Supporting The Gut-Immune Axis: Overview
In understanding the gut-immune axis and the role that immunobiotics, colostrum, and probiotics play, we will first dive into some of the anatomy of the intestinal lining as well as an example of how the immune cells in the lamina propria can become activated due to the translocation of gut-derived endotoxins called lipopolysaccharides. We will then explore the mechanisms of action underlying the incredible roles that immunobiotics, colostrum, and probiotics play in supporting the gut-immune axis, while also providing an incredible resource containing all of these ingredients and more!
Intestinal Barrier Anatomy
The intestinal barrier is a highly sophisticated system that separates the internal milieu of the intestinal lumen—where digestion and absorption occur—from the systemic environment of the body. From the innermost to the outermost layer, the intestinal wall is composed of the mucosa (which includes the epithelium, lamina propria, and muscularis mucosae), the submucosa, the muscularis propria (consisting of an inner circular muscle layer, intermuscular space, and outer longitudinal muscle layer), and the serosa. We will limit our focus to those initial layers, such as the epithelium and lamina propria, in order to establish an understanding of the gut-immune axis.
1. Mucus Layer: The mucus layer is a protective coating that lines the length of the gastrointestinal tract, varying in thickness and composition from the stomach through the small intestine to the large intestine. It is primarily composed of mucins, high-molecular-weight glycoproteins that can bind pathogens and form a physical barrier to their entry. In the small intestine, the mucus layer is thinner and discontinuous, facilitating nutrient absorption with minimal obstruction. The large intestine has a more complex, dual-layered mucus structure: an inner dense layer devoid of bacteria that protects epithelial cells from direct exposure to luminal contents, and an outer, less dense layer colonized by commensal microbiota.
2. Intestinal Epithelium: Directly beneath the mucus layer, the intestinal epithelium is a single layer of epithelial cells including enterocytes, goblet cells, enteroendocrine cells, and paneth cells. Each cell type has distinct functions: enterocytes absorb nutrients; goblet cells secrete mucins; enteroendocrine cells release hormones regulating digestion; and paneth cells produce antimicrobial peptides (e.g., defensins) that contribute to the gut's innate immunity. This layer features tight junctions that regulate paracellular permeability, maintaining selective barrier function against pathogens while allowing ion and water flux.
Tight Junctions: The integrity of the intestinal epithelium relies critically on tight junctions, which are sophisticated multiprotein complexes that occlude the intercellular spaces between adjacent epithelial cells, positioned just above the lamina propria. These junctions are primarily composed of claudins, occludins, and junctional adhesion molecules (JAMs), each playing distinct roles in maintaining barrier function. Claudins are integral for forming the core of the tight junction strands, significantly influencing their selective permeability properties. The structure and function of tight junctions also depend on other proteins like zonula occludens that link these 3 proteins to the actin cytoskeleton.
3. Lamina Propria: The lamina propria, situated beneath the epithelium, is rich in connective tissue, blood vessels, lymphatics, and a diverse array of immune cells including T cells, B cells, macrophages, dendritic cells, and mast cells. These cells are integral to the mucosal immune response:
T cells in the lamina propria are predominantly effector and regulatory subsets that manage responses to antigens presented by epithelial and dendritic cells.
B cells produce immunoglobulin A (IgA), the predominant antibody in mucosal areas, critical for neutralizing pathogens.
Dendritic cells can sample luminal antigens and migrate to local lymph nodes to initiate adaptive immune responses.
Macrophages and mast cells mediate innate defense and contribute to inflammatory responses crucial for clearing infections but also for maintaining tolerance to commensal microbes.
Example: A Demonstration of the Gut-Immune Axis in Action
Now that we understand some of the anatomy basics, let's dive into an example of the gut-immune axis in action in order to fully establish just how interconnected these systems are. For example, lipopolysaccharide (LPS), an endotoxin and component of the outer membrane of Gram-negative bacteria, can cross the intestinal barrier and enter systemic circulation, impacting health significantly (Dysbiosis can often lead to an increase in certain types of Gram-negative bacteria which are potential sources of LPS. This can occur due to a reduction in competitive exclusion by beneficial microbes that are typically abundant in a healthy gut).
In more detail, the transport of LPS across the intestinal barrier occurs through two main pathways: transcellular and paracellular. In the transcellular pathway, LPS crosses the intestinal epithelium through the cells themselves. This transport can be facilitated by chylomicrons, which are lipoprotein particles formed in the intestinal cells (enterocytes) during the absorption of dietary fats.
