I don't know if you have any feelings, people now seem to be more "delicate" than they were decades ago.
This is really not an illusion, from the last century to the present, the incidence of human inflammatory diseases and autoimmune diseases is indeed increasing, and many scholars believe that this is inseparable from the air, water pollutants, as well as the increase in processed foods and food additives.
When it comes to food additives, in fact, Singularity Cake itself is not very exclusive. Refined sugar and lipids are another matter, in order to maintain the appearance of the product taste and shelf life of the additives are still more necessary, and they have also been tested, for healthy people is still safe is not.
However, this is true for healthy people, but not necessarily for a body that already has certain pathological changes.
A paper published today in the journal Cell Metabolism found that [1] two super super commonly used edible pigments, Luminous Red and Sunset Yellow, can actually induce colitis in mice with overexpression of IL-23! The mechanism behind this is related to IFN-γ, CD4+ T cells, and two specific intestinal bacteria. The research team came from mount Sinai Icahn School of Medicine in the United States.
Hey, eating, but it's really invincible...
The cause of this study is a bit of a oolong.
Speaking of autoimmune diseases, the team at Mount Sinai Icahn School of Medicine originally did research on inflammatory bowel disease (IBD).
Some previous studies have found that immune factors play an important role in the development of IBD, and interleukin-23 (IL-23) is the best and most thoroughly studied. Not only have human genome-wide association studies found a relationship between the IL-23 pathway and IBD, but recent clinical studies have also shown that treatments for IL-23 work well for different forms of IBD, such as Crohn's disease (CD) and ulcerative colitis (UC).
However, despite so many research results, there is no degree of research to determine that the upregulation of IL-23 expression can induce colitis in mice. That is, IL-23 is at best one of the factors that promote the development of colitis, rather than the underlying driver of the disease.
The Icahn Team at Mount Sinai has done similar research before and published a paper in 2018. At that time, they used tamoxifen (TAM) to induce mouse myelin cells to overexpress IL-23 through genetic engineering methods, but they had to cooperate with a special dietary regimen to induce colitis in mice.
That is very curious, what kind of rat food, so magical, eat actually onset the disease?
The paper began by trying to find the true ingredients in the mouse diet that induce the onset of colitis. But when researchers analyzed it painstakingly, they found that the truth was... An edible coloring used to mark whether there is a drug in rat food, Red 40.
Red 40 is strange to say, and it also has a name called Allura Red, that is, Temptation Red. Temptation Red is one of the most used food colorings in the world, with old data from 2011 showing that Temptation Red produces more than 2.3 million kilograms a year. You can also look at the colored drink snacks on hand, and whether there is a temptation red in the ingredient list.
After reading the paper, I couldn't help but go to a supermarket, not only the temptation red but also the sunset yellow
Although giving mice alone to induce red, or allowing mice alone to overexpress IL-23, did not induce colitis, when these two things appeared together, the mice immediately developed severe intestinal inflammation, and both the cecum and colon showed significant leukocyte infiltration, crypt loss, epithelial damage, and ulcers.
Given the super widespread use of temptation red, the researchers also deliberately tested two human foods containing temptation red, Kool-Aid and Pedialyte. Singularity Cake went to search for it, which is two electrolyte water punches, that is, beverage powder.
Naturally, they were also able to induce colitis in IL-23 overexpressed mice. Subsequent analyses also found that CD4+ T cells played a very important role in this, and the IFN-γ expressed by CD4+ T under the drive of IL-23 was the key.
Lure red + IL-23, significant colitis pathology can be observed on day 56
In fact, the results of this study are still a bit surprising, because the time of appearance of lure red is not short, and after extensive safety tests, it has not been found to be cytotoxic, carcinogenic or inducing genetic mutations. And humans have eaten temptation red for so many years, and they have not found anything that causes colitis or anything.
Researchers have an immunological concept in their heads – is it tolerated?
When the researchers tried to replace the order in which IL-23 and temptation red appeared, that is, let the mice eat the temptation red first, and then induce the expression of IL-23, the mice did not develop colitis.
If the CD4+ T of the mice that eat the temptation red is transplanted to the IL-23 overexpression mouse, then they will not have colitis when they eat the temptation red; conversely, the mice that have eaten the temptation red by transplanting the CD4+ T cells of the control group mice can still induce severe colitis in subsequent experiments.
It seems that there is indeed a process of "tolerance".
CD4+ T cells are the key to lure red
Among the many cytokines expressed by CD4+ T cells, IFN-γ is the core of pathology
The next step is to look for the mechanism behind the phenomenon.
Since it is "edible" and the story takes place in the intestine, it is difficult not to suspect that the gut microbiome has also mixed a foot in it. Sure enough, in sterile (GF) mice, the phenomenon of IL-23 + temptation red = colitis will not occur, which shows that the intestinal bacteria really have a role.
The next step is to think of Fa'er screening for specific intestinal bacteria. The researchers first roughly determined the range through antibiotics, then used sequencing to find more "active" flora, and finally compared with the database of enterobacteria related to the metabolism of lure red, and finally identified two types of enterobacteria, Bacteroides ovatus and Enteroccucus faecalis as the key to tempting red to "make bad".
Under the action of enterobacteria, the 1-amino-2 naphthol-6 sulfonate sodium salt (ANSA-Na) produced by the lure red metabolism is the more direct eccentric. However, ANSA-Na alone can not be done, or there must be intestinal bacteria, what is the story behind this, I don't know for the time being.
ANSA-Na is the real "black hand"
Because ANSA-Na was born out of the azo structure in the temptation red, the researchers suspected that other azo pigments also had the effect of promoting colitis, so they tested another food color, Yellow, or Sunset Yellow. You all get the results. The non-azo pigments erythro red (Red 3) and bright blue (Blue 1) did not cause colitis in IL-23 overexpressed mice.
But the study was conducted in mice after all, and it's unclear whether the same mechanism is available to humans. It can only be said that autoimmune diseases are really difficult to engage in, immunity can be really complicated, and there are too many intestinal bacteria tubes...
Resources:
[1]https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00181-9#%20
The author of this article | Generation Silk Rain