Oral Immune Therapy: A Promising New Approach to Treating Inflammatory Bowel Disease (IBD)
Understanding IBD and Its Immune-Driven Mechanisms
Inflammatory Bowel Disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic condition caused by an abnormal interaction between the immune system, the gut environment, and genetic susceptibility. While the gut is the primary site of inflammation, the systemic immune response also plays a central role, leading to inflammation that can spread beyond the digestive tract. Current treatments often suppress the immune system to reduce inflammation, but this strategy increases the risk of infections and certain cancers.
The pathogenesis of IBD involves more than just immune activation. Research shows that increased gut permeability, bacterial translocation, and elevated lipopolysaccharide (LPS) levels are common in patients with immune-mediated disorders. However, intestinal barrier loss alone is not enough to initiate disease—there must be a triggering immune response. This makes the gut immune system an attractive target for therapies aimed at resetting immune balance without the risks of systemic immune suppression.
The Role of Autophagy and Macrophages in IBD
Autophagy, a cellular recycling process, is vital for maintaining gut health. In the intestines, it helps break down harmful bacteria and regulates immune responses. Types of autophagy such as macroautophagy and xenophagy play critical roles in antimicrobial defense. Genome-wide association studies have linked autophagy-related genes to IBD, suggesting that dysfunctional autophagy contributes to chronic inflammation.
Additionally, macrophages, key immune cells found in the gut, are constantly replenished from blood monocytes, unlike those in most other tissues. These intestinal macrophages help regulate regulatory T cells (Tregs), making them important players in maintaining immune balance. When this balance is disrupted—due to faulty autophagy or heightened activation via Toll-like receptors (TLRs)—it can contribute to IBD development.
Oral Immune Therapy: Modulating the Immune System Through the Gut
Oral immune therapy is an emerging strategy that harnesses the gut’s natural ability to influence the entire immune system. By introducing non-absorbable antigens or immune-modulating agents through the digestive tract, it stimulates the gut immune system to send calming signals to the rest of the body. This process can promote immune tolerance through Tregs without the need for widespread immune suppression.
Unlike traditional drugs, oral immune therapy does not rely on systemic absorption. Instead, it works locally at the gut mucosa level, reducing inflammation via mechanisms such as:
- Promotion of Tregs (CD4+CD25+ and Foxp3+ cells)
- Reduction in pro-inflammatory cytokines like TNF-α
- Modulation of antigen-presenting cells and macrophages
- Interaction with the microbiota to regulate immune responses
Case Study: Imm124E as an Oral Immune Therapy Agent
One promising oral immune therapy agent is Imm124E, a non-absorbable, IgG-enriched colostrum-derived product from enterotoxigenic E. coli. It contains anti-LPS antibodies and glycosphingolipid adjuvants that stimulate the gut immune system without entering the bloodstream.
In animal studies, oral administration of Imm124E significantly improved inflammatory conditions. In the ob/ob mouse model of diabetes and non-alcoholic steatohepatitis (NASH), Imm124E:
- Decreased serum TNF-α levels
- Increased Treg and NKT cell populations
- Improved liver enzyme levels and glucose metabolism
In a human open-label trial involving patients with type 2 diabetes and biopsy-confirmed NASH, 30 days of oral Imm124E:
- Increased serum GLP-1 and adiponectin
- Boosted Tregs (CD25+ and Foxp3+)
- Improved glucose control, lipid levels, and liver enzyme profiles
- Showed no adverse events or immune reactions to bovine antibodies
Further, in a mouse model of TNBS-induced colitis, Imm124E increased levels of IL-10, a key anti-inflammatory cytokine, promoted Treg activity, and improved colon health by reducing histological damage and inflammation scores.
These studies highlight how oral immune therapy with Imm124E can safely alter systemic immunity by acting locally on the gut, offering both preventive and therapeutic benefits with minimal side effects.
Conclusion: A Safer Path Forward in IBD Treatment
Oral immune therapy represents a groundbreaking approach to managing IBD and other immune-related conditions. Rather than suppressing the entire immune system, it modulates immune function through the gut, reducing harmful inflammation while preserving the body’s ability to fight infections.
With the added benefit of non-invasive delivery, low cost, minimal toxicity, and a favorable safety profile, oral immune therapy offers an exciting and practical alternative to traditional immunosuppressive treatments. As more clinical research emerges, therapies like Imm124E may soon become standard care for IBD and other autoimmune diseases, providing hope for millions of patients worldwide.
The Gut Microbiome and Its Role in IBD
The gut microbiome plays a key role in maintaining immune balance and intestinal health. It helps train the immune system, supports digestion, and maintains the intestinal barrier. Healthy gut bacteria, such as Bacteroidetes and Firmicutes, promote anti-inflammatory responses by acting on immune cells like dendritic cells and T cells. They help prevent gut inflammation and maintain tolerance to food and harmless microbes.
In people with inflammatory bowel disease (IBD), the gut microbiome becomes unbalanced—a condition called dysbiosis. This imbalance can increase gut permeability, allowing harmful bacterial products like lipopolysaccharides (LPS) to cross the gut barrier. These products trigger inflammation by stimulating immune cells to release cytokines like TNF-α and IL-8.
Some bacteria, like Bacteroides fragilis, support anti-inflammatory signals through IL-10, while others, like segmented filamentous bacteria, promote inflammation by activating Th17 cells. Pathogenic E. coli strains resistant to immune defenses are often found in Crohn’s disease.
Overall, the microbiome can either calm or provoke the immune system. When this balance is disrupted, chronic inflammation may result. Treatments like fecal microbiota transplantation (FMT) aim to restore a healthy gut ecosystem and reduce IBD symptoms by rebalancing the microbial environment.
More info:
Milk: a postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation. Accumulating evidence underlines that milk is a complex signaling and epigenetic imprinting network that promotes stable FoxP3 expression and long-lasting Treg differentiation, crucial postnatal events preventing atopic and autoimmune diseases.
Clin Transl Allergy. 2016 May 12;6:18. doi: 10.1186/
s13601-016-0108-9. eCollection 2016
*Note for video commentary. There is also tolerance and checkpoint blockade toxicity requiring interferon for intracellular clearance of microorganisms and debris.
Immune For Life
M. Ferrari
After decades of chronic health conditions and serious gut issues like IBS and SIBO, immune deficiencies and an autoimmune condition discover how I recovered my health thanks to natural oral immune therapeutics (maf and gcmaf). Due to a premature birth and being formula fed, I was a SAM child in real life. My book is a step by step journey you won't want to miss that illustrates how to regain or maintain health for all ages.