People are obsessed with gut health. They should be, because without a healthy gut, you would be a sitting target for continual bacterial invasion from the interior of your gut. When that occurs, it is called metabolic endotoxemia, and it sets off inflammatory fires through the body (1).
However, it is only the gram-negative bacteria that cause the problem if they contain a fragment known as lipopolysaccharide (LPS) on their surface. The usual bacterial suspects are E. coli, Shigella, and Klebsiella. If a bacterial fragment containing LPS enters the blood, it can bind to a receptor (TLR-4) found on virtually every cell in your body, which dramatically increases inflammation, especially in the tissue that lines the gut wall..
Fortunately, you have two barriers to prevent that from happening. The first is a healthy mucus layer.
The mucus layer acts as a dynamic barrier that separates the bacteria, toxins, and partially digested food from reaching the surface cells of the gut lining (2 and 3).
One of the most beneficial microbes in your gut (i.e., Akkermansia muciniphila) resides in the upper layer of the mucus layer and maintains the mucus layer to protect the human side of the gut from the trillions of bacteria just waiting for the opportunity to enter your body. Akkermansia accounts for about 3-5 percent of the total bacteria in your gut (4).
Having low levels of Akkermansia is associated with a significant number of chronic conditions, such as obesity, diabetes, and neurological disease (5). Not surprisingly, all of these chronic conditions are also associated with insulin resistance (6). The best way to keep these bacteria out of your body is to maintain a high population of Akkermansia in the mucus barrier. That can be easily accomplished by a consistent combination of calorie restriction, omega-3 fatty acids, and polyphenols (7, 8 & and 9). In other words, all the dietary interventions that activate AMPK.
But what about a leaky gut? This is the second and most important barrier to protect you from toxin or microbial invasion. What prevents bacterial fragments like LPA, or larger protein fragments (i.e., like partially digested gluten) from getting into your blood and causing inflammation is that single layer of cells (i.e., epithelial cells) that acts as a gate to prevent toxins or undigested protein fragments from entering your body to cause immunological reactions (10). Not surprisingly, the integrity of this primary barrier is also controlled by AMPK (11, 12, and 13).
This leads to a better understanding of the gluten-related disorders. There are two types of conditions associated with gluten intake. One is celiac disease, which is an autoimmune disease. If gluten fragments can enter the body via a leaky gut, they can trigger an autoimmune response. This occurs in about 1 percent of the population. This leads to the immune system attacking the gut lining and causing lasting damage.
The other condition is non-celiac gluten sensitivity (NCGS), which occurs in 1-3 percent of the population. These individuals have no sign of celiac disease but share many of its symptoms (14). These individuals appear to have sensitivity to FODMAPS (fermentable oligo-, di-, monosaccharides, and polyols). In either condition, it seems the problem starts with a leaky gut.
Metabolic Engineering® is designed to activate AMPK activity to treat a leaky gut and its associated diseases such as celiac disease and gluten sensitivity. Furthermore, treating a leaky gut leads to insulin resistance (15). This may explain the connection between a leaky gut and other chronic conditions such as obesity, type 2 diabetes, heart disease, liver disease, kidney disease, as well as neurological diseases such as Alzheimer’s, Parkinson’s, and depression (16).
References
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3. France MM, Turner JR. The mucosal barrier at a glance. J Cell Sci. 2017 Jan 15;130(2):307-314 (2017). doi: 10.1242/jcs.193482.
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9. Rodríguez-Daza MC, de Vos WM. Polyphenols as drivers of a homeostatic gut microecology and immuno-metabolic traits of Akkermansia muciniphila: From mouse to man. Int J Mol Sci. 24:45 (2022). doi: 10.3390/ijms24010045.
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12. Olivier S, Leclerc J, Grenier A, Foretz M, Tamburini J, Viollet B. AMPK activation promotes tight junction assembly in intestinal epithelial Caco-2 Cells. Int J Mol Sci. 20:5171 (2019). doi: 10.3390/ijms20205171.
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