However, the paracellular pathway involves the passage of LPS between the cells of the intestinal epithelium. This pathway is generally very restrictive due to the tight junctions that seal the space between epithelial cells. However, in pathological states characterized by increased gut barrier permeability—such as in inflammation, infection, or due to the disruption of tight junction integrity—this pathway becomes more pronounced.
The translocated LPS can then bind to TLRs (such as TLR4) on immune cells in the lamina propria, including macrophages and dendritic cells. This binding will then trigger these cells to release pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β, initiating an inflammatory response and possibly contributing to an even more permeable intestinal barrier.
This scenerio of dysbiosis serves as an example demonstrating how intertwined the gut and immune system are.
With That Said, How Can We Support the Gut-Immune Axis Using the Power of Immunobiotics, Colostrum, & More?
Immunobiotics can be described as postbiotics known to specifically target and beneficially modulate the immune system. In more detail, Lactobacillus plantarum L-137 is a strain of lactic acid bacteria, common in many probiotic formulations. However, the HK Lactobacillus plantarum L-137 variant is heat-killed, meaning it is no longer viable but still possesses remarkable immunomodulatory properties.
In a study utilizing healthy individuals, daily intake of 10 mg HK L-137 over 12 weeks enhanced T-cell proliferation. T cells, also known as T lymphocytes, are a type of white blood cell that play a central role in cell-mediated immunity. In addition, in this same study, concentrations of short-chain fatty acids (SCFAs) in the feces were significantly higher after 6 months, indicating a positive shift in gut microbial metabolism which is known to support gut barrier integrity.
Colostrum is the first form of milk produced by mammals immediately following the delivery of their offspring.
Nutritional Composition:
Immunoglobulins (Ig): Colostrum is particularly rich in immunoglobulins such as IgA, IgG, and IgM. IgA, within the body, plays a large role in supporting mucosal immunity (This term refers to the immune responses that occur at mucosal surfaces, such as those that line the gastrointestinal tract), helping to protect the intestinal epithelium against pathogens.
Growth Factors: Including insulin-like growth factors (IGF-I and IGF-II), transforming growth factors (TGF-α and TGF-β), and epidermal growth factor (EGF). These factors can help to promote growth and repair of the intestinal lining.
Lactoferrin: This is an iron-binding glycoprotein with antimicrobial and anti-inflammatory properties. It can help to inhibit the growth of pathogenic bacteria by sequestering iron, which bacteria need to multiply. Additionally, and related, lactoferrin can help to modulate immune responses and reduce inflammation within the gut.
Supporting the proliferation of beneficial gut microbes is an incredible way to support the gut-immune axis. Many beneficial bacteria contribute to the production of short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate through the fermentation of dietary fibers. SCFAs serve multiple functions; they can provide energy to epithelial cells, strengthen the gut barrier by promoting the assembly and maintenance of tight junctions, and modulate immune responses by influencing the behavior of immune cells such as T cells, dendritic cells, and macrophages.
Moreover, these microbes compete with pathogenic bacteria for nutrients and binding sites on the gut mucosa, reducing the risk of pathogen colonization and subsequent infection. They can also produce bacteriocins and other antimicrobial compounds that help to inhibit the growth of harmful bacteria. Additionally, by stimulating the production of mucins, beneficial bacteria help enhance the mucus layer's capability to trap and eliminate pathogens, reducing their contact with the gut epithelium.
Nouri StayWell Synbiotic
All of these (HK L-137, probiotics, and colostrum) and more are formulated within Nouri StayWell Synbiotic. It combines an array of incredible ingredients, including colostrum, probiotics, HK L-137, L-glutamine, various vitamins, and minerals; and it was expertly designed to support both intestinal and immune health. It also contains zero fillers, additives, or sugar, ensuring that each ingredient directly contributes to its efficacy.
The stick packs are also incredibly convenient, making it easy to maintain a consistent intake of these amazing nutrients, especially for those with busy lifestyles or for use while traveling. They recommend mixing 1 stick pack with 8-12 oz of liquid.
StayWell is an absolutely remarkable blend to support the gut-immune axis, and Nouri does such a wonderful job at making their products accessible to all. With that, go and check out Nouri StayWell Synbiotic over at dailynouri.com, and use code CHLOE20 to get 20% off.
*Always consult with a licensed medical professional for all of your medical needs and before taking any nutritional supplement.
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