Food Freedom Friday Edition 233 - Immunity & Your Gut

Your gut is home to a very large number of microbes collectively known as the gut microbiota or the microbiome. It is made up of approximately 38 trillion microbes which is at least as many cells as you have in your entire body and collectively they contain 150 times more genes than the human genome.

Symbiosis is term that describes any type of close biological interaction between two different species that live together. Your body has developed a mutually beneficial relationship, a symbiotic partnership, with these microbes. 

Science is only beginning to unravel the extent of this mutual influence, but it’s already clear that your microbiome’s massive and huge impact on your health and the body’s homeostasis (state of balance) is fundamental for your survival. 

The gut microbiota influences many aspects of your physiology, from metabolism, to the cardiovascular system and the nervous system, for example. The microbiome also has important interactions with your immune system.

The Gut And The Immune System

Your immune system is the group of cells and molecules that protect you from disease by monitoring our body and responding to any foreign (non-self) substances they perceive as threats, particularly infectious microbes. Your immune system has co-evolved along with your microbiome, not only to create defenses against pathogens, but also to develop tolerance for beneficial microbes. There is a mutualistic relationship between your immune system and your gut microbiota, regulating one another and cooperating to support each other highlighted by the fact that 70–80% of your  immune cells are found in your gut.

The dialogue between your immune system and your microbiome begins at birth. As you grow, the microbiome shapes the development of your immune system, and the immune system shapes the composition of the microbiota. This communication and mutual regulation is maintained throughout life creating the foundation for healthy interaction between the gut and the immune system. 

In normal conditions, the immune system promotes the growth of beneficial microbes and helps maintain a stable microbial community, while in return, a healthy microbiome produces molecular signals that support the development of immune cells and contribute to the fine tuning of immune responses. A healthy crosstalk between the gut and the immune system supports protective responses against pathogens, promotes tolerance to harmless microbes and their products, and helps maintain self-tolerance (the ability of your immune system to not react harmfully to your own body). 

Intestinal Barrier Function

The intestinal wall is the primary interface between the gut and your body. It acts as a dynamic barrier that isolates your body from gut microbes but allows desirable interactions to take place. The intestinal barrier is made up of physical and chemical elements. The physical barrier is created by the epithelial cells that line the gut, the molecules on their surface, and the mucus they produce; the chemical barrier is created by inflammatory molecules (cytokines), antibodies, and antimicrobial substances produced by epithelial and immune cells. 

Epithelial cells can adjust their antimicrobial response to eliminate pathogenic infections, destroy infected cells, and influence the composition of the gut flora through pattern recognition receptors (PRRs). Proper PRR signaling is important for the maintenance of tolerance to good microbes, for the elimination of intestinal infections, and consequently, for the maintenance of a balanced microbiome. 

Epithelial cells also respond to metabolites produced by the microbiome, such as short-chain fatty acids (SCFAs), polyamines, and amino acids. Many microbial metabolites cross the epithelial barrier and are absorbed into the blood, through which they can reach other tissues in our body. Microbial metabolites can influence the development, maturation, and function of circulating and tissue-resident immune cells in different organs, including the brain Through these metabolites, the microbiome is able to fine-tune immune responses throughout the body.

The barrier function of the intestinal wall is also maintained by immune cells. Healthy intestinal barrier function allows certain gut-derived molecules to get into the body, while keeping others out. This supports better immune and brain performance.

The Role Of Leaky Gut

The integrity of the intestinal barrier is fundamental for a healthy gut. A healthy intestinal barrier will keep pathogens and harmful microbial products away from your body, while being selectively permeable to microbial signaling molecules and metabolites that contribute to the health of our biological processes.

Dysfunctions in the intestinal barrier alter its permeability and lead to what is commonly known as “leaky gut.” Leaky gut is fundamentally about two things:

·       Larger molecules being allowed to pass through intact cell membranes due to changes in the transport mechanisms

·       Loosening of the tight junctions between epithelial cells. This means that the intestinal barrier becomes permeable to things to things you don’t want to get in. 

Changes in the permeability of the intestinal barrier compromise its ability to block the access of undesired materials into your body. This may result in chronic inflammatory reactions and altered immune responses.

