Study reveals how gut microbes help ensure healthy, successful pregnancy

Pregnancy poses a unique challenge to the body’s immune system. The mother must protect herself from infections while also tolerating the semi foreign fetus. When this balance breaks down, immune cells can attack fetal tissues, leading to pregnancy loss. According to senior author Dr. Melody Zeng, the team wanted to uncover whether gut bacteria might influence this immune adaptation, given their known effects on inflammation and immune regulation.

To explore this, researchers used two mouse models: one completely germ free (raised in sterile conditions without bacteria, viruses, or fungi) and another treated with broad spectrum antibiotics to disrupt the microbiome. Compared with pregnant mice with healthy gut bacteria, these germ free and antibiotic treated mice showed excessive placental inflammation and up to 50 percent fetal loss. Their immune systems overproduced inflammatory T cells and antibodies that mistakenly targeted fetal tissues.

By contrast, mice with an intact microbiome had abundant myeloid derived suppressor cells (MDSCs) and RORγt⁺ regulatory T cells (pTregs)—immune cells that foster tolerance toward the fetus. The researchers traced these protective effects to tryptophan derived metabolites in the maternal bloodstream, produced by beneficial gut bacteria. When germ free mice were given these metabolites or the bacteria that make them, fetal survival increased from 50 to 95 percent. Administering unrelated bacteria had no such effect, confirming the specificity of this mechanism.

Corroborating evidence came from human tissue samples. Women who had experienced recurrent miscarriages showed lower levels of tryptophan metabolites and fewer tolerance inducing immune cells in uterine tissue, mirroring the mouse findings.

The study points toward a new frontier in reproductive medicine—targeting the gut microbiome to support healthy pregnancies. “Our research shows that certain gut bacteria help the immune system learn to see the fetus as safe,” said Dr. Zeng. The team now plans to explore microbial or metabolite based therapies that could help women facing infertility or unexplained pregnancy loss, bringing the concept of “gut to womb communication” into clinical focus.

REFERENCE: Brown, J. A., et al. (2025). Gut microbiota promotes immune tolerance at the maternal-fetal interface. Cell. doi: 10.1016/j.cell.2025.11.022. https://www.cell.com/cell/abstract/S0092-8674(25)01318-2