Relationship between gut microbiome and autoimmunity

When we talk about a human body the first thing that comes to our mind are cells which are the building block of our body. But an interesting fact is that there are about 10 times as many as microbial cells in the human body as there are human cells, known as the gut microbiome. This has been the most favorite topic for researchers all around the world and they are trying to study this gut microbiome related to various aspects. In this report, we are going to understand the relationship between gut microbiome and autoimmunity.

What is autoimmunity?

Autoimmunity is a condition when the immune cells are misdirected and it attacks the body itself when the immune system cannot differentiate between self and non-self cells. There are many autoimmune diseases like rheumatoid arthritis, type 1 diabetes, etc. Though the reason behind autoimmune diseases is still not clear but there are various researches going on.

How gut microbiome is affecting our immune system?

1. Microbiome difference in healthy and disease individual

The genes of gut microbiome keep on interacting with the human genes and so human beings are best described as superorganisms. Many human genes are changed during a single microbial infection such as tuberculosis and so the foreign and host protein interaction is studied nowadays by researchers. It was observed in one of the researches that there are different proteins present in diseased patients due to altered gut microbiome.

2. Microbes subvert host immune system

Many pathogenic microbes enter our body and change various processes like transcription which sometimes result in dysregulation of receptors like vitamin D nuclear receptor (VDR). Since the VDR regulates 1000s of genes and also regulates key components of innate immune response including toll like receptor , which helps in clearing pathogens, and thus its dysregulation leads to autoimmune diseases. Those microbes which are capable of dysregulating such receptors increase their chance of survival, for example, Epstein Barr virus which is found in many autoimmune diagnoses.

3. Pathogens incorporated in the microbiome

When receptors like VDR are dysregulated the immune system becomes compromised and more vulnerable to pathogens which are known as successive infection. The pathogens then upregulate and downregulate various gene transcription as a result there is an accumulation of microbial  metabolite, which disturbs human metabolism and a shift from the homeostatic state of the microbiome, is observed. Eventually, as more pathogens incorporate in the gut microbiome the patients start observing symptoms relate to autoimmune diseases. The symptoms depend on species, location, and virulence of the pathogen.

4. Molecular mimicry

The structural and sequence homology of microbial proteins and genes with human proteins is known as molecular mimicry. It makes it difficult for the immune system to differentiate itself and nonself. This results in the production of autoantibodies that target human proteins causing collateral damage. For example, the pentamers of the Hepatitis C virus have a high level of similarity to the human proteome.

5. Familial inheritance of autoimmunity

Different types of autoimmune diseases are shared in the family tree. The researchers tried to find out the reason behind the inheritance of such autoimmune diseases it was observed that the autoimmune diseases run in families because they share common gut microbiome so it was concluded that autoimmunity is passed in families because of inheritance of familial microbiome but not mendelian inheritance.

Conclusion

Researchers are trying to find a treatment that targets the root cause of autoimmune diseases i.e by activating an innate immune response. There is a treatment that reactivates the VDR which helps in restoring the innate immune response. There is some clear image of the cause of some diseases like diabetes which were thought to be caused due to obesity, It is now believed that both the diseases are caused due to microbes by successive infection.