Importance Of Immunoglobulin A

An immune system antibody called immunoglobulin A (IgA) plays a big role in producing a healthy gut microbiome.  IgA is a type of antibody produced by plasma cells. IgA can bind and coat specific microbes, microbial components, dietary components, and other antigens in the intestine. This creates an additional physical barrier that prevents potentially harmful interactions with the immune system.

IgA supports the establishment of a balanced gut by regulating its composition, controlling microbial gene expression, increasing microbial diversity, and enhancing mutualism between the gut microbiota and the host. In turn, the microbiome impacts the production of IgA by influencing the accumulation of plasma cells, as well as the diversity and severity of IgA responses. IgA concentration in the gut is constantly adjusted in response to changes in microbiome, with increases in microbial diversity leading to increases in the diversity of the IgA pool.

Plant Fibers For Brain And Immune Health

Gut microbes get most of their nutrients from your diet and help you digest a lot of the food you eat. It probably comes as no surprise that diet has a huge impact on the composition of gut microbiome and, consequently, on your immune system. Diet influences many aspects of the microbiome-immune system communication, including, for example, the permeability of the intestinal barrier and the types of microbes targeted by IgA.

Modern diets, particularly those of the Western world, are characterized by an excessive intake of highly palatable energy-dense foods, including high levels of processed and refined grains, manufactured and artificial saturated fats, simple sugars and refined salt, but low amounts of plant-derived fibers. Sadly, this is the dietary pattern that is being increasingly linked to immune dysfunctions that are directly associated with the microbiome. For example, high dietary intake of refined salt or of long-chain fatty acids may stimulate the harmful actions of certain immune cells in the gut, which, in turn, may increase the risk of autoimmune reactions.

On the other hand, short-chain fatty acids (SCFAs), which are produced from insoluble dietary fibers by certain microbial species, promote the activity of regulatory T cells (Treg). SCFA, like acetate and butyrate, are made when gut microbes ferment insoluble fiber and carbohydrates (e.g., resistant starches, oat bran, pectins, fructooligosaccharides). Treg cells prevent inflammatory reactions against harmless intestinal microbes by suppressing the abnormal activation of other immune cells. Treg cells are thus particularly important in maintaining immune tolerance to the gut microbiome, dietary components, and self-antigens.

SCFAs also support the integrity of the epithelial barrier, increase the production of IgA, and promote gut homeostasis by increasing intestinal secretions and decreasing inflammatory responses. SCFAs can reach other organs, such as the brain, for example, where they also decrease neuroinflammatory responses that are known to underlie many neurodegenerative diseases. SCFAs are one of the reasons why fiber-rich diets support our immune system. Eating a diet rich in plant foods that can be converted into SCFA helps keep the brain and immune system healthy.

The Impact Of The Microbiome On Your Health

Many people are affected by health challenges related to poor immunity and inflammation. Diet can play a large role in worsening or improving these issues, because of interactions between the gut microbiota and immune system. 

Microbes produce a large number of metabolic products and other compounds that can directly interact with your physiology. The immune system monitors the metabolic state of the gut microbiome and relays that information to other tissues in the body to adjust their physiological processes.

The set of compounds produced by the gut microbiome depends on its composition and diversity. Microbial imbalances in the gut (referred to as dysbiosis) can affect the production of the molecular signals that underlie the communication between the gut microbiome and your physiological pathways and have a significant impact on those processes. Metabolic changes in the microbiome can even lead to the production of toxic products.

Dysbiosis can be caused by numerous environmental factors, including as the use of antibiotics and psychological and physical stress. However, diet stands out as one of the most impactful factors.

Dysbiosis can lead to disruption of the epithelial barrier, increasing your susceptibility to infections. Dysbiosis may also promote inadequate immune reactions to the gut microbiome, leading to chronic inflammation and tissue damage. The consequences of dysbiosis can manifest throughout the body by influencing tissue-specific immunity and triggering dysfunctions in other organs. These abnormal interactions may lead to allergies and may even compromise immunological self-tolerance, leading to autoimmune disorders.

A healthy interaction between your immune system and the gut microbiome is crucial for the maintenance of your body’s homeostasis (balance) and health. Imbalances in the gut microbiome may dysregulate immune responses and lead to the development of chronic inflammatory and autoimmune dysfunctions. This is why it is important to take good care of our gut. And this starts with what you choose to eat.