# Bifidobacterium animalis subsp. Lactis BL‐99 Improves Maternal and Fetal Immune Responses and Pregnancy Outcomes in Pregnant Antibiotics‐Treated Mice

## TL;DR

A specific Bifidobacterium strain improved immune responses and placental weight in pregnant mice treated with antibiotics.

## Contribution

BL-99 supplementation mitigates antibiotic-induced immune and placental issues in pregnant mice.

## Key findings

- BL-99 increased placental weight in antibiotic-treated pregnant mice.
- BL-99 improved maternal immune responses by altering Th1 and Treg cells.
- BL-99 enhanced fetal immune cell subsets and activation status.

## Abstract

The maternal gut microbiome is involved in adapting immune responses to the presence of the semiallogeneic foetus. We have previously shown that antibiotics‐induced gut dysbiosis, alterations in the maternal immune response and decreased foetal and placental weight. Here, we tested whether Bifidobacterium animalis subsp. lactis BL‐99 (BL‐99) could improve antibiotics‐induced gut dysbiosis, maternal immune responses and foetal and placental weight. To do so, pregnant mice received antibiotics in their drinking water (day 9‐16) and BL‐99 via oral gavage (day 9‐18). After sacrifice (day 18) immune responses were measured using flowcytometry. BL‐99 increased placental weight in antibiotics‐treated pregnant mice. BL‐99 did not significantly change the maternal microbiome, but improved maternal immune responses by decreasing splenic Th1 cells and Treg cells, and increasing FoxP3/RoRγT double‐positive cells in the Peyer's patches to levels observed in control pregnant mice. BL‐99 also improved monocyte subsets and activation status. Additionally, BL‐99 changed foetal monocyte subsets and activational status and increased foetal splenic Th cells. We thus showed that the effect of antibiotics treatment on immune cells and placental weight was mitigated by supplementation of BL‐99. We suggest that pregnancy complications associated with a disturbed microbiome and immune responses, such as preeclampsia or obese pregnancies, could benefit from BL‐99 supplementation. This should be tested in future studies.

Pregnant mice treated with antibiotics showed gut dysbiosis, which is associated with reduced fetal and placental weight, and disrupted maternal and fetal immune responses. Supplementation via oral gavage with Bifidobacterium animalis subsp. lactis BL‐99 increased B. animalis levels in the gut, but did not fully restore microbiome balance. However, BL‐99 supplementation significantly improved placental weight and immune responses, both in the mother and fetus, without affecting fetal weight.