Argonne National Laboratory

New insights into regulating the gut’s microbial community

August 27, 2015

The human body is home to billions of microbial cells, a number roughly three to 10 times greater than the number of human cells. Many of these microbes reside in the gastrointestinal system, or gut, and form a symbiotic relationship with their human hosts. These “commensal” organisms do not causes illness and in fact provide us with crucial metabolic and nutritional benefits that we need in order to survive.

Potentially dangerous pathogenic microorganisms can also grow in our guts, however, and the human immune system must therefore distinguish between those microbes that benefit us and those that might harm us.

One of the primary battlefields between the mammalian host and its resident microorganisms, both good and bad, is the gut mucosal surface. Here the host secretes a variety of factors to regulate these microbes including mucus, antimicrobial peptides, and immunoglobulin A (IgA). Tagging by IgA is known to be one of the primary methods by which the immune system identifies unwanted organisms in order to eliminate them. In this way, IgA can help protect the body from pathogens such as viruses, bacteria, and toxins.

IgA also contributes, however, to maintaining an equilibrium with helpful microbes within the gut. Mice and humans with defects in their ability to secrete IgA are more susceptible to gastrointestinal disorders such as inflammatory bowel disease and celiac disease. IgA may regulate commensal community composition, gene expression, and motility, which in turn influence host epithelial physiology and innate immunity.

In a study published in the journal Immunity, researchers at Argonne National Laboratory (Theodore Flynn, Jason Koval, and Dionysios Antonopoulos) and the University of Chicago (Jeffrey Bunker and Albert Bendelac) have gained new insight into the role IgA plays in regulating the gut’s microbial community. Utilizing a novel approach to physically sort IgA-tagged cells, then extract DNA from those cells, and sequence the identifying genes from each one, the researchers were able to find groups of commensal bacteria targeted by the immune system in both mice and humans.

These findings indicate that multiple layers of the immune system are involved in flagging and controlling commensal bacteria, and that the IgA produced by different immune mechanisms (T-dependent and T-independent IgA) targets distinct populations of commensals. Furthermore, targeting of specific commensals was most pronounced in the small intestine.

Overall, these results shed an important new light on the role of IgA secretion in regulating specific populations of commensal bacteria and lay the groundwork for the development of future therapeutic interventions in the treatment of microbiota-associated pathologies such as inflammatory bowel disease, obesity, diabetes, and celiac disease.