Your Gut Bacteria May Hold the Secret to Preventing Miscarriage

Beneficial gut bacteria may be crucial for preventing pregnancy loss by training a mother's immune system to accept the developing fetus, according to groundbreaking research from Weill Cornell Medicine. The study found that specific gut microbes produce metabolites that help recruit protective immune cells to the placenta, potentially offering new hope for women experiencing recurrent miscarriages.

How Do Gut Bacteria Protect Pregnancies?

The research team discovered that gut microbes produce metabolites from the amino acid tryptophan, which maintain protective immune cells at the maternal-fetal interface. These metabolites promote the recruitment of two types of protective immune cells: myeloid-derived suppressor cells (MDSCs) and RORγt+ regulatory T-cells (pTregs). "During pregnancy it's very important that the mom's immune system is trained to recognize that the fetus is not harmful," said senior author Melody Zeng, associate professor of immunology in pediatrics at Weill Cornell Medicine. "That prevents the maternal immune system from attacking the fetus, which can lead to recurrent miscarriages or still births."

What Happens When Gut Health Is Compromised?

The researchers studied two groups of mice with disrupted gut microbiomes: germ-free mice bred in sterile environments and mice treated with antibiotics. Both groups experienced significantly worse pregnancy outcomes compared to mice with healthy gut bacteria. The compromised microbiome groups developed several problematic immune responses:

• Excessive Inflammation: Increased inflammation in the placenta that led to fetal death
• Harmful T Cells: Excessive numbers of interferon-gamma-producing T cells that can attack the developing fetus
• Attacking Antibodies: Production of antibodies that target the fetus rather than protecting it

When researchers gave germ-free mice tryptophan metabolites or the specific bacteria that produce them, fetal survival rates dramatically improved from 50% to 95%.

Could This Explain Human Miscarriages?

The findings may have significant implications for human pregnancies. For more than half of women who experience repeat miscarriage, the underlying cause remains unknown according to the American College of Obstetricians and Gynecologists. When the research team examined tissue samples from women who had experienced recurrent miscarriages, they found reduced levels of the same tryptophan-derived metabolites and fewer tolerance-inducing immune cells that were protective in the mouse studies.

"The same immune cells we identified in the mice seem to be important for human pregnancies," said the study's first author, Julia Brown, a postdoctoral associate in pediatrics at Weill Cornell Medicine. "We need to do additional studies to confirm the role of these immune cells and tryptophan metabolites in human pregnancies."

The research team is now working toward developing targeted therapies that could enhance beneficial gut microbes or their metabolites to improve pregnancy outcomes. They plan to collaborate with physicians to evaluate supplements or interventions that could help women struggling with infertility or unexplained recurrent miscarriages, potentially offering new treatment options where none currently exist.