Researchers have discovered that a powerful guardian gene known to protect against a variety of autoimmune diseases, including type 1 diabetes, is triggered by the bacteria in our gut. This finding offers a clue to the complex interaction between our genes, immune system and gut microbiota.
Scientists at the Harvard Medical School set out to investigate what factors influence the activity of a powerful gene complex known as the human leukocyte antigen (HLA). It has been known for some time that specific variants of HLA genes in humans and major histocompatibility complexes (MHC) in mice can protect against diseases such as type 1 diabetes, but how that influence is exerted has been a mystery.
The team focused on gut bacteria as being a potential catalyst for modulating the genes' activity. In a series of experiments, non-obese diabetic (NOD) mice engineered to carry a guardian gene were treated with gut bacteria killing antibiotics at various times in their development.
The mice treated with antibiotics during the first six weeks of life were found to subsequently develop symptoms of early stage type 1 diabetes despite holding the protective guardian gene. On the other hand, when treated with antibiotics at between six and 10 weeks of age, the mice still displayed signs of genetic diabetic resistance.
These results imply that early-life formation of gut microbiota has a significant effect on gene modulation influencing immune system behavior. The experiment also delivered antibiotics to mother mice in the 10 days before giving birth and discovered this also disrupted their offspring's genetic protections. This particularly highlights the influence of a mother's microbiota on her offspring.
Exactly how the bacteria in the gut affects gene activity is still unknown, but the researchers suggest that this offers clear evidence of how disrupting the early development of an individual's gut microbiome can usurp any genetic predisposition and alter proper immune function.
"Our findings need to be borne out in further experiments," says co-lead of the study Diane Mathis. "However, our results powerfully illustrate the notion that early antibiotic exposure can modulate disease risk and that avoiding or at least minimizing antibiotic treatment in infants and pregnant women during critical periods of development may be a good idea."
The last experiment the team conducted involved fecal transplants from mice with the guardian gene to mice without that genetic protection. The mice receiving the fecal transplant displayed a reduction in pancreatic cell inflammation, the general marker signaling the onset of type 1 diabetes. This solidifies the role gut bacteria plays in regulating our immune system and suggests future treatments for autoimmune diseases could be targeted at the gut microbiome.
The new research was published in the journal Proceedings of the National Academy of Sciences.
Source: Harvard Medical School
