Antibody repertoires against the microbiome

Humans live in symbiosis with microorganisms by maintaining a diverse population of bacteria and yeasts on their barrier surfaces, collectively named the microbiota. These microorganisms provide a range of benefits related to digestion, production of nutrients, detoxification, protection against pathogens and regulation of the immune system. The microbiota is engaged in a dynamic interaction with the immune system, affecting different aspects of its development and function. When one or more steps in this fine cross-talk fail, autoimmune or auto-inflammatory diseases (inadvertently targeting healthy human tissues) may occur. Despite growing efforts to investigate the interaction between microbiota and the immune system, studies of how the mutualistic relationship between the adaptive immune system and the microbiota affect health and disease are in their infancy. As an important part of the immune system antibodies have a crucial role in protecting the host from infections. Immunoglobulin A (IgA) antibodies are a major functional component of the immune system at mucosal sites such as the intestines. In addition to the intestines, it has been appreciated that microbiota- reactive antibodies can be found in the blood of healthy humans suggesting that the human body is prepared to respond to microorganisms that may escape the gastrointestinal tract. Lately it was reported that another type of antibodies (IgG) generated to target specific members of the microbiota can actively protect the host from infection of pathogenic bacteria spreading in the whole body. These findings support the ability of microbiota to affect and shape the immune system beyond the gastrointestinal tract. Here, a novel and broad approach is proposed to study the interaction between the microbiota and the immune system. Up to one million microbial elements will be tested using high throughput systems, typically applied in biotechnology, alongside next generation sequencing technologies. This combination of complementary approaches with deep sequencing will serve as a powerful tool to unravel the complex interaction of the microbiota and the immune system. The availability of this pipeline will allow to perform a broad research on different biological questions. Aside of insights into the underlying biological processes, these efforts will identify novel biomarkers and may pave the way for the development of new therapeutic approaches.

The human body is covered in microorganisms that live primarily on the skin and in the digestive tract and are referred to as the `microbiome`. An imbalance in microbiome composition can trigger autoimmune or autoinflammatory diseases (i.e., immune system reactions mistakenly directed against the human body). Despite growing efforts to understand the interactions between the microbiome and the human immune system, there are currently few systematic studies of this in the absence of suitable experimental systems. Conventional methods (such as antibody assays for Corona) usually only measure immune responses against an exemplary structure. However, the microbiome consists of thousands of microorganisms and hundreds of thousands of structures that have never been analyzed. In this work, we applied a new technology to analyze immune responses against 244000 microbial structures simultaneously. We have shown that even healthy people produce various antibodies against their own microbiome that affect human health. This technology has broad applications to better understand autoimmune or autoinflammatory diseases and to develop new therapies.