Serum-derived Bovine Immunoglobulin Research Articles

Serum-Derived Bovine Immunoglobulin Promotes Barrier Integrity and Lowers Inflammation for 24 Human Adults Ex Vivo.

Serum-derived bovine immunoglobulin (SBI) prevents translocation and inflammation via direct binding of microbial components. Recently, SBI also displayed potential benefits through gut microbiome modulation. To confirm and expand upon these preliminary findings, SBI digestion and colonic fermentation were investigated using the clinically predictive ex vivo SIFR® technology (for 24 human adults) that was, for the first time, combined with host cells (epithelial/immune (Caco-2/THP-1) cells). SBI (human equivalent dose (HED) = 2 and 5 g/day) and the reference prebiotic inulin (IN; HED = 2 g/day) significantly promoted gut barrier integrity and did so more profoundly than a dietary protein (DP), especially upon LPS-induced inflammation. SBI also specifically lowered inflammatory markers (TNF-α and CXCL10). SBI and IN both enhanced SCFA (acetate/propionate/butyrate) via specific gut microbes, while SBI specifically stimulated valerate/bCFA and indole-3-propionic acid (health-promoting tryptophan metabolite). Finally, owing to the high-powered cohort (n = 24), treatment effects could be stratified based on initial microbiota composition: IN exclusively stimulated (acetate/non-gas producing) Bifidobacteriaceae for subjects classifying as Bacteroides/Firmicutes-enterotype donors, coinciding with high acetate/low gas production and thus likely better tolerability of IN. Altogether, this study strongly suggests gut microbiome modulation as a mechanism by which SBI promotes health. Moreover, the SIFR® technology was shown to be a powerful tool to stratify treatment responses and support future personalized nutrition approaches.

Dysbiosis in Irritable Bowel Syndrome.

The human gut microbiota fosters the development of a dynamic group of microorganisms impacted by diverse variables that include genetics, diet, infection, stress, ingested drugs, such as antibiotics and small intestine bacterial overgrowth (SIBO) as well as the gut microbiota itself. These factors may influence the change in microbial composition, which results in dysbiosis (microbial imbalance) and exposes the gut to pathogenic insults. Dysbiosis is incidental to the etiology of inflammatory diseases such as irritable bowel syndrome (IBS) and metabolic diseases, including type 2 diabetes and obesity. IBS exhibits different symptoms like abdominal pain or discomfort, distention/bloating, and flatulence. To treat IBS, modification of dysregulated gut microbiota can be done using treatment strategies like a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet, antibiotics that cannot be absorbed like rifaximin and neomycin, probiotics and prebiotics, and fecal microbiota transplantation (FMT). The remedial modalities in the existing literature have been demonstrated to be efficacious in the prevention and mitigation of IBS. Additionally, newer curative approaches with serum-derived bovine immunoglobulin (SBI) are an effective option. The focal point of the review paper is the pathophysiology of IBS, mainly due to dysbiosis and the various factors that advance dysbiosis. Here, we have also discussed the different treatment strategies targeting dysbiosis that effectively treat IBS. How to cite this article: Abraham P, Pratap N. Dysbiosis in Irritable Bowel Syndrome. J Assoc Physicians India 2023;71(9):75-81.

Serum-Derived Bovine Immunoglobulin Stimulates SCFA Production by Specific Microbes in the Ex Vivo SIFR® Technology

Serum-derived bovine immunoglobulins (SBI) exert health benefits mediated by their ability to bind microbial components, thereby preventing translocation and subsequent inflammation. While in vivo studies have shown that a fraction of SBI also reaches the colon, little is known about the impact of SBI on the dense colonic microbiota that has great potential to impact human health. This study, therefore, investigated the impact of three bovine plasma protein fractions (SBI, bovine plasma (BP) and albumin-enriched bovine plasma (ABP)) on the gut microbiota of six human adults using the novel ex vivo SIFR® technology, recently demonstrated to generate predictive findings for clinical studies. When dosed at an equivalent of 5 g/day, all protein fractions significantly increased health-related metabolites-acetate, propionate, and butyrate. Upon simulating small intestinal absorption, SBI still markedly increased acetate and propionate, demonstrating that SBI is more resistant to small intestinal digestion and absorption compared to the other protein sources. Despite noticeable interindividual differences in microbiota composition among human adults, SBI consistently stimulated a narrow spectrum of gut microbes, which largely differed from the ones that are typically involved in carbohydrate fermentation. The SBI-fermenting consortium included B. vulgatus and L. edouardi (correlating with acetate and propionate) along with Dorea longicatena, Coprococcus comes and the butyrate-producing bacterium SS3/4 (correlating with butyrate). Overall, this study revealed that protein bovine fractions can contribute to health benefits by specifically modulating the human gut microbiota. While health benefits could follow from the production of SCFA, a broader range of protein-derived metabolites could also be produced. This study also confirms that the concept of prebiotics (substrates selectively utilized by host microorganisms conferring a health benefit) could go beyond the use of ingestible carbohydrates and extend to partially indigestible proteins.

