was numerically reduced in last 2 weeks' treatment (P = 0.078). Duodenal mucosal mRNA expression; serum C4, FGF‐19, and KT ratio; small bowel or colon permeability; and stool microbiome were not significantly different after SBI therapy, compared to baseline. In duodenal brushings, there was considerable microbiota structure difference (β diversity analysis P = 0.072, UniFrac) and, on taxonomic analysis, increased abundance of Proteobacteria Burkholderiales, Firmicutes Catonella, and unclassified genus organisms with SBI therapy. Thus, SBI therapy for 8 weeks in IBS‐D patients is associated with improved bowel function; the mechanism of benefit is unclear, though there were microbiota structure differences in duodenal brushings. Further studies in patients with low‐grade inflammation and intestinal barrier dysfunction at baseline are indicated.

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

PurposePrevious 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.MethodsA 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 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.ResultsThe area under the curve from time 0 minute to 180 minutes for essential and total amino acids as well as tryptophan increased following ingestion of 5 g, 10 g, or 20 g of SBI, with a significant difference between placebo and all doses of SBI (p<0.05) for essential amino acids and tryptophan but only the 10 g and 20 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 minutes following administration of a single dose or multiple doses of SBI.ConclusionOral 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 g/day.

Retrospective Chart Review Study of Patients Receiving Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI) for Nutritional Management of Irritable Bowel Syndrome with Diarrhea (IBS-D)

Introduction: IBS-D is a common condition with few effective treatment options. The prescription medical food, SBI, has been shown to manage chronic loose and frequent stools in IBS-D patients. The safety and effectiveness of SBI as a therapy for IBS-D was further examined in this multi-center, IRB-reviewed study for overall and individual symptom response. Methods: Symptom data including stool frequency and consistency (Bristol Stool Scale 1-7), abdominal pain intensity (0 = no pain to 10 = worst pain) and adverse events (AEs) were collected from medical charts on 116 patients. Criteria for inclusion in primary analysis were patients having baseline recorded scores for stool consistency and abdominal pain, failure of standard-of-care (SOC) treatment, and not having received confounding IBS-D medications while on SBI. Results: The majority of patients who met criteria for analysis (n = 34) were white (94%), female (71%) with a median age of 53 (28, 85) and received SBI therapy for a mean duration of 23.2±24.1 wks [median 15.5 wks (0.4, 97.9)]. Mean baseline symptom scores were: stool frequency 5.24 (range 2 to 20); stool consistency 6.00 (range 4 to 7) and abdominal pain 4.56 (range 2 to 10). Twenty-five of the 34 patients had baseline abdominal pain scores >2 and stool consistency scores ≥ 5 to assess overall response; nine patients were excluded based on absence of pain (recorded score = 0) and normal stool score (Bristol Stool Scale = 4) at baseline. Of the 25 patients, 16 (64%) were responders with stool consistency < 5 and a 30% reduction in abdominal pain scores following SBI therapy. Using a generalized linear regression model for individual symptoms, the number of stools per day decreased by 3.24 (95% Confidence Interval (CI) 0.50, 5.98; P = 0.022), stool consistency improved by 1.86 (95% CI, 1.39, 2.33; P < 0.0001) and abdominal pain/discomfort intensity decreased by 3.03 (95% CI 1.668, 4.39; P < 0.0001). Thirteen of the 116 patients experienced one or more AEs while on SBI therapy. The main AEs were nausea (n = 5 patients) and an increase abdominal discomfort (n = 2 patients). No serious AEs were reported. Conclusion: Though retrospective, the inclusion criteria of SOC failure prior to SBI administration with demonstrated high combined abdominal pain and stool consistency response, as well as statistically significant individual symptom improvement, demonstrate SBI's clinical utility in IBS-D management. Additional chart reviews continue.

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 pro-inflammatory 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.

P-003 Remission of Pouchitis in Patients Following Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI) Therapy

P-003 Remission of Pouchitis in Patients Following Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI) Therapy

Clinical Management of Lymphocytic Colitis With Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI)

The pathophysiology of lymphocytic colitis (LC) is not completely understood. Current hypotheses implicate abnormal mucosal immune response to luminal antigens in combination with genetic predisposition. Five cases detail the outcomes of adding serum-derived bovine immunoglobulin/protein isolate (SBI) for the nutritional management of these unresponsive LC patients. SBI's unique mechanism includes binding microbial components and maintaining normal GI immune balance which makes it a candidate therapy in LC patients. Five patients were administered SBI for LC. All patients were female with an average age of 71±7.1 yrs. Patient 1 was admitted to the hospital with 20-24 bowel movements (BM) per day with cramps and urgency. Biopsies from a colonoscopy were consistent with LC. She was placed on mesalamine and methylprednisolone without any change. Patient 2 had tried and failed multiple tapering doses of budesonide for 2 yrs with continual multiple, loose stools per day. Patient 3 had been diagnosed with IBS-D for 15 yrs and failed all over-the-counter options. Recent biopsies, however, indicated LC. Patient 4 had a poor response to steroids and psyllium fiber for 2.5 yrs with a history of fecal incontinence (FI). Patient 5 had a diagnosis of LC for 1.5 yrs; she had a history of anal fistula repairs with multiple loose BM in the a.m. accompanied by intermittent episodes of FI. She had no response to mesalamine, loperamide or antibiotics. Incorporating SBI dramatically improved symptoms for all patients. Patient 1 was discharged from the hospital on SBI 5g QD and continued on 1.2g mesalamine having 4 formed BM without cramping, urgency or bleeding. However, if the patient missed more than two days of SBI, she quickly experienced 10-14 watery BM daily. Patient 2 first began SBI 5g BID with budesonide, but was able to discontinue the steroid while maintaining normal BM on SBi monotherapy. Patient 3 was placed on budesonide and SBI 5g QD normal BM within a week. Patient 4 began SBI 5g QD in addition to psyllium fiber and at follow-up reported formed stools with no episodes of FI. After initiating SBI 5g QD, Patient 5 reported 1-2 formed BM without FI. All patients are currently maintained on SBI in combination with the therapies indicated above for more than 6 months. No side effects have been experienced on SBI during that time. The exact manner in which SBI manages LC is not known. The outcomes of these cases, however, suggest that LC patients may benefit from the distinct nutritional proteins in SBI for management of their conditions. Larger, well-controlled studies in patients with LC and/or FI should be performed to corroborate these findings.

Serum-Derived Bovine Immunoglobulin/Protein Isolate for the Management of Diarrhea Associated with Chronic Pancreatitis and Pancreatic Insufficiency: A Novel Approach

Chronic pancreatitis (CP) is a debilitating disorder that ultimately leads to pancreatic insufficiency (PI) and its sequelae. Patients with CP often experience abdominal pain, bloating, nausea, vomiting, weight loss, and steatorrhea. The dearth of pancreatic enzyme secretion in these patients leads to maldigestion, excess fat in the stool, and compromised nutritional status. A typical treatment for management of CP is pancreatic digestive enzyme therapy with pancrelipase, but it is usually ineffective in controlling pain and clinical symptoms, with potential risk of intestinal strictures. Serum-derived bovine immunoglobulin/protein isolate (SBI) is a prescription medical food that has been shown to manage chronic loose and frequent stools in patients with IBS-D, IBD, and HIV enteropathy. SBI has a multifaceted mode of action that through binding of microbial components, results in a downstream reduction in inflammatory markers and up-regulation of tight junction proteins, thus increasing barrier function. This results in improved nutrient utilization, as reported in non-clinical and clinical studies. For this reason, SBI was added to the therapy regimen of a CP/PI patient. The patient is a 73 year old female diagnosed with idiopathic CP and PI in 2012. She has a history of papillary stenosis diagnosed by ERCP with sphincterotomy. She also had chronic pancreatic steatorrhea that was managed with 5-6 doses of pancrelipase per day (at meals and snacks). This patient developed persistent bloating, distension, abdominal pain, and constipation, secondary to pancrelipase therapy. SBI 5g BID was added to her therapy regimen. Upon follow-up 7 weeks later, the patient reported improved discomfort, bloating and regularity of bowel movements to 1 every 2-3 days. The dosing of pacrealipase therapy was reduced due to this favorable response to SBI. She continues on SBI and is doing remarkably well in managing her condition, including her steatorrhea. Three other patients with CP/PI have also responded well to SBI therapy. For this patient, SBI proved to be a novel, safe option for the management of gastrointestinal issues associated with CP/PI. The ability of SBI to return the gut to homeostasis, restore barrier function, and thus allow for the proper absorption of nutrients from the diet may be the reason for its efficacy in this patient. A larger, well-controlled study in CP/PI patients is recommended.

Ischemic Colitis Managed by Serum-Derived Bovine Immunoglobulin/Protein Isolate

There are numerous causes of ischemic colitis, including compromised vascular circulation due to disease or certain medications which can elicit a reflex mesenteric vasoconstriction and result in diarrhea. Reported are 2 cases which detail the outcomes of including serum-derived bovine immunoglobulin/protein isolate (SBI) for the nutritional management of ischemic colitis with chronic loose and frequent stools. SBI has a unique mechanism which includes binding microbial components, maintaining normal GI immune balance, managing barrier function and improving nutrient utilization which may be useful in the management of ischemic colitis. Patient 1 was 82-year-old Caucasian female with a history of hypertension, diabetes mellitus and irritable bowel syndrome with diarrhea (IBS-D), with 4-5 bowel movements (BM)/day for 20 years. She was previously treated with dicyclomine and tricyclic antidepressants for 7 years. Her diarrhea worsened over the past 4 months to ˜10 BM/day. Because of the change in patient's chronic symptoms, a colonoscopy was performed, revealing mild to moderate colitis secondary to ischemia (Figure 1). Patient 2 was a 74-year-old African American male with ESRD/CAD/PVD admitted to hospital with an episode of rectal bleeding. Colonoscopy revealed ischemic colitis and the patient was discharged. He then developed diarrhea (5-6 BM/day). Clostridium difficile was negative by PCR so the patient was started on cholestyramine to help resolve the diarrhea but could not tolerate treatment. For both patients, SBI 5g QD was administered and the response reported here. Patient 1's BM improved to 2-3/day within 4 weeks. A repeat colonoscopy was performed 2 months after initiating SBI therapy and there was no evidence of colonic inflammation or ulcers (Figure 1). Patient 2's symptoms improved dramatically within a couple weeks, with fully formed stools (1-2 BM/day). Both patients continue on SBI 5g QD therapy for management of their condition and remain stable. Previously published reports of SBI in chronic mesenteric ischemia and other intestinal disorders support these patient observations. Although mesenteric ischemia can resolve on its own, the outcomes of these cases and the temporal nature of SBI administration suggest that these patients with ischemic colitis and associated chronic, loose stools may have benefited from this nutritional intervention. A well-controlled study in mesenteric ischemia patients is advised.Figure 1

Management of Small Intestinal Bacterial Overgrowth, (SIBO) Through Dietary and Nutritional Intervention

Introduction: Small intestinal bacterial overgrowth (SIBO) is a dysbiosis of the normal intestinal flora. An increase in the number of organisms present in the small intestine can cause symptoms such as abdominal discomfort, bloating, flatulence, cramps, constipation and/or diarrhea. Changes in epithelial cells due to inflammation, including the blunting of the villi and other less visibly apparent damage to the brush border, can also occur, thus decreasing the nutritional status in SIBO patients. Specifically, fat maldigestion and malabsorption can lead to deficiencies in fat-soluble vitamins A, D and E. Other vitamin and mineral deficiencies can result from SIBO, including vitamin B12, thiamine, nicotinamide and iron. Unfortunately, repeated antibiotic doses may help sustain these deficiencies by altering the host microbiota, continually effecting patient health over time. This can result in antibiotic associated diarrhea or potential antibiotic resistance. Therefore, nutritional therapies that may delay the need for recurrent antibiotic use should be a part of the management of patients who develop SIBO. Methods: Literature reviewing SIBO treatment options is summarized and how oral administration of Serum-derived Bovine Immunoglobulin/Protein Isolate (SBI) may have similar activity via the known mechanism of action is discussed. Results: Dietary changes and nutritional intervention has been shown to modify the microbiota in both healthy patients and in those with gastrointestinal disorders. This has been also been documented for the use of the FODMAP diet, probiotics, and SBI. Given the findings reported by Salem and Roberts (2014) that dietary manipulation through the FODOMAP diet and probiotics may play a fundamental role in the treatment of SIBO and by Weinstock and Jasion (2014) that SBI can help manage SIBO in patients refractory to conventional and rifaximin therapy, the use of SBI for the dietary management of SIBO patient may also be appropriate. SBI has already been shown to bind to proinflammatory microbial components and prevent bacterial translocation (Detzel et al., 2015). Conclusion: When managing SIBO physicians should consider dietary approaches that help replace potential deficiencies in vitamins and minerals. The use of distinctive proteins sources such as SBI which binds to microbial components of bacterial overgrowth in the small intestine should be considered. A detailed study of SBI use in patients with SIBO is warranted.

Remission of Seven Pouchitits Patients Following Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI) Therapy

Remission of Seven Pouchitits Patients Following Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI) Therapy

Use of Serum-Derived Bovine Immunoglobulin/Protein Isolate (SBI) for the Management of DMARD-Induced Chronic Loose and Frequent Stools

Serum-derived bovine immunoglobulin/protein isolate (SBI) is a prescription medical food intended for the dietary management of gastrointestinal disorders that present with chronic loose and frequent stools, namely IBS-D, IBD, and HIV enteropathy. As a medical food, SBI provides distinctive, specially formulated proteins in the form of immunoglobulins not attainable in the normal diet that bind microbial components. This results in a downstream reduction in inflammatory markers and up-regulation of tight junction proteins, thus decreasing permeability and increasing barrier function. These actions assist in managing underlying components associated with gastrointestinal conditions. Furthermore, SBI has been well-tolerated in fragile populations and has no contraindications with other medications. Due to its mode of actions, safety, and supporting clinical reports, SBI was used for the management of intractable diarrhea in an elderly female suffering from a variety of co-morbid conditions. Her response was retrospectively collected. This patient is a 61 year old African American female with a past medical history of systemic lupus erythematosus (SLE), type II diabetes, COPD, and depression. In addition to standard therapeutics to treat her co-morbid conditions, she had been given methotrexate, a disease-modifying antirheumatic drug (DMARD) to treat her SLE. However, this patient developed diarrhea due to the anti-folate drug and discontinued therapy. She was subsequently given leflunomide, another DMARD, but again discontinued after 2 weeks due to worsening of stool frequency and consistency which persisted even after she stopped the drug. Diagnostic colonoscopy results were negative for microscopic colitis and stool tests were negative for infectious agents, including C. difficile. At this time, SBI 5 g BID was initiated. Within 1 month, this patient reported management of stool frequency and consistency and continues on therapy. This patient, who developed persistent, chronic loose and frequent stools induced by methotrexate treatment, was able to manage her condition upon administration of SBI. This case highlights the applicability of this medical food for the management of chronic loose and frequent stools in patients who may have DMARD-induced diarrhea.

Management of inflammatory bowel disease with oral serum-derived bovine immunoglobulin.

The clinical effect of oral serum-derived bovine immunoglobulin/protein isolate (SBI) on symptom and disease management in patients with inflammatory bowel disease (IBD) is reported in this retrospective case series. A single-center, retrospective chart review of IBD patients [N = 45; Crohn's disease (CD), n = 38 and ulcerative colitis (UC), n = 7] with limited to no response to traditional pharmaceutical therapies in controlling symptoms was performed after providing SBI (5 g/day) for nutritional support. Patients were contacted at least monthly to assess response to SBI for symptom management measured by a Likert scale (0 = none; 1 = minimal; 2 = moderate; 3 = significant; 4 = complete). Analysis of variance (ANOVA) was performed on response to therapy based on patient characteristics (age, gender, race) and IBD diagnosis. A multivariate ordered logistical regression model was performed to determine the odds ratio in overall disease management between week 1 and week 12. Finally, the overall group response and percent improvement to SBI was determined over 12 weeks. The odds ratio from the regression model demonstrated that IBD patients were 2.8 times more likely to report clinical improvement in symptom scores with the addition of SBI to their therapeutic regimens [95% confidence interval (CI) 1.266-6.016, p = 0.011]. Disease management was not significantly associated with age, gender, race or disease state. The percentage of patients reporting a response to SBI therapy at week 1 was 49% which increased to 76% after 12 weeks with the fraction of responders gaining significant symptom improvement doubling during the same time period (9% versus 20%). Overall, this group of IBD patients showed increased, steady response to SBI therapy between week 1 and 12 with no reported side effects. These results suggest that SBI improves clinical management of IBD patients who are not fully managed on traditional therapies. SBI should be considered for the nutritional support of IBD regardless of disease activity, location, phenotype, duration, or complexity.

Serum-derived bovine immunoglobulin/protein isolate in the alleviation of chemotherapy-induced mucositis.

BackgroundGastrointestinal (GI) mucositis caused by chemotherapy is associated with diarrhoea and intestinal barrier disruption caused by apoptosis, immune dysfunction and microbiome alterations. Serum-derived bovine immunoglobulin/protein isolate (SBI) has been shown to manage HIV-associated enteropathy and irritable bowel syndrome with diarrhoea (IBS-D). We investigated in a rat model whether SBI was effective in alleviating symptoms of irinotecan-induced GI mucositis.MethodsAnimals were gavaged with 250 or 500 mg/kg of SBI twice daily for 4 days, before intraperitoneal administration of 200 mg/kg irinotecan. Twice daily gavaging of SBI continued for 6 days post-irinotecan. Animals were monitored for bodyweight changes and incidence of diarrhoea and clinical symptoms of stress. Tissues and blood samples were collected at necropsy 6 h, and 2, 4 and 6 days post-irinotecan. H&E-stained colon and jejunum were analysed for histological damage.ResultsThe overall incidence, severity and duration of diarrhoea, and clinical symptoms of mucositis were decreased in irinotecan-treated animals that had received SBI. Animals receiving 500 mg/kg SBI also tended to lose less bodyweight than animals treated only with irinotecan (P > 0.10). SBI-gavaged animals had less pronounced irinotecan-induced changes in neutrophil (P = 0.04959) and lymphocyte (P = 0.0035) levels, and lower tissue damage scores than those receiving irinotecan alone (P < 0.0001).ConclusionsTwice daily oral gavage of SBI was well-tolerated and reduced the incidence, severity and duration of irinotecan-induced mucositis. SBI was associated with less pronounced changes in inflammatory cell levels and tissue damage to colon and jejunum. Ongoing experiments aim to investigate the mechanisms of SBI-associated gastrointestinal protection.