While the development of Type 1 diabetes (T1D) in humans is obviously multifactorial, the formation of recent understandings regarding intestinal hyperpermeability (“Leaky-gut syndrome”) and autoimmunity has shed significant light on a major progenitor in the development of T1D. Traditionally, the etiology of autoimmune conditions was largely limited to the events of molecular mimicry (foreign invaders resembling non-foreign components of the body), the bystander effect (abnormal activation of autoreactive T-cells by microbes or xenobiotics like heavy metals), and viral persistence (activation of antiviral immune responses to previously dormant viral antigens) [1] [2]. While the mechanisms associated with molecular mimicry, the bystander effect, and viral persistence have certainly been shown to elicit autoimmune responses, the development of intestinal hyperpermeability may strongly outweigh the typically identified progenitors for the manifestation of autoimmunity – T1D in particular.
The permeability of the intestinal lining is largely regulated by the protein zonulin, which through a cascade of receptor activation, elicits the disengagement of the protein complexes forming the tight junctions between epithelial cells lining the intestinal wall [3]. The zonulin pathway normally functions in modulating the selective transfer of fluids, macromolecules (such as digested food particles), and leukocytes (immune cells) between the blood circulation and the intestinal lumen (the small intestine interior) [4]. Additionally, the zonulin pathway within the GI tract is also believed to play a role in protecting against the colonization of unwanted microbes within the small intestine (however, SIBO can excessively induce the production of zonulin and procure the development of Leaky-gut) [5]. I’ve written an article on SIBO if you want to know more about that. One of the most potent upregulators in the production of zonulin is the gluten family of proteins, gliadin being the chief troublemaker. Gliadin binds to a particular receptor embedded within the intestinal lining and elicits the release of zonulin and the subsequent increase in intestinal permeability [6] [7]. This upregulation invoked by gliadin takes place in all human beings, not just those with Celiac Disease or Non-Celiac Gluten Sensitivity [8]. For those with T1D, it should be noted that a similar immunological response to the ingestion of gluten can be invoked by the ingestion of A1 beta-casein protein from dairy products stemming from A1 cows [9] [10]. Accordingly, the removal of gluten and A1 dairy sources from the diet can be a requisite for the resolution of autoimmune conditions, especially for those who are knowingly or unknowingly gluten sensitive [11] [12]. Along similar lines, a direct link has been mapped between a specific protein found in wheat (Glo-3a), the upregulation of zonulin, and the attacking of pancreatic beta cells in those exhibiting a genetic susceptibility to the onset of T1D [13]. This pancreatic autoimmunity can be exacerbated in those who have a degraded mucosal barrier within the small intestine, which can be brought about by inflammatory action within the gut (the same inflammation can also increase the gut’s permeability in and of itself). Multiple experiments have demonstrated the onset of T1D being preceded by an increase in intestinal permeability, and the GALT (gut-associated lymphoid tissue) easily plays one of the chief roles here [14]. The transportation of lymphocytes (immune cells) from the GALT to the pancreas is mediated by a particular molecule (MAdCAM-1) and a particular integrin (alpha 4 beta 7) whose expression is elevated in those with T1D [15]. Thus, one mechanism through which T1D may manifest in an individual is as follows: a foreign antigen (or antigens) from within the GI tract, whose delivery to the pancreas is facilitated by intestinal hyperpermeability (Leaky-gut) stemming from zonulin upregulation by such provokers as gluten, beta-casomorphin-7 (from A1 cow’s milk), heavy metals, or certain microbes, promotes the onset of pancreatic autoimmunity in a genetically susceptible person [16]. Therefore, in reversing the above etiology, the gut lining would need to be healed, the gut microbiota would need to be restored to normal, and the foreign antigens present within the blood/lymphatic circulation and extracellular matrices would need to be detoxified and excreted from the body. While the reversal of autoimmune conditions certainly can and has been done, it is important to remember that each individual’s etiology may be unique, and thus may require a very individualized program to bring the mind and body into a state of equilibrium, in which natural functionality and health may be expressed by default. References:
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AuthorDenton Coleman is an Exercise Physiologist and Medical Researcher. Archives
October 2023
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