Structure of immunoglobulin A
Immunoglobulin A (IgA) is an antibody that is produced in the mucosal linings and is thought to play a critical role in maintaining the homeostasis between the body and the microbiome. IgA deficiency has been related to celiac disease and people who suffer from this deficiency are prone to bacterial infections. While studying IgA in mice, folks from Washington University, St. Louis noticed that IgA was not found in the feces of some mice, but was found in high levels in others. They investigated this high/low fecal IgA phenotype and showed that it was directly related to the microbiome. Their results were published last week in Nature.
The researchers began by doing various experiments between the high and low IgA mice. They first noted that mothers would pass their IgA phenotype to all their offspring, showing the trait was vertically transmitted. They then put high and low IgA mice in the same cages and learned that the low IgA trait was dominant, and high IgA mice would rapidly become low IgA mice. In order to discover if a virus was responsible, the scientists filtered the feces of low IgA mice to remove any bacteria and then transferred it into high IgA mice. These mice remained high in IgA, meaning that a bacteria, fungi, or other larger organisms were likely responsible.
The scientists then began experimentation with antibiotics. When broad spectrum antibiotics were given to low IgA mice it eliminated most of the bacteria in their gut. When these mice were given fecal transplants from high IgA mice, they became high IgA mice. This trait was also transferred to their progeny, and their children became high IgA mice. In addition, when the antibiotic ampicillin was administered to low IgA mice, their feces became high in IgA. Overall, these experiments led the scientists to believe that bacteria were responsible for the secreted IgA levels, and that ampicillin had the ability to kill whichever bacteria caused the low IgA phenotype.
The scientists then performed genetic analysis on all of their mice's stools to see which bacteria were present in high and low IgA fecal samples. There was one bacterial genus, Suterella, which was common to only low IgA mice. When this bacteria was cultured and given to high IgA mice, it caused them to become low IgA mice. Suterella apparently has the ability to confer the low IgA phenotype. (Interestingly, we had previously written about Suterella and its link to Down Syndrome and autism.)
Finally, the scientists studied the mechanism that could prevent IgA from being secreted in the low IgA mice, and they learned that it is likely the microbiome is both degrading IgA itself, and that it is degrading the proteins in the mucous responsible for secreting IgA.
Taken together these results show a very robust link between a specific phenotype and the microbiome. Before this study, most relationships between phenotypes, such as obesity, and the microbiome were merely associations, rather than causative. This study though, is crucial in that it shows secreted IgA levels can be directly caused by the microbiome, and there is a mechanism that explains the phenomenon.
