Virtually every immune-mediated disease is on the rise, from asthma to allergies to various autoimmune diseases. Historically, scientists have blamed excessive hygiene as a root cause of an over-vigilant immune system. This hygiene hypothesis revolves around the concept that our microbial friends (the 100 trillion single-celled microbes in our intestine) helped train our naive immune system in early life, so as to enhance its ability to tolerate our external environment. However, the sterility of modern life, including cesarean section birthing, lack of breast feeding, reduced family size, and exposure to antibiotics, is to blame for minimizing our exposure to good bugs—which, in turn, renders our immune system less forgiving and more reactionary.
Although researchers have long recognized that our gut microflora are highly malleable in early life, the hygiene hypothesis of inflammatory disease has expanded to include the role of our daily diet—as the types of foods we consume powerfully impact the composition and activity of the many bugs that our intestine harbors.
BOTH BACTERIAL AND FOOD METABOLITES INTERACT WITH IMMUNE CELLS
You see, in allergies, asthma, and autoimmunity, the immune system is stuck in a hypervigilant state, overreacting to stimuli that it should normally be tolerant of. By changing our diets and the type of bacteria we have in our intestines, we can turn down the thermostat on our immune system and pivot it back to a “tolerant” state.
Below are examples of how our diet can influence our immune system:
- Ingested foods that can directly latch onto immune system receptors (vitamin D, vitamin A, phytochemicals, omega-3 fatty acids)
- Foods can influence the formation of bacterial metabolites, such as short-chain fatty acids, which in turn influence immune system receptors
- Foods, such as sugar and excessive fats, can shift the composition of the gut microbiome, leading to intestinal permeability and leakage of bacterial endotoxin (aka lipopolysaccharide) into the bloodstream, which latches onto immune receptors and causes inflammation and both leptin and insulin resistance
- Dietary amino acids can interact with the immune system
SHORT-CHAIN FATTY ACIDS (SCFAs) BENEFICIALLY MODULATE THE IMMUNE SYSTEM
Ingestion of fibers leads to bacterial synthesis of SCFAs in the colon. (To learn more about short-chain fatty acids, READ THIS article).
SCFAs help quell the immune response in many ways:
- Prompt mucus production in gut epithelial cells
- Induce secretion of beneficial immunoglobulins (IgA) in the gut
- Increase production of regulatory T cells (particularly butyrate)
- Block inflammasome activation
- Inhibit gut-derived inflammation (NF-kB)
One way that intestinal production of SCFAs is able to influence the immune system is by way of metabolite-sensing G-protein-coupled receptors (GPCRs). These receptors are present on colon cells, virtually all immune cells, the cells of the pancreas, and even fat cells. But SCFAs aren’t the only molecules that latch onto these critical receptors; omega-3 fatty acids, present in fish oil, olive oil, and even the amino acid tryptophan, can latch onto these receptors, modulating the immune system.
SCFAs EPIGENETICALLY MODULATE THE IMMUNE SYSTEM
Short-chain fatty acids modulate the way inflammatory genes are expressed. They do this by modifying the activity of the cellular wheels that tightly wind up the nearly six feet of DNA found inside your cell. Since DNA is wrapped so snugly inside each cell, it can only be read, or expressed, and is able to make proteins, including those that make proinflammatory cytokines and the like, when it’s loosened by these cellular histones. This “open-sesame” effect occurs during the addition of acetyl groups to histones, causing them to relax and thus expose and activate DNA. In contrast, the addition of methyl groups leads to gene silencing of DNA’s messages.
Blocking histone acetylation has thus become a very popular strategy to suppress inflammation, as this effect would lead to gene silencing and reduced synthesis of inflammatory products. Drug companies are making histone deacetylases, or HDACs, to trick cancer and inflamed cells to be less problematic by suppressing the expression of bad genes. It turns out one SCFA called butyrate is particularly powerful at suppressing acetylation through increasing activity of HDACs, thereby reducing inflammation.
In addition to SCFAs, the most powerful way to influence gene expression is to consume color-rich herbs, spices, and polyphenols, specifically:
- grape seed extract
- alpha-lipoic acid
- vitamin D
Further Reading: Belly Fat Effect unveils the whole story about diet-gut bacteria interactions, the circadian clock system and metabolism, fat burning, appetite, and much more.
To dive deeper into the effect of SCFAs, allergies, and inflammation, check out these recently published articles.
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