> Whats scary is that we have more and more civilization diseases and we have no idea whats causing them beside guesses.
We do have some good mechanistic hypotheses, but most reviews fail to describe them because a lot of research is hand wavy. However, things are slowly reaching mainstream.
Let's consider type 1 diabetes (T1D), which is a common autoimmune disorder where beta cells in the pancreas get destroyed by your own immune system. T1D was rare a century ago, and we know from patient records that incidence increases rapidly whenever a society becomes industrialized. For example, take the Karelia region split between Finland and Russia. People on both sides of the border have the same genetic background. However, children on the Finish side have 10x more incidence of insulin autoantibodies [1]. Microbiomes on both sides are actually very different, with Russian children resembling ancient non-industrialized ones.
The immune system is essentially a huge distributed memory where individual cells recognize small protein or lipid fragments as self or foreign, and then collectively decide whether there is an infection in the particular microenvironment they are exploring. We know T1D typically begins because the immune system recognizes a particular insulin chunk, the amino acid sequence SHLVEALYLVCGERGFF, as foreign. In other more complex autoimmune disorders this part is less clear.
It turns out that many gut bacteria mimic that particular insulin chunk [2]. That probably gives these commensal bacteria the ability to survive and avoid immune responses, and it is a flag of the symbiotic relationship these bacteria have developed with higher organisms in the last 100 million years. Now, the bacterial ecosystem of a modern gut has a lot less diversity than it should and therefore it is very fragile. We don't know exactly what happens before T1D, but one possibility is that these bacteria grow too much in abundance and therefore initiate autoimmunity as T cells found in the pancreas of T1D patients can't distinguish between one protein chunk from these bacteria and insulin.
There are similar patterns in other autoimmune disorders like multiple sclerosis. This patent aims to edit bacterial mimics that cause autoimmunity using a CRISPR system in a pill [3].
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4950857/ (Figure 1)
[2] https://www.medrxiv.org/content/10.1101/2022.05.11.22274678v... (Extended Table 1)
[3] https://patents.google.com/patent/US11224621B2/en (see e.g. Example 4)