How the body recognizes beneficial bacteria

Trillions of bacteria and other microbes thrive in our gut microbiome, and over the past decade, scientists have become increasingly aware of the important role

In a study published in the journal Immunology, researchers from MIT and the Broadbeach Institute of Harvard Infectious Diseases and Microbiome Project (IDMP), as well as the Massachusetts General Hospital's Center for Computational and Integrative Biology and the Department of Molecular Biology, took a new step

An antigen, SusC, was found and tolerated in the T cells of every healthy person the team observed

Daniel Graham, co-author of the study and director of functional genomics at IDMP, said: "For people with episodes of Crohn's disease, their T cells recognize this microbiome antigen, but instead of showing resistance to it, they develop an inflammatory response

In the eyes of T cells

Prior to their experiments, Graham, first author and visiting graduate student Thomas Pedersen, co-senior author and core institute member Ramnik Xavier, director of the Broad Immunology Program and co-director of IDMP, and his colleagues predicted that there may be many reasons why

"You can't answer these questions without knowing what the T cells see," Graham explains

To understand the promise of T cells, the team received help

The hBOTA analysis revealed more than 60 common antigens, mainly composed

The researchers hope to find "universal" gut microbiota antigens from many, if not all, human participants that can be tolerated by T cells, which makes the SusC discovery even more exciting

"Over the years, the Broad Institute's microbiome project and research into Crohn's disease have made progress, from identifying the starting microbiome for treating patients with primary celiac disease, to elucidating how microbes educate the immune system and linking specific bacterial metabolites to inflammation, and now presents a blueprint to identify microbial epitopes, calm or activate T cells," Xavier said

Clinical possibilities

The discovery of SusC allowed the research team to go beyond their initial experiments to explore how T cells in patients with gastrointestinal disorders respond

The team believes that it is possible to monitor the progression of Crohn's disease using SusC and similar antigens, which may allow clinicians to predict disease outbreaks before they break out

"We have shown in this study that T cells respond very dynamically to the microbiome," Graham said

Funding for this study was provided in part: the National Institutes of Health Center for Inflammatory Bowel Disease, the Helmsley Foundation, the MIT Center for Microinformatics and Therapeutics and Professor Kurt J.