A 2022 American Gastroenterological Association clinical practice guideline evaluated pharmacologic therapies for irritable bowel syndrome with diarrhea (IBS-D) using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline provides conditional recommendations for eluxadoline, rifaximin, alosetron, loperamide, tricyclic antidepressants, and antispasmodics, and a conditional recommendation against selective serotonin reuptake inhibitors; however, serum-derived bovine immunoglobulin/protein isolate (SBI; EnteraGam®) was not included among the reviewed or recommended therapies. Therefore, while this guideline provides relevant context regarding evidence-supported pharmacologic options for IBS-D, it does not directly provide evidence supporting the use of EnteraGam® for pathophysiologic gastrointestinal conditions. [1]
Multiple review articles have evaluated the potential role of SBI in gastrointestinal disorders characterized by impaired intestinal barrier function, inflammation, and chronic diarrhea. These publications suggest that SBI may provide nutritional support in conditions such as IBS-D and HIV-associated enteropathy through proposed mechanisms including binding and neutralizing microbial and pro-inflammatory antigens, supporting intestinal barrier integrity, promoting a more favorable gut microbiota, reducing gut permeability, and helping maintain immune homeostasis. While these reviews describe improvements in gastrointestinal symptoms and nutritional status reported in preliminary human studies and preclinical models, the evidence is largely derived from narrative reviews rather than randomized comparative clinical trials. [2], [3], [4], [5], [6]
Within IBS-D, a 2017 review described SBI as a potential adjunctive medical food that may be incorporated into individualized treatment plans alongside dietary interventions and pharmacologic therapies such as rifaximin and eluxadoline. The review emphasized that management should be tailored to symptom severity, psychosocial factors, and patient-specific needs because no standard treatment algorithm exists. SBI was presented as one component of a multimodal, patient-centered approach rather than a replacement for established therapies. [2], [3], [4], [5], [6]
A 2021 commentary proposed a theoretical role for SBI in COVID-19 based on the interaction between gastrointestinal health and systemic inflammation. The authors hypothesized that SARS-CoV-2 infection may increase intestinal permeability, alter the gut microbiome, and contribute to systemic inflammation and cytokine release. They suggested that SBI, a protein preparation composed of >90% protein containing approximately 50% IgG, 10% bovine serum albumin, 6% transferrin, and 5% combined IgA/IgM, could potentially mitigate these processes by binding inflammatory antigens, reducing intestinal permeability, improving the gut microbiome, and interfering with viral protein binding to ACE2 receptors. However, these proposed benefits were hypothesis-generating and based on biologic rationale and preclinical evidence rather than clinical efficacy studies in patients with COVID-19. [2], [3], [4], [5], [6]