What is already known
Our body makes specific antibodies to prevent gut microbes from traveling from the gut to other tissues, but how these antibodies target the trillions of bacteria in the gut remains a mystery.
What this research adds
Researchers introduced one of eight species of bacteria into the guts of germ-free mice to investigate the cross-reactivity of immunoglobulin A — the most common type of antibody. Rather than targeting multiple species, IgAs mostly recognized one of the eight bacterial species, or even one strain of a species. Only two of the IgAs recognized all eight species of bacteria. When fed to mice with a weakened immune system, these antibodies could be found in stool samples, suggesting that they survive the harsh environment of the digestive tract.
Conclusions
The findings may inform strategies for treating intestinal diseases by targeting pathogens without killing beneficial gut bacteria.
Our body makes specific antibodies to prevent gut microbes from traveling from the gut to other tissues, but how these antibodies target the trillions of bacteria in the gut remains a mystery. Now, a study in mice suggests that immunoglobulin A — the most common type of antibody — are extremely specific to specific gut bacteria.
The findings, published in Science Immunology, may inform strategies for treating intestinal diseases by targeting pathogens without killing beneficial gut bacteria.
Scientists have known that the body makes IgA antibodies that bind to gut bacteria, and past research suggested that IgA in the gut can recognize many different species of bacteria.
These findings are in contrast with results from the new study conducted by Jeremiah Faith at Icahn School of Medicine at Mount Sinai and colleagues, who introduced one of eight species of bacteria into the guts of germ-free mice to investigate IgA cross-reactivity. The bacteria transferred to the gut of mice were representative of the diversity of microbes in the human gut.
Binding specificity
After living with bacteria in their guts, germ-free mice started to produce high levels of IgA antibodies.
After three weeks, the researchers extracted IgA antibodies from the blood and stool of the mice and tested how well the antibodies bound to other bacterial species. Rather than targeting multiple species, the IgAs mostly recognized one of the eight bacterial species.
“By unraveling the complex specificity of bacteria-induced gut IgA antibodies in gnotobiotic models, our findings highlight the potential role of gut IgAs in the symbiotic host-microbe interactions, because the coating of bacteria by IgA antibodies influences not only the homeostasis of the mucosal immune system but also the physiology of bacteria themselves,” the authors say.
Surviving the digestive tract
Next, the team colonized the germ-free mice’s gut with all eight species of bacteria. Three weeks later, the team used the animals’ antibody-producing B cells to generate large quantities of identical IgA antibodies.
Out of 21 IgAs, 19 targeted only one bacterial species, or even one strain of a species. Only two of the IgAs recognized all eight species of bacteria. When fed to mice with a weakened immune system, these antibodies could be found in stool samples, suggesting that they survive the harsh environment of the digestive tract.
“This observation implies the potential usage of in vitro engineered IgA antibodies as therapeutics,” the researchers say.
