Back to leaky gut, briefly…
For those of you unfamiliar with the term epithelial cells, this is a single layer of cells that line the inside of the intestinal tract and provide a selectively permeable barrier. That is, healthy cells are tightly packed together, only allowing digested food through, while protecting the body from pathogens, undigested food, waste products, and so forth.
When an inflammatory reaction compromises the integrity of this barrier, such as seen in inflammatory bowel diseases, for example (thus allowing things out that should be kept in) we refer to this as a leaky gut.
A new technology has been developed that is allowing scientists to better study the epithelial cells, called organ-on-a-chip. These are microchips lined by living human cells. They have been used, apparently, to study various organ functions in a highly controlled environment. Studying epithelial cells has proven a challenge in the past because of the incredible complexity of the gut biome. Researchers at the University of Texas, using this organ-on-chip technology, have created a model of the human intestine, which allowed them to isolate one factor at a time.[i]
The scientists induced inflammation in these cells (which they termed gut inflammation-on-a-chip) by treating them with a chemical called dextran sodium sulfate (DSS) which is known to induce colitis. Exposure to the chemical impaired the function of the epithelial barrier, distorted the size and shape of the intestinal villi, and caused decreased mucus production. They noticed that contact between the dysfunctional epithelial cells and immune cells led to greatly increased oxidative stress and that, in turn, led to an increase in the production of inflammatory cytokines. Healthy epithelial cells, on the other hand, suppressed oxidative stress and the production of these inflammatory cytokines. “These results show that impaired integrity of the intestinal barrier is the trigger to initiate the inflammatory cascade.”[ii]
They tested the effects of probiotics in this model and discovered “Probiotic treatment effectively reduced the oxidative stress, but it failed to ameliorate the epithelial barrier dysfunction and proinflammatory response when the probiotic administration happened after the DSS-induced barrier disruption.” Thus, they conclude, that in order to stop the inflammatory cascade, epithelial barrier function must first be restored and maintained.
If this all actually translates to in vivo experimentation, it would indicate that in order to successfully treat leaky gut, it’s necessary to reduce inflammation first, before taking probiotics: helminths, prebiotics , short-chain fatty acids, improved diet, and so forth are your first line natural treatments. Interestingly, those of us heavily involved in using the Specific Carbohydrate Diet noticed this phenomenon years ago. As a nutritionist, I always recommended several months of the diet and other natural anti-inflammatory treatments BEFORE staring clients on probiotics. When gut inflammation levels were at their highest at the start of the diet, probiotics were often extremely problematic, causing a myriad of side effects.
[i] Shin, W, Kim, HJ. Intestinal barrier dysfunction orchestrates the onset of inflammatory host-microbiome cross-talk in a human gut inflammation-on-a-chip. Proceedings of the National Academy of Sciences of the United States of America. 2018;115(45) E10539-E10547. https://doi.org/10.1073/pnas.1810819115