Evaluation of Serum-Derived Bovine Immunoglobulin Protein Isolate in Subjects With Decompensated Cirrhosis With Ascites.

BackgroundBacterial translocation plays a pivotal role in the natural course of cirrhosis and its complications. Serum-derived bovine immunoglobulin (SBI) is an oral medical food that has been shown to both reduce inflammation in the intestines and neutralize bacteria. It represents a unique intervention that has not been studied in this population.MethodologyWe conducted a prospective open-label trial with an eight-week treatment phase of SBI. Individuals were assessed using lactulose breath testing, serum markers for enterocyte damage and bacterial translocation, and the Chronic Liver Disease Questionnaire (CLDQ) prior to and after completion of the treatment phase.ResultsWe evaluated nine patients with a diagnosis of decompensated cirrhosis with ascites. Subjects had a mean Model for End-Stage Liver Disease (MELD) score of 11.6 ± 3.0 and were not taking lactulose or antibiotics. All subjects tolerated SBI well with no significant adverse events or changes to any of the six domains of the CLDQ. Laboratory tests including liver tests and MELD score remained stable over the course of treatment. There were no significant changes in the rates of small intestinal bacterial overgrowth (55.6% vs 55.6%, p = 1.00) or serum levels of lipopolysaccharide-binding protein, intestinal fatty acid-binding protein, or soluble CD14 (p-values 0.883, 0.765, and 0.748, respectively) when comparing values prior to and immediately after treatment.ConclusionsNo adverse events or significant changes to the quality of life were detected while on treatment. There were no statistically significant differences in our outcomes when comparing individuals before and after treatment in this small prospective proof-of-concept pilot study. Further prospective randomized studies could be beneficial.

Serum-derived Bovine Immunoglobulin Effect on Mucositis

Serum-derived Bovine Immunoglobulin Effect on Mucositis

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-derived bovine immunoglobulin for children with diarrhea-predominant irritable bowel syndrome.

BackgroundOral serum-derived bovine immunoglobulin (SBI)/protein isolate is a medical food intended to manage chronic diarrhea. It has been shown to improve pain and diarrhea in adults with diarrhea-predominant irritable bowel syndrome (d-IBS).AimTo determine if SBI can improve symptoms in children with d-IBS.MethodsWe performed a randomized, double-blind, placebo-controlled, pilot study (NCT02609529) to evaluate the effectiveness of SBI in children 8–18 years with d-IBS. We recorded stool number, abdominal pain, and stool form in all patients for 1 week and then assigned the patients at a ratio of 2:1 to treatment with SBI 5 g BID or placebo for 3 weeks. The patients and their parents completed the Pediatric Quality of Life Inventory™ for Gastrointestinal Symptoms (PedsQOL) and the Pediatric Functional Disability Index (FDI). In addition, complete blood counts and serum chemistries were recorded at the start and end of treatment to evaluate safety.ResultsFifteen patients (nine SBI, six placebo) completed the study. Both SBI and placebo groups reported nonstatistical reductions in stool frequency per week. The SBI group showed a significant reduction in stool frequency at weeks 1 and 2 but not at the end of treatment. The SBI group also demonstrated statistical improvements in abdominal pain and stool form by 3 weeks. The placebo group did not achieve similar improvements. The overall FDI and PedsQOL scores, as well as PedsQOL subscale scores for pain, discomfort when eating, diarrhea, worry about stomach aches, and communication, improved significantly in the SBI group, but not in the placebo group. No serious adverse events occurred. Serum chemistries and hemograms were normal at baseline and at the end of study in all patients.ConclusionIn this single-center, exploratory pilot study, we demonstrated that 10 g SBI per day was safe in children with d-IBS and improved symptoms. Larger studies, with longer treatment duration, seem warranted based on these initial positive results.

Clinical Efficacy of Serum-Derived Bovine Immunoglobulin in Patients With Refractory Inflammatory Bowel Disease

BackgroundInflammatory bowel disease (IBD) can have autoimmunity and/or intestinal barrier dysfunction as part of pathophysiology and may be refractory to all available treatment options. Serum-derived bovine immunoglobulin (SBI) binds microbial components with postulated downstream effects of normalized gut immune and barrier function, which may be useful for managing IBD. The purpose of our study was to evaluate the effectiveness of SBI in the management of refractory IBD, particularly symptoms of chronic diarrhea and loose stools. MethodsWe retrospectively analyzed charts for patients diagnosed with IBD (n = 40) who were refractory to standard treatment. Patients received oral SBI 5 g daily for a period of at least 6 weeks. Twelve patients with IBD fulfilled study inclusion criteria. Each patient graded the severity and frequency of gastrointestinal symptoms before starting SBI and at 6 weeks of treatment using a standardized patient assessment form. Means and standard deviations for all symptom scores at baseline and week 6 of treatment were analyzed. ResultsMean symptom scores decreased significantly for nausea (P = 0.02 for severity and P = 0.03 for mean symptom score) and diarrhea (P = 0.0006, P = 0.0001 and P = 0.0001 for severity, frequency and mean symptom score, respectively). ConclusionsTherapy with SBI alleviated some refractory gastrointestinal symptoms in patients with IBD, including nausea and diarrhea. Increased duration, dosage and/or frequency of SBI might provide additional symptom improvement and could be tested through controlled clinical trials with larger sample sizes and longer follow-up.

Gut Microbiota-Based Therapies for Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a common, heterogeneous disorder characterized by abdominal pain associated with changes in bowel habits. The pathogenesis of IBS is multifactorial and may relate to alterations in the gut microbiota, changes in visceral sensation and motility, and genetic and environmental factors. Administration of systemic antibiotics may increase the risk of IBS by altering gastrointestinal homeostasis. Therapeutic interventions for IBS with diarrhea that are thought to target alterations in the gut microbiota include the nonsystemic antibiotic rifaximin, the medical food serum-derived bovine immunoglobulin, prebiotics, probiotics, and dietary modification. SYN-010 is a modified-release statin formulation that reduces methane production by Methanobrevibacter smithii and is currently in development for the treatment of patients with constipation-predominant IBS. Use of these interventions in the management of patients with IBS may function to restore a healthy gut microbiota and ameliorate symptoms of IBS.

Medicinal Foods for Functional GI Disorders.

Over the past 10years, there has been a dramatic increase in basic and clinical research involving functional gastrointestinal disorders (FGIDs). New diagnostic and biomarker procedures are helping to identify physiologic disruptions associated with FGIDs on cellular and molecular levels. Simultaneously, clinicians are using new approaches to help manage patients with FGIDs. Among these, an important component of care has been the use of medical foods. These include probiotics, prebiotics, synbiotics, peppermint oil, caraway oil, curcumin, bovine immunoglobulin and many others. The putative effects of different medical foods make these therapies attractive for the management of FGIDs. These include effects on several pathophysiological mechanisms such as anti-inflammatory, smooth muscle relaxation, analgesia, mitigation of gut barrier dysfunction, and stimulation or inhibition of gastrointestinal receptors. Recent research has also demonstrated the efficacy of medical food products such as peppermint oil and serum-derived bovine immunoglobulin for the management of irritable bowel syndrome. Older data supports the probiotic VSL#3 and Bifidobacterium species. For functional dyspepsia, positive effects have been observed with the combination of caraway seed oil and peppermint oil as well as with STW-5, a botanical combination preparation, although robust RCTs are lacking. With advancing knowledge regarding the pathogenesis of FGIDs, it is likely that the compounds available in the medical food category will increase dramatically, and they could play an important role in the management of several common and bothersome gastrointestinal conditions in the future.

Serum Derived Bovine Immunoglobulin (SBI) is Safe and Well Tolerated in Patients With Recurrent C. difficile Infection (RCDI) Treated Medically

Serum Derived Bovine Immunoglobulin (SBI) is Safe and Well Tolerated in Patients With Recurrent C. difficile Infection (RCDI) Treated Medically

Serum Derived Bovine Immunoglobulin (SBI) is Safe and Well Tolerated in Patients Undergoing Fecal Microbiota Transplant (FMT) for Recurrent C. difficile Infection (RCDI)

Serum Derived Bovine Immunoglobulin (SBI) is Safe and Well Tolerated in Patients Undergoing Fecal Microbiota Transplant (FMT) for Recurrent C. difficile Infection (RCDI)

Economic and Clinical Impact of Serum-Derived Bovine Immunoglobulin / Protein Isolate (SBI) in the Management of Chronic Diarrhea in Inflammatory Bowel Disease (IBD)

Economic and Clinical Impact of Serum-Derived Bovine Immunoglobulin / Protein Isolate (SBI) in the Management of Chronic Diarrhea in Inflammatory Bowel Disease (IBD)

Oral Serum-Derived Bovine Immunoglobulin for Management of Infectious Diarrhea due to Norovirus and Cryptosporidiosis in Solid Organ Transplant Patients

Abstract Diarrhea and its sequelae are commonly seen in renal transplant recipients. Current effective options to treat many causes of infectious diarrhea in this population are limited. Oral serum-derived bovine immunoglobulin was recently successfully used to manage 2 renal transplant patients with diarrhea due to cryptosporidiosis and norovirus infection, respectively.

Su2085 - Safety, Tolerability, and Efficacy of Serum-Derived Bovine Immunoglobulin in Children with Diarrhea-Predominant Irritable Bowel Syndrome

Su2085 - Safety, Tolerability, and Efficacy of Serum-Derived Bovine Immunoglobulin in Children with Diarrhea-Predominant Irritable Bowel Syndrome

Oral serum bovine immunoglobulin improves IBS-D symptoms analyzed from patient medical charts.

Purpose: To examine clinical practice effectiveness of a medical food containing serum-derived bovine immunoglobulin (SBI) for the management of symptoms in irritable bowel syndrome with diarrhea (IBS-D) patients. Methods: From 165 IBS-D patient medical charts [mean age=59.6 years (range: 19-98), female (n=109), Caucasian (n=144)], recorded daily stools/consistency, abdominal pain, and patient/ physician reported quality of life (QoL) scores were retrospectively collected on those prescribed SBI for a minimum of 8 weeks. A generalized estimating equations model was used to analyze and compare changes for scores of symptoms and QoL. Results: Where data existed in charts, 46% of patients on SBI had a combined mean score reduction in daily stools, improvement in stool consistency (Bristol Stool Scale from >5 to <5) and decrease in abdominal pain (?30%). Significant improvements (p<0.001) in individual symptom and QoL scores with a high response were also reported for daily stools (76%), consistency (78%), abdominal pain (69%), as well as patient (79%) and physician QoL (73%). Eleven patients experienced 13 adverse events (AEs) while receiving SBI with nausea (n=6) most prevalent. No serious AEs were reported, but 4 patients discontinued SBI. Conclusion: In this retrospective chart analysis of IBS-D patients who took a medical food containing SBI for 8 weeks, there were statistical improvements in daily stool number, stool consistency, abdominal pain and QoL scores supporting its use IBS-D.

Oral serum bovine immunoglobulin improves IBS-D symptoms analyzed from patient medical charts.

Purpose: To examine clinical practice effectiveness of a medical food containing serum-derived bovine immunoglobulin (SBI) for the management of symptoms in irritable bowel syndrome with diarrhea (IBS-D) patients. Methods: From 165 IBS-D patient medical charts [mean age=59.6 years (range: 19-98), female (n=109), Caucasian (n=144)], recorded daily stools/consistency, abdominal pain, and patient/ physician reported quality of life (QoL) scores were retrospectively collected on those prescribed SBI for a minimum of 8 weeks. A generalized estimating equations model was used to analyze and compare changes for scores of symptoms and QoL. Results: Where data existed in charts, 46% of patients on SBI had a combined mean score reduction in daily stools, improvement in stool consistency (Bristol Stool Scale from >5 to <5) and decrease in abdominal pain (?30%). Significant improvements (p<0.001) in individual symptom and QoL scores with a high response were also reported for daily stools (76%), consistency (78%), abdominal pain (69%), as well as patient (79%) and physician QoL (73%). Eleven patients experienced 13 adverse events (AEs) while receiving SBI with nausea (n=6) most prevalent. No serious AEs were reported, but 4 patients discontinued SBI. Conclusion: In this retrospective chart analysis of IBS-D patients who took a medical food containing SBI for 8 weeks, there were statistical improvements in daily stool number, stool consistency, abdominal pain and QoL scores supporting its use IBS-D.

Management of Antibiotic-Associated Diarrhea After C. difficile Infection With a Serum-Derived Bovine Immunoglobulin Preparation

Clostridium difficile infection (CDI) has a high mortality, morbidity and large economic cost and can cause mild diarrhea to a fulminant, life threatening colitis. Antibiotics, though effective can lead to antibiotic-associated diarrhea (AAD). Serum-derived bovine immunoglobulin (SBI) has been shown to bind/neutralize toxins A&B from hypervirulent ribotypes in vitro and reduce CDI-induced mortality by 50% in a low-protein fed mouse model. Due to these activities and its reported efficacy in managing chronic loose and frequent stools, SBI was administered to 4 patients with CDI experiencing AAD. Patient 1 (89 yrs Caucasian female) had a history of severe CDI in 2012 unresponsive to metronidazole requiring vancomycin for 2-wks and a 1-mo taper. Following a urinary tract infection resolved with antibiotics, CDI reoccurred and was resolved with additional vancomycin, but the patient had AAD unresponsive to loperamide. Patient 2 (76 yrs Caucasian male) had CDI-induced colitis treated with a 20-day course of metronidazole, but had continued diarrhea. Probiotics had no effect. Patient 3 (59 yrs Caucasian female) had a history of chronic IBS-C, controlled by lubiprostone. After an upper respiratory tract infection treated with amoxicillin/clavulanic acid, she developed severe, watery, foul smelling stools (8-12/d) within 48 hrs. The patient was switched to azithromycin and discontinued lubiprostone. Despite switching to azithromycin, it did not stop her diarrhea and was found to be CDI positive by PCR. Patient 4 (89 yrs Caucasian male) had myelodysplatic syndrome, ASCVD s/p CABG, was hospitalized with acute exacerbations of COPD treated with IV piperacillin/tazobactam, and developed diarrhea on day 4. PCR stool analysis revealed CDI and the patient was switched to oral vancomycin. Post-discharge, his diarrhea persisted after 5 days of vancomycin therapy. Patient 1 was given SBI 5g BID and after 1-week had improved stool consistency/frequency and a better sense of well-being. Patient 2 received SBI 5g TID for 9-d and it managed chronic loose and frequent stools. Patient 3 dosed with SBI 5g BID had normal stool frequency/consistency within 72 hrs. He was maintained asymptomatically on SBI for 30-d. Despite a positive CDI stool test by PCR, routine colonoscopy 6-wks later revealed no clinical signs of disease. Watery stools in Patient 4 were managed with the combination of 200mg fidaxomicin BID and SBI 5g BID after 48 hrs. After the 10-day course of fidaxomicin, SBI was continued for an additional 14-d with no recurrent symptoms. It is hypothecized that SBI may help restore normal barrier function by binding to microbial components produced after antibiotic therapy, thereby reducing immune activation which degrades the intestinal barrier. These cases suggest that SBI is useful in helping nutritionally manage AAD.

Management of Severe Watery Stools With Fecal Incontinence in Ileorectal Anastomosis Patient With Serum-Derived Bovine Immunoglobulin Therapy

Management of Severe Watery Stools With Fecal Incontinence in Ileorectal Anastomosis Patient With Serum-Derived Bovine Immunoglobulin Therapy

Serum-Derived Bovine Immunoglobulin Protein Isolate Binds Conserved Bacterial Epitopes Without Affecting Probiotic or Commensal Bacteria Growth

Serum-Derived Bovine Immunoglobulin Protein Isolate Binds Conserved Bacterial Epitopes Without Affecting Probiotic or Commensal Bacteria